Study of Apremilast to Evaluate the Safety and Effectiveness for Patients With Rheumatoid Arthritis

• Sponsor: Amgen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01285310
• Collaborator: (none)
• Enrollment: 237
• Locations: 50
• Arms: 3
• Actual Duration (Months): 21.1
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.2

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 rheumatoid arthritis, specifically in improving signs and symptoms of rheumatoid arthritis (tender and swollen joints, pain, physical function and structure) in treated patients who have had an inadequate response to Methotrexate.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Apremilast 30 mg; Drug: Apremilast 20 mg; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 237 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study, To Compare the Efficacy and Safety of Two Doses of Apremilast (CC-10004) in Subjects With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate
• Actual Study Start Date: Dec 9, 2010
• Actual Primary Completion Date: Feb 21, 2012
• Actual Study Completion Date: Sep 10, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Apremilast 30 mg	Drug: Apremilast 30 mg; 30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.; Other Names: CC-10004
Experimental: Apremilast 20 mg	Drug: Apremilast 20 mg; 20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.; Drug: Placebo; Oral Placebo tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in active treatment / active treatment extension phase. Participants who are nonresponders will advance early to 20 mg Apremilast BID at Week 16.
Placebo Comparator: Placebo	Drug: Placebo; Oral Placebo tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in active treatment / active treatment extension phase. Participants who are nonresponders will advance early to 20 mg Apremilast BID at Week 16.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 16 [Baseline and Week 16]

   Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 20% improvement in 68 tender joint count; ≥ 20% improvement in 66 swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein.

Secondary Outcome Measures

1. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16 [Baseline and Week 16]

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

2. Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 24 [Baseline and Week 24]

   Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: ≥ 20% improvement in 68 tender joint count; ≥ 20% improvement in 66 swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein

3. Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 24 [Baseline and Week 24]

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

4. Change From Baseline in the Medical Outcome Study Short Form 36-item (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). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. 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.

5. Change From Baseline in the 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), Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = 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

6. Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 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), Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = 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

7. Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Week 16 [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 (TJC28) 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; C-reactive protein (CRP) Subject's global assessment of disease activity (SGA ) DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. 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.

8. Percentage Change From Baseline in the Tender Joint Count at Week 16 [Baseline and Week 16]

   Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

9. Percentage Change From Baseline in the Swollen Joint Count at Week 16 [Baseline and Week 16]

   Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

10. Percentage Change From Baseline in the Subject Assessment of Pain at Week 16 [Baseline and Week 16]

    The Subject Assessment of Pain was measured asking the participant 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.

11. Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 16 [Baseline and Week 16]

    The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

12. Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 16 [Baseline and Week 16]

    The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

13. Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 16 [Baseline and Week 16]

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

14. Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 16 [Baseline and Week 16]

    C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.

15. Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 16 [Baseline and Week 16]

    The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.

16. 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 was 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.

17. Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16 [Baseline and Week 16]

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

18. Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 16 [Baseline and Week 16]

    The FACIT-Fatigue scale was 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.

19. Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 16 [Baseline and Week 16]

    EULAR response criteria classify each participant 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

20. Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 16 [Baseline and Week 16]

    Percentage of participants with an American College of Rheumatology 50% Improvement (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 50% improvement in 68 tender joint count; ≥ 50% improvement in 66 swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.

21. Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 16 [Baseline and Week 16]

    Percentage of participants with an American College of Rheumatology 70% Improvement (ACR70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: ≥ 70% improvement in 68 tender joint count; ≥ 70% improvement in 66 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein

22. Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 24 [Baseline and Week 24]

    Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 50% improvement in 68 tender joint count; ≥ 50% improvement in 66 swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.

23. Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 24 [Baseline and Week 24]

    Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 70% improvement in 68 tender joint count; ≥ 70% improvement in 66 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.

24. Change From Baseline in the Medical Outcome Study Short Form 36-item (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). 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.

25. Change From Baseline in the 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), Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = 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

26. Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 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), Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = 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

27. Change From Baseline in Disease Activity Score 28 (DAS28) Using CRP 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) Subject's Global Assessment of Disease Activity. DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. 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.

28. Percentage Change From Baseline in the Tender Joint Count at Week 24 [Baseline and Week 24]

    Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

29. Percentage Change From Baseline in the Swollen Joint Count at Week 24 [Baseline and Week 24]

    Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

30. Percentage Change From Baseline in the Subject Assessment of Pain at Week 24 [Baseline and Week 24]

    The Subject Assessment of Pain was measured asking the participant 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.

31. Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 24 [Baseline and Week 24]

    The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

32. Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 24 [Baseline and Week 24]

    The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

33. Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 [Baseline and Week 24]

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

34. Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 24 [Baseline and Week 24]

    C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.

35. Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24 [Baseline and Week 24]

    The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.

36. 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 was 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.

37. Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24 [Baseline and Week 24]

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

38. Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) 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.

39. Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 24 [Baseline and Week 24]

    EULAR response criteria classify each participant 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

40. Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 52 [Baseline and Week 52]

    Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 20% improvement in 68 tender joint count; ≥ 20% improvement in 66 swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein.

41. Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52 [Baseline and Week 52]

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

42. Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain 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.

43. Change From Baseline in the Clinical Disease Activity Index (CDAI) 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), Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = 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

44. Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 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), Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS),, where 0 mm = lowest disease activity and 100 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = 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

45. Change From Baseline in the Disease Activity Score 28 (DAS 28) Using CRP 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 (TJC28) 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; C-reactive protein (CRP) Subject's global assessment of disease activity (SGA). DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. 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.

46. Percentage Change From Baseline in the Tender Joint Count at Week 52 [Baseline and Week 52]

    Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

47. Percentage Change From Baseline in the Swollen Joint Count at Week 52 [Baseline and Week 52]

    Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

48. Percentage Change From Baseline in the Subject Assessment of Pain at Week 52 [Baseline and Week 52]

    The Subject Assessment of Pain was measured asking the participant 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.

49. Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 52 [Baseline and Week 52]

    The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

50. Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 52 [Baseline and Week 52]

    The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

51. Percentage Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 52 [Baseline and Week 52]

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

52. Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 52 [Baseline and Week 52]

    C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.

53. Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52 [Baseline and Week 52]

    The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.

54. Change From Baseline in the FACIT-Fatigue Scale Score at Week 52 [Baseline and Week 52]

    The FACIT-Fatigue scale was 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.

55. Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 52 [Baseline and Week 52]

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

56. Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 52 [Baseline and Week 52]

    Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 50% improvement in 68 tender joint count; ≥ 50% improvement in 66 swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.

57. Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 52 [Baseline and Week 52]

    Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: ≥ 70% improvement in 68 tender joint count; ≥ 70% improvement in 66 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein

58. Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) 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.

59. Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP 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. 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

60. Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Year 2 [Baseline and Year 2]

    Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 20% improvement in 68 tender joint count; ≥ 20% improvement in 66 swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

61. Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Year 2 [Baseline and Year 2]

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

62. Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Year 2 [Baseline and Year 2]

    The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) was a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. 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. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

63. Change From Baseline in the Clinical Disease Activity Index (CDAI) at Year 2 [Baseline and Year 2]

    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), Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = 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 The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

64. Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Year 2 [Baseline and Year 2]

    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), Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = 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 The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

65. Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Year 2 [Baseline and Year 2]

    The DAS 28 measures the severity of disease at a specific time and is derived from the following variables: 28 tender joint count (TJC28) 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; C-reactive protein (CRP) Subject's global assessment of disease activity (SGA ). 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. DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

66. Percentage Change From Baseline in the Individual American College of Rheumatology Components at Year 2 [Baseline and Year 2]

    The Individual ACR Components were defined as follows: Tender Joint Count (out of 68 joints) Swollen Joint Count (out of 66 joints) Subject Assessment of Pain (0 to 100 mm VAS) Subject Global Assessment of Disease Activity (0 to 100 mm VAS) Physician Global Assessment of Disease Activity (0 to 100 mm VAS) HAQ-DI Score Acute Phase Reactant High Sensitivity C-Reactive Protein (hsCRP, mg/dL) Erythrocyte Sedimentation Rate (ESR) The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

67. Change From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Year 2 [Baseline and Year 2]

    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. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

68. Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Year 2 [Baseline and Year 2]

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

69. Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Year 2 [Baseline and Year 2]

    Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 50% improvement in 68 tender joint count; ≥ 50% improvement in 66 swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

70. Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Year 2 [Baseline and Year 2]

    Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: ≥ 70% improvement in 68 tender joint count; ≥ 70% improvement in 66 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

71. Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Year 2 [Baseline and Year 2]

    The FACIT-Fatigue scale was 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. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

72. Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Year 2 [Baseline and Year 2]

    EULAR response criteria classify each participant 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 The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must have a documented diagnosis of Rheumatoid Arthritis (1987 American College of Rheumatology Criteria) with onset of signs/symptoms of disease ≥ 4 months of duration from randomization.

• Must be receiving treatment on an outpatient basis.

• Must have active disease despite current methotrexate treatment as defined below:

• ≥ 6 swollen joints (66 swollen joint count) AND

• ≥ 6 tender joints (68 tender joint count)

-. Must meet at least one of the four lab requirements below:

• High Sensitivity C-Reactive Protein (hsCRP) ≥ 10 mg/L

• Erythrocyte Sedimentation Rate (ESR) > 28 mm after the first 1 hour

• Positive for Rheumatoid Factor (RF)

• Positive for Anti-cyclic Citrullinated Peptide (anti-CCP) antibodies

• For participants participating in the Magnetic Resonance Imaging (MRI) assessment:

• Must have Rheumatoid Arthritis joint involvement, as assessed by swollen joint counts in: 1) at least two Metacarpophalangeal (MCP) swollen joints on the same hand, or 2) at least one swollen Metacarpophalangeal (MCP) joint and swollen wrist on the same hand.

• Must have been treated with methotrexate for at least 4 months prior to randomization, and must be on stable dose. Participants will be required to maintain their stable dose through Week 52 of the study. Oral folate (folic acid) supplementation is required with a minimum dose of 5 mg/week, or instead leucovorin may be used up to 10 mg/week orally.

• Non-steroidal anti-inflammatory drugs (NSAIDs) and pain medications are allowed, however, must be on stable regimen for at least 7 days prior to randomization and through Week 52 of the study.

• Oral corticosteroids (if taken) are allowed, however, must be on stable dose of prednisone ≤ 10 mg/day or equivalent for at least 28 days prior to randomization and through Week 52 of the study.

• Must meet the following laboratory criteria at screening:

• White blood cell count ≥ 3000/mm^{3 (≥ 3.0 x 10}9/L) and < 14,000/mm^{3 (< 14 x 10}9/L)

• Platelet count (≥ 100,000/μL ((≥ 100 x 10^9/L)

• Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)

• Aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase or serum glutamic-pyruvic transaminase (ALT/ SGPT) ≤ 2 x upper limit of normal (ULN). If initial test shows Aspartate aminotransferase (AST) or alanine aminotransferase (SLT) or 2 times the upper limit of normal (ULN), one repeat test is allowed during the screening period.

• Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L). If initial test result is > 2 mg/dL, one repeat test is allowed during the screening period.

• Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)

• Hemoglobin A1c ≤ 9.0%

• Negative for hepatitis B surface antigen

• Negative for hepatitis C antibody

• Males who engage in activity in which conception is possible must use protocol described barrier contraception while on Investigational Product and for at least 28 days after the last dose of Investigational Product.

• 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 protocol described contraception while on Investigational Product and for at least 28 days after taking the last dose or Investigational Product.

Exclusion Criteria:

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.

• Rheumatic autoimmune disease other than Rheumatoid Arthritis, including systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis or significant systemic involvement secondary to Rheumatoid Arthritis (eg, vasculitis, pulmonary fibrosis or Felty syndrome). Sjögren syndrome secondary to Rheumatoid Arthritis is allowable.

• Functional Class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis.

• Prior history of, or current, inflammatory joint disease other than Rheumatoid Arthritis (eg, gout, reactive arthritis, psoriatic arthritis, ankylosing spondylitis, Lyme disease).

• Receiving treatment with Disease-modifying antirheumatic drugs (DMARDs) (other than methotrexate), including biologic Disease-modifying antirheumatic drugs (DMARDs)Previous use is only allowed after adequate washout prior to randomization.

• Inadequate response to treatment with an anti-tumor necrosis factor (anti-TNF) agent. Patients who terminated previous anti-tumor necrosis factor (anti-TNF) treatment due to cost or safety reason, such as discomfort with the subcutaneous injections, may participate in this study after adequate washout.

• Treatment with any investigational agent within four weeks (or five half-lives of the investigational drug, whichever is longer) of screening.

• Previous treatment with any cell depleting therapies, including investigational agents.

• Treatment with intravenous gamma globulin, plasmapheresis or Prosorba® column within 6 months of baseline.

• Intra-articular or parenteral corticosteroids are not allowed within 6 weeks prior to randomization.

• Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation.

• Pregnant women or nursing (breast feeding) mothers.

• Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including severe or very severe chronic obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus as defined by Hemoglobin A1c > 9.0%) or gastrointestinal (GI) disease.

• Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids.

• Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding onychomycosis) or any major episode of infection requiring hospitalization or treatment with IV or oral antibiotics within 4 weeks of screening.

• History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).

• History of malignancy, including solid tumors and hematologic malignancies (except basal cell carcinoma of the skin that has been excised and cured).

• History of alcohol, drug or chemical abuse within the 6 months prior to screening.

• Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

• Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.

• Any condition that in the investigator's opinion would interfere significantly with the efficacy evaluations, including the pain and joint assessments (eg, fibromyalgia).

For Magnetic Resonance Imaging (MRI) Only:

• Receiving medication(s) or will require medication(s) during the study that impact on vascular flow (eg, nitrates, calcium channel blockers, ergot containing drugs) on the day of the Magnetic Resonance Imaging (MRI test and in the investigator's judgement the subject cannot hold back from taking these medications on the day of the Magnetic Resonance Imaging (MRI) prior to the Magnetic Resonance Imaging (MRI) test. The subject can continue taking the medication(s) at any time after the Magnetic Resonance Imaging (MRI) test is completed, as clinically indicated and scheduled. Exclusions of antihypertensive and migraine medications can be determined after discussion with the Sponsor.

• Unable to undergo an Magnetic Resonance Imaging (MRI) examination, including but not limited to the presence of a pacemaker, defibrillator, or other implanted device such as anterior interbody cages, aneurysm clip, pedicle screws, or any other metal contained in the body (eg, such as tattoos that contain metallic pigment, or metal in the eyes from metal grinding [eg, a metal worker, etc]), or severe claustrophobia, or any other contraindication to an Magnetic Resonance Imaging (MRI) as per local imaging center guidelines.

• Allergic or adverse reactions to gadolinium

• Estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73m2 (based on the Modification of Diet in Renal Disease [MDRD] formula).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ArthroCare, Arthritis Care Research	Gilbert	Arizona	United States	85234
2	Arizona Research Center	Phoenix	Arizona	United States	85023
3	TriWest Research Associates	La Mesa	California	United States	91942
4	Desert Medical Advances	Palm Desert	California	United States	92260
5	Stanford University Medical Center	Palo Alto	California	United States	94304
6	Med Investigations/Sierra	Roseville	California	United States	95661
7	Inland Rheumatology Clinical Trials, Inc.	Upland	California	United States	91786
8	Denver Arthritis Clinic	Denver	Colorado	United States	80230
9	In Vivo Clinical Research	Doral	Florida	United States	33166
10	San Marcus Research Clinic	Miami	Florida	United States	33015
11	Advanced Pharma CR, LLC	Miami	Florida	United States	33175
12	Jeffrey Alper, MD Research	Naples	Florida	United States	34102
13	Suncoast Clinical Research	New Port Richey	Florida	United States	34652
14	Tampa Medical Group, PA	Tampa	Florida	United States	33614
15	Alastair Kennedy, MD	Vero Beach	Florida	United States	32962
16	LaPorte County Institute for Clinical Research, Inc.	Michigan City	Indiana	United States	46360
17	Associated Internal Medicine Specialists, PC	Battle Creek	Michigan	United States	49015
18	Saint Paul Rheumatology	Eagan	Minnesota	United States	55121
19	Physician's East	Greenville	North Carolina	United States	27834
20	David R. Mandel, M.D., Inc.	Mayfield	Ohio	United States	44143
21	Health Research of Oklahoma	Oklahoma City	Oklahoma	United States	73103
22	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
23	Austin Regional Clinic	Austin	Texas	United States	78759
24	Metroplex Research Center	Dallas	Texas	United States	75231
25	Modern Research Associates	Dallas	Texas	United States	75231
26	Sun Research Institute	San Antonio	Texas	United States	78215
27	Stone Oak Rheumatology	San Antonio	Texas	United States	78232
28	Center for Excellence in Aging and Geriatric Health	Williamsburg	Virginia	United States	23185
29	Arthritis Northwest, Rheumatology	Spokane	Washington	United States	99204
30	Revmatologie s.r.o.	Brno		Czechia	638 00
31	L.K.N. Arthrocentrum s.r.o.	Hlucin		Czechia	748 01
32	ARTMEDI UPD s.r.o.	Hostivice		Czechia	253 01
33	Revmatologicky ustav	Praha		Czechia	128 50
34	Revmatologicka ambulance	Praha		Czechia	140 00
35	Fakultni Thomayerova nemocnice s poliklinikou	Praha		Czechia	140 59
36	PV - MEDICAL, s.r.o.	Zlin		Czechia	760 01
37	NZOZ Osteo-Medic s.c. Artur Racewicz, Jerzy Supronik	Bialystok		Poland	15-351
38	NZOZ Centrum Osteoporozy i Chorob Kostno-Stawowych	Bialystok		Poland	15-461
39	Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy	Bydgoszcz		Poland	85-168
40	Centrum Kliniczno-Badawcze	Elblag		Poland	82-300
41	Centrum Leczenia Chorob Cywilizacyjnych	Gdynia		Poland	81-384
42	Centrum Leczenia Chorob Cywilizacyjnych	Katowice		Poland	40-478
43	Malopolskie Centrum Medyczne (408)	Krakow		Poland	30-552
44	Niepubliczny Zaklad Opieki Zdrowotnej REUMED	Lublin		Poland	20-607
45	Prywatna Praktyka Lekarska Pawel Hrycaj	Poznan		Poland	61-397
46	Centrum Leczenia Chorob Cywilizacyjnych	Warszawa		Poland	02-777
47	Hospital Universitario a Coruña	A Coruña		Spain	15006
48	Hospital Universitario de Canarias	La Laguna		Spain	38320
49	Hospital Clinico Universitario de Santiago	Santiago de Compostela		Spain	15706
50	Hospital Sierrallana	Torrelavega		Spain	39300

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01285310
• Other Study ID Numbers: CC-10004-RA-002; 2010-019926-15
• First Posted: Jan 28, 2011
• Last Update Posted: May 8, 2020
• Last Verified: Apr 1, 2020

• Keywords provided by Amgen: Rheumatoid, Arthritis
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Thalidomide; Apremilast

Study Results

Participant Flow

Recruitment Details	A total of 302 subjects were screened for inclusion in this study, and 237 participants randomized in parallel in a 1:1:1 ratio to treatment groups. The first participant was enrolled on 27 December 2010; the last participant completed week 24 visit on 23 February 2012.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg	Placebo/Apremilast 20mg EE	Placebo / Apremilast 20 mg XO
Arm/Group Description	Participants initially randomized to placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg Apremilast twice daily (early escape), and were designated as Placebo/Apremilast 20mg EE.	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 (BID) for up to Week 52 in the active treatment. At week 52, participants were given the option to remain on active treatment for 1 additional year (extension phase) as assigned during the active treatment 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 (BID) for up to Week 52 in the active treatment. At week 52, participants were given the option to remain on active treatment for 1 additional year (extension phase) as assigned during the active treatment phase.	Participants initially randomized to receive placebo twice daily and were transitioned due to early escape (EE) at Week 16 to receive 20 mg apremilast for up to week 24. At week 24, participants were continued on Apremilast 20 mg BID for up to Week 52. At week 52, they were given the option to remain on active treatment for 1 additional year (extension phase) as assigned during the active treatment phase.	Participants initially randomized to receive placebo twice daily who were transitioned at Week 24 (XO) to receive 20 mg apremilast for up to Week 52. At week 52, they were given the option to remain on active treatment for 1 additional year (extension phase) as assigned during the active treatment phase.
Period Title: Placebo Controlled Phase: Weeks 0-24
STARTED	79	82	76	0	0
COMPLETED	70	67	61	0	0
NOT COMPLETED	9	15	15	0	0
Period Title: Placebo Controlled Phase: Weeks 0-24
STARTED	0	63	60	27	42
COMPLETED	0	31	34	17	23
NOT COMPLETED	0	32	26	10	19

Baseline Characteristics

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg	Total
Arm/Group Description	Placebo: Oral Placebo tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in active treatment / active treatment extension phase. Participants who are nonresponders were transitioned early to 20 mg Apremilast BID at Week 16.	Apremilast 20 mg: 20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase and continued 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.	Apremilast 30 mg: 30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase and continued 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.	Total of all reporting groups
Overall Participants	79	82	76	237
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.5 (12.45)	58.6 (11.84)	52.6 (11.87)	56.0 (12.26)
Sex: Female, Male (Count of Participants)
Female	62 78.5%	65 79.3%	55 72.4%	182 76.8%
Male	17 21.5%	17 20.7%	21 27.6%	55 23.2%
Duration of Rheumatoid Arthritis Diagnosis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	11.98 (12.104)	8.46 (6.856)	7.76 (7.833)	9.41 (9.351)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 16
Description	Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 20% improvement in 68 tender joint count; ≥ 20% improvement in 66 swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject'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; participants who were randomized in error and did not receive any dose of study drug were excluded. Participants who withdrew early or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	79	82	76
Number [percentage of participants]	35.4 44.8%	28 34.1%	34.2 45%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	Comments	Significance testing was done using the following closed procedure; if the overall test among treatments is statistically significant at the 0.05 level, pair-wise comparisons (30 mg versus PBO, and 20 mg versus PBO, using a 0.05 two-sided significance level) will be performed
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3134
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-7.4
	Confidence Interval	(2-Sided) 95%; -27.1 to 7.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% CI of the proportion difference is based on a normal approximation to the binomial distribution

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8721
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -16.2 to 13.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% CI is based on a 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 (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set; participants with a baseline value and at least 1 post-baseline 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 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	78	80	76
Mean (Standard Deviation) [units on a scale]	-0.106 (0.4173)	-0.114 (0.5036)	-0.209 (0.4469)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-0.004
	Confidence Interval	() %; to
	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 30 mg
	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	-0.091
	Confidence Interval	() %; to
	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.

3. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 24
Description	Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: ≥ 20% improvement in 68 tender joint count; ≥ 20% improvement in 66 swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject'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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily	Participants initially randomized to receive 30 mg apremilast tablets twice daily
Measure Participants	79	82	76
Number [percentage of participants]	24.1 30.5%	19.5 23.8%	27.6 36.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-4.5
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	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	3.6
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean 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 post-baseline 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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	78	80	76
Mean (Standard Deviation) [units on a scale]	-0.069 (0.4328)	-0.080 (0.4653)	-0.227 (0.4910)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-0.007
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.150
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model for the change from baseline at Week 24, treatment group as a factor and the baseline value as a covariate.

5. Secondary Outcome

Title	Change From Baseline in the Medical Outcome Study Short Form 36-item (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). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. 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 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	78	78	75
Mean (Standard Deviation) [units on a scale]	1.48 (6.937)	1.64 (7.036)	3.33 (6.970)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-0.17
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model for the change from baseline at Week 16; treatment group as a factor and the baseline value as a covariate

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	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	1.77
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model for the change from baseline at Week 16; treatment group as a factor and the baseline value as a covariate.

6. Secondary Outcome

Title	Change From Baseline in the 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), Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = 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 post-baseline value at or prior to Week 16 are included. LOCF imputation was used.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	77	79	76
Mean (Standard Deviation) [units on a scale]	-11.52 (14.850)	-9.49 (12.998)	-11.38 (13.230)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	1.21
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	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	-0.70
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 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), Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = 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 post-baseline value at or prior to Week 16 are included. LOCF imputation was used.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	79	82	76
Number [percentage of participants]	17.7 22.4%	12.2 14.9%	10.5 13.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-5.5
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	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	-7.2
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Week 16
Description	The DAS28 measures the severity of disease at a specific time and is derived from the following variables: 28 tender joint count (TJC28) 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; C-reactive protein (CRP) Subject's global assessment of disease activity (SGA ) DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. 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 post-baseline value at or prior to Week 16 are included. LOCF imputation was used.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	78	80	76
Least Squares Mean (Standard Error) [units on a scale]	-0.90 (1.272)	-0.73 (1.079)	-0.90 (1.168)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	0.14
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage Change From Baseline in the Tender Joint Count at Week 16
Description	Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	78	81	76
Least Squares Mean (Standard Error) [percent change]	-33.08 (5.154)	-26.92 (5.058)	-33.68 (5.221)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	6.15
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model (Ancova) 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 30 mg
	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	-0.61
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model (Ancova) 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	Percentage Change From Baseline in the Swollen Joint Count at Week 16
Description	Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	78	81	76
Least Squares Mean (Standard Error) [percent change]	-36.96 (5.432)	-34.38 (5.328)	-40.22 (5.502)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	2.58
	Confidence Interval	(2-Sided) %; to
	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 30 mg
	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	-3.26
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percentage Change From Baseline in the Subject Assessment of Pain at Week 16
Description	The Subject Assessment of Pain was measured asking the participant 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 post-baseline value at or prior to Week 16 are included; LOCF imputation was used.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	78	80	76
Least Squares Mean (Standard Error) [percent change]	30.50 (16.584)	-5.03 (16.369)	-7.87 (16.800)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-35.54
	Confidence Interval	() %; to
	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 30 mg
	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	-38.37
	Confidence Interval	() %; to
	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.

12. Secondary Outcome

Title	Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 16
Description	The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." 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 post-baseline value at or prior to Week 16 are included; LOCF imputation was used.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	79	82	76
Least Squares Mean (Standard Error) [percent change]	10.84 (10.004)	-3.50 (9.872)	11.19 (10.131)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-14.35
	Confidence Interval	() %; to
	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 30 mg
	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	0.34
	Confidence Interval	() %; to
	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	Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 16
Description	The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." 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 post-baseline 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 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	77	80	76
Least Squares Mean (Standard Error) [percent change]	-28.82 (4.478)	-28.22 (4.440)	-32.66 (4.540)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	0.59
	Confidence Interval	(2-Sided) %; to
	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 30 mg
	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	-3.84
	Confidence Interval	() %; to
	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.

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	78	80	76
Least Squares Mean (Standard Error) [percent change]	-9.43 (5.307)	-3.50 (5.234)	-10.20 (5.416)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	5.93
	Confidence Interval	() %; to
	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 30 mg
	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	-0.77
	Confidence Interval	() %; to
	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

15. Secondary Outcome

Title	Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 16
Description	C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	78	81	76
Least Squares Mean (Standard Error) [percent change]	41.99 (30.559)	46.69 (30.027)	100.04 (31.127)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	4.70
	Confidence Interval	() %; to
	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 30 mg
	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	58.05
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 16
Description	The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	78	81	76
Least Squares Mean (Standard Error) [percent change]	6.81 (10.633)	13.98 (10.522)	-9.39 (10.681)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	7.18
	Confidence Interval	() %; to
	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 30 mg
	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	-16.19
	Confidence Interval	() %; to
	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.

17. 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 was 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 post-baseline value at or prior to Week 16 are included. LOCF imputation was used.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	78	78	75
Least Squares Mean (Standard Error) [units on a scale]	2.7 (0.96)	1.5 (0.96)	2.6 (0.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-1.2
	Confidence Interval	() %; to
	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 30 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.1
	Confidence Interval	() %; to
	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

18. Secondary Outcome

Title	Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16
Description	The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set; participants with a baseline value and at least 1 post-baseline 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 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	79	82	76
Number [percentage of participants]	39.2 49.6%	35.4 43.2%	52.6 69.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-3.9
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	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	13.4
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 16
Description	The FACIT-Fatigue scale was 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 post-baseline value at or prior to Week 16 are included; LOCF imputation was used.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets 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	79	82	76
Number [percentage of participants]	39.2 49.6%	35.4 43.2%	42.1 55.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-3.9
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	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	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 16
Description	EULAR response criteria classify each participant 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.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	79	82	76
Number [percentage of participants]	46.8 59.2%	41.5 50.6%	44.7 58.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-5.4
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	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	2.1
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 16
Description	Percentage of participants with an American College of Rheumatology 50% Improvement (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 50% improvement in 68 tender joint count; ≥ 50% improvement in 66 swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject'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.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily..
Measure Participants	79	82	76
Number [percentage of participants]	11.4 14.4%	4.9 6%	9.2 12.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	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	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 16
Description	Percentage of participants with an American College of Rheumatology 70% Improvement (ACR70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: ≥ 70% improvement in 68 tender joint count; ≥ 70% improvement in 66 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject'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 = The FAS consisted of all participants who were randomized as specified per protocol during the placebo controlled period. The last observed joint assessment (at baseline or post-baseline) was used for joints unassessed 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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape).	.Participants initially randomized to receive 20 mg apremilast tablets twice daily	Participants initially randomized to receive 30 mg apremilast tablets twice daily
Measure Participants	79	82	76
Number [percent of participants]	2.5 3.2%	1.2 1.5%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-1.3
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	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	-2.5
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 24
Description	Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 50% improvement in 68 tender joint count; ≥ 50% improvement in 66 swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject'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 = The FAS consisted of all participants who were randomized as specified per protocol during the placebo controlled period. The last observed joint assessment (at baseline or post-baseline) was used for joints unassessed at Week 24.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily	.Participants initially randomized to receive 30 mg apremilast tablets twice daily
Measure Participants	79	82	76
Number [percentage of participants]	6.3 8%	4.9 6%	15.8 20.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-1.5
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	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	9.5
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 24
Description	Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 70% improvement in 68 tender joint count; ≥ 70% improvement in 66 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject'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 = The FAS consisted of all participants who were randomized as specified per protocol during the placebo controlled period. The last observed joint assessment (at baseline or post-baseline) was used for joints unassessed at Week 24.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily	Participants initially randomized to receive 30 mg apremilast tablets twice daily
Measure Participants	79	82	76
Number [percentage of participants]	3.8 4.8%	2.4 2.9%	5.3 7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-1.4
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	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	1.5
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Change From Baseline in the Medical Outcome Study Short Form 36-item (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). 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 24

Outcome Measure Data

Analysis Population Description

Full analysis set; participants with a baseline value and at least 1 post-baseline 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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE ..	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	78	78	75
Least Squares Mean (Standard Error) [units on a scale]	1.78 (0.849)	1.66 (0.850)	3.76 (0.865)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-0.12
	Confidence Interval	() %; to
	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 30 mg
	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	1.98
	Confidence Interval	() %; to
	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.

26. Secondary Outcome

Title	Change From Baseline in the 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), Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = 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 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. LOCF imputation was used.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily	Participants initially randomized to receive 30 mg apremilast tablets twice daily
Measure Participants	77	79	76
Least Squares Mean (Standard Error) [units on a scale]	-10.40 (1.597)	-9.46 (1.571)	-11.63 (1.602)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	0.94
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-1.24
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

27. Secondary Outcome

Title	Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 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), Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = 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 post-baseline 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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	79	82	76
Number [percentage of participants]	16.5 20.9%	12.2 14.9%	21.1 27.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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 proportions
	Estimated Value	-4.3
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	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 proportions
	Estimated Value	4.6
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

28. Secondary Outcome

Title	Change From Baseline in Disease Activity Score 28 (DAS28) Using CRP 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) Subject's Global Assessment of Disease Activity. DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. 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 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. LOCF imputation was used.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive placebo tablets twice daily. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE .	Participants initially randomized to receive 20 mg apremilast tablets twice daily	Participants initially randomized to receive 30 mg apremilast tablets twice daily
Measure Participants	78	80	76
Least Squares Mean (Standard Error) [units on a scale]	-0.82 (0.139)	-0.78 (0.137)	-0.91 (0.141)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	0.03
	Confidence Interval	() %; to
	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 30 mg
	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	-0.09
	Confidence Interval	() %; to
	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.

29. Secondary Outcome

Title	Percentage Change From Baseline in the Tender Joint Count at Week 24
Description	Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Full analysis set; participants with a baseline value and at least 1 post-baseline 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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily	Participants initially randomized to receive 30 mg apremilast tablets twice daily
Measure Participants	78	81	76
Least Squares Mean (Standard Error) [percent change]	-30.81 (5.909)	-26.21 (5.800)	-27.80 (5.987)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	4.60
	Confidence Interval	() %; to
	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 30 mg
	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	3.01
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model for the change from baseline at Week 24; treatment group as a factor and the baseline value as a covariate.

30. Secondary Outcome

Title	Percentage Change From Baseline in the Swollen Joint Count at Week 24
Description	Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Full analysis set; participants with a baseline value and at least 1 post-baseline 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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily	Participants initially randomized to receive 30 mg apremilast tablets twice daily
Measure Participants	78	81	76
Least Squares Mean (Standard Error) [percent change]	-34.41 (5.876)	-32.56 (5.764)	-41.43 (5.952)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	1.86
	Confidence Interval	() %; to
	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 30 mg
	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	-7.02
	Confidence Interval	() %; to
	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

31. Secondary Outcome

Title	Percentage Change From Baseline in the Subject Assessment of Pain at Week 24
Description	The Subject Assessment of Pain was measured asking the participant 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 post-baseline 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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	78	80	76
Least Squares Mean (Standard Error) [percent change]	28.16 (16.111)	-6.66 (15.902)	-9.66 (16.320)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-34.82
	Confidence Interval	() %; to
	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 30 mg
	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	-37.82
	Confidence Interval	() %; to
	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

32. Secondary Outcome

Title	Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 24
Description	The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." 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 post-baseline 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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily..
Measure Participants	78	80	76
Least Squares Mean (Standard Error) [percent change]	15.04 (8.566)	0.70 (8.453)	2.54 (8.675)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-14.34
	Confidence Interval	() %; to
	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 30 mg
	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	-12.50
	Confidence Interval	() %; to
	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.

33. Secondary Outcome

Title	Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 24
Description	The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." 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 post-baseline 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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily..
Measure Participants	77	80	76
Least Squares Mean (Standard Error) [percent change]	-29.98 (4.740)	-24.13 (4.700)	-31.78 (4.805)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	5.85
	Confidence Interval	() %; to
	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 30 mg
	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	-1.80
	Confidence Interval	() %; to
	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.

34. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Full analysis set; participants with a baseline value and at least 1 post-baseline 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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape)and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	78	80	76
Least Squares Mean (Standard Error) [percent change]	-6.59 (5.171)	-5.01 (5.100)	-12.30 (5.277)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	1.57
	Confidence Interval	() %; to
	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 30 mg
	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	-5.72
	Confidence Interval	() %; to
	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.

35. Secondary Outcome

Title	Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 24
Description	C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Full analysis set; participants with a baseline value and at least 1 post-baseline 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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	78	81	76
Least Squares Mean (Standard Error) [percent change]	39.14 (30.504)	47.43 (29.972)	106.22 (31.071)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	8.29
	Confidence Interval	() %; to
	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 30 mg
	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	67.09
	Confidence Interval	() %; to
	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.

36. Secondary Outcome

Title	Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24
Description	The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Full analysis set; participants with a baseline value and at least 1 post-baseline 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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	.Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	78	81	76
Least Squares Mean (Standard Error) [percent change]	-0.06 (9.531)	11.99 (9.431)	-6.60 (9.573)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	12.05
	Confidence Interval	() %; to
	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 30 mg
	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	-6.54
	Confidence Interval	() %; to
	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.

37. 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 was 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 post-baseline 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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned to 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	78	78	75
Least Squares Mean (Standard Error) [units on a scale]	1.7 (1.01)	0.5 (1.01)	3.4 (1.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-1.2
	Confidence Interval	() %; to
	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 30 mg
	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	1.7
	Confidence Interval	() %; to
	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

38. Secondary Outcome

Title	Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24
Description	The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean 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 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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	.Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	79	82	76
Number [percentage of participants]	20.3 25.7%	25.6 31.2%	32.9 43.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	5.4
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	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	12.6
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

39. Secondary Outcome

Title	Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) 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 post-baseline 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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned onto 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily	Participants initially randomized to receive 30 mg apremilast tablets twice daily
Measure Participants	79	82	76
Number [percentage of participants]	26.6 33.7%	14.6 17.8%	26.3 34.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	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	-0.3
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

40. Secondary Outcome

Title	Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 24
Description	EULAR response criteria classify each participant 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 24

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. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were transitioned to 20 mg apremilast twice daily (early escape) and were designated as Placebo/Apremilast 20mg EE.	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	79	82	76
Number [percentage of participants]	40.5 51.3%	29.3 35.7%	35.5 46.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	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	-11.2
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	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	-5.0
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

41. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 52
Description	Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 20% improvement in 68 tender joint count; ≥ 20% improvement in 66 swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The Apremilast participants as Randomized/Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included. Reporting Groups

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	23	39	55	55
Number (95% Confidence Interval) [percentage of participants]	47.8 60.5%	51.3 62.6%	30.9 40.7%	38.2 16.1%

42. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The Apremilast participants as Randomized/Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included.

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned transitioned to receive 20 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	24	39	55	55
Mean (Standard Deviation) [units on a scale]	-0.219 (0.4287)	-0.192 (0.4728)	-0.155 (0.5501)	-0.277 (0.4281)

43. Secondary Outcome

Title	Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain 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 participants as Randomized/Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included.

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	24	39	55	55
Mean (Standard Deviation) [units on a scale]	2.11 (6.959)	3.50 (10.146)	2.56 (9.978)	5.23 (10.227)

44. Secondary Outcome

Title	Change From Baseline in the Clinical Disease Activity Index (CDAI) 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), Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = 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 participants as Randomized/Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included.

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	23	39	55	55
Mean (Standard Deviation) [units on a scale]	-16.22 (8.722)	-20.70 (14.253)	-14.77 (14.220)	-17.68 (13.331)

45. Secondary Outcome

Title	Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 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), Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS),, where 0 mm = lowest disease activity and 100 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = 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 participants as Randomized/Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included.

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	24	39	56	55
Number (95% Confidence Interval) [percentage of participants]	16.7 21.1%	41.0 50%	25.0 32.9%	27.3 11.5%

46. Secondary Outcome

Title	Change From Baseline in the Disease Activity Score 28 (DAS 28) Using CRP 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 (TJC28) 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; C-reactive protein (CRP) Subject's global assessment of disease activity (SGA). DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. 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 participants as Randomized/Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included.

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	23	39	54	55
Mean (Standard Deviation) [units on a scale]	-1.18 (0.717)	-1.68 (1.243)	-1.10 (1.290)	-1.38 (1.264)

47. Secondary Outcome

Title	Percentage Change From Baseline in the Tender Joint Count at Week 52
Description	Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The Apremilast participants as Randomized/Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included.

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	24	40	56	55
Mean (Standard Deviation) [percent change]	-55.47 (24.072)	-62.70 (38.785)	-43.88 (38.728)	-54.03 (43.200)

48. Secondary Outcome

Title	Percentage Change From Baseline in the Swollen Joint Count at Week 52
Description	Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The Apremilast participants as Randomized/Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included..

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	24	40	56	55
Mean (Standard Deviation) [percent change]	-59.40 (28.088)	-67.73 (42.431)	-57.31 (45.480)	-66.74 (30.277)

49. Secondary Outcome

Title	Percentage Change From Baseline in the Subject Assessment of Pain at Week 52
Description	The Subject Assessment of Pain was measured asking the participant 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 participants as Randomized/Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included.

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	24	39	55	55
Mean (Standard Deviation) [percent change]	44.63 (184.396)	15.78 (176.601)	-11.69 (42.608)	-3.73 (98.150)

50. Secondary Outcome

Title	Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 52
Description	The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." 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 participants as Randomized/Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included.

Arm/Group Title	Placebo/Apremilast 20 EE	Placebo / Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	24	39	55	55
Mean (Standard Deviation) [percent change]	14.20 (76.243)	33.31 (186.069)	-5.20 (73.593)	8.22 (83.321)

51. Secondary Outcome

Title	Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 52
Description	The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." 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 participants as Randomized/Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included.

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	23	40	56	55
Mean (Standard Deviation) [percent change]	-41.30 (35.683)	-49.10 (45.037)	-41.19 (47.417)	-44.85 (41.822)

52. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The Apremilast Participants as Randomized/Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included.

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	24	39	55	54
Mean (Standard Deviation) [percent change]	-13.32 (35.634)	-10.53 (49.600)	-8.20 (44.369)	-22.46 (31.856)

53. Secondary Outcome

Title	Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 52
Description	C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The Apremilast Participants as Randomized/Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included.

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	23	40	55	55
Mean (Standard Deviation) [percent change]	13.34 (90.641)	82.14 (226.455)	104.25 (210.138)	79.33 (205.501)

54. Secondary Outcome

Title	Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52
Description	The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The Apremilast Participants as Randomized/ Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included.

Arm/Group Title	Placebo/Apremilast 20 EE	Placebo / Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	23	40	55	54
Mean (Standard Deviation) [percent change]	-6.28 (40.585)	17.15 (244.497)	4.83 (51.294)	-15.99 (53.892)

55. Secondary Outcome

Title	Change From Baseline in the FACIT-Fatigue Scale Score at Week 52
Description	The FACIT-Fatigue scale was 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 Participants as Randomized/ Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included.

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	24	39	55	55
Mean (Standard Deviation) [units on a scale]	3.50 (11.085)	3.18 (9.236)	2.87 (9.650)	3.47 (11.115)

56. Secondary Outcome

Title	Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 52
Description	The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The Apremilast Participants as Randomized/Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included.

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	24	39	55	55
Number (95% Confidence Interval) [percentage of participants]	58.3 73.8%	43.6 53.2%	40.0 52.6%	58.2 24.6%

57. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 52
Description	Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 50% improvement in 68 tender joint count; ≥ 50% improvement in 66 swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Apremilast participants as randomized during the apremilast exposure period.

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	.Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	29	42	82	76
Number (95% Confidence Interval) [percentage of participants]	3.4 4.3%	11.9 14.5%	4.9 6.4%	5.3 2.2%

58. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 52
Description	Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: ≥ 70% improvement in 68 tender joint count; ≥ 70% improvement in 66 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Apremilast participants as randomized/transitioned (AAR Population); population consists of all participants who were randomized or transitioned 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 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	24	40	56	55
Number (95% Confidence Interval) [percentage of participants]	0.0 0%	5.0 6.1%	7.1 9.3%	5.5 2.3%

59. Secondary Outcome

Title	Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) 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 participants as Randomized/Transitioned (AAR) Population; participants with a Baseline value and a Week 52 value are included.

Arm/Group Title	Placebo/Apremilast 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	24	39	55	55
Number (95% Confidence Interval) [percentage of participants]	41.7 52.8%	61.5 75%	45.5 59.9%	40.0 16.9%

60. Secondary Outcome

Title	Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP 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. 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 52

Outcome Measure Data

Analysis Population Description

The Apremilast Participants as Randomized/ Transitioned (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 20mg EE	Placebo/Apremilast 20 mg XO	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants who received placebo twice daily up to Week 16 and were then transitioned to receive 20 mg apremilast twice daily.	Participants who received placebo twice daily up to Week 24 and were then transitioned to receive 20 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	23	39	54	55
Number (95% Confidence Interval) [percentage of participants]	69.6 88.1%	82.1 100.1%	63.0 82.9%	65.5 27.6%

61. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Year 2
Description	Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 20% improvement in 68 tender joint count; ≥ 20% improvement in 66 swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame	Baseline and Year 2

Outcome Measure Data

Analysis Population Description

Analysis not performed.

Arm/Group Title	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Apremilast 20 mg: 20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.	Apremilast 30 mg: 30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Measure Participants	0	0

62. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis not performed.

Arm/Group Title	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Apremilast 20 mg: 20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.	Apremilast 30 mg: 30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Measure Participants	0	0

63. Secondary Outcome

Title	Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Year 2
Description	The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) was a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. 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. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame	Baseline and Year 2

Outcome Measure Data

Analysis Population Description

Analysis not performed.

Arm/Group Title	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Apremilast 20 mg: 20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.	Apremilast 30 mg: 30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Measure Participants	0	0

64. Secondary Outcome

Title	Change From Baseline in the Clinical Disease Activity Index (CDAI) at Year 2
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), Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = 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 The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame	Baseline and Year 2

Outcome Measure Data

Analysis Population Description

Analysis not performed.

Arm/Group Title	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Apremilast 20 mg: 20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.	Apremilast 30 mg: 30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Measure Participants	0	0

65. Secondary Outcome

Title	Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Year 2
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), Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest; Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = 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 The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame	Baseline and Year 2

Outcome Measure Data

Analysis Population Description

Analysis not performed.

Arm/Group Title	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to receive 20 mg apremilast tablets twice daily.	Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Measure Participants	0	0

66. Secondary Outcome

Title	Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Year 2
Description	The DAS 28 measures the severity of disease at a specific time and is derived from the following variables: 28 tender joint count (TJC28) 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; C-reactive protein (CRP) Subject's global assessment of disease activity (SGA ). 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. DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame	Baseline and Year 2

Outcome Measure Data

Analysis Population Description

Analysis not performed.

Arm/Group Title	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Apremilast 20 mg: 20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.	Apremilast 30 mg: 30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Measure Participants	0	0

67. Secondary Outcome

Title	Percentage Change From Baseline in the Individual American College of Rheumatology Components at Year 2
Description	The Individual ACR Components were defined as follows: Tender Joint Count (out of 68 joints) Swollen Joint Count (out of 66 joints) Subject Assessment of Pain (0 to 100 mm VAS) Subject Global Assessment of Disease Activity (0 to 100 mm VAS) Physician Global Assessment of Disease Activity (0 to 100 mm VAS) HAQ-DI Score Acute Phase Reactant High Sensitivity C-Reactive Protein (hsCRP, mg/dL) Erythrocyte Sedimentation Rate (ESR) The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame	Baseline and Year 2

Outcome Measure Data

Analysis Population Description

Analysis not performed.

Arm/Group Title	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Apremilast 20 mg: 20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.	Apremilast 30 mg: 30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Measure Participants	0	0

68. Secondary Outcome

Title	Change From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Year 2
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. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame	Baseline and Year 2

Outcome Measure Data

Analysis Population Description

Analysis not performed.

Arm/Group Title	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Apremilast 20 mg: 20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.	Apremilast 30 mg: 30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Measure Participants	0	0

69. Secondary Outcome

Title	Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Year 2
Description	The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame	Baseline and Year 2

Outcome Measure Data

Analysis Population Description

Analysis not performed.

Arm/Group Title	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Apremilast 20 mg: 20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.	Apremilast 30 mg: 30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Measure Participants	0	0

70. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Year 2
Description	Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 50% improvement in 68 tender joint count; ≥ 50% improvement in 66 swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame	Baseline and Year 2

Outcome Measure Data

Analysis Population Description

Analysis not performed.

Arm/Group Title	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Apremilast 20 mg: 20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.	Apremilast 30 mg: 30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Measure Participants	0	0

71. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Year 2
Description	Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: ≥ 70% improvement in 68 tender joint count; ≥ 70% improvement in 66 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject'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); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame	Baseline and Year 2

Outcome Measure Data

Analysis Population Description

Analysis not performed.

Arm/Group Title	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Apremilast 20 mg: 20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.	Apremilast 30 mg: 30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Measure Participants	0	0

72. Secondary Outcome

Title	Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Year 2
Description	The FACIT-Fatigue scale was 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. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame	Baseline and Year 2

Outcome Measure Data

Analysis Population Description

Analysis not performed.

Arm/Group Title	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Apremilast 20 mg: 20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.	Apremilast 30 mg: 30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Measure Participants	0	0

73. Secondary Outcome

Title	Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Year 2
Description	EULAR response criteria classify each participant 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 The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame	Baseline and Year 2

Outcome Measure Data

Analysis Population Description

Analysis not performed.

Arm/Group Title	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Apremilast 20 mg: 20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.	Apremilast 30 mg: 30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Measure Participants	0	0

Adverse Events

Time Frame	All AEs were recorded by the Investigator from the time the participant signed the informed consent to 28 days after the last dose of investigational product.
Arm/Group Title	Week 24: Placebo		Week 24: Apremilast 20 mg		Week 24: Apremilast 30 mg		Study Termination: Apremilast 20 mg		Study Termination: Apremilast 30 mg
Arm/Group Description	Participants randomized to 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 randomized to receive 20 mg apremilast tablets twice daily during the 24-week placebo-controlled phase.		Participants randomized to receive 30 mg apremilast tablets twice daily during the 24-week placebo-controlled phase.		Participants who received 20 mg apremilast, regardless of when the apremilast exposure started (at Week 0, 16, or 24), up until Study Termination.		Participants who received 30 mg apremilast, regardless of when the apremilast exposure started (at Week 0, 16, or 24), up until Study Termination.
All Cause Mortality
	Week 24: Placebo		Week 24: Apremilast 20 mg		Week 24: Apremilast 30 mg		Study Termination: Apremilast 20 mg		Study Termination: Apremilast 30 mg
	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)
Serious Adverse Events
	Week 24: Placebo		Week 24: Apremilast 20 mg		Week 24: Apremilast 30 mg		Study Termination: Apremilast 20 mg		Study Termination: Apremilast 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/79 (1.3%)		6/82 (7.3%)		4/76 (5.3%)		16/153 (10.5%)		7/76 (9.2%)
Blood and lymphatic system disorders
Leukocytosis	0/79 (0%)		0/82 (0%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Cardiac disorders
Atrial fibrillation	0/79 (0%)		1/82 (1.2%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Supraventricular tachycardia	0/79 (0%)		0/82 (0%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Cardiac congestive failure	0/79 (0%)		0/82 (0%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Gastrointestinal disorders
Peritonitis	0/79 (0%)		0/82 (0%)		0/76 (0%)		0/153 (0%)		1/76 (1.3%)
General disorders
Foreign body reaction	0/79 (0%)		0/82 (0%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Hepatobiliary disorders
Cholelithiasis	0/79 (0%)		0/82 (0%)		0/76 (0%)		2/153 (1.3%)		0/76 (0%)
Infections and infestations
Cellulitis	0/79 (0%)		0/82 (0%)		1/76 (1.3%)		0/153 (0%)		1/76 (1.3%)
Staphylococcal abscess	0/79 (0%)		0/82 (0%)		1/76 (1.3%)		0/153 (0%)		1/76 (1.3%)
Appendicitis	0/79 (0%)		1/82 (1.2%)		0/76 (0%)		1/153 (0.7%)		1/76 (1.3%)
Empyema	0/79 (0%)		0/82 (0%)		1/76 (1.3%)		0/153 (0%)		1/76 (1.3%)
Herpes Zoster	0/79 (0%)		0/82 (0%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Meningitis viral	0/79 (0%)		1/82 (1.2%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Viral upper respiratory tract infection	0/79 (0%)		0/82 (0%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Injury, poisoning and procedural complications
Concussion	0/79 (0%)		1/82 (1.2%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Ankle fracture	0/79 (0%)		0/82 (0%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Pubis Fracture	0/79 (0%)		0/82 (0%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Wrist Fracture	0/79 (0%)		0/82 (0%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	0/79 (0%)		1/82 (1.2%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	0/79 (0%)		0/82 (0%)		1/76 (1.3%)		0/153 (0%)		1/76 (1.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm	0/79 (0%)		0/82 (0%)		1/76 (1.3%)		0/153 (0%)		1/76 (1.3%)
Basal cell carcinoma	0/79 (0%)		1/82 (1.2%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Mesothelioma malignant advanced	0/79 (0%)		0/82 (0%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Nervous system disorders
Transient ischaemic attack	0/79 (0%)		1/82 (1.2%)		0/76 (0%)		2/153 (1.3%)		0/76 (0%)
Loss of consciousness	0/79 (0%)		0/82 (0%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Psychiatric disorders
Bipolar disorder	0/79 (0%)		0/82 (0%)		1/76 (1.3%)		0/153 (0%)		1/76 (1.3%)
Suicidal ideation	0/79 (0%)		0/82 (0%)		1/76 (1.3%)		0/153 (0%)		1/76 (1.3%)
Renal and urinary disorders
Renal failure acute	0/79 (0%)		0/82 (0%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/79 (0%)		0/82 (0%)		1/76 (1.3%)		0/153 (0%)		1/76 (1.3%)
Costochondritis	1/79 (1.3%)		0/82 (0%)		0/76 (0%)		0/153 (0%)		0/76 (0%)
Vascular disorders
Rheumatoid vasculitis	0/79 (0%)		0/82 (0%)		0/76 (0%)		0/153 (0%)		1/76 (1.3%)
Varicose vein	0/79 (0%)		0/82 (0%)		0/76 (0%)		1/153 (0.7%)		0/76 (0%)
Other (Not Including Serious) Adverse Events
	Week 24: Placebo		Week 24: Apremilast 20 mg		Week 24: Apremilast 30 mg		Study Termination: Apremilast 20 mg		Study Termination: Apremilast 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/79 (19%)		26/82 (31.7%)		23/76 (30.3%)		49/153 (32%)		29/76 (38.2%)
Gastrointestinal disorders
Nausea	6/79 (7.6%)		7/82 (8.5%)		10/76 (13.2%)		13/153 (8.5%)		10/76 (13.2%)
Diarrhoea	2/79 (2.5%)		7/82 (8.5%)		6/76 (7.9%)		14/153 (9.2%)		6/76 (7.9%)
Abdominal pain upper	3/79 (3.8%)		3/82 (3.7%)		5/76 (6.6%)		3/153 (2%)		5/76 (6.6%)
Vomiting	1/79 (1.3%)		1/82 (1.2%)		3/76 (3.9%)		3/153 (2%)		5/76 (6.6%)
Infections and infestations
Nasopharyngitis	4/79 (5.1%)		6/82 (7.3%)		3/76 (3.9%)		11/153 (7.2%)		6/76 (7.9%)
Upper respiratory tract infecetion	2/79 (2.5%)		3/82 (3.7%)		5/76 (6.6%)		9/153 (5.9%)		7/76 (9.2%)
Metabolism and nutrition disorders
Decreased appetite	0/79 (0%)		2/82 (2.4%)		4/76 (5.3%)		4/153 (2.6%)		4/76 (5.3%)
Nervous system disorders
Headache	1/79 (1.3%)		9/82 (11%)		7/76 (9.2%)		12/153 (7.8%)		8/76 (10.5%)
Vascular disorders
Hypertension	0/79 (0%)		2/82 (2.4%)		0/76 (0%)		9/153 (5.9%)		1/76 (1.3%)

Limitations/Caveats

The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

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.