PALACE4: Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis (PsA)

Sponsor

Amgen (Industry)

Overall Status

Completed

CT.gov ID

NCT01307423

Collaborator

(none)

529

Enrollment

118

Locations

Arms

80.2

Actual Duration (Months)

4.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether apremilast is safe and effective in the treatment of patients with psoriatic arthritis who have not been previously treated with DMARDs.

Apremilast is proposed to improve signs and symptoms of psoriatic arthritis (tender and swollen joints, pain, physical function) in treated patients.

Condition or Disease	Intervention/Treatment	Phase
Psoriatic Arthritis	Drug: Apremilast 20mg Drug: Apremilast 30mg Drug: Placebo	Phase 3

Detailed Description

Psoriatic arthritis (PsA) is an inflammatory arthritis that occurs in 6-39% of psoriasis patients. The immunopathogenesis of PsA, which mirrors but is not identical to that seen in psoriatic plaques, reflects a complex interaction among resident dendritic, fibroblastic and endothelial cells, and inflammatory cells attracted to the synovium by cytokines and chemokines. Apremilast (CC-10004) is a novel oral agent that modulates multiple inflammatory pathways through targeted phosphodiesterase type 4 (PDE4) enzyme inhibition. Therefore, apremilast has the potential to be effective in the treatment of PsA.

Study Design

Study Type:

Interventional

Actual Enrollment :

529 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) in Subjects With Active Psoriatic Arthritis Who Have Not Been Previously Treated With Disease-modifying Antirheumatic Drugs

Actual Study Start Date :

Dec 9, 2010

Actual Primary Completion Date :

Feb 21, 2013

Actual Study Completion Date :

Aug 16, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Apremilast 20mg Apremilast 20mg twice daily, orally	Drug: Apremilast 20mg Apremilast 20mg twice daily, orally Other Names: CC-10004
Experimental: Apremilast 30mg Apremilast 30mg twice daily, orally	Drug: Apremilast 30mg Apremilast 30mg twice daily, orally Other Names: CC-10004
Placebo Comparator: Placebo + 20mg Apremilast Placebo + 20mg Apremilast tablets administered twice daily	Drug: Apremilast 20mg Apremilast 20mg twice daily, orally Other Names: CC-10004 Drug: Placebo Placebo
Placebo Comparator: Placebo + 30mg Apremilast Placebo + 30mg Apremilast tablets administered twice daily	Drug: Apremilast 30mg Apremilast 30mg twice daily, orally Other Names: CC-10004 Drug: Placebo Placebo

Outcome Measures

Primary Outcome Measures

Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16 [Baseline and Week 16]
A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: -Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); -Patient's global assessment of disease activity (measured on a 100 mm VAS); -Physician's global assessment of disease activity (measured on a 100 mm VAS); -Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); -C-Reactive Protein.

Secondary Outcome Measures

Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 16 [Baseline and Week 16]
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative changes from baseline in the overall score indicate improvement in functional ability.
Percentage of Participants With an ACR 20 Response at Week 24 [Baseline and Week 24]
Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein.
Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 24 [Baseline and Week 24]
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative changes from Baseline in the overall score indicate improvement in functional ability.
Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16 [Baseline and Week 16]
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). SF-36 domain scores were first calculated to range from 0 to100 and then transformed to norm-based scores (the norm-based scores in the US general population have an average of 50 and a standard deviation of 10). Norm-based scores were used in analyses, with higher scores indicating a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.
Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16 [Baseline and Week 16]
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS.
Change From Baseline in Patient's Assessment of Pain at Week 16 [Baseline and Week 16]
The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16 [Baseline and Week 16]
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Change From Baseline in Dactylitis Severity Score at Week 16 [Baseline to Week 16]
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16 [Baseline and Week 16]
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22
Change From Baseline in the Disease Activity Score (DAS28) After 16 Weeks of Treatment [Baseline and Week 16]
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16 [Baseline and Week 16]
The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 24 [Baseline and Week 24]
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). SF-36 domain scores were first calculated to range from 0 to100 and then transformed to norm-based scores (the norm-based scores in the US general population have an average of 50 and a standard deviation of 10). Norm-based scores were used in analyses, with higher scores indicating a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.
Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24 [Baseline and Week 24]
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS.
Change From Baseline in Participants Assessment of Pain at Week 24 [Baseline and Week 24]
The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24 [Baseline and Week 24]
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Change From Baseline in Dactylitis Severity Score at Week 24 [Baseline and Week 24]
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 [Baseline and Week 24]
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22.
Change From Baseline in Disease Activity Score (DAS 28) at Week 24 [Baseline and Week 24]
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 [Baseline and Week 24]
The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Percentage of Participants With ≥ 20% Improvement in Maastricht Ankylosing Spondylitis Entheses Score at Week 16 [Baseline and Week 16]
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16 [Baseline and Week 16]
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16 [Baseline and Week 16]
The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2
Percentage of Participants With MASES Improvement ≥ 20% at Week 24 [Baseline and Week 24]
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24 [Baseline and Week 24]
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Percentage of Participants With Good or Moderate EULAR Response at Week 24 [Baseline and Week 24]
The EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on th DAS-28. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2 A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2.
Percentage of Participants With a ACR 50 Response at Week 16 [Baseline and Week 16]
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein.
Percentage of Participants With a ACR 70 Response at Week 16 [Baseline and Week 16]
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein.
Percentage of Participants With a ACR 50 Response at Week 24 [Baseline and Week 24]
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein.
Percentage of Participants With a ACR 70 Response at Week 24 [Baseline and Week 24]
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein.
Percentage of Participants With Pre-existing Enthesopathy Whose Maastricht Ankylosing Spondylitis Entheses Score Improves to 0 at Week 16 [Baseline and Week 16]
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves to 0 at Week 16 [Baseline and Week 16]
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Percentage of Participants Achieving a MASES Score of Zero at Week 24 [Baseline and Week 24]
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24 [Baseline and Week 24]
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Percentage of Participants With a ACR 20 Response at Week 52 [Baseline and Week 52]
Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 20% improvement in 78 tender joint count; ≥ 20% improvement in 76 swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52 [Baseline and Week 52]
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative changes from Baseline in the overall score indicate improvement in functional ability.
Change From Baseline in the SF-36v2 Physical Functioning Scale Score at Week 52 [Baseline and Week 52]
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.
Percentage of Participants With a Modified PsARC Response at Week 52 [Baseline and Week 52]
Measure Description: Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Change From Baseline in the Participants Assessment of Pain Using the Visual Analog Scale at Week 52 [Baseline and Week 52]
The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52 [Baseline and Week 52]
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Change From Baseline in the Dactylitis Severity Score at Week 52 [Baseline and Week 52]
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present
Change From Baseline in the CDAI Score at Week 52 [Baseline and Week 52]
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: 28 tender joint count (TJC), 28 swollen joint count (SJC), Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22.
Change From Baseline in the DAS28 at Week 52 [Baseline and Week 52]
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Change From Baseline in the FACIT-Fatigue Scale Score at Week 52 [Baseline and Week 52]
The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Percentage of Participants With MASES Improvement ≥ 20% at Week 52 [Baseline and Week 52]
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 52 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline by ≥ 1 at Week 52 [Baseline and Week 52]
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52 [Baseline and Week 52]
The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. A Good response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 A Moderate Response is defined as either: an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. Two-sided 95% confidence interval is based on the Clopper-Pearson method
Percentage of Participants With an ACR 50 Response at Week 52 [Baseline and Week 52]
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 50% improvement in 78 tender joint count; ≥ 50% improvement in 76 swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: o Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Percentage of Participants With an ACR 70 Response at Week 52 [Baseline and Week 52]
A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 70% improvement in 78 tender joint count; ≥ 70% improvement in 76 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Percentage of Participants With Pre-existing Enthesopathy Whose MASES Improves From Baseline to 0 at Week 52 [Baseline and Week 52]
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval was based on the Clopper-Pearson method.
Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline to 0 at Week 52 [Baseline and Week 52]
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit and ranges from 0 to 20. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase [Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants (placebo participants who remained on placebo through week 24 and participants randomized to the APR 20 mg BID or APR 30 mg BID)]
A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE is any AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or constitutes an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale: Mild: asymptomatic or with mild symptoms, Moderate: symptoms causing moderate discomfort or Severe: symptoms causing severe discomfort or pain.
Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period [Week 0 to Week 260; median duration of exposure to apremilast 20 mg BID was 168.93 weeks and 229.36 weeks for apremilast 30 mg BID]
A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE is any AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or constitutes an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale: Mild: asymptomatic or with mild symptoms, Moderate: symptoms causing moderate discomfort or Severe: symptoms causing severe discomfort or pain.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

Male or female, aged ≥ 18 years at time of consent.
Must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
Able to adhere to the study visit schedule and other protocol requirements.
Have a documented diagnosis of Psoriatic Arthritis (PsA, by any criteria) of ≥ 3 months duration.
Meet the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for PsA at time of screening.
Have ≥ 3 swollen AND ≥ 3 tender joints.
Have not been previously treated with disease-modifying antirheumatic drugs (DMARDS) (small molecules or biologics)
Be receiving treatment on an outpatient basis.
If taking oral corticosteroids, must be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 1 month prior to screening.
If taking nonsteroidal anti-inflammatory drugs (NSAIDs) or narcotic analgesics, must be on stable dose for at least 2 weeks prior to screening and until they have completed the Week 24 study visit.
Low potency topical corticosteroids (Appendix M or locally available equivalent) will be allowed as background therapy for treatment of psoriasis on the face, axillae and groin in accordance with the manufacturers' suggested usage during the course of the study. Subjects with scalp psoriasis will be permitted to use coal tar shampoo and/or salicylic acid scalp preparations on scalp lesions. A non-medicated skin emollient (eg, Eucerin cream) will also be permitted for body lesions only. Subjects must not use these treatments within 24 hours prior to the clinic visit.
Meet the following laboratory criteria:

White blood cell count ≥ 3000/mm3 (≥ 3.0 x 109/L) and < 14,000/mm3 (< 14 x 109/L)
Platelet count ≥ 100,000/mm3 (≥ 100 x 109/L)
Serum creatinine ≤ 1.5 mg/dL(≤ 132.6 μmol/L)
Aspartate aminotransferase/Serum glutamic oxaloacetic transaminase (AST/SGOT) and Alanine aminotransferase/Serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2 x upper limit of normal (ULN)
Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L)
Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)
Hemoglobin A1c ≤ 9.0%

Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane]) while on IP and for at least 28 days after the last dose of IP.
Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use 2 forms of contraception while on investigational product (IP) and for at least 28 days after the last dose of IP: one highly effective form (ie, hormonal, intrauterine device [IUD], tubal ligation, vasectomized partner) and one additional form (latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane], diaphragm, sponge). If one highly effective form of contraception cannot be used, then 2 forms of barrier contraception must be used, ie, latex condom or any nonlatex condom NOT made out of natural (animal) membrane (eg, polyurethane) with either of the following: sponge with spermicide or diaphragm with spermicide.

Exclusion Criteria:

History of clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major uncontrolled disease.
Any condition, including the presence of laboratory abnormalities that places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
Clinically significant abnormality on 12-lead electrocardiography (ECG) at Screening.
Pregnant or breast feeding.
History of allergy to any component of the IP.
Hepatitis B surface antigen positive at screening.
Hepatitis C antibody positive at screening.
AST/SGOT and/or ALT/SGPT > 1.5 x ULN and total bilirubin > ULN or albumin < lower limit of normal (LLN).
History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).
Active tuberculosis or a history of incompletely treated tuberculosis.
Clinically significant abnormality based upon chest radiograph with at least PA view (radiograph must be taken within 12 weeks prior to Screening or during the Screening visit). An additional lateral view is strongly recommended but not required.
Active substance abuse or a history of substance abuse within 6 months prior to Screening.
Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening. Any treatment for such infections must have been completed at least 4 weeks prior to Screening.
Malignancy or history of malignancy (except for treated [ie, cured] basal cell or squamous cell in situ skin carcinomas and treated [ie, cured] cervical intraepithelial neoplasia [CIN] or carcinoma in situ of the cervix).
Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
Erythrodermic, guttate, or pustular psoriasis.
Topical therapy for psoriasis, except as noted in the Inclusion Criteria, within 2 weeks of randomization (including but not limited to topical corticosteroids, topical retinoids or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin).
Rheumatic autoimmune disease other than PsA, including systemic lupus erythematosis (SLE), mixed connective tissue disease (MCTD), scleroderma, or polymyositis.
Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis (Appendix Q).
Prior history of or current inflammatory joint disease other than PsA (eg, gout, reactive arthritis, RA, ankylosing spondylitis, Lyme disease).
Prior use of disease modifying antirheumatic drugs (DMARDS; small molecules or biologics).
Use of the following systemic therapy(ies) within 4 weeks of randomization, including but not limited to corticosteroids (except as noted in inclusion criteria), oral retinoids and fumaric acid esters.
Use of phototherapy within 4 weeks of randomization (ie, UVB, PUVA).
Previous treatment with any cell depleting therapies, including investigational agents (eg, rituximab, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20).
Treatment with intravenous gamma globulin, plasmapheresis, or Prosorba® column within 6 months of baseline.
Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation.
Prior treatment with apremilast.
Use of any investigational drug within 4 weeks of randomization, or 5 pharmacokinetic/ pharmacodynamic half lives, if known (whichever is longer).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Research Center	Phoenix	Arizona	United States	85023
2	Desert Medical Advances	Palm Desert	California	United States	92260
3	In Vivo Clinical Research	Doral	Florida	United States	33166
4	Centre For Rheumatology, Immun. And Arthritis	Fort Lauderdale	Florida	United States	33334
5	North Florida Dermatology	Jacksonville	Florida	United States	32204
6	Florida Center for Dermatology, PA	Saint Augustine	Florida	United States	32086
7	Tampa Medical Group Pa	Tampa	Florida	United States	33614
8	Atlanta Dermatology, Vein and Research Center, PC	Alpharetta	Georgia	United States	30022
9	Arthritis and Rheumatology of Georgia	Atlanta	Georgia	United States	30342
10	Sonora Clinical Research, LLC	Boise	Idaho	United States	83702
11	Rockford Orthopedic Associates, LLC	Rockford	Illinois	United States	61107
12	The Arthritis Center	Springfield	Illinois	United States	62704
13	Indiana. University	Indianapolis	Indiana	United States	46202
14	Klein and Associates MD, PA	Cumberland	Maryland	United States	21502
15	Klein and Associates MD, PA	Hagerstown	Maryland	United States	21740
16	Clinical Pharmacology Study Group	Worcester	Massachusetts	United States	01605
17	Justus Fiechtner MD PC	Lansing	Michigan	United States	48910
18	Heartland Clinical Research, Inc.	Omaha	Nebraska	United States	68134
19	Physicians East	Greenville	North Carolina	United States	27834
20	Unifour Medical Research Associatets LLC	Hickory	North Carolina	United States	28602
21	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
22	Clinical Research Center of Reading, LLP	West Reading	Pennsylvania	United States	19610
23	West Tennessee Research Institute	Jackson	Tennessee	United States	38305
24	Austin Regional Clinic	Austin	Texas	United States	78731
25	Center for Clinical Studies	Houston	Texas	United States	77065
26	Houston Medical Research	Houston	Texas	United States	77090
27	Luckster Enterprises	San Antonio	Texas	United States	78232
28	Center for Clinical Studies	Webster	Texas	United States	77598
29	Rheumatology and Immunotherapy Center	Franklin	Wisconsin	United States	53132
30	PharmaSeek	Middleton	Wisconsin	United States	53562
31	Monash Medical Centre	Clayton	Victoria	Australia	3168
32	Eastern Health Clinical School	Box Hill		Australia	3128
33	Repatriation General Hospital	Daws Park		Australia	5041
34	Menzies Centre for Population Health Research	Hobart		Australia	7000
35	Optimus Clinical Research Pty. Ltd	Kogarah		Australia	2217
36	The Queen Elizabeth Hospital	Woodville		Australia	5011
37	UZ Leuven	Leuven		Belgium	3000
38	CHU de Liege	Liège		Belgium	4000
39	Multiprofile Hospital for Active Treatment Trimontsium	Plovdiv		Bulgaria	4000
40	17 Diagnostic and Consulting Centre Sofia EOOD	Sofia		Bulgaria	1505
41	Multiprofile Hospital for Active Treatment Sv. Ivan Rilski	Sofia		Bulgaria	1606
42	Diagnostic-Consultative Center Sveta Anna	Sofia		Bulgaria	1709
43	Diagnostic Consulting Center N4	Varna		Bulgaria	9010
44	Arthritis Research Centre of Canada	Vancouver	British Columbia	Canada	V5Z1L7
45	PerCuro Clinical Research	Victoria	British Columbia	Canada	V8P5P6
46	Manitoba Clinic	Winnipeg	Manitoba	Canada	R3A1M3
47	St. Clare's Health Care Corporation of St. John's	St John's	Newfoundland and Labrador	Canada	A1C-5B8
48	Ultranova Skincare	Barrie	Ontario	Canada	L4M 6L2
49	William Bensen's Private Practice	Hamilton	Ontario	Canada	L8N1Y2
50	Rheumatology Research Associates	Ottawa	Ontario	Canada	K1H1A2
51	Wilderman Medical Clinic	Thornhill	Ontario	Canada	L4J1W3
52	Probity Medical Research Inc	Waterloo	Ontario	Canada	N2J1C4
53	Darryl Toth's Private Practice	Windsor	Ontario	Canada	N8W 1E6
54	Centre de Rhumatologie St-Louis	Sainte Foy	Quebec	Canada	G1W 4R4
55	Saskatoon Osteoporosis Centre	Saskatoon	Saskatchewan	Canada	S7K 0H6
56	Affidea Praha s.r.o	Praha 11		Czechia	148 00
57	Revmatologicky ustav	Praha 2		Czechia	128 50
58	Revmatologicka Ambulance	Praha 4		Czechia	140 00
59	PV - MEDICAL, s.r.o.	Zlin		Czechia	760 01
60	East Tallinn Central Hospital	Tallinn		Estonia	EE-11412
61	North Estonia Regional Hospital	Tallinn		Estonia	EE-13419
62	Clinical Research Centre Ltd	Tartu		Estonia	50106
63	Hotel Dieu	Nantes Cedex 01		France	44093
64	Groupe Hospitalier Archet I et II	Nice		France	6002
65	Hopital Lariboisiere	Paris Cedex 10		France	75475
66	Fondation Hôpital Saint-Joseph	Paris		France	75014
67	Qualiclinic kft	Budapest		Hungary	1036
68	Synexus Magyarország Kft.	Budapest		Hungary	1036
69	Honvéd Kórház - Állami Egészségügyi Központ	Budapest		Hungary	1062
70	Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum	Debrecen		Hungary	4032
71	Pest Megyei Flor Ferenc Korhaz	Kistarcsa		Hungary	2143
72	Principal SMO Kft.	Mako		Hungary	6900
73	MAV Korhaz es Rendelointezet Szolnok	Szolnok		Hungary	5000
74	Azienda Ospedaliera Universitaria San Martino	Genova		Italy	16132
75	Ospedale Luigi Sacco	Milano		Italy	20157
76	AOU della II Universita degli Studi di Napoli	Napoli		Italy	80130
77	Fondazione PTV Policlinico Tor Vergata	Roma		Italy	00133
78	Ospedale Civile Maggiore Borgo Trento	Verona		Italy	37126
79	Chungnam National University Hospital	DaeJeon		Korea, Republic of	301-721
80	Inha University Hosiptal	Incheon		Korea, Republic of	400-711
81	Gachon University Gil Medical Center	Incheon		Korea, Republic of	405-760
82	Siauliai Hospital	Siauliai		Lithuania	LT-76231
83	Waikato hospital	Hamilton		New Zealand	3204
84	North Shore Hospital	Takapuna		New Zealand	1309
85	Timaru Hospital	Timaru		New Zealand	8601
86	Bytomskie Centrum Medyczne Silesiana Sp. z o.o.	Bialystok		Poland	15-099
87	Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy	Bydgoszcz		Poland	85-168
88	Centrum Medyczne Silesiana Sp. z o.o.	Bytom		Poland	41-902
89	Synexus SCM Sp. z o.o.	Gdynia		Poland	81-384
90	Synexus SCM Sp. z o.o.	Katowice		Poland	Poland
91	Niepubliczny Zaklad Opieki Zdrowotnej REUMED	Lublin		Poland	20-582
92	Prywatna Praktyka Lekarska	Poznan		Poland	61-397
93	REUMATIKA-Centrum Reumatologii Niepubliczny Zaklad Opieki Zdrowotnej	Warszawa		Poland	00-235
94	Synexus SCM Sp. z o.o. Oddz. Warszawa	Warszawa		Poland	01-192
95	Synexus SCM Sp. z o.o.	Wroclaw		Poland	50-088
96	Sf. Maria Clinical Hospital	Bucharest		Romania	011172
97	Emergency County Clinical Hospital	Cluj-Napoca		Romania	400006
98	Sf Apostol Andrei Emergency Clinical County Hospital	Galati		Romania	800578
99	C.M.I. Dr. Ciornohuz Adriana	Iasi		Romania	700127
100	Veterans of Wars Regional Clinical Hospital	Kemerovo		Russian Federation	650000
101	Kemerovo State Medical Academy of Roszdrav	Kemerovo		Russian Federation	650066
102	Research Medical Complex Vashe Zdorovie	Kezch		Russian Federation	214025
103	Krasnoyarsk State Medical Academy	Krasnoyarsk		Russian Federation	660022
104	City Clinical Hospital #5	Nizhniy Novgorod		Russian Federation	603005
105	Research Institute of Clinical Immunology	Novosibirsk		Russian Federation	630099
106	Research Institute of Clinical and Experimental Lymphology	Novosibirsk		Russian Federation	630117
107	Penza Regional Clinical Hospital n.a. N.N. Burdenko	Penza		Russian Federation	440026
108	Departmental Hospital at Smolensk Station RZhD JSC	Smolensk		Russian Federation	214025
109	Tomsk Regional Clinical Hospital	Tomsk		Russian Federation	634063
110	Regional Clinical Hospital	Vladimir		Russian Federation	600023
111	Voronezh Regional Clinical Hopsital #1, Voronezh State Medical Academy	Voronezh		Russian Federation	394066
112	Taipei Veterans General Hospital	Taipei		Taiwan	11217
113	National Taiwan University Hospital	Tapei		Taiwan	10002
114	Barnsley Hospital	Barnsley South Yorkshire		United Kingdom	S75 2EP
115	Haywood Hospital	Burslem		United Kingdom	ST6 7AG
116	Cannock Chase Hospital	Cannock		United Kingdom	WS11 5XY
117	Poole Hospital	Poole		United Kingdom	BH1 5JB
118	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD

Sponsors and Collaborators

Amgen

Investigators

Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Publications

Mease PJ, Kavanaugh A, Ogdie A, Wells AF, Bergman M, Gladman DD, Richter S, Teng L, Jardon S, Smolen JS. Baseline Disease Activity Predicts Achievement of cDAPSA Treatment Targets With Apremilast: Phase III Results in DMARD-naïve Patients With Psoriatic Arthritis. J Rheumatol. 2022 Jul;49(7):694-699. doi: 10.3899/jrheum.210906. Epub 2022 Apr 15.

Responsible Party:

Amgen

ClinicalTrials.gov Identifier:

NCT01307423

Other Study ID Numbers:

CC-10004-PSA-005
2010-020324-22

First Posted:

Mar 2, 2011

Last Update Posted:

Jun 14, 2022

Last Verified:

Apr 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Keywords provided by Amgen

phosphodiesterase type 4

Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details	The study was conducted in 16 countries including the United States, Canada, Europe, New Zealand, Australia and Russia.
Pre-assignment Detail	This study consisted of a 24-week randomized, double-blind, placebo-controlled phase, a 28-week randomized, double-blind active treatment phase and a 4-year open-label safety phase, for an overall study duration of 5 years.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg	Placebo/ Apremilast 20 mg EE	Placebo / Apremilast 20 mg XO	Placebo / Apremilast 30 mg EE	Placebo / Apremilast 30 mg XO	Placebo/Apremilast 20 mg [Long-Term Safety Phase (LTSP)]	Placebo/Apremilast 30 mg (Long-Term Safety Phase)
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase and continued to receive 20 mg apremilast tablets twice daily for up to 4.5 years in the active treatment / long-term safety phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase and continued to receive 30 mg apremilast tablets twice daily for up to 4.5 years in the active treatment / long-term safety phase.	Participants initially randomized to receive placebo twice daily who were re-randomized due to early escape (EE) at Week 16 to receive 20 mg apremilast twice daily in the active treatment phase.	Participants initially randomized to receive placebo twice daily who were re-randomized at Week 24 (XO) to receive 20 mg apremilast twice daily in the active treatment phase.	Participants initially randomized to receive placebo twice daily who were re-randomized due to early escape (EE) at Week 16 to receive 30 mg apremilast twice daily in the active treatment phase.	Participants initially randomized to receive placebo twice daily who were re-randomized at Week 24 to receive 30 mg apremilast twice daily in the active treatment phase.	Participants initially randomized to placebo tablets twice daily during the 24-week placebo-controlled phase were re-randomized to 20 mg apremilast tablets twice daily at Week 16 or Week 24 and continued receiving apremilast 20 mg tablets twice daily in active treatment / long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to the 30 mg apremilast BID dose).	Participants initially randomized to placebo tablets BID during the 24-week placebo-controlled phase were re-randomized to apremilast 30 mg tablets twice daily at Week 16 or Week 24 and continued receiving apremilast 30 mg tablets twice daily in the active treatment / long-term safety phase.
Period Title: Placebo-controlled Phase (Week 0 - 24)
STARTED	176	175	177	0	0	0	0	0	0
Received Treatment	176	175	175	0	0	0	0	0	0
Completed Week 16	166	168	166	0	0	0	0	0	0
Early Escape at Week 16	103	73	79	0	0	0	0	0	0
COMPLETED	156	160	155	0	0	0	0	0	0
NOT COMPLETED	20	15	22	0	0	0	0	0	0
Period Title: Placebo-controlled Phase (Week 0 - 24)
STARTED	0	151	150	46	26	46	26	0	0
COMPLETED	0	132	141	38	23	43	25	0	0
NOT COMPLETED	0	19	9	8	3	3	1	0	0
Period Title: Placebo-controlled Phase (Week 0 - 24)
STARTED	0	122	134	0	0	0	0	57	67
COMPLETED	0	99	109	0	0	0	0	48	60
NOT COMPLETED	0	23	25	0	0	0	0	9	7
Period Title: Placebo-controlled Phase (Week 0 - 24)
STARTED	0	99	109	0	0	0	0	48	60
COMPLETED	0	90	91	0	0	0	0	40	49
NOT COMPLETED	0	9	18	0	0	0	0	8	11
Period Title: Placebo-controlled Phase (Week 0 - 24)
STARTED	0	89	91	0	0	0	0	40	49
COMPLETED	0	81	86	0	0	0	0	38	44
NOT COMPLETED	0	8	5	0	0	0	0	2	5
Period Title: Placebo-controlled Phase (Week 0 - 24)
STARTED	0	81	86	0	0	0	0	38	44
COMPLETED	0	71	80	0	0	0	0	37	41
NOT COMPLETED	0	10	6	0	0	0	0	1	3

Baseline Characteristics

Arm/Group Title	Placebo	Apremilast 20mg	Apremilast 30mg	Total
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Total of all reporting groups
Overall Participants	176	175	176	527
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.5 (11.58)	49.2 (12.00)	48.4 (12.52)	49.4 (12.05)
Sex: Female, Male (Count of Participants)
Female	86 48.9%	95 54.3%	96 54.5%	277 52.6%
Male	90 51.1%	80 45.7%	80 45.5%	250 47.4%
Duration of Psoriatic Arthritis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.42 (5.103)	3.19 (4.706)	3.62 (5.041)	3.41 (4.947)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16
Description	A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: -Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); -Patient's global assessment of disease activity (measured on a 100 mm VAS); -Physician's global assessment of disease activity (measured on a 100 mm VAS); -Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); -C-Reactive Protein.
Time Frame	Baseline and Week 16

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20mg	Apremilast 30mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Number [percentage of participants]	15.9 9%	28.0 16%	30.7 17.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments	In order to maintain the Type 1 error at the 0.05 significance level, the Hochberg procedure was to be used. The results of the endpoint were to be considered statistically significant if both the 30 mg apremilast dose versus placebo comparison and the 20 mg versus placebo comparison were statistically significant at the 0.05 significance level, or one of the comparisons was statistically significant at the 0.025 level.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0062
	Comments
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	12.1
	Confidence Interval	(2-Sided) 95% 3.5 to 20.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments	In order to maintain the Type 1 error at the 0.05 significance level, the Hochberg procedure was to be used. The results of the endpoint were to be considered statistically significant if both the 30 mg apremilast dose versus placebo comparison and the 20 mg versus placebo comparison were statistically significant at the 0.05 significance level, or one of the comparisons was statistically significant at the 0.025 level.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	14.8
	Confidence Interval	(2-Sided) 95% 6.1 to 23.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

2. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 16
Description	The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative changes from baseline in the overall score indicate improvement in functional ability.
Time Frame	Baseline and Week 16

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Least Squares Mean (Standard Error) [units on a scale]	0.012 (0.0350)	-0.156 (0.0349)	-0.205 (0.0350)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments	Pairwise comparisons (30 mg vs placebo and 20 mg vs placebo) were conducted conditional on the primary endpoint results. If the primary endpoint was statistically significant for both apremilast dose groups, pairwise comparisons for the HAQ-DI were to be evaluated at the 0.05 level using the Hochberg procedure. If only one apremilast dose was statistically significant, then only the comparison between that apremilast dose and placebo was conducted for the HAQ-DI score, at the 0.025 level.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	ANCOVA
	Comments	Based on an analysis of covariance (ANCOVA) model with treatment group as a factor, and the baseline value as a covariate.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.168
	Confidence Interval	(2-Sided) 95% -0.265 to -0.071
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments	Pairwise comparisons (30 mg vs placebo and 20 mg vs placebo) were conducted conditional on the primary endpoint results. If the primary endpoint was statistically significant for both apremilast dose groups, pairwise comparisons for the HAQ-DI were to be evaluated at the 0.05 level using the Hochberg procedure. If only one apremilast dose was statistically significant, then only the comparison between that apremilast dose and placebo was conducted for the HAQ-DI score, at the 0.025 level.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANCOVA
	Comments	Based on an analysis of covariance (ANCOVA) model with treatment group as a factor, and the baseline value as a covariate

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.217
	Confidence Interval	(2-Sided) 95% -0.314 to -0.120
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With an ACR 20 Response at Week 24
Description	Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein.
Time Frame	Baseline and Week 24

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Number [percentage of participants]	13.1 7.4%	29.1 16.6%	24.4 13.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0002
	Comments	Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	16.1
	Confidence Interval	(2-Sided) 95% 7.7 to 24.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0063
	Comments	Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	11.4
	Confidence Interval	(2-Sided) 95% 3.3 to 19.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

4. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 24
Description	The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame	Baseline and Week 24

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive Apremilast 20 mg tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Least Squares Mean (Standard Error) [units on a scale]	0.012 (0.0370)	-0.156 (0.0368)	-0.207 (0.0369)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0014
	Comments	Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
	Method	ANCOVA
	Comments	Based on an analysis of covariance model for the change from baseline at Week 24, with treatment group as a factor and baseline value as a covariate

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.168
	Confidence Interval	(2-Sided) 95% -0.271 to -0.065
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<.0001
	Comments	Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
	Method	ANCOVA
	Comments	Based on an analysis of covariance model for the change from baseline at Week 24, with treatment group as a factor and baseline value as a covariate

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.219
	Confidence Interval	(2-Sided) 95% -0.322 to -0.117
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16
Description	The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). SF-36 domain scores were first calculated to range from 0 to100 and then transformed to norm-based scores (the norm-based scores in the US general population have an average of 50 and a standard deviation of 10). Norm-based scores were used in analyses, with higher scores indicating a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.
Time Frame	Baseline and Week 16

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive Apremilast 20 mg tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Least Squares Mean (Standard Error) [units on a scale]	0.01 (0.588)	2.39 (0.586)	3.19 (0.590)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0043
	Comments	Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above.
	Method	ANCOVA
	Comments	Based on an analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and baseline value as a covariate

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.38
	Confidence Interval	(2-Sided) 95% 0.75 to 4.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0002
	Comments	Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
	Method	ANCOVA
	Comments	Based on an analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and baseline value as a covariate

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.18
	Confidence Interval	(2-Sided) 95% 1.55 to 4.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16
Description	Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS.
Time Frame	Baseline and Week 16

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Number [percentage of participants]	24.4 13.9%	38.9 22.2%	45.5 25.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0037
	Comments	Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above.
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	14.4
	Confidence Interval	(2-Sided) 95% 4.8 to 24.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<.0001
	Comments	Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above.
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	21.0
	Confidence Interval	(2-Sided) 95% 11.3 to 30.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

7. Secondary Outcome

Title	Change From Baseline in Patient's Assessment of Pain at Week 16
Description	The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time Frame	Baseline and Week 16

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Least Squares Mean (Standard Error) [mm]	-2.6 (1.81)	-7.7 (1.79)	-10.5 (1.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0485
	Comments	Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
	Method	ANCOVA
	Comments	Based on an analysis of covariance (ANCOVA) model with treatment group as a factor, and the baseline value as a covariate

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.0
	Confidence Interval	(2-Sided) 95% -10.0 to -0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0022
	Comments	Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
	Method	ANCOVA
	Comments	Based on an analysis of covariance (ANCOVA) model with treatment group as a factor, and the baseline value as a covariate

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-7.8
	Confidence Interval	(2-Sided) 95% -12.8 to -2.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16
Description	The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time Frame	Baseline and Week 16

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	115	117	111
Least Squares Mean (Standard Error) [units on a scale]	-0.5 (0.24)	-0.5 (0.24)	-1.5 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.7696
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95% -0.8 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0038
	Comments	Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95% -1.7 to -0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate

9. Secondary Outcome

Title	Change From Baseline in Dactylitis Severity Score at Week 16
Description	Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time Frame	Baseline to Week 16

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	90	89	84
Least Squares Mean (Standard Error) [units on a scale]	-1.0 (0.25)	-1.9 (0.25)	-1.7 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95% -1.6 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95% -1.4 to -0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate

10. Secondary Outcome

Title	Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16
Description	The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22
Time Frame	Baseline and Week 16

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	163	166	164
Least Squares Mean (Standard Error) [units on a scale]	-1.98 (0.770)	-6.89 (0.763)	-7.63 (0.768)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.91
	Confidence Interval	(2-Sided) 95% -7.04 to -2.78
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.65
	Confidence Interval	(2-Sided) 95% -7.78 to -3.51
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate

11. Secondary Outcome

Title	Change From Baseline in the Disease Activity Score (DAS28) After 16 Weeks of Treatment
Description	The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time Frame	Baseline and Week 16

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	164	164	167
Least Squares Mean (Standard Error) [units on a scale]	-0.15 (0.076)	-0.61 (0.076)	-0.68 (0.075)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95% -0.67 to -0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.53
	Confidence Interval	(2-Sided) 95% -0.74 to -0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate

12. Secondary Outcome

Title	Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16
Description	The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Time Frame	Baseline and Week 16

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	167	168	166
Least Squares Mean (Standard Error) [units on a scale]	0.07 (0.631)	1.19 (0.629)	2.62 (.0633)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95% -0.63 to 2.87
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	2.55
	Confidence Interval	(2-Sided) 95% 0.80 to 4.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate

13. Secondary Outcome

Title	Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 24
Description	The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). SF-36 domain scores were first calculated to range from 0 to100 and then transformed to norm-based scores (the norm-based scores in the US general population have an average of 50 and a standard deviation of 10). Norm-based scores were used in analyses, with higher scores indicating a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.
Time Frame	Baseline and Week 24

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Least Squares Mean (Standard Error) [units on a scale]	0.16 (0.609)	2.13 (0.605)	3.88 (0.611)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	1.97
	Confidence Interval	(2-Sided) 95% 0.28 to 3.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.72
	Confidence Interval	(2-Sided) 95% 2.02 to 5.41
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate

14. Secondary Outcome

Title	Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24
Description	Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS.
Time Frame	Baseline and Week 24

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive Apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Number [percentage of participants]	17.0 9.7%	36.6 20.9%	35.2 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	19.5
	Confidence Interval	(2-Sided) 95% 10.5 to 28.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	18.2
	Confidence Interval	(2-Sided) 95% 9.2 to 27.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution

15. Secondary Outcome

Title	Change From Baseline in Participants Assessment of Pain at Week 24
Description	The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time Frame	Baseline and Week 24

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Least Squares Mean (Standard Error) [mm]	-3.8 (1.83)	-9.4 (1.82)	-9.6 (1.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.6
	Confidence Interval	(2-Sided) 95% -10.6 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.7
	Confidence Interval	(2-Sided) 95% -10.8 to -0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate

16. Secondary Outcome

Title	Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24
Description	The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time Frame	Baseline and Week 24

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase..	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	111	113	106
Least Squares Mean (Standard Error) [units on a scale]	-0.6 (0.25)	-0.9 (0.25)	-1.5 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95% -1.0 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95% -1.6 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.

17. Secondary Outcome

Title	Change From Baseline in Dactylitis Severity Score at Week 24
Description	Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time Frame	Baseline and Week 24

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive Apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	87	85	79
Least Squares Mean (Standard Error) [units on a scale]	-1.0 (0.26)	-2.0 (0.26)	-1.7 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95% -1.7 to -0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95% -1.4 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.

18. Secondary Outcome

Title	Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24
Description	The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22.
Time Frame	Baseline and Week 24

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Least Squares Mean (Standard Error) [units on a scale]	-2.23 (0.807)	-7.30 (0.803)	-7.36 (0.810)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.07
	Confidence Interval	(2-Sided) 95% -7.31 to -2.84
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.14
	Confidence Interval	(2-Sided) 95% -7.38 to -2.89
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model (Ancova) for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.

19. Secondary Outcome

Title	Change From Baseline in Disease Activity Score (DAS 28) at Week 24
Description	The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time Frame	Baseline and Week 24

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Least Squares Mean (Standard Error) [units on a scale]	-0.22 (0.084)	-0.69 (0.084)	-0.68 (0.084)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.47
	Confidence Interval	(2-Sided) 95% -0.70 to -0.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95% -0.69 to -0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model (Ancova) for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.

20. Secondary Outcome

Title	Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24
Description	The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Time Frame	Baseline and Week 24

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive Apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Least Squares Mean (Standard Error) [units on a scale]	0.25 (0.652)	1.37 (0.648)	2.58 (0.655)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95% -0.68 to 2.93
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model (Ancova) for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	2.33
	Confidence Interval	(2-Sided) 95% 0.52 to 4.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model (Ancova) for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.

21. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive Apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	115	117	111
Number [percentage of participants]	46.1 26.2%	48.7 27.8%	63.1 35.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.6
	Confidence Interval	(2-Sided) 95% -10.2 to 15.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	17.0
	Confidence Interval	(2-Sided) 95% 4.2 to 29.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution

22. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive Apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	90	89	84
Number [percentage of participants]	60.0 34.1%	66.3 37.9%	61.9 35.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	6.3
	Confidence Interval	(2-Sided) 95% -7.8 to 20.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95% -12.6 to 16.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

23. Secondary Outcome

Title	Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16
Description	The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2
Time Frame	Baseline and Week 16

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Number [percentage of participants]	25.0 14.2%	41.1 23.5%	44.3 25.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	16.1
	Confidence Interval	(2-Sided) 95% 6.4 to 25.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	19.3
	Confidence Interval	(2-Sided) 95% 9.6 to 29.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

24. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	115	117	111
Number [percentage of participants]	48.7 27.7%	54.7 31.3%	66.7 37.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	6.0
	Confidence Interval	(2-Sided) 95% -6.8 to 18.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	18.0
	Confidence Interval	(2-Sided) 95% 5.3 to 30.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution

25. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	90	89	84
Number [percentage of participants]	57.8 32.8%	69.7 39.8%	63.1 35.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	11.9
	Confidence Interval	(2-Sided) 95% -2.1 to 25.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	5.3
	Confidence Interval	(2-Sided) 95% -9.2 to 19.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

26. Secondary Outcome

Title	Percentage of Participants With Good or Moderate EULAR Response at Week 24
Description	The EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on th DAS-28. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2 A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2.
Time Frame	Baseline and Week 24

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Number [percentage of participants]	17.0 9.7%	34.9 19.9%	28.4 16.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	17.8
	Confidence Interval	(2-Sided) 95% 8.8 to 26.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	11.4
	Confidence Interval	(2-Sided) 95% 2.7 to 20.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

27. Secondary Outcome

Title	Percentage of Participants With a ACR 50 Response at Week 16
Description	Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein.
Time Frame	Baseline and Week 16

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive Apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	176	175	176
Number [Percentage of participants]	4.5 2.6%	11.4 6.5%	11.4 6.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	6.9
	Confidence Interval	(2-Sided) 95% 1.3 to 12.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	6.8
	Confidence Interval	(2-Sided) 95% 1.2 to 12.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

28. Secondary Outcome

Title	Percentage of Participants With a ACR 70 Response at Week 16
Description	Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein.
Time Frame	Baseline and Week 16

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Number [percentage of participants]	1.1 0.6%	4.0 2.3%	4.0 2.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 95% -0.4 to 6.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.8
	Confidence Interval	(2-Sided) 95% -0.4 to 6.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution

29. Secondary Outcome

Title	Percentage of Participants With a ACR 50 Response at Week 24
Description	Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein.
Time Frame	Baseline and Week 24

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Number [percentage of participants]	6.3 3.6%	16.0 9.1%	12.5 7.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	9.8
	Confidence Interval	(2-Sided) 95% 3.2 to 16.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	6.3
	Confidence Interval	(2-Sided) 95% 0.2 to 12.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution

30. Secondary Outcome

Title	Percentage of Participants With a ACR 70 Response at Week 24
Description	Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein.
Time Frame	Baseline and Week 24

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	176
Number [percentage of participants]	4.0 2.3%	4.0 2.3%	4.5 2.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95% -4.1 to 4.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95% -3.7 to 4.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

31. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	115	117	111
Number [percentage of participants]	19.1 10.9%	21.4 12.2%	36.9 21%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 95% -8.1 to 12.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	17.8
	Confidence Interval	(2-Sided) 95% 6.3 to 29.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

32. Secondary Outcome

Title	Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves to 0 at Week 16
Description	Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time Frame	Baseline and Week 16

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	90	89	84
Number [percentage of participants]	33.3 18.9%	42.7 24.4%	40.5 23%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	9.4
	Confidence Interval	(2-Sided) 95% -4.8 to 23.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	7.1
	Confidence Interval	(2-Sided) 95% -7.2 to 21.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

33. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	115	117	111
Number [percentage of participants]	22.6 12.8%	29.1 16.6%	37.8 21.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	6.5
	Confidence Interval	(2-Sided) 95% -4.8 to 17.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	15.2
	Confidence Interval	(2-Sided) 95% 3.4 to 27.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

34. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	90	89	84
Number [percentage of participants]	35.6 20.2%	46.1 26.3%	40.5 23%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	10.5
	Confidence Interval	(2-Sided) 95% -3.8 to 24.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	4.9
	Confidence Interval	(2-Sided) 95% -9.5 to 19.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.

35. Secondary Outcome

Title	Percentage of Participants With a ACR 20 Response at Week 52
Description	Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 20% improvement in 78 tender joint count; ≥ 20% improvement in 76 swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time Frame	Baseline and Week 52

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	62	67	131	138
Number (95% Confidence Interval) [Percentage of Participants]	59.7 33.9%	56.7 32.4%	53.4 30.3%	58.7 11.1%

36. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52
Description	The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame	Baseline and Week 52

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.	Participants initially randomized to receive 20 mg apremilast tablets twice daily	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	62	68	132	139
Mean (Standard Deviation) [units on a scale]	-0.21 (0.450)	-0.25 (0.533)	-0.32 (0.559)	-0.39 (0.567)

37. Secondary Outcome

Title	Change From Baseline in the SF-36v2 Physical Functioning Scale Score at Week 52
Description	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.
Time Frame	Baseline and Week 52

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	62	68	132	139
Mean (Standard Deviation) [units on a scale]	7.76 (8.236)	6.87 (7.241)	5.68 (8.467)	5.87 (8.008)

38. Secondary Outcome

Title	Percentage of Participants With a Modified PsARC Response at Week 52
Description	Measure Description: Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time Frame	Baseline and Week 52

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.	Participants initially randomized to receive 20 mg apremilast tablets twice daily	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	61	67	131	139
Number (95% Confidence Interval) [Percentage of Participants]	73.8 41.9%	79.1 45.2%	75.6 43%	75.9 14.4%

39. Secondary Outcome

Title	Change From Baseline in the Participants Assessment of Pain Using the Visual Analog Scale at Week 52
Description	The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time Frame	Baseline and Week 52

Outcome Measure Data

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

Arm/Group Title	Placebo/Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	62	68	132	139
Mean (Standard Deviation) [mm]	-13.1 (25.57)	-18.9 (24.28)	-15.6 (27.29)	-14.2 (28.14)

40. Secondary Outcome

Title	Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52
Description	The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time Frame	Baseline and Week 52

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo/Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	41	42	91	176
Mean (Standard Deviation) [units on a scale]	-1.7 (2.38)	-1.8 (2.34)	-1.5 (2.62)	-1.8 (3.03)

41. Secondary Outcome

Title	Change From Baseline in the Dactylitis Severity Score at Week 52
Description	Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present
Time Frame	Baseline and Week 52

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily
Measure Participants	32	38	70	64
Mean (Standard Deviation) [units on a scale]	-2.2 (1.89)	-2.9 (2.47)	-2.2 (4.09)	-2.9 (3.55)

42. Secondary Outcome

Title	Change From Baseline in the CDAI Score at Week 52
Description	The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: 28 tender joint count (TJC), 28 swollen joint count (SJC), Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22.
Time Frame	Baseline and Week 52

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	61	67	131	137
Mean (Standard Deviation) [units on a scale]	-11.0 (10.288)	-14.67 (11.943)	-14.32 (11.128)	-13.98 (10.541)

43. Secondary Outcome

Title	Change From Baseline in the DAS28 at Week 52
Description	The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time Frame	Baseline and Week 52

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	62	68	130	138
Mean (Standard Deviation) [units on a scale]	-1.08 (1.113)	-1.28 (1.044)	-1.37 (1.128)	-1.39 (0.970)

44. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	62	67	131	139
Mean (Standard Deviation) [units on a scale]	6.03 (8.787)	4.27 (9.461)	2.39 (10.197)	5.89 (10.471)

45. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	41	42	91	85
Number (95% Confidence Interval) [Percentage of Participants]	70.7 40.2%	81.0 46.3%	65.9 37.4%	69.4 13.2%

46. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily	Participants initially randomized to receive 20 mg apremilast tablets twice daily	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	32	38	70	64
Number (95% Confidence Interval) [Percentage of Participants]	93.8 53.3%	94.7 54.1%	87.1 49.5%	85.9 16.3%

47. Secondary Outcome

Title	Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52
Description	The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. A Good response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 A Moderate Response is defined as either: an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. Two-sided 95% confidence interval is based on the Clopper-Pearson method
Time Frame	Baseline and Week 52

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	62	68	130	138
Number [Percentage of Participants]	64.5 36.6%	73.5 42%	75.4 42.8%	79.0 15%

48. Secondary Outcome

Title	Percentage of Participants With an ACR 50 Response at Week 52
Description	Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 50% improvement in 78 tender joint count; ≥ 50% improvement in 76 swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: o Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time Frame	Baseline and Week 52

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily
Measure Participants	62	67	129	138
Number (95% Confidence Interval) [Percentage of Participants]	30.6 17.4%	25.4 14.5%	27.1 15.4%	31.9 6.1%

49. Secondary Outcome

Title	Percentage of Participants With an ACR 70 Response at Week 52
Description	A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 70% improvement in 78 tender joint count; ≥ 70% improvement in 76 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time Frame	Baseline and Week 52

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	61	68	131	138
Number (95% Confidence Interval) [Percentage of Participants]	8.2 4.7%	10.3 5.9%	13.7 7.8%	18.1 3.4%

50. Secondary Outcome

Title	Percentage of Participants With Pre-existing Enthesopathy Whose MASES Improves From Baseline to 0 at Week 52
Description	Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval was based on the Clopper-Pearson method.
Time Frame	Baseline and Week 52

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	41	42	91	85
Number (95% Confidence Interval) [percentage of participants]	39.0 22.2%	61.9 35.4%	39.6 22.5%	45.9 8.7%

51. Secondary Outcome

Title	Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline to 0 at Week 52
Description	Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit and ranges from 0 to 20. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time Frame	Baseline and Week 52

Outcome Measure Data

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

Arm/Group Title	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily	Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	32	38	70	64
Number (95% Confidence Interval) [Percentage of Participants]	75.0 42.6%	78.9 45.1%	68.6 39%	68.8 13.1%

52. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase
Description	A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE is any AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or constitutes an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale: Mild: asymptomatic or with mild symptoms, Moderate: symptoms causing moderate discomfort or Severe: symptoms causing severe discomfort or pain.
Time Frame	Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants (placebo participants who remained on placebo through week 24 and participants randomized to the APR 20 mg BID or APR 30 mg BID)

Outcome Measure Data

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

Arm/Group Title	Placebo	Apremilast 20mg	Apremilast 30mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).	Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.	Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Measure Participants	176	175	175
Any TEAE	73 41.5%	87 49.7%	99 56.3%
Any Drug-Related TEAE	25 14.2%	40 22.9%	58 33%
Any Severe TEAE	6 3.4%	4 2.3%	2 1.1%
Any Serious TEAE (SAE)	5 2.8%	3 1.7%	1 0.6%
Drug-Related (SAE)	0 0%	0 0%	1 0.6%
Any TEAE Leading to Drug Interruption	8 4.5%	11 6.3%	9 5.1%
Any TEAE Leading to Drug Withdrawal	4 2.3%	4 2.3%	6 3.4%
Any TEAE Leading to Death	0 0%	0 0%	0 0%

53. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period
Description	A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE is any AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or constitutes an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale: Mild: asymptomatic or with mild symptoms, Moderate: symptoms causing moderate discomfort or Severe: symptoms causing severe discomfort or pain.
Time Frame	Week 0 to Week 260; median duration of exposure to apremilast 20 mg BID was 168.93 weeks and 229.36 weeks for apremilast 30 mg BID

Outcome Measure Data

Analysis Population Description
Apremilast Subjects as Treated (AAT) were those who received at least 1 dose of apremilast at any time during the study. Participants were included in the treatment group corresponding to the apremilast dosing regimen they actually received, irrespective of the treatment group to which they were randomized or re-randomized.

Arm/Group Title	Apremilast 20 mg (Pre-Switch)	Apremilast 20/30 mg (Post-Switch)	Apremilast 30 mg
Arm/Group Description	Participants who received 20 mg apremilast tablets twice daily, regardless of when the apremilast exposure started (at Week 0, 16 or 24). Only the TEAEs that occurred during apremilast 20 mg BID were counted.	Participants who switched from apremilast 20 mg tablets twice daily to apremilast 30 mg twice daily. Only the TEAEs that occurred during the apremilast 30 mg treatment were included.	Participants who received apremilast 30 mg twice daily regardless of when the apremilast-exposure started (at Week 0, 16, or 24).
Measure Participants	252	122	252
Any TEAE	188 106.8%	60 34.3%	204 115.9%
Any Drug-Related TEAE	89 50.6%	16 9.1%	113 64.2%
Any Severe TEAE	24 13.6%	3 1.7%	23 13.1%
Any Serious TEAE (SAE)	35 19.9%	5 2.9%	36 20.5%
Drug-Related (SAE)	6 3.4%	1 0.6%	6 3.4%
Any TEAE Leading to Drug Interruption	41 23.3%	5 2.9%	36 20.5%
Any TEAE Leading to Drug Wirhdrawal	22 12.5%	2 1.1%	26 14.8%
Any TEAE Leading to Death	0 0%	0 0%	0 0%

Adverse Events

	Weeks 0-24: Placebo (Placebo-Controlled Phase)		Weeks 0-24: Apremilast 20 mg		Weeks 0-24: Apremilast 30 mg		APR Exposure Period Up to 5 Years: Apremilast 20 mg		APR Exposure Period Up to 5 Years: Apremilast 20mg/30 mg		APR Exposure Period Up to 5 Years: Apremilast 30 mg
Time Frame	AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants and reported for the Apremilast Exposure Period from Week 0 to Week 260; median duration of apremilast 20 mg BID was 168.93 weeks and 229.36 weeks for apremilast 30 mg twice daily
Adverse Event Reporting Description

Arm/Group Title	Weeks 0-24: Placebo (Placebo-Controlled Phase)		Weeks 0-24: Apremilast 20 mg		Weeks 0-24: Apremilast 30 mg		APR Exposure Period Up to 5 Years: Apremilast 20 mg		APR Exposure Period Up to 5 Years: Apremilast 20mg/30 mg		APR Exposure Period Up to 5 Years: Apremilast 30 mg
Arm/Group Description	Participants received placebo tablets twice daily during the placebo-controlled phase. Includes data through Week 16 for participants who escaped early, and through Week 24 for all other participants.		Participants received 20 mg apremilast tablets PO twice daily during the 24-week placebo-controlled phase.		Participants received 30 mg apremilast tablets PO twice daily during the 24-week placebo-controlled phase.		Participants who received apremilast 20 mg twice daily regardless of when the apremilast exposure started (at Week 0, 16 or 24). Only TEAEs that occurred during apremilast 20 mg BID treatment (before the switch to 30 mg apremilast) were included.		Participants who switched from apremilast 20 mg twice daily to apremilast 30 mg BID. Only the TEAEs that occurred during apremilast 30 mg twice daily treatment were included.		Participants who received apremilast 30 mg twice daily throughout the study regardless of when the apremilast exposure started (at Week 0, 16, or 24).
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Weeks 0-24: Placebo (Placebo-Controlled Phase)		Weeks 0-24: Apremilast 20 mg		Weeks 0-24: Apremilast 30 mg		APR Exposure Period Up to 5 Years: Apremilast 20 mg		APR Exposure Period Up to 5 Years: Apremilast 20mg/30 mg		APR Exposure Period Up to 5 Years: Apremilast 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/176 (2.8%)		3/175 (1.7%)		1/175 (0.6%)		35/252 (13.9%)		5/122 (4.1%)		36/252 (14.3%)
Blood and lymphatic system disorders
Lymphadenopathy mediastinal	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Cardiac disorders
Acute myocardial infarction	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Angina pectoris	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		2/252 (0.8%)
Angina unstable	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Atrial fibrillation	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Atrial flutter	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		2/252 (0.8%)
Atrioventricular block	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Atrioventricular block second degree	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Coronary artery disease	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		2/252 (0.8%)
Coronary artery occlusion	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Palpitations	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Pericarditis	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Stress cardiomyopathy	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Ear and labyrinth disorders
Vertigo	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Endocrine disorders
Goitre	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Eye disorders
Retinal vein thrombosis	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Gastrointestinal disorders
Abdominal pain lower	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Anal fissure	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Colitis	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Diarrhoea	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Enterocele	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Inguinal hernia	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		1/122 (0.8%)		3/252 (1.2%)
Irritable bowel syndrome	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Pancreatitis acute	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Rectal haemorrhage	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Umbilical hernia	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		2/252 (0.8%)
General disorders
Non-cardiac chest pain	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Hepatobiliary disorders
Cholecystitis	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Cholelithiasis	0/176 (0%)		0/175 (0%)		0/175 (0%)		2/252 (0.8%)		0/122 (0%)		1/252 (0.4%)
Immune system disorders
Anaphylactic reaction	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Infections and infestations
Chronic sinusitis	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Chronic tonsillitis	0/176 (0%)		1/175 (0.6%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Clostridium difficile colitis	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		1/122 (0.8%)		0/252 (0%)
Diabetic gangrene	1/176 (0.6%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		0/252 (0%)
Gallbladder empyema	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Infective exacerbation of chronic obstructive airways disease	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Lower respiratory tract infection	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Meningitis bacterial	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		1/122 (0.8%)		0/252 (0%)
Pelvic abscess	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Pneumococcal bacteraemia	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		1/122 (0.8%)		0/252 (0%)
Pneumonia	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		1/122 (0.8%)		0/252 (0%)
Pyelonephritis	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Pyelonephritis acute	0/176 (0%)		0/175 (0%)		1/175 (0.6%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Urinary tract infection bacterial	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Injury, poisoning and procedural complications
Contusion	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Incisional hernia	1/176 (0.6%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		1/122 (0.8%)		0/252 (0%)
Multiple fractures	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Multiple injuries	0/176 (0%)		1/175 (0.6%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Post procedural fistula	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Radius fracture	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Road traffic accident	0/176 (0%)		1/175 (0.6%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Tibia fracture	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Investigations
Alanine aminotransferase increased	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Aspartate aminotransferase increased	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Metabolism and nutrition disorders
Hypocalcaemia	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Obesity	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/176 (0%)		1/175 (0.6%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Back pain	0/176 (0%)		1/175 (0.6%)		0/175 (0%)		2/252 (0.8%)		0/122 (0%)		0/252 (0%)
Intervertebral disc disorder	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Musculoskeletal pain	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Musculoskeletal stiffness	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Psoriatic arthropathy	1/176 (0.6%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		2/252 (0.8%)
Spinal osteoarthritis	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Cervix carcinoma stage 0	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Lung squamous cell carcinoma stage unspecified	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Papilloma	0/176 (0%)		1/175 (0.6%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Prostate cancer	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Nervous system disorders
Carpal tunnel syndrome	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Epilepsy	0/176 (0%)		1/175 (0.6%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Sciatica	0/176 (0%)		1/175 (0.6%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Spinal cord compression	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Transient ischaemic attack	0/176 (0%)		0/175 (0%)		0/175 (0%)		2/252 (0.8%)		0/122 (0%)		1/252 (0.4%)
Vertigo CNS origin	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Psychiatric disorders
Confusional state	0/176 (0%)		1/175 (0.6%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Renal and urinary disorders
Calculus ureteric	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Hydronephrosis	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		1/252 (0.4%)
Nephrolithiasis	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		1/252 (0.4%)
Pyuria	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Reproductive system and breast disorders
Cystocele	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Endometrial atrophy	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Endometrial hyperplasia	1/176 (0.6%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		0/252 (0%)
Metrorrhagia	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Postmenopausal haemorrhage	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Rectocele	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Haemoptysis	1/176 (0.6%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		0/252 (0%)
Nasal polyps	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Pulmonary embolism	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Skin and subcutaneous tissue disorders
Psoriasis	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		2/252 (0.8%)
Vascular disorders
Femoral artery occlusion	0/176 (0%)		0/175 (0%)		0/175 (0%)		0/252 (0%)		0/122 (0%)		1/252 (0.4%)
Varicose vein	0/176 (0%)		0/175 (0%)		0/175 (0%)		1/252 (0.4%)		0/122 (0%)		0/252 (0%)
Other (Not Including Serious) Adverse Events
	Weeks 0-24: Placebo (Placebo-Controlled Phase)		Weeks 0-24: Apremilast 20 mg		Weeks 0-24: Apremilast 30 mg		APR Exposure Period Up to 5 Years: Apremilast 20 mg		APR Exposure Period Up to 5 Years: Apremilast 20mg/30 mg		APR Exposure Period Up to 5 Years: Apremilast 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/176 (17%)		51/175 (29.1%)		65/175 (37.1%)		121/252 (48%)		24/122 (19.7%)		141/252 (56%)
Gastrointestinal disorders
Diarrhoea	3/176 (1.7%)		12/175 (6.9%)		21/175 (12%)		30/252 (11.9%)		2/122 (1.6%)		31/252 (12.3%)
Dyspepsia	2/176 (1.1%)		8/175 (4.6%)		0/175 (0%)		14/252 (5.6%)		0/122 (0%)		4/252 (1.6%)
Nausea	5/176 (2.8%)		16/175 (9.1%)		28/175 (16%)		24/252 (9.5%)		2/122 (1.6%)		39/252 (15.5%)
Infections and infestations
Nasopharyngitis	3/176 (1.7%)		3/175 (1.7%)		3/175 (1.7%)		20/252 (7.9%)		5/122 (4.1%)		23/252 (9.1%)
Sinusitis	1/176 (0.6%)		6/175 (3.4%)		4/175 (2.3%)		16/252 (6.3%)		6/122 (4.9%)		12/252 (4.8%)
Upper respiratory tract infection	4/176 (2.3%)		6/175 (3.4%)		7/175 (4%)		26/252 (10.3%)		5/122 (4.1%)		31/252 (12.3%)
Urinary tract infection	1/176 (0.6%)		2/175 (1.1%)		2/175 (1.1%)		10/252 (4%)		3/122 (2.5%)		18/252 (7.1%)
Musculoskeletal and connective tissue disorders
Back pain	0/176 (0%)		1/175 (0.6%)		3/175 (1.7%)		14/252 (5.6%)		0/122 (0%)		10/252 (4%)
Nervous system disorders
Headache	4/176 (2.3%)		6/175 (3.4%)		15/175 (8.6%)		15/252 (6%)		0/122 (0%)		26/252 (10.3%)
Psychiatric disorders
Depression	1/176 (0.6%)		1/175 (0.6%)		2/175 (1.1%)		5/252 (2%)		2/122 (1.6%)		13/252 (5.2%)
Respiratory, thoracic and mediastinal disorders
Cough	2/176 (1.1%)		6/175 (3.4%)		4/175 (2.3%)		11/252 (4.4%)		1/122 (0.8%)		13/252 (5.2%)
Skin and subcutaneous tissue disorders
Psoriasis	6/176 (3.4%)		1/175 (0.6%)		2/175 (1.1%)		6/252 (2.4%)		1/122 (0.8%)		13/252 (5.2%)
Vascular disorders
Hypertension	1/176 (0.6%)		4/175 (2.3%)		4/175 (2.3%)		15/252 (6%)		0/122 (0%)		16/252 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.

Results Point of Contact

Name/Title	Anne McClain
Organization	Celgene Corporation
Phone	1-888-260-1599
Email	clinicaltrialdisclosure@celgene.com

Responsible Party:

Amgen

ClinicalTrials.gov Identifier:

NCT01307423

Other Study ID Numbers:

CC-10004-PSA-005
2010-020324-22

First Posted:

Mar 2, 2011

Last Update Posted:

Jun 14, 2022

Last Verified:

Apr 1, 2020