Trial Outcomes & Findings for Safety and Efficacy Study of Apremilast to Treat Psoriatic Arthritis (NCT NCT01925768)

NCT ID: NCT01925768

Last Updated: 2020-05-12

Results Overview

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 self-assessment of pain (measured on a 0 to 10 unit numeric rating scale \[NRS\]); * Patient's global self-assessment of disease activity (measured on a 0 to 10 unit NRS); * Physician's global assessment of disease activity (measured on a 0 to 10 unit NRS); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[HAQ-DI\]); * C-Reactive Protein (CRP) Those who withdrew early or who did not have sufficient data at Week 16 were counted as non-responders.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 219 participants
• Primary outcome timeframe: Baseline and Week 16
• Results posted on: 2020-05-12

Participant Flow

The study consisted of a 24-week randomized, double-blind, placebo-controlled treatment phase, followed by a 28-week active treatment phase and a 52-week open-label extension phase, for an overall study duration of 113 weeks. 219 subjects were enrolled from 59 centers across 10 countries.

Randomized participants were stratified by their baseline prednisone use (yes or no) and by their previous disease modifying antirheumatic drug (DMARD) use (excluding biologics). Participants were allowed to take non-steroidal anti-inflammatory agents and/or low dose corticosteroids during the study.

Participant milestones

Measure	Placebo/Apremilast (PBO) Participants were randomized to placebo tablets twice daily (BID) during the double-blind, 24-week placebo-controlled phase. Those whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator and transitioned onto apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape. Participants who completed the double-blind, 24-week treatment phase entered into the blinded, active treatment phase for an additional 28 weeks (Week 24 to Week 52) and continued receiving Apremilast 30 mg tablets BID. Participants who completed the active treatment phase entered into the open-label extension phase for an additional year (Week 52 to Week 104) continuing to receive apremilast 30 mg tablets BID until the end of the study (up to Week 104 visit) or until early discontinuation.	Apremilast (APR) Participants were randomized to apremilast 30 mg tablets BID during the double-blind, 24-week placebo-controlled phase. Those whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape. Participants who completed the double-blind 24-week treatment phase entered into the blinded active treatment phase for an additional 28 weeks (Week 24 to Week 52) and continued receiving Apremilast 30 mg tablets BID. All participants who completed the 52-week treatment phase entered into the open-label extension phase (Week 52 to Week 104) for an additional year continuing to receive apremilast 30 mg tablets BID until the end of the study (up to Week 104 visit) or until early discontinuation.
Placebo-controlled Phase (Week 0 - 24) STARTED	109	110
Placebo-controlled Phase (Week 0 - 24) Received Treatment	109	109
Placebo-controlled Phase (Week 0 - 24) Completed Week 16	101	91
Placebo-controlled Phase (Week 0 - 24) Escaped Early (EE)	35	13
Placebo-controlled Phase (Week 0 - 24) COMPLETED	98	87
Placebo-controlled Phase (Week 0 - 24) NOT COMPLETED	11	23
ActiveTreatment/Extension (Weeks 24-104) STARTED	95	85
ActiveTreatment/Extension (Weeks 24-104) COMPLETED	75	67
ActiveTreatment/Extension (Weeks 24-104) NOT COMPLETED	20	18

Reasons for withdrawal

Measure	Placebo/Apremilast (PBO) Participants were randomized to placebo tablets twice daily (BID) during the double-blind, 24-week placebo-controlled phase. Those whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator and transitioned onto apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape. Participants who completed the double-blind, 24-week treatment phase entered into the blinded, active treatment phase for an additional 28 weeks (Week 24 to Week 52) and continued receiving Apremilast 30 mg tablets BID. Participants who completed the active treatment phase entered into the open-label extension phase for an additional year (Week 52 to Week 104) continuing to receive apremilast 30 mg tablets BID until the end of the study (up to Week 104 visit) or until early discontinuation.	Apremilast (APR) Participants were randomized to apremilast 30 mg tablets BID during the double-blind, 24-week placebo-controlled phase. Those whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape. Participants who completed the double-blind 24-week treatment phase entered into the blinded active treatment phase for an additional 28 weeks (Week 24 to Week 52) and continued receiving Apremilast 30 mg tablets BID. All participants who completed the 52-week treatment phase entered into the open-label extension phase (Week 52 to Week 104) for an additional year continuing to receive apremilast 30 mg tablets BID until the end of the study (up to Week 104 visit) or until early discontinuation.
Placebo-controlled Phase (Week 0 - 24) Lost to Follow-up	1	0
Placebo-controlled Phase (Week 0 - 24) Protocol Violation	1	2
Placebo-controlled Phase (Week 0 - 24) Adverse Event	5	10
Placebo-controlled Phase (Week 0 - 24) Lack of Efficacy	3	6
Placebo-controlled Phase (Week 0 - 24) Withdrawal by Subject	1	4
Placebo-controlled Phase (Week 0 - 24) Non-compliance with study drug	0	1
ActiveTreatment/Extension (Weeks 24-104) Lack of Efficacy	6	6
ActiveTreatment/Extension (Weeks 24-104) Withdrawal by Subject	7	9
ActiveTreatment/Extension (Weeks 24-104) Lost to Follow-up	2	1
ActiveTreatment/Extension (Weeks 24-104) Death	0	1
ActiveTreatment/Extension (Weeks 24-104) Adverse Event	5	1

Baseline Characteristics

Safety and Efficacy Study of Apremilast to Treat Psoriatic Arthritis

Baseline characteristics by cohort

Measure	Placebo (PBO) n=109 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=110 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Total n=219 Participants Total of all reporting groups
Age, Continuous	48.0 years STANDARD_DEVIATION 13.75 • n=5 Participants	50.7 years STANDARD_DEVIATION 12.22 • n=7 Participants	49.3 years STANDARD_DEVIATION 13.04 • n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	58 Participants n=7 Participants	123 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	52 Participants n=7 Participants	96 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	105 Participants n=5 Participants	109 Participants n=7 Participants	214 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Duration of Psoriatic Arthritis	3.59 years STANDARD_DEVIATION 5.497 • n=5 Participants	4.04 years STANDARD_DEVIATION 4.482 • n=7 Participants	3.82 years STANDARD_DEVIATION 5.007 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 16

Population: Full Analysis Set (FAS) population consisting of all participants randomized as specified in the protocol.

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 self-assessment of pain (measured on a 0 to 10 unit numeric rating scale [NRS]);
• Patient's global self-assessment of disease activity (measured on a 0 to 10 unit NRS);
• Physician's global assessment of disease activity (measured on a 0 to 10 unit NRS);
• Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
• C-Reactive Protein (CRP) Those who withdrew early or who did not have sufficient data at Week 16 were counted as non-responders.

Outcome measures

Measure	Placebo (PBO) n=109 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=110 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Week 16	20.2 percentage of participants	38.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; Participants with a baseline and at least 1 postbaseline value during the placebo-controlled phase were included in the analysis (mixed effects model for repeated measure \[MMRM\])

HAQ-DI 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. A higher score indicates worse physical functioning, and a negative change from baseline indicates improvement.

Outcome measures

Measure	Placebo (PBO) n=109 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=109 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24	-0.169 units on a scale Standard Error 0.0581	-0.273 units on a scale Standard Error 0.0572

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: FAS population.

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 self-assessment of pain (measured on a 0 to 10 unit numeric rating scale [NRS]);
• Patient's global self-assessment of disease activity (measured on a 0 to 10 unit NRS);
• Physician's global assessment of disease activity (measured on a 0 to 10 unit NRS);
• Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
• C-Reactive Protein (CRP) Those who withdrew early or who did not have sufficient data at Week 16 were counted as non-responders.

Outcome measures

Measure	Placebo (PBO) n=109 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=110 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) at Week 24	24.8 percentage of participants	43.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; Participants with a baseline value and at least one post-baseline value (after exclusion of data for early escaped participants) during the placebo-controlled phase are included in the analysis.

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 9.4. 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. A higher value indicates higher disease activity, and a negative change from baseline indicates improvement.

Outcome measures

Measure	Placebo (PBO) n=108 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=109 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Change From Baseline in the 28-Joint Disease Activity Score Using C-reactive Protein as the Acute-Phase Reactant (DAS28 [CRP]) at Week 24	-0.76 units on a scale Standard Error 0.140	-1.26 units on a scale Standard Error 0.138

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set; Participants with a baseline and at least 1 postbaseline value during the placebo-controlled phase were included in the analysis (mixed effects model for repeated measure \[MMRM\])

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 (PBO) n=106 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=107 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Change From Baseline in the Medical Outcomes Short Form Health Survey (SF-36) V2 Physical Function Domain Score at Week 24	1.26 units on a scale Standard Error 0.908	3.94 units on a scale Standard Error 0.888

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set. Subjects with a baseline value and at least one post-baseline value (after exclusion of data for early escaped subjects) during the placebo-controlled phase are included in the MMRM model.

The SF-36 (v 2.0) 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). The physical component summary (PCS) score includes the physical functioning, role physical, bodily pain, and general health domains. Minimum clinically important difference (MCID) for the scale scores, as well as the PCS and MCS, is defined as a 2.5-point improvement (increase) from baseline. The summary scores range from 0 to 100, with lower scores reflecting more disability, and higher scores reflecting less disability and better health. The 8 domains are regrouped into the PCS and MCS scores.

Outcome measures

Measure	Placebo (PBO) n=106 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=106 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Change From Baseline in the 36-item SF-36 Physical Component Summary Score at Week 24	1.60 units on a scale Standard Error 0.959	5.00 units on a scale Standard Error 0.949

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full Analysis Set; Analysis includes participants with a baseline and at least one post-baseline value; last observation carried forward (LOCF) imputation was used

Morning stiffness was the participant's assessment of how long their morning stiffness lasted after first waking up in the morning, on average, during the previous week. A higher value indicates longer duration, and a negative change from baseline indicates improvement.

Outcome measures

Measure	Placebo (PBO) n=109 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=109 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Change From Baseline in the Duration of Morning Stiffness at Week 24	21.9 minutes Standard Deviation 137.11 • Interval -460.0 to -879.0	-5.7 minutes Standard Deviation 83.41 • Interval -175.0 to -679.0

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full Analysis Set; Participants who withdrew early or who did not have sufficient data at Week 24 were counted as non-responders

Morning stiffness severity was the participant's assessment of how severe their morning stiffness was after first waking up in the morning, on average, during the previous week. The severity was recorded as none, mild, moderate, moderately severe, or very severe. The response of no improvement includes subjects who had no change or worsened. Improvement is defined as the change from baseline of a more severe assessment to less severe assessment.

Outcome measures

Measure	Placebo (PBO) n=109 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=110 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Percentage of Participants With Improved Change in Severity of Morning Stiffness at Week 24	20.2 percentage of participants	40.0 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 during the placebo-controlled phase were included in the mixed effects model for repeated measures (MRMM).

HAQ-DI 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. A higher score indicates worse physical functioning, and a negative change from baseline indicates improvement.

Outcome measures

Measure	Placebo (PBO) n=109 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=109 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16	-0.055 units on a scale Standard Error 0.0513	-0.205 units on a scale Standard Error 0.0523

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value during the placebo-controlled phase were included in the mixed effects model for repeated measures (MRMM).

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 9.4. 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. A negative change from baseline indicates improvement.

Outcome measures

Measure	Placebo (PBO) n=108 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=109 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Change From Baseline in the Disease Activity Score DAS28 (CRP) at Week 16	-0.39 units on a scale Standard Error 0.129	-1.07 units on a scale Standard Error 0.133

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value during the placebo-controlled phase were included in the mixed effects model for repeated measures (MRMM).

The SF-36 (v 2.0) 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 (PBO) n=106 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=107 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Change From Baseline in 36-item Short Form Health Survey (SF-36) V 2 Physical Functioning Domain at Week 16	-1.04 units on a scale Standard Error 0.927	2.43 units on a scale Standard Error 0.962

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set; Analysis includes participants with a baseline and at least one post-baseline value; last observation carried forward (LOCF) imputation was used

Morning stiffness was the participant's assessment of how long their morning stiffness lasted after first waking up in the morning, on average, during the previous week. A higher value indicates longer duration, and a negative change from baseline indicates improvement.

Outcome measures

Measure	Placebo (PBO) n=109 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=109 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Mean Change From Baseline in the Duration of Morning Stiffness at Week 16	21.7 minutes Standard Deviation 136.85	-7.2 minutes Standard Deviation 60.73

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full Analysis Set; Participants who discontinued early prior to Week 16 and those who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders

Morning stiffness severity was the participant's assessment of how severe their morning stiffness was after first waking up in the morning, on average, during the previous week. The severity was recorded as none, mild, moderate, moderately severe, or very severe. Improvement is defined as the change from baseline of a more severe assessment to less severe assessment. Full Analysis Set; Participants who discontinued early prior to Week 16 and those who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.

Outcome measures

Measure	Placebo (PBO) n=109 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=110 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Percentage of Participants Whose Severity of Morning Stiffness at Week 16 Improved From Baseline	25.7 percentage of participants	46.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline and at Weeks 2, 4, 6, 8, 12 and 20

Population: Full analysis set; participants discontinued early prior to the visit and participants who did not have sufficient data for a definitive determination of response status for the visit were counted as nonresponders.

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 self-assessment of pain (measured on a 0 to 10 unit numeric rating scale [NRS]);
• Patient's global self-assessment of disease activity (measured on a 0 to 10 unit NRS);
• Physician's global assessment of disease activity (measured on a 0 to 10 unit NRS);
• Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
• C-Reactive Protein (CRP)

Outcome measures

Measure	Placebo (PBO) n=109 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=110 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Weeks 2, 4, 6, 8, 12 and 20 Week 6	19.3 percentage of participants	37.3 percentage of participants
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Weeks 2, 4, 6, 8, 12 and 20 Week 2	6.4 percentage of participants	16.4 percentage of participants
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Weeks 2, 4, 6, 8, 12 and 20 Week 4	15.6 percentage of participants	24.5 percentage of participants
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Weeks 2, 4, 6, 8, 12 and 20 Week 8	22.9 percentage of participants	36.4 percentage of participants
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Weeks 2, 4, 6, 8, 12 and 20 Week 12	28.4 percentage of participants	40.0 percentage of participants
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Weeks 2, 4, 6, 8, 12 and 20 Week 20	24.8 percentage of participants	43.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 52 and 104

Population: Apremilast Participants as Randomized or Transitioned, which includes all participants who randomized or escaped/transitioned (at Week 16 or Week 24) to apremilast, and with available data at each time point.

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 self-assessment of pain (measured on a 0 to 10 unit numeric rating scale [NRS]);
• Patient's global self-assessment of disease activity (measured on a 0 to 10 unit NRS);
• Physician's global assessment of disease activity (measured on a 0 to 10 unit NRS);
• Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
• C-Reactive Protein (CRP)

Outcome measures

Measure	Placebo (PBO) n=90 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=79 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Weeks 52 and 104 Week 52	60.0 percentage of partcipants Interval 49.1 to 70.2	67.1 percentage of partcipants Interval 55.6 to 77.3
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Weeks 52 and 104 Week 104	66.2 percentage of partcipants Interval 54.3 to 76.8	59.4 percentage of partcipants Interval 46.9 to 71.1

SECONDARY outcome

Timeframe: Baseline and Weeks 52 and 104

Population: Apremilast participants as randomized or transitioned; The Placebo/Apremilast 30 mg BID group includes participants initially randomized to placebo and switched to apremilast 30 mg BID at Week 16 or 24 and with available data at each time point.

HAQ-DI 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. A higher score indicates worse physical functioning, and a negative change from baseline indicates improvement.

Outcome measures

Measure	Placebo (PBO) n=91 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=80 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 52 and 104 Week 52	-0.323 units on a scale Standard Deviation 0.5759	-0.395 units on a scale Standard Deviation 0.5297
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 52 and 104 Week 104	-0.382 units on a scale Standard Deviation 0.5639	-0.357 units on a scale Standard Deviation 0.6102

SECONDARY outcome

Timeframe: Baseline and Weeks 52 and 104

Population: Apremilast participants as randomized or transitioned. The Placebo/Apremilast30 mg BID group includes participants initially randomized to placebo and switched to apremilast 30 mg BID at Week 16 or 24 and with available data at each time point.

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 9.4. 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. A negative change from baseline indicates improvement.

Outcome measures

Measure	Placebo (PBO) n=90 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=79 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Change From Baseline in the Disease Activity Score (DAS28) at Week 52 and 104 Week 104	-1.62 units on a scale Standard Deviation 1.086	-1.70 units on a scale Standard Deviation 1.305
Change From Baseline in the Disease Activity Score (DAS28) at Week 52 and 104 Week 52	-1.46 units on a scale Standard Deviation 0.985	-1.71 units on a scale Standard Deviation 1.054

SECONDARY outcome

Timeframe: Baseline and Weeks 52 and 104

Population: Apremilast Subjects as Randomized or Transitioned; The Placebo/30 mg BID group includes participants initially randomized to placebo and switched to apremilast 30 mg BID at Week 16 or 24and with available data at each time point.

The SF-36 (v 2.0) 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 (PBO) n=91 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=80 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Change From Baseline in 36-item SF-36 (V2.0) Physical Functioning Domain Score at Weeks 52 and 104 Week 52	5.11 units on a scale Standard Deviation 9.842	6.00 units on a scale Standard Deviation 9.990
Change From Baseline in 36-item SF-36 (V2.0) Physical Functioning Domain Score at Weeks 52 and 104 Week 104	5.78 units on a scale Standard Deviation 9.932	5.95 units on a scale Standard Deviation 10.827

SECONDARY outcome

Timeframe: Baseline and Weeks 52 and 104

Population: Apremilast participants as randomized or transitioned; The Placebo/ Apremilast 30 mg BID group includes participants initially randomized to placebo and switched to apremilast 30 mg BID at Week 16 or 24 And with available data at each time point.

Morning stiffness was the participant's assessment of how long their morning stiffness lasted after first waking up in the morning, on average, during the previous week. A higher value indicates longer duration, and a negative change from baseline indicates improvement.

Outcome measures

Measure	Placebo (PBO) n=91 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=80 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Change From Baseline in the Duration of Morning Stiffness at Weeks 52 and 104 Week 52	3.3 minutes Standard Deviation 174.41	-5.7 minutes Standard Deviation 93.62
Change From Baseline in the Duration of Morning Stiffness at Weeks 52 and 104 Week 104	-11.9 minutes Standard Deviation 165.36	-7.0 minutes Standard Deviation 71.34

SECONDARY outcome

Timeframe: Baseline and Weeks 52 and 104

Population: Apremilast participants as randomized or transitioned. The Placebo/30 mg BID group includes subjects initially randomized to placebo and switched to apremilast 30 mg BID at Week 16 or 24 and with available data at each time point

Morning stiffness severity was the participant's assessment of how severe their morning stiffness was after first waking up in the morning, on average, during the previous week. The severity was recorded as none, mild, moderate, moderately severe, or very severe. Improvement is defined as the change from baseline of a more severe assessment to less severe assessment.

Outcome measures

Measure	Placebo (PBO) n=91 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=80 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Percentage of Participants Whose Severity of Morning Stiffness at Week 52 and 104 Improved From Baseline Week 104	50.7 percentage of participants	59.4 percentage of participants
Percentage of Participants Whose Severity of Morning Stiffness at Week 52 and 104 Improved From Baseline Week 52	57.1 percentage of participants	57.5 percentage of participants

SECONDARY outcome

Timeframe: Date of first dose of study drug to Week 24; median duration of exposure during placebo controlled phase was 24.14 weeks

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

A TEAE is an AE with a start date on or after the date of the first dose of Investigational Product (IP). An AE is any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.

Outcome measures

Measure	Placebo (PBO) n=109 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg n=109 Participants Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the 24 Week Placebo Controlled Phase Any TEAE	69 Participants	73 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the 24 Week Placebo Controlled Phase Any serious TEAE	5 Participants	3 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the 24 Week Placebo Controlled Phase Any serious drug-related TEAE	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the 24 Week Placebo Controlled Phase Any TEAE leading to study drug withdrawal	5 Participants	10 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the 24 Week Placebo Controlled Phase Any TEAE leading to study dose interruption	7 Participants	10 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the 24 Week Placebo Controlled Phase Any TEAE leading to death	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the 24 Week Placebo Controlled Phase Any drug-related TEAE	18 Participants	30 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the 24 Week Placebo Controlled Phase Any severe TEAE	4 Participants	2 Participants

SECONDARY outcome

Timeframe: Start of lst dose of IP up to week 104: Weeks 0 to104 for those initially randomized to APR 30 mg BID, Weeks 16 -104 for PBO-treated patients who EE to APR at Week 16 and from Weeks 24-104 for PBO-treated patients who transitioned to APR at Week 24

Population: APR participants as treated (AAT) population; AAT = participants who received at least 1 dose of APR at any time during the study, (those initially randomized to the APR 30 BID at Week 0, those initially randomized to placebo who entered EE and transitioned to APR at Week 16, and those initially randomized to PBO who transitioned to APR at Week 24)

A TEAE is an AE with a start date on or after the date of the first dose of Investigational Product (IP). An AE is any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.

Outcome measures

Measure	Placebo (PBO) n=206 Participants Participants randomized to placebo tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for early escape (EE), at the discretion of the investigator were transitioned onto apremilast 30 mg tablets BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.	Apremilast (APR) 30 mg Participants randomized to apremilast 30 mg tablets BID during the blinded, 24-week placebo-controlled phase. Participants whose improvement was less than 10% in both swollen and tender joint counts at Week 16 were eligible for EE, at the discretion of the investigator and continued receiving apremilast 30 mg BID in a blinded fashion. Those who had a 10% or more improvement in either swollen or tender joint counts at Week 16 were not eligible for early escape.
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Apremilast-Exposure Period Any TEAE	157 Participants	—
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Apremilast-Exposure Period Any drug-related TEAE	52 Participants	—
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Apremilast-Exposure Period Any TEAE leading to death	1 Participants	—
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Apremilast-Exposure Period Any severe TEAE	8 Participants	—
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Apremilast-Exposure Period Any serious TEAE	15 Participants	—
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Apremilast-Exposure Period Any serious drug-related TEAE	0 Participants	—
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Apremilast-Exposure Period Any TEAE leading to study dose interruption	28 Participants	—
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Apremilast-Exposure Period Any TEAE leading to study drug withdrawal	17 Participants	—

Adverse Events

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

Serious events: 5 serious events

Other events: 37 other events

Deaths: 0 deaths

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

Serious events: 3 serious events

Other events: 41 other events

Deaths: 0 deaths

APR Exposure Period: Apremilast

Serious events: 15 serious events

Other events: 83 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo-Controlled Phase: Placebo (Weeks 0-24) n=109 participants at risk Participants who were randomized to placebo tablets twice daily (BID) during the double-blind, 24-week placebo-controlled phase.	Placebo-Controlled Phase: Apremilast (Weeks 0-24) n=109 participants at risk Participants who were randomized to apremilast tablets twice daily during the double-blind, 24-week placebo-controlled phase.	APR Exposure Period: Apremilast n=206 participants at risk Participants who received apremilast any point during the course of the study, on Day 0, 16 or Day 24 and continued to receive apremilast 30 mg tablets BID up to week 104.
Blood and lymphatic system disorders Iron deficiency anaemia	0.92% 1/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Cardiac disorders Angina pectoris	0.92% 1/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Cardiac disorders Atrial fibrillation	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Cardiac disorders Cardiomyopathy alcoholic	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Cardiac disorders Coronary artery disease	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.97% 2/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Cardiac disorders Hypertensive heart disease	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Cardiac disorders Myocardial infarction	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
General disorders Chest pain	0.92% 1/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Hepatobiliary disorders Biliary colic	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.92% 1/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Hepatobiliary disorders Cholelithiasis	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Infections and infestations Arthritis infective	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.92% 1/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Injury, poisoning and procedural complications Head injury	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.92% 1/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.92% 1/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Injury, poisoning and procedural complications Spinal column injury	0.92% 1/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.92% 1/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Respiratory papilloma	0.92% 1/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Psychiatric disorders Anxiety	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Renal and urinary disorders Ureteric obstruction	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Vascular disorders Arteriosclerosis	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.00% 0/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	0.49% 1/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.

Other adverse events

Measure	Placebo-Controlled Phase: Placebo (Weeks 0-24) n=109 participants at risk Participants who were randomized to placebo tablets twice daily (BID) during the double-blind, 24-week placebo-controlled phase.	Placebo-Controlled Phase: Apremilast (Weeks 0-24) n=109 participants at risk Participants who were randomized to apremilast tablets twice daily during the double-blind, 24-week placebo-controlled phase.	APR Exposure Period: Apremilast n=206 participants at risk Participants who received apremilast any point during the course of the study, on Day 0, 16 or Day 24 and continued to receive apremilast 30 mg tablets BID up to week 104.
Gastrointestinal disorders Diarrhoea	11.0% 12/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	14.7% 16/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	16.5% 34/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Gastrointestinal disorders Nausea	1.8% 2/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	8.3% 9/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	8.7% 18/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Infections and infestations Bronchitis	2.8% 3/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	4.6% 5/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	5.3% 11/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Infections and infestations Nasopharyngitis	6.4% 7/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	8.3% 9/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	8.3% 17/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Infections and infestations Upper respiratory tract infection	10.1% 11/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	4.6% 5/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	8.3% 17/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Nervous system disorders Headache	3.7% 4/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	7.3% 8/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	6.3% 13/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.
Vascular disorders Hypertension	6.4% 7/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	6.4% 7/109 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.	6.3% 13/206 • AE's are reported: 1. Placebo-controlled phase (Weeks 0-24) 2. Up to 104 weeks for all participants randomized or transitioned onto apremilast at any time during the study (apremilast-exposure phase). AEs were monitored for 37 months Median duration of exposure during the placebo-controlled phase was 24.14 weeks and 81 weeks during the apremilast exposure phase.

Additional Information

Anne McClain, Senior Manager

Celgene Corporation

Phone: 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