Trial Outcomes & Findings for Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis (PsA) (NCT NCT01307423)

Last Updated: 2022-06-14

Results Overview

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

529 participants

Primary outcome timeframe

Baseline and Week 16

Results posted on

2022-06-14

Participant Flow

The study was conducted in 16 countries including the United States, Canada, Europe, New Zealand, Australia and Russia.

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

Participant milestones
Measure	Placebo Participants initially randomized to receive 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 receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase and continued to receive 20 mg apremilast tablets twice daily for up to 4.5 years in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase and continued to receive 30 mg apremilast tablets twice daily for up to 4.5 years in the active treatment / long-term safety phase.	Placebo/ Apremilast 20 mg EE Participants initially randomized to receive placebo twice daily who were re-randomized due to early escape (EE) at Week 16 to receive 20 mg apremilast twice daily in the active treatment phase.	Placebo / Apremilast 20 mg XO Participants initially randomized to receive placebo twice daily who were re-randomized at Week 24 (XO) to receive 20 mg apremilast twice daily in the active treatment phase.	Placebo / Apremilast 30 mg EE Participants initially randomized to receive placebo twice daily who were re-randomized due to early escape (EE) at Week 16 to receive 30 mg apremilast twice daily in the active treatment phase.	Placebo / Apremilast 30 mg XO Participants initially randomized to receive placebo twice daily who were re-randomized at Week 24 to receive 30 mg apremilast twice daily in the active treatment phase.	Placebo/Apremilast 20 mg [Long-Term Safety Phase (LTSP)] Participants initially randomized to placebo tablets twice daily during the 24-week placebo-controlled phase were re-randomized to 20 mg apremilast tablets twice daily at Week 16 or Week 24 and continued receiving apremilast 20 mg tablets twice daily in 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 the 30 mg apremilast BID dose).	Placebo/Apremilast 30 mg (Long-Term Safety Phase) Participants initially randomized to placebo tablets BID during the 24-week 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 tablets twice daily in the active treatment / long-term safety phase.
Placebo-controlled Phase (Week 0 - 24) STARTED	176	175	177	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Received Treatment	176	175	175	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Completed Week 16	166	168	166	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Early Escape at Week 16	103	73	79	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) COMPLETED	156	160	155	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) NOT COMPLETED	20	15	22	0	0	0	0	0	0
Active Treatment Phase (Week 25-52) STARTED	0	151	150	46	26	46	26	0	0
Active Treatment Phase (Week 25-52) COMPLETED	0	132	141	38	23	43	25	0	0
Active Treatment Phase (Week 25-52) NOT COMPLETED	0	19	9	8	3	3	1	0	0
Long-term Safety Phase (Year 2) STARTED	0	122	134	0	0	0	0	57	67
Long-term Safety Phase (Year 2) COMPLETED	0	99	109	0	0	0	0	48	60
Long-term Safety Phase (Year 2) NOT COMPLETED	0	23	25	0	0	0	0	9	7
Long-term Safety Phase (Year 3) STARTED	0	99	109	0	0	0	0	48	60
Long-term Safety Phase (Year 3) COMPLETED	0	90	91	0	0	0	0	40	49
Long-term Safety Phase (Year 3) NOT COMPLETED	0	9	18	0	0	0	0	8	11
Long-term Safety Phase (Year 4) STARTED	0	89	91	0	0	0	0	40	49
Long-term Safety Phase (Year 4) COMPLETED	0	81	86	0	0	0	0	38	44
Long-term Safety Phase (Year 4) NOT COMPLETED	0	8	5	0	0	0	0	2	5
Long-term Safety Phase (Year 5) STARTED	0	81	86	0	0	0	0	38	44
Long-term Safety Phase (Year 5) COMPLETED	0	71	80	0	0	0	0	37	41
Long-term Safety Phase (Year 5) NOT COMPLETED	0	10	6	0	0	0	0	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants initially randomized to receive 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 receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase and continued to receive 20 mg apremilast tablets twice daily for up to 4.5 years in the active treatment / long-term safety phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase and continued to receive 30 mg apremilast tablets twice daily for up to 4.5 years in the active treatment / long-term safety phase.	Placebo/ Apremilast 20 mg EE Participants initially randomized to receive placebo twice daily who were re-randomized due to early escape (EE) at Week 16 to receive 20 mg apremilast twice daily in the active treatment phase.	Placebo / Apremilast 20 mg XO Participants initially randomized to receive placebo twice daily who were re-randomized at Week 24 (XO) to receive 20 mg apremilast twice daily in the active treatment phase.	Placebo / Apremilast 30 mg EE Participants initially randomized to receive placebo twice daily who were re-randomized due to early escape (EE) at Week 16 to receive 30 mg apremilast twice daily in the active treatment phase.	Placebo / Apremilast 30 mg XO Participants initially randomized to receive placebo twice daily who were re-randomized at Week 24 to receive 30 mg apremilast twice daily in the active treatment phase.	Placebo/Apremilast 20 mg [Long-Term Safety Phase (LTSP)] Participants initially randomized to placebo tablets twice daily during the 24-week placebo-controlled phase were re-randomized to 20 mg apremilast tablets twice daily at Week 16 or Week 24 and continued receiving apremilast 20 mg tablets twice daily in 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 the 30 mg apremilast BID dose).	Placebo/Apremilast 30 mg (Long-Term Safety Phase) Participants initially randomized to placebo tablets BID during the 24-week 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 tablets twice daily in the active treatment / long-term safety phase.
Placebo-controlled Phase (Week 0 - 24) Adverse Event	4	4	6	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Lack of Efficacy	1	3	2	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Withdrawal by Subject	8	4	10	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Randomization Error	0	0	1	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Lost to Follow-up	5	1	2	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Protocol Violation	1	0	0	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Other	1	2	0	0	0	0	0	0	0
Placebo-controlled Phase (Week 0 - 24) Non-compliance with Study Drug	0	1	1	0	0	0	0	0	0
Active Treatment Phase (Week 25-52) Adverse Event	0	3	2	2	2	0	0	0	0
Active Treatment Phase (Week 25-52) Lack of Efficacy	0	5	5	3	1	0	0	0	0
Active Treatment Phase (Week 25-52) Non-compliance with Study Drug	0	0	0	0	0	1	0	0	0
Active Treatment Phase (Week 25-52) Withdrawal by Subject	0	11	2	0	0	1	1	0	0
Active Treatment Phase (Week 25-52) Lost to Follow-up	0	0	0	2	0	0	0	0	0
Active Treatment Phase (Week 25-52) Other	0	0	0	1	0	0	0	0	0
Active Treatment Phase (Week 25-52) Protocol Violation	0	0	0	0	0	1	0	0	0
Long-term Safety Phase (Year 2) Adverse Event	0	2	7	0	0	0	0	1	1
Long-term Safety Phase (Year 2) Lack of Efficacy	0	7	5	0	0	0	0	4	3
Long-term Safety Phase (Year 2) Noncompliance with study drug	0	0	1	0	0	0	0	0	0
Long-term Safety Phase (Year 2) Withdrawal by Subject	0	13	12	0	0	0	0	3	2
Long-term Safety Phase (Year 2) Miscellaneous	0	1	0	0	0	0	0	1	1
Long-term Safety Phase (Year 3) Adverse Event	0	1	2	0	0	0	0	3	4
Long-term Safety Phase (Year 3) Lack of Efficacy	0	2	4	0	0	0	0	1	2
Long-term Safety Phase (Year 3) Noncompliance with Study Drug	0	1	1	0	0	0	0	0	0
Long-term Safety Phase (Year 3) Withdrawal by Subject	0	2	8	0	0	0	0	2	4
Long-term Safety Phase (Year 3) Lost to Follow-up	0	2	3	0	0	0	0	1	1
Long-term Safety Phase (Year 3) Miscellaneous	0	1	0	0	0	0	0	1	0
Long-term Safety Phase (Year 4) Adverse Event	0	2	0	0	0	0	0	0	0
Long-term Safety Phase (Year 4) Lack of Efficacy	0	1	0	0	0	0	0	0	1
Long-term Safety Phase (Year 4) Withdrawal by Subject	0	5	4	0	0	0	0	1	4
Long-term Safety Phase (Year 4) Lost to Follow-up	0	0	1	0	0	0	0	0	0
Long-term Safety Phase (Year 4) Miscellaneous	0	0	0	0	0	0	0	1	0
Long-term Safety Phase (Year 5) Adverse Event	0	1	1	0	0	0	0	0	1
Long-term Safety Phase (Year 5) Lack of Efficacy	0	2	1	0	0	0	0	0	0
Long-term Safety Phase (Year 5) Withdrawal by Subject	0	6	2	0	0	0	0	0	1
Long-term Safety Phase (Year 5) Lost to Follow-up	0	1	0	0	0	0	0	0	0
Long-term Safety Phase (Year 5) Miscellaneous	0	0	2	0	0	0	0	1	1

Baseline Characteristics

Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis (PsA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Total n=527 Participants Total of all reporting groups
Age, Continuous	50.5 years STANDARD_DEVIATION 11.58 • n=93 Participants	49.2 years STANDARD_DEVIATION 12.00 • n=4 Participants	48.4 years STANDARD_DEVIATION 12.52 • n=27 Participants	49.4 years STANDARD_DEVIATION 12.05 • n=483 Participants
Sex: Female, Male Female	86 Participants n=93 Participants	95 Participants n=4 Participants	96 Participants n=27 Participants	277 Participants n=483 Participants
Sex: Female, Male Male	90 Participants n=93 Participants	80 Participants n=4 Participants	80 Participants n=27 Participants	250 Participants n=483 Participants
Duration of Psoriatic Arthritis	3.42 years STANDARD_DEVIATION 5.103 • n=93 Participants	3.19 years STANDARD_DEVIATION 4.706 • n=4 Participants	3.62 years STANDARD_DEVIATION 5.041 • n=27 Participants	3.41 years STANDARD_DEVIATION 4.947 • n=483 Participants

PRIMARY outcome

Timeframe: Baseline and Week 16

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

Outcome measures

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16	15.9 percentage of participants	28.0 percentage of participants	30.7 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 changes from baseline in the overall score indicate improvement in functional ability.

Outcome measures

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 16	0.012 units on a scale Standard Error 0.0350	-0.156 units on a scale Standard Error 0.0349	-0.205 units on a scale Standard Error 0.0350	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; Participants who discontinued early, escaped 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

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With an ACR 20 Response at Week 24	13.1 percentage of participants	29.1 percentage of participants	24.4 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 changes from Baseline in the overall score indicate improvement in functional ability.

Outcome measures

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 24	0.012 units on a scale Standard Error 0.0370	-0.156 units on a scale Standard Error 0.0368	-0.207 units on a scale Standard Error 0.0369	—

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). SF-36 domain scores were first calculated to range from 0 to100 and then transformed to norm-based scores (the norm-based scores in the US general population have an average of 50 and a standard deviation of 10). Norm-based scores were used in analyses, with higher scores indicating 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

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16	0.01 units on a scale Standard Error 0.588	2.39 units on a scale Standard Error 0.586	3.19 units on a scale Standard Error 0.590	—

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=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=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

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16	24.4 percentage of participants	38.9 percentage of participants	45.5 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

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in Patient's Assessment of Pain at Week 16	-2.6 mm Standard Error 1.81	-7.7 mm Standard Error 1.79	-10.5 mm Standard Error 1.80	—

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 Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.

Outcome measures

Outcome measures
Measure	Placebo n=115 Participants Participants initially randomized to receive 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 20mg n=117 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=111 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16	-0.5 units on a scale Standard Error 0.24	-0.5 units on a scale Standard Error 0.24	-1.5 units on a scale Standard Error 0.25	—

SECONDARY outcome

Timeframe: Baseline to 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 severity 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

Outcome measures
Measure	Placebo n=90 Participants Participants initially randomized to receive 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 20mg n=89 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=84 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in Dactylitis Severity Score at Week 16	-1.0 units on a scale Standard Error 0.25	-1.9 units on a scale Standard Error 0.25	-1.7 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

Outcome measures
Measure	Placebo n=163 Participants Participants initially randomized to receive 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 20mg n=166 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=164 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16	-1.98 units on a scale Standard Error 0.770	-6.89 units on a scale Standard Error 0.763	-7.63 units on a scale Standard Error 0.768	—

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 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

Outcome measures
Measure	Placebo n=164 Participants Participants initially randomized to receive 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 20mg n=164 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=167 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in the Disease Activity Score (DAS28) After 16 Weeks of Treatment	-0.15 units on a scale Standard Error 0.076	-0.61 units on a scale Standard Error 0.076	-0.68 units on a scale Standard Error 0.075	—

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

Outcome measures
Measure	Placebo n=167 Participants Participants initially randomized to receive 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 20mg n=168 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=166 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16	0.07 units on a scale Standard Error 0.631	1.19 units on a scale Standard Error 0.629	2.62 units on a scale Standard Error .0633	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Outcome measures

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 24	0.16 units on a scale Standard Error 0.609	2.13 units on a scale Standard Error 0.605	3.88 units on a scale Standard Error 0.611	—

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 determination of response status at Week 24 were counted as non-responders.

Outcome measures

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24	17.0 percentage of participants	36.6 percentage of participants	35.2 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Outcome measures

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in Participants Assessment of Pain at Week 24	-3.8 mm Standard Error 1.83	-9.4 mm Standard Error 1.82	-9.6 mm Standard Error 1.83	—

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.

Outcome measures

Outcome measures
Measure	Placebo n=111 Participants Participants initially randomized to receive 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 20mg n=113 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=106 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24	-0.6 units on a scale Standard Error 0.25	-0.9 units on a scale Standard Error 0.25	-1.5 units on a scale Standard Error 0.26	—

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.

Outcome measures

Outcome measures
Measure	Placebo n=87 Participants Participants initially randomized to receive 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 20mg n=85 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=79 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in Dactylitis Severity Score at Week 24	-1.0 units on a scale Standard Error 0.26	-2.0 units on a scale Standard Error 0.26	-1.7 units on a scale Standard Error 0.27	—

SECONDARY outcome

Timeframe: Baseline and Week 24

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

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24	-2.23 units on a scale Standard Error 0.807	-7.30 units on a scale Standard Error 0.803	-7.36 units on a scale Standard Error 0.810	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Outcome measures

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in Disease Activity Score (DAS 28) at Week 24	-0.22 units on a scale Standard Error 0.084	-0.69 units on a scale Standard Error 0.084	-0.68 units on a scale Standard Error 0.084	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Outcome measures

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24	0.25 units on a scale Standard Error 0.652	1.37 units on a scale Standard Error 0.648	2.58 units on a scale Standard Error 0.655	—

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 Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.

Outcome measures

Outcome measures
Measure	Placebo n=115 Participants Participants initially randomized to receive 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 20mg n=117 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=111 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With ≥ 20% Improvement in Maastricht Ankylosing Spondylitis Entheses Score at Week 16	46.1 percentage of participants	48.7 percentage of participants	63.1 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 severity 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

Outcome measures
Measure	Placebo n=90 Participants Participants initially randomized to receive 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 20mg n=89 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=84 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16	60.0 percentage of participants	66.3 percentage of participants	61.9 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.

The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2

Outcome measures

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16	25.0 percentage of participants	41.1 percentage of participants	44.3 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 Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.

Outcome measures

Outcome measures
Measure	Placebo n=115 Participants Participants initially randomized to receive 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 20mg n=117 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=111 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With MASES Improvement ≥ 20% at Week 24	48.7 percentage of participants	54.7 percentage of participants	66.7 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 severity 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

Outcome measures
Measure	Placebo n=90 Participants Participants initially randomized to receive 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 20mg n=89 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=84 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24	57.8 percentage of participants	69.7 percentage of participants	63.1 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.

The EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on th DAS-28. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2 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

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With Good or Moderate EULAR Response at Week 24	17.0 percentage of participants	34.9 percentage of participants	28.4 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: 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

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With a ACR 50 Response at Week 16	4.5 Percentage of participants	11.4 Percentage of participants	11.4 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: 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

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With a ACR 70 Response at Week 16	1.1 percentage of participants	4.0 percentage of participants	4.0 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Outcome measures

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With a ACR 50 Response at Week 24	6.3 percentage of participants	16.0 percentage of participants	12.5 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Outcome measures

Outcome measures
Measure	Placebo n=176 Participants Participants initially randomized to receive 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 20mg n=175 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=176 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With a ACR 70 Response at Week 24	4.0 percentage of participants	4.0 percentage of participants	4.5 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 16

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 Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.

Outcome measures

Outcome measures
Measure	Placebo n=115 Participants Participants initially randomized to receive 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 20mg n=117 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=111 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With Pre-existing Enthesopathy Whose Maastricht Ankylosing Spondylitis Entheses Score Improves to 0 at Week 16	19.1 percentage of participants	21.4 percentage of participants	36.9 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 16

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 severity 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

Outcome measures
Measure	Placebo n=90 Participants Participants initially randomized to receive 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 20mg n=89 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=84 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves to 0 at Week 16	33.3 percentage of participants	42.7 percentage of participants	40.5 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 24

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 Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.

Outcome measures

Outcome measures
Measure	Placebo n=115 Participants Participants initially randomized to receive 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 20mg n=117 Participants Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30mg n=111 Participants Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Apremilast 30 mg Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Percentage of Participants Achieving a MASES Score of Zero at Week 24	22.6 percentage of participants	29.1 percentage of participants	37.8 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 24

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 severity 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.