Trial Outcomes & Findings for PALACE 2: Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis (NCT NCT01212757)

NCT ID: NCT01212757

Last Updated: 2020-05-06

Results Overview

Percentage of participants with an ACR20 response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦C-Reactive Protein.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 488 participants
• Primary outcome timeframe: Baseline and Week 16
• Results posted on: 2020-05-06

Participant Flow

This study was a multicenter study with 84 sites from the United States, Canada, Europe, Russia, Australia, South Africa and Taiwan.

This study consisted of a 24-week randomized, double-blind, placebo-controlled phase, a 28-week randomized, double-blind active treatment phase and a 4-year open-label safety phase, for an overall study duration of 5 years.

Participant milestones

Measure	Placebo Participants initially randomized to placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Placebo / Apremilast 20 mg EE Participants initially randomized to placebo twice daily in the 24-week placebo-controlled phase were re-randomized due to early escape (EE) at Week 16 and began receiving 20 mg apremilast tablets twice a day in the active treatment phase.	Placebo / Apremilast 20 mg XO Participants initially randomized to receive placebo twice daily in the 24-week placebo-controlled phase were re-randomized at Week 24 (XO) to 20 mg apremilast tablets twice daily in the active treatment phase.	Placebo / Apremilast 30 mg EE Participants initially randomized to placebo twice daily in the 24-week placebo controlled phase were re-randomized due to early escape (EE) at Week 16 to 30 mg apremilast tablets twice daily in the active-treatment phase.	Placebo / Apremilast 30 mg XO Participants initially randomized to placebo twice daily in the 24-week placebo-controlled phase were re-randomized at Week 24 to 30 mg apremilast tablets twice daily in the active treatment phase.	Placebo/Apremilast 20 mg (Long-Term Safety Phase) Participants initially randomized to placebo tablets twice daily during the placebo controlled phase were re-randomized to 20 mg apremilast twice daily at Week 16 or Week 24 and continued receiving apremilast 20 mg twice daily in the active treatment / long-term safety phase. (After 30 mg apremilast twice daily was identified as the optimal dose, all participants receiving 20 mg apremilast twice daily were switched to the 30 mg apremilast twice daily dose).	Placebo/Apremilast 30 mg (Long-Term Safety Phase) Participants initially randomized to placebo tablets twice daily during the placebo controlled phase were re-randomized to apremilast 30 mg tablets twice daily at Week 16 or Week 24 and continued receiving apremilast 30 mg twice daily in the active treatment / long-term safety phase.
Placebo-controlled Phase (Week 0 - 24) STARTED	162	163	163	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Received Treatment	159	163	162	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Completed Week 16	148	151	149	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Early Escape at Week 16	88	59	64	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) COMPLETED	143	143	142	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) NOT COMPLETED	19	20	21	0	0	0	0	0	0
Active Treatment Phase (Weeks 24 - 52) STARTED	0	137	134	43	27	41	28	0	0
Active Treatment Phase (Weeks 24 - 52) COMPLETED	0	125	114	35	25	34	28	0	0
Active Treatment Phase (Weeks 24 - 52) NOT COMPLETED	0	12	20	8	2	7	0	0	0
Long-Term Safety Phase (Year 2) STARTED	0	119	109	0	0	0	0	58	60
Long-Term Safety Phase (Year 2) COMPLETED	0	107	95	0	0	0	0	48	51
Long-Term Safety Phase (Year 2) NOT COMPLETED	0	12	14	0	0	0	0	10	9
Long-Term Safety Phase (Year 3) STARTED	0	107	95	0	0	0	0	48	51
Long-Term Safety Phase (Year 3) COMPLETED	0	89	84	0	0	0	0	42	46
Long-Term Safety Phase (Year 3) NOT COMPLETED	0	18	11	0	0	0	0	6	5
Long-Term Safety Phase (Year 4) STARTED	0	89	84	0	0	0	0	41	46
Long-Term Safety Phase (Year 4) COMPLETED	0	80	77	0	0	0	0	37	39
Long-Term Safety Phase (Year 4) NOT COMPLETED	0	9	7	0	0	0	0	4	7
Long-Term Safety Phase (Year 5) STARTED	0	80	77	0	0	0	0	38	39
Long-Term Safety Phase (Year 5) COMPLETED	0	72	69	0	0	0	0	33	37
Long-Term Safety Phase (Year 5) NOT COMPLETED	0	8	8	0	0	0	0	5	2

Reasons for withdrawal

Measure	Placebo Participants initially randomized to placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Placebo / Apremilast 20 mg EE Participants initially randomized to placebo twice daily in the 24-week placebo-controlled phase were re-randomized due to early escape (EE) at Week 16 and began receiving 20 mg apremilast tablets twice a day in the active treatment phase.	Placebo / Apremilast 20 mg XO Participants initially randomized to receive placebo twice daily in the 24-week placebo-controlled phase were re-randomized at Week 24 (XO) to 20 mg apremilast tablets twice daily in the active treatment phase.	Placebo / Apremilast 30 mg EE Participants initially randomized to placebo twice daily in the 24-week placebo controlled phase were re-randomized due to early escape (EE) at Week 16 to 30 mg apremilast tablets twice daily in the active-treatment phase.	Placebo / Apremilast 30 mg XO Participants initially randomized to placebo twice daily in the 24-week placebo-controlled phase were re-randomized at Week 24 to 30 mg apremilast tablets twice daily in the active treatment phase.	Placebo/Apremilast 20 mg (Long-Term Safety Phase) Participants initially randomized to placebo tablets twice daily during the placebo controlled phase were re-randomized to 20 mg apremilast twice daily at Week 16 or Week 24 and continued receiving apremilast 20 mg twice daily in the active treatment / long-term safety phase. (After 30 mg apremilast twice daily was identified as the optimal dose, all participants receiving 20 mg apremilast twice daily were switched to the 30 mg apremilast twice daily dose).	Placebo/Apremilast 30 mg (Long-Term Safety Phase) Participants initially randomized to placebo tablets twice daily during the placebo controlled phase were re-randomized to apremilast 30 mg tablets twice daily at Week 16 or Week 24 and continued receiving apremilast 30 mg twice daily in the active treatment / long-term safety phase.
Placebo-controlled Phase (Week 0 - 24) Adverse Event	4	5	12	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Lack of Efficacy	3	2	2	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Withdrawal by Subject	7	9	3	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Randomization Error	3	0	1	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Lost to Follow-up	1	1	2	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Protocol Violation	0	1	1	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Other	1	2	0	0	0	0	0	0	0
Active Treatment Phase (Weeks 24 - 52) Adverse Event	0	2	3	1	0	2	0	0	0
Active Treatment Phase (Weeks 24 - 52) Lack of Efficacy	0	5	7	4	0	2	0	0	0
Active Treatment Phase (Weeks 24 - 52) Non-compliance with Study Drug	0	0	2	0	0	0	0	0	0
Active Treatment Phase (Weeks 24 - 52) Withdrawal by Subject	0	3	7	3	1	3	0	0	0
Active Treatment Phase (Weeks 24 - 52) Lost to Follow-up	0	1	0	0	1	0	0	0	0
Active Treatment Phase (Weeks 24 - 52) Other	0	1	1	0	0	0	0	0	0
Long-Term Safety Phase (Year 2) Miscellaneous	0	0	0	0	0	0	0	0	1
Long-Term Safety Phase (Year 2) Adverse Event	0	1	1	0	0	0	0	2	2
Long-Term Safety Phase (Year 2) Lack of Efficacy	0	4	2	0	0	0	0	4	0
Long-Term Safety Phase (Year 2) Withdrawal by Subject	0	7	9	0	0	0	0	4	6
Long-Term Safety Phase (Year 2) Lost to Follow-up	0	0	2	0	0	0	0	0	0
Long-Term Safety Phase (Year 3) Adverse Event	0	4	1	0	0	0	0	2	0
Long-Term Safety Phase (Year 3) Lack of Efficacy	0	8	5	0	0	0	0	3	1
Long-Term Safety Phase (Year 3) Non-compliance with study drug	0	0	1	0	0	0	0	0	0
Long-Term Safety Phase (Year 3) Withdrawal by Subject	0	5	1	0	0	0	0	1	1
Long-Term Safety Phase (Year 3) Lost to Follow-up	0	0	0	0	0	0	0	0	1
Long-Term Safety Phase (Year 3) Protocol Violation	0	1	0	0	0	0	0	0	0
Long-Term Safety Phase (Year 3) Miscellaneous	0	0	3	0	0	0	0	0	2
Long-Term Safety Phase (Year 4) Miscellaneous	0	2	0	0	0	0	0	0	1
Long-Term Safety Phase (Year 4) Adverse Event	0	1	2	0	0	0	0	1	1
Long-Term Safety Phase (Year 4) Lack of Efficacy	0	2	2	0	0	0	0	1	1
Long-Term Safety Phase (Year 4) Withdrawal by Subject	0	4	2	0	0	0	0	1	3
Long-Term Safety Phase (Year 4) Death	0	0	1	0	0	0	0	0	1
Long-Term Safety Phase (Year 4) Lost to Follow-up	0	0	0	0	0	0	0	1	0
Long-Term Safety Phase (Year 5) Withdrawal by Subject	0	3	3	0	0	0	0	1	1
Long-Term Safety Phase (Year 5) Adverse Event	0	2	2	0	0	0	0	2	0
Long-Term Safety Phase (Year 5) Lack of Efficacy	0	1	2	0	0	0	0	2	1
Long-Term Safety Phase (Year 5) Non-compliance with study drug	0	1	0	0	0	0	0	0	0
Long-Term Safety Phase (Year 5) Miscellaneous	0	1	1	0	0	0	0	0	0

Baseline Characteristics

PALACE 2: Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis

Baseline characteristics by cohort

Measure	Placebo n=159 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=163 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=162 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Total n=484 Participants Total of all reporting groups
Age, Continuous	51.2 years STANDARD_DEVIATION 10.97 • n=5 Participants	50.9 years STANDARD_DEVIATION 11.82 • n=7 Participants	50.5 years STANDARD_DEVIATION 11.20 • n=5 Participants	50.9 years STANDARD_DEVIATION 11.32 • n=4 Participants
Sex: Female, Male Female	85 Participants n=5 Participants	95 Participants n=7 Participants	95 Participants n=5 Participants	275 Participants n=4 Participants
Sex: Female, Male Male	74 Participants n=5 Participants	68 Participants n=7 Participants	67 Participants n=5 Participants	209 Participants n=4 Participants
Duration of Psoriatic Arthritis	7.76 years STANDARD_DEVIATION 8.254 • n=5 Participants	7.83 years STANDARD_DEVIATION 8.621 • n=7 Participants	6.82 years STANDARD_DEVIATION 7.592 • n=5 Participants	7.47 years STANDARD_DEVIATION 8.163 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set consisting of all participants randomized as specified in the protocol; participants who were randomized in error and did not receive any dose of study drug were excluded. Participants who withdrew early or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.

Percentage of participants with an ACR20 response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦C-Reactive Protein.

Outcome measures

Measure	Placebo n=159 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=163 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=162 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16	18.9 percentage of participants	37.4 percentage of participants	32.1 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included; Last observation carried forward (LOCF) imputation was used.

The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

Outcome measures

Measure	Placebo n=153 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=159 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=154 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 16	-0.053 units on a scale Standard Error 0.0358	-0.157 units on a scale Standard Error 0.0351	-0.193 units on a scale Standard Error 0.0354	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.

Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦C-Reactive Protein.

Outcome measures

Measure	Placebo n=159 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=163 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=162 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With an ACR 20 Response at Week 24	15.7 percentage of participants	31.3 percentage of participants	24.7 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.

The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

Outcome measures

Measure	Placebo n=153 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=159 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=154 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24	-0.085 units on a scale Standard Error 0.0377	-0.165 units on a scale Standard Error 0.0370	-0.206 units on a scale Standard Error 0.0372	—

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included; LOCF was used.

The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.

Outcome measures

Measure	Placebo n=153 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=159 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=153 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16	0.81 units on a scale Standard Error 0.678	2.17 units on a scale Standard Error 0.664	2.91 units on a scale Standard Error 0.671	—

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; Participants who discontinued early, or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.

Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: - 78 tender joint count, - 76 swollen joint count, - Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; - Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS.

Outcome measures

Measure	Placebo n=159 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=163 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=162 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16	33.3 percentage of participants	47.9 percentage of participants	48.1 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included; LOCF was used.

The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.

Outcome measures

Measure	Placebo n=151 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=157 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=152 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in Patient's Assessment of Pain at Week 16	-7.0 mm Standard Error 1.93	-12.5 mm Standard Error 1.89	-11.9 mm Standard Error 1.90	—

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; participants with a baseline MASES \> 0 (i.e., pre-existing enthesopathy) and at least 1 postbaseline value at or prior to Week 16 are included; LOCF was used.

The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.

Outcome measures

Measure	Placebo n=100 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=105 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=97 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16	-1.0 units on a scale Standard Error 0.29	-0.9 units on a scale Standard Error 0.28	-1.4 units on a scale Standard Error 0.29	—

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set. Participants with a baseline dactylitis severity score \> 0 (i.e., pre-existing dactylitis) and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.

Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.

Outcome measures

Measure	Placebo n=63 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=75 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=70 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in Dactylitis Severity Score at Week 16	-1.1 units on a scale Standard Error 0.28	-0.8 units on a scale Standard Error 0.26	-1.3 units on a scale Standard Error 0.26	—

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: - 28 tender joint count (TJC), - 28 swollen joint count (SJC), - Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; - Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22.

Outcome measures

Measure	Placebo n=149 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=155 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=146 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16	-3.30 units on a scale Standard Error 0.871	-7.75 units on a scale Standard Error 0.851	-6.81 units on a scale Standard Error 0.869	—

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.

The DAS28 measures the severity of disease at a specific time and is derived from the following variables: - 28 tender joint count - 28 swollen joint count, which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; - C-reactive protein (CRP) - Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.

Outcome measures

Measure	Placebo n=150 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=156 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=151 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in the Disease Activity Score (DAS28) at Week 16	-0.27 units on a scale Standard Error 0.082	-0.74 units on a scale Standard Error 0.080	-0.67 units on a scale Standard Error 0.080	—

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.

The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.

Outcome measures

Measure	Placebo n=153 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=157 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=154 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16	0.63 units on a scale Standard Error 0.724	0.91 units on a scale Standard Error 0.712	2.75 units on a scale Standard Error 0.715	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.

The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.

Outcome measures

Measure	Placebo n=153 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=159 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=154 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 24	1.44 units on a scale Standard Error 0.688	2.97 units on a scale Standard Error 0.673	3.30 units on a scale Standard Error 0.679	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.

Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS.

Outcome measures

Measure	Placebo n=159 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=163 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=162 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24	24.5 percentage of participants	39.9 percentage of participants	32.1 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.

The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.

Outcome measures

Measure	Placebo n=152 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=158 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=153 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in Patient's Assessment of Pain at Week 24	-8.0 mm Standard Error 1.90	-11.5 mm Standard Error 1.86	-9.7 mm Standard Error 1.88	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; participants with a baseline MASES \> 0 (i.e., pre-existing enthesopathy) and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.

The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.

Outcome measures

Measure	Placebo n=100 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=105 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=98 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24	-0.9 units on a scale Standard Error 0.29	-0.9 units on a scale Standard Error 0.28	-1.3 units on a scale Standard Error 0.29	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set. Participants with a baseline dactylitis severity score \> 0 (i.e., pre-existing dactylitis) and at least 1 postbaseline value at or prior to Week 24 are included. LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.

Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.

Outcome measures

Measure	Placebo n=63 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=75 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=71 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in Dactylitis Severity Score at Week 24	-1.1 units on a scale Standard Error 0.27	-0.9 units on a scale Standard Error 0.25	-1.4 units on a scale Standard Error 0.26	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22.

Outcome measures

Measure	Placebo n=149 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=155 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=148 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24	-3.21 units on a scale Standard Error 0.884	-7.71 units on a scale Standard Error 0.864	-6.35 units on a scale Standard Error 0.878	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.

The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.

Outcome measures

Measure	Placebo n=150 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=157 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=152 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in the Disease Activity Score (DAS28) at Week 24	-0.27 units on a scale Standard Error 0.084	-0.73 units on a scale Standard Error 0.082	-0.65 units on a scale Standard Error 0.083	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.

The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.

Outcome measures

Measure	Placebo n=153 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=157 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=154 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24	0.52 units on a scale Standard Error 0.721	0.68 units on a scale Standard Error 0.710	2.65 units on a scale Standard Error 0.713	—

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; participants with a baseline MASES \> 0 (i.e., pre-existing enthesopathy) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.

Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.

Outcome measures

Measure	Placebo n=104 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=107 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=101 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With MASES Improvement ≥ 20% at Week 16	52.9 percentage of participants	54.2 percentage of participants	56.4 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; participants with a baseline dactylitis severity score \> 0 (i.e., pre-existing dactylitis) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.

Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.

Outcome measures

Measure	Placebo n=66 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=77 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=73 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16	59.1 percentage of participants	62.3 percentage of participants	61.6 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; Participants who discontinued early, or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.

A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2.

Outcome measures

Measure	Placebo n=159 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=163 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=162 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16	31.4 percentage of participants	53.4 percentage of participants	48.8 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; participants with a baseline MASES \> 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.

Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.

Outcome measures

Measure	Placebo n=104 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=107 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=101 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With MASES Improvement ≥ 20% at Week 24	51.0 percentage of participants	57.0 percentage of participants	57.4 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; participants with a baseline dactylitis severity score \> 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.

Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.

Outcome measures

Measure	Placebo n=66 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=77 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=73 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24	62.1 percentage of participants	68.8 percentage of participants	68.5 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.

EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2.

Outcome measures

Measure	Placebo n=159 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=163 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=162 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With Good or Moderate EULAR Response at Week 24	21.4 percentage of participants	41.7 percentage of participants	33.3 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; Participants who discontinued early, or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.

Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: o Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); o Patient's global assessment of disease activity (measured on a 100 mm VAS); o Physician's global assessment of disease activity (measured on a 100 mm VAS); o Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); o C-Reactive Protein.

Outcome measures

Measure	Placebo n=159 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=163 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=162 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With a ACR 50 Response at Week 16	5.0 percentage of participants	14.7 percentage of participants	10.5 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; Participants who discontinued early, or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.

Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: o Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); o Patient's global assessment of disease activity (measured on a 100 mm VAS); o Physician's global assessment of disease activity (measured on a 100 mm VAS); o Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); o C-Reactive Protein.

Outcome measures

Measure	Placebo n=159 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=163 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=162 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With an ACR 70 Response at Week 16	0.6 percentage of participants	3.7 percentage of participants	1.2 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.

Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: o Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); o Patient's global assessment of disease activity (measured on a 100 mm VAS); o Physician's global assessment of disease activity (measured on a 100 mm VAS); o Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); o C-Reactive Protein.

Outcome measures

Measure	Placebo n=159 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=163 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=162 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With an ACR 50 Response at Week 24	8.8 percentage of participants	14.1 percentage of participants	11.7 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.

Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦C-Reactive Protein.

Outcome measures

Measure	Placebo n=159 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=163 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=162 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With a ACR 70 Response at Week 24	3.1 percentage of participants	5.5 percentage of participants	2.5 percentage of participants	—

SECONDARY outcome

Timeframe: Week 16

Population: Full analysis set; participants with a baseline MASES \> 0 (i.e., pre-existing enthesopathy) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.

Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.

Outcome measures

Measure	Placebo n=104 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=107 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=101 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants Achieving a MASES Score of Zero at Week 16	23.1 percentage of participants	29.0 percentage of participants	20.8 percentage of participants	—

SECONDARY outcome

Timeframe: Week 16

Population: Full analysis set; participants with a baseline dactylitis severity score \> 0 (i.e., pre-existing dactylitis) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.

Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.

Outcome measures

Measure	Placebo n=66 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=77 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=73 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants Achieving a Dactylitis Score of Zero at Week 16	40.9 percentage of participants	42.9 percentage of participants	41.1 percentage of participants	—

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set; participants with a baseline MASES \> 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.

Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.

Outcome measures

Measure	Placebo n=104 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=107 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=101 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants Achieving a MASES Score of Zero at Week 24	24.0 percentage of participants	29.9 percentage of participants	22.8 percentage of participants	—

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set; participants with a baseline dactylitis severity score \> 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.

Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.

Outcome measures

Measure	Placebo n=68 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=59 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=68 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24	40.9 percentage of participants	44.2 percentage of participants	46.6 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population consists of all participants who were randomized or re-randomized to apremilast at any time during the study. Only those participants who had sufficient data for a definitive determination of response status at Week 52 are included.

Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method.

Outcome measures

Measure	Placebo n=60 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=61 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=121 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=116 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With a ACR 20 Response at Week 52	53.3 percentage of participants Interval 40.0 to 66.3	47.5 percentage of participants Interval 34.6 to 60.7	52.9 percentage of participants Interval 43.6 to 62.0	52.6 percentage of participants Interval 43.1 to 61.9

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.

The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

Outcome measures

Measure	Placebo n=60 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=63 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=125 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=117 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52	-0.208 units on a scale Standard Deviation 0.4831	-0.310 units on a scale Standard Deviation 0.5990	-0.192 units on a scale Standard Deviation 0.5729	-0.330 units on a scale Standard Deviation 0.5089

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.

The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.

Outcome measures

Measure	Placebo n=60 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=63 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=124 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=115 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in the SF-36 Physical Functioning Scale Score at Week 52	4.13 units on a scale Standard Deviation 9.106	5.97 units on a scale Standard Deviation 9.612	4.05 units on a scale Standard Deviation 8.752	4.97 units on a scale Standard Deviation 9.656

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants who had sufficient data for a definitive determination of response status at Week 52 are included.

Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. Two-sided 95% confidence interval is based on the Clopper-Pearson method.

Outcome measures

Measure	Placebo n=60 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=60 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=123 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=114 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With a Modified PsARC Response at Week 52	78.3 percentage of participants Interval 65.8 to 87.9	73.3 percentage of participants Interval 60.3 to 83.9	72.4 percentage of participants Interval 63.6 to 80.0	74.6 percentage of participants Interval 65.6 to 82.3

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.

The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.

Outcome measures

Measure	Placebo n=60 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=62 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=125 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=117 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in the Patient Assessment of Pain at Week 52	-15.6 mm Standard Deviation 23.77	-16.0 mm Standard Deviation 24.48	-13.5 mm Standard Deviation 27.78	-12.9 mm Standard Deviation 26.54

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a baseline value \> 0 (i.e., pre-existing enthesopathy) and a Week 52 value are included.

The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.

Outcome measures

Measure	Placebo n=40 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=39 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=80 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=78 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52	-2.5 units on a scale Standard Deviation 4.41	-2.5 units on a scale Standard Deviation 2.73	-1.7 units on a scale Standard Deviation 3.12	-2.1 units on a scale Standard Deviation 2.82

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a baseline value \> 0 (i.e., pre-existing dactylitis) and a Week 52 value are included.

Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.

Outcome measures

Measure	Placebo n=23 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=27 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=57 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=60 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in the Dactylitis Severity Score at Week 52	-1.9 units on a scale Standard Deviation 1.14	-2.1 units on a scale Standard Deviation 2.32	-1.8 units on a scale Standard Deviation 1.98	-1.8 units on a scale Standard Deviation 2.06

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22.

Outcome measures

Measure	Placebo n=60 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=60 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=123 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=114 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in the CDAI Score at Week 52	-13.66 units on a scale Standard Deviation 9.811	-13.13 units on a scale Standard Deviation 13.148	-12.03 units on a scale Standard Deviation 10.492	-14.38 units on a scale Standard Deviation 11.531

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.

The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.

Outcome measures

Measure	Placebo n=60 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=62 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=125 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=117 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in the DAS28 at Week 52	-1.18 units on a scale Standard Deviation 1.015	-1.18 units on a scale Standard Deviation 1.366	-1.11 units on a scale Standard Deviation 1.059	-1.30 units on a scale Standard Deviation 1.033

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.

The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.

Outcome measures

Measure	Placebo n=59 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=63 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=123 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=115 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Change From Baseline in the FACIT-Fatigue Scale Score at Week 52	1.97 units on a scale Standard Deviation 8.544	4.95 units on a scale Standard Deviation 9.414	2.45 units on a scale Standard Deviation 9.481	4.38 units on a scale Standard Deviation 9.847

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants with a baseline MASES \> 0 (i.e., pre-existing enthesopathy) and who had sufficient data for a definitive determination of response status at Week 52 are included.

Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 52 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method.

Outcome measures

Measure	Placebo n=40 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=39 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=80 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=78 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With MASES Improvement ≥ 20% at Week 52	72.5 percentage of participants Interval 56.1 to 85.4	79.5 percentage of participants Interval 63.5 to 90.7	70.0 percentage of participants Interval 58.7 to 79.7	69.2 percentage of participants Interval 57.8 to 79.2

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; Participants with a baseline dactylitis severity score \> 0 (i.e., pre-existing dactylitis) and who had sufficient data for a definitive determination of response status at Week 52 are included.

Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method.

Outcome measures

Measure	Placebo n=23 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=27 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=57 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=60 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 52	95.7 percentage of participants Interval 78.1 to 99.9	88.9 percentage of participants Interval 70.8 to 97.6	80.7 percentage of participants Interval 68.1 to 90.0	85.0 percentage of participants Interval 73.4 to 92.9

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants who had sufficient data for a definitive determination of response status at Week 52 are included.

A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2.

Outcome measures

Measure	Placebo n=60 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=62 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=125 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=117 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52	70.0 percentage of participants	64.5 percentage of participants	68.0 percentage of participants	67.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants who had sufficient data for a definitive determination of response status at Week 52 are included.

Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method.

Outcome measures

Measure	Placebo n=59 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=62 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=120 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=118 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With an ACR 50 Response at Week 52	30.5 percentage of participants Interval 19.2 to 43.9	27.4 percentage of participants Interval 16.9 to 40.2	26.7 percentage of participants Interval 19.0 to 35.5	18.6 percentage of participants Interval 12.1 to 26.9

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants who had sufficient data for a definitive determination of response status at Week 52 are included.

Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method.

Outcome measures

Measure	Placebo n=59 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=63 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=123 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=118 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants With an ACR 70 Response at Week 52	16.9 percentage of participants Interval 8.4 to 29.0	14.3 percentage of participants Interval 6.7 to 25.4	9.8 percentage of participants Interval 5.1 to 16.4	6.8 percentage of participants Interval 3.0 to 12.9

SECONDARY outcome

Timeframe: Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants with a baseline value \> 0 (i.e., pre-existing enthesopathy) and who had sufficient data for a definitive determination of response status at Week 52 are included.

Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method.

Outcome measures

Measure	Placebo n=40 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=39 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=80 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=78 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants Achieving a MASES Score of Zero at Week 52	42.5 percentage of participants Interval 27.0 to 59.1	41.0 percentage of participants Interval 25.6 to 57.9	40.0 percentage of participants Interval 29.2 to 51.6	37.2 percentage of participants Interval 26.5 to 48.9

SECONDARY outcome

Timeframe: Week 52

Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; Participants with a baseline dactylitis severity score \> 0 (i.e., pre-existing dactylitis) and who had sufficient data for a definitive determination of response status at Week 52 are included.

Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method.

Outcome measures

Measure	Placebo n=23 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=27 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=57 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg n=60 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Percentage of Participants Achieving a Dactylitis Score of Zero at Week 52	78.3 percentage of participants Interval 56.3 to 92.5	77.8 percentage of participants Interval 57.7 to 91.4	57.9 percentage of participants Interval 44.1 to 70.9	65.0 percentage of participants Interval 51.6 to 76.9

SECONDARY outcome

Timeframe: Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants (placebo participants who remained on placebo through week 24 and participants randomized to the APR 20 mg BID or APR 30 mg BID)

Population: Safety population included all participants who were randomized and received at least one dose of IP.

A treatment emergent adverse event (TEAE) is an AE with a start date on or after the date of the first dose of Investigational Product (IP). The severity of each adverse event (AE) and serious AE (SAE) was assessed by the investigator and graded based on a scale from Mild - mild symptoms to Severe AEs (non-serious or serious). A serious adverse event (SAE) is any AE which:

• Resulted in death
• Was life-threatening
• Required inpatient hospitalization or prolongation of existing hospitalization
• Resulted in persistent or significant disability/incapacity
• Was a congenital anomaly/birth defect
• Constituted an important medical event

Outcome measures

Measure	Placebo n=159 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=163 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=162 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Number of Participants With Treatment Emergent Adverse Events During the Placebo-Controlled Phase Any TEAE	72 Participants	106 Participants	96 Participants	—
Number of Participants With Treatment Emergent Adverse Events During the Placebo-Controlled Phase Any Drug-Related TEAE	28 Participants	53 Participants	57 Participants	—
Number of Participants With Treatment Emergent Adverse Events During the Placebo-Controlled Phase Any Severe TEAE	5 Participants	3 Participants	11 Participants	—
Number of Participants With Treatment Emergent Adverse Events During the Placebo-Controlled Phase Any Serious TEAE (SAE)	3 Participants	6 Participants	4 Participants	—
Number of Participants With Treatment Emergent Adverse Events During the Placebo-Controlled Phase Any Drug-Related SAE	0 Participants	3 Participants	1 Participants	—
Number of Participants With Treatment Emergent Adverse Events During the Placebo-Controlled Phase Any TEAE Leading to Drug Interruption	11 Participants	16 Participants	31 Participants	—
Number of Participants With Treatment Emergent Adverse Events During the Placebo-Controlled Phase Any TEAE Leading to Drug Withdrawal	3 Participants	5 Participants	12 Participants	—
Number of Participants With Treatment Emergent Adverse Events During the Placebo-Controlled Phase Any TEAE Leading to Death	0 Participants	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Week 0 to week 260; overall median duration of exposure to apremilast 20 mg and 30 mg BID was 198 weeks

Population: Apremilast subjects as treated who received at least 1 dose of apremilast at any time during the study at week 0, week 16 or week 24.

A treatment emergent adverse event (TEAE) is an AE with a start date on or after the date of the first dose of Investigational Product (IP). The severity of each adverse event (AE) and serious AE (SAE) was assessed by the investigator and graded based on a scale from Mild - mild symptoms to Severe AEs (non-serious or serious). A serious adverse event (SAE) is any AE which:

• Resulted in death
• Was life-threatening
• Required inpatient hospitalization or prolongation of existing hospitalization
• Resulted in persistent or significant disability/incapacity
• Was a congenital anomaly/birth defect
• Constituted an important medical event

Outcome measures

Measure	Placebo n=234 Participants Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Apremilast 20 mg n=113 Participants Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the active treatment/long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to 30 mg apremilast BID dose).	Apremilast 30 mg n=234 Participants Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Number of Participants With TEAEs During the Apremilast-Exposure Period Any TEAE	202 participants	53 participants	207 participants	—
Number of Participants With TEAEs During the Apremilast-Exposure Period Any Drug-related TEAE	102 participants	5 participants	100 participants	—
Number of Participants With TEAEs During the Apremilast-Exposure Period Any Severe TEAE	35 participants	2 participants	37 participants	—
Number of Participants With TEAEs During the Apremilast-Exposure Period Any Serious TEAE	41 participants	5 participants	41 participants	—
Number of Participants With TEAEs During the Apremilast-Exposure Period Any Serious Drug-related TEAE	6 participants	1 participants	6 participants	—
Number of Participants With TEAEs During the Apremilast-Exposure Period Any TEAE Leading to Drug Interruption	47 participants	4 participants	65 participants	—
Number of Participants With TEAEs During the Apremilast-Exposure Period Any TEAE Leading to Drug Withdrawal	24 participants	3 participants	30 participants	—
Number of Participants With TEAEs During the Apremilast-Exposure Period Any TEAE Leading to Death	0 participants	0 participants	2 participants	—

Adverse Events

Weeks 0-24: Placebo (Placebo-Controlled Phase)

Serious events: 3 serious events

Other events: 38 other events

Deaths: 0 deaths

Weeks 0-24: Apremilast 20 mg (Placebo- Controlled Phase)

Serious events: 6 serious events

Other events: 73 other events

Deaths: 0 deaths

Weeks 0-24: Apremilast 30 mg (Placebo- Controlled Phase)

Serious events: 4 serious events

Other events: 82 other events

Deaths: 0 deaths

APR Exposure Period Up to 5 Years: APR 20 mg

Serious events: 41 serious events

Other events: 154 other events

Deaths: 0 deaths

APR Exposure Period Up to 5 Years: APR 20mg/30 mg

Serious events: 5 serious events

Other events: 19 other events

Deaths: 0 deaths

APR Exposure Period Up to 5 Years: APR 30 mg

Serious events: 41 serious events

Other events: 166 other events

Deaths: 0 deaths

Serious adverse events

Measure	Weeks 0-24: Placebo (Placebo-Controlled Phase) n=159 participants at risk Participants received placebo tablets twice daily during the placebo-controlled phase. Includes data through Week 16 for participants who escaped early, and through Week 24 for all other participants.	Weeks 0-24: Apremilast 20 mg (Placebo- Controlled Phase) n=163 participants at risk Participants received 20 mg apremilast tablets PO BID during the 24-week placebo-controlled phase.	Weeks 0-24: Apremilast 30 mg (Placebo- Controlled Phase) n=162 participants at risk Participants received 30 mg apremilast tablets PO BID during the 24-week placebo-controlled phase.	APR Exposure Period Up to 5 Years: APR 20 mg n=234 participants at risk Participants who received apremilast 20 mg tablets twice daily regardless of when the apremilast exposure started (at Week 0, 16 or 24). Only the TEAEs that occurred during apremilast 20 mg BID treatment (before the switch to 30 mg apremilast) were included.	APR Exposure Period Up to 5 Years: APR 20mg/30 mg n=113 participants at risk Participants who switched from apremilast 20 mg BID to apremilast 30 mg BID. Only the TEAEs that occurred during APR 30 mg BID treatment were included.	APR Exposure Period Up to 5 Years: APR 30 mg n=234 participants at risk Participants who received 30 mg apremilast twice daily regardless of when their apremilast-exposure started (at Weeks 0, 16, or 24).
Gastrointestinal disorders Oesophagitis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Vascular disorders Peripheral vascular disorder	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Vascular disorders Arterial thrombosis limb	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.85% 2/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Vascular disorders Deep vein thrombosis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Blood and lymphatic system disorders Anaemia	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Cardiac disorders Acute myocardial infarction	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.85% 2/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Cardiac disorders Angina unstable	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Cardiac disorders Atrial fibrillation	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Cardiac disorders Atrial tachycardia	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Cardiac disorders Cardiac arrest	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Cardiac disorders Hypertensive heart disease	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.62% 1/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Cardiac disorders Myocardial ischaemia	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.61% 1/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.85% 2/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Cardiac disorders Palpitations	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.61% 1/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.85% 2/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Congenital, familial and genetic disorders Hydrocele	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Ear and labyrinth disorders Vertigo	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.61% 1/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Endocrine disorders Goitre	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Abdominal adhesions	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Colitis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Diarrhoea	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.61% 1/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.85% 2/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Gastric volvulus	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Gastritis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.61% 1/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Hernial eventration	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Hiatus hernia	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Inguinal hernia	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Inguinal hernia, obstructive	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Intestinal obstruction	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Intestinal perforation	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Pancreatitis acute	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
General disorders Pyrexia	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.85% 2/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Hepatobiliary disorders Cholecystitis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Hepatobiliary disorders Cholelithiasis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.85% 2/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Hepatobiliary disorders Hepatitis acute	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Immune system disorders Hypersensitivity	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Abscess soft tissue	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.88% 1/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Arthritis infective	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Bronchitis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Cellulitis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Diverticulitis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.85% 2/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Gastroenteritis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.88% 1/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Gastrointestinal bacterial infection	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Lobar pneumonia	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Vascular disorders Hypertension	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.62% 1/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Neuroborreliosis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Oral candidiasis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Peritoneal abscess	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Pneumonia	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Scrotal abscess	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Sepsis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Septic shock	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Skin candida	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Urinary tract infection bacterial	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Injury, poisoning and procedural complications Contusion	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Injury, poisoning and procedural complications Dislocation of vertebra	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Injury, poisoning and procedural complications Foreign body	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Injury, poisoning and procedural complications Graft haemorrhage	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Injury, poisoning and procedural complications Head injury	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Injury, poisoning and procedural complications Limb injury	0.63% 1/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Injury, poisoning and procedural complications Tendon injury	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.62% 1/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Injury, poisoning and procedural complications Vascular pseudoaneurysm	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.85% 2/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Musculoskeletal and connective tissue disorders Acquired claw toe	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Vascular disorders Peripheral ischaemia	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Musculoskeletal and connective tissue disorders Bunion	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Musculoskeletal and connective tissue disorders Foot deformity	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.62% 1/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.85% 2/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.63% 1/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	1.3% 3/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.85% 2/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.88% 1/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Musculoskeletal and connective tissue disorders Psoriatic arthropathy	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	1.3% 3/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of thyroid gland	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign renal neoplasm	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer stage 0	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.88% 1/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostatic adenoma	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.88% 1/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) T-cell lymphoma	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tonsil cancer	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Nervous system disorders Brain stem stroke	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Nervous system disorders Carotid artery disease	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Nervous system disorders Cerebral infarction	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.85% 2/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Nervous system disorders Cerebrovascular accident	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Nervous system disorders Diabetic neuropathy	0.63% 1/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Nervous system disorders Headache	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.62% 1/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Nervous system disorders Migraine	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Nervous system disorders Tension headache	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.62% 1/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Nervous system disorders Transient ischaemic attack	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Psychiatric disorders Anxiety	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.61% 1/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Psychiatric disorders Depression	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.61% 1/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	1.3% 3/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Psychiatric disorders Schizoaffective disorder	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Renal and urinary disorders Calculus ureteric	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Renal and urinary disorders Renal failure acute	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Renal and urinary disorders Renal tubular necrosis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Renal and urinary disorders Urethral stenosis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Reproductive system and breast disorders Menometrorrhagia	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.62% 1/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Reproductive system and breast disorders Ovarian cyst	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.61% 1/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Reproductive system and breast disorders Pelvic floor muscle weakness	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.88% 1/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Reproductive system and breast disorders Uterine haemorrhage	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Reproductive system and breast disorders Uterine polyp	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Reproductive system and breast disorders Uterine prolapse	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Respiratory, thoracic and mediastinal disorders Nasal turbinate hypertrophy	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.61% 1/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Skin and subcutaneous tissue disorders Lichen planus	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Skin and subcutaneous tissue disorders Psoriasis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Vascular disorders Aortic aneurysm	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Vascular disorders Subclavian artery stenosis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.43% 1/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks

Other adverse events

Measure	Weeks 0-24: Placebo (Placebo-Controlled Phase) n=159 participants at risk Participants received placebo tablets twice daily during the placebo-controlled phase. Includes data through Week 16 for participants who escaped early, and through Week 24 for all other participants.	Weeks 0-24: Apremilast 20 mg (Placebo- Controlled Phase) n=163 participants at risk Participants received 20 mg apremilast tablets PO BID during the 24-week placebo-controlled phase.	Weeks 0-24: Apremilast 30 mg (Placebo- Controlled Phase) n=162 participants at risk Participants received 30 mg apremilast tablets PO BID during the 24-week placebo-controlled phase.	APR Exposure Period Up to 5 Years: APR 20 mg n=234 participants at risk Participants who received apremilast 20 mg tablets twice daily regardless of when the apremilast exposure started (at Week 0, 16 or 24). Only the TEAEs that occurred during apremilast 20 mg BID treatment (before the switch to 30 mg apremilast) were included.	APR Exposure Period Up to 5 Years: APR 20mg/30 mg n=113 participants at risk Participants who switched from apremilast 20 mg BID to apremilast 30 mg BID. Only the TEAEs that occurred during APR 30 mg BID treatment were included.	APR Exposure Period Up to 5 Years: APR 30 mg n=234 participants at risk Participants who received 30 mg apremilast twice daily regardless of when their apremilast-exposure started (at Weeks 0, 16, or 24).
Gastrointestinal disorders Abdominal pain	0.63% 1/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	2.5% 4/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	1.2% 2/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	6.0% 14/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.8% 9/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Abdominal pain upper	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	2.5% 4/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.1% 5/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	4.7% 11/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.88% 1/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	5.6% 13/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Diarrhoea	5.0% 8/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	11.0% 18/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	15.4% 25/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	14.1% 33/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	17.1% 40/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Dyspepsia	0.63% 1/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	2.5% 4/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.1% 5/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	5.1% 12/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	5.1% 12/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Nausea	1.9% 3/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	9.2% 15/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	16.0% 26/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	10.7% 25/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.88% 1/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	15.8% 37/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Gastrointestinal disorders Vomiting	1.3% 2/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.1% 5/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.7% 6/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	4.3% 10/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.88% 1/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	5.1% 12/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Bronchitis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.1% 5/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.7% 6/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	8.1% 19/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.88% 1/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	12.8% 30/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Influenza	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	2.5% 4/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	1.9% 3/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	5.6% 13/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	4.3% 10/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Nasopharyngitis	3.8% 6/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	5.5% 9/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	5.6% 9/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	12.0% 28/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.5% 4/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	12.8% 30/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Pharyngitis	1.3% 2/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.61% 1/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	1.2% 2/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.4% 8/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.88% 1/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	6.4% 15/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Rhinitis	0.63% 1/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.61% 1/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.62% 1/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	2.1% 5/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	5.6% 13/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Sinusitis	2.5% 4/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	2.5% 4/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	1.9% 3/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	7.3% 17/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.88% 1/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	6.4% 15/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Upper respiratory tract infection	3.8% 6/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	8.6% 14/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	6.8% 11/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	17.9% 42/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.5% 4/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	15.8% 37/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Infections and infestations Urinary tract infection	1.3% 2/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	1.8% 3/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.62% 1/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	7.7% 18/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.5% 4/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	5.6% 13/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Metabolism and nutrition disorders Hypercholesterolaemia	0.63% 1/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.61% 1/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	6.0% 14/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.0% 7/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.1% 5/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	1.9% 3/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	9.4% 22/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	6.0% 14/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.62% 1/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	4.7% 11/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	1.8% 2/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	5.1% 12/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Nervous system disorders Headache	4.4% 7/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	5.5% 9/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	11.1% 18/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	9.8% 23/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	12.4% 29/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Psychiatric disorders Depression	1.3% 2/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.61% 1/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	5.6% 13/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.0% 7/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Psychiatric disorders Insomnia	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	1.8% 3/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.62% 1/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	6.0% 14/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	5.1% 12/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	2.5% 4/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	1.9% 3/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	5.1% 12/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	0.00% 0/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	6.4% 15/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks
Vascular disorders Hypertension	4.4% 7/159 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	2.5% 4/163 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.1% 5/162 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	9.0% 21/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	3.5% 4/113 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks	9.4% 22/234 • AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs are reported for the Apremilast Exposure Period from Week 0 to Week 260; overall median exposure to apremilast was 198 weeks

Additional Information

Associate Director, Clinical Trials Disclosure

Celgene Corporation

Phone: 1-888-260-1599

Email: clinicaltrialdisclosure@celgene.com

Results disclosure agreements

• Principal investigator is a sponsor employee Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 days. Investigator must delete confidential information before submission or defer publication to permit patent applications.
• Publication restrictions are in place

Restriction type: OTHER