Psoriatic Arthritis
Conditions
Keywords
Psoriatic Arthritis, Psoriasis, Arthritis, inflammation, skin condition, inflammatory cells, apremilast, CC-10004, phosphodiesterase type 4
Brief summary
The purpose of this study is to determine whether apremilast is safe and effective in the treatment of patients with psoriatic arthritis, specifically in improving signs and symptoms of psoriatic arthritis (tender and swollen joints, pain, physical function) in treated patients.
Detailed description
Psoriatic arthritis (PsA) is an inflammatory arthritis that occurs in 6-39% of psoriasis patients. The immunopathogenesis of PsA, which mirrors but is not identical to that seen in psoriatic plaques, reflects a complex interaction among resident dendritic, fibroblastic and endothelial cells, and inflammatory cells attracted to the synovium by cytokines and chemokines. Apremilast (CC-10004) is a novel oral agent that modulates multiple inflammatory pathways through targeted phosphodiesterase type 4 (PDE4) enzyme inhibition. Therefore, apremilast has the potential to be effective in the treatment of PsA.
Interventions
DRUGApremilast 20mg
Apremilast 20 mg twice daily, orally
DRUGApremilast 30mg
Apremilast 30 mg twice daily, orally
Placebo + 20 mg Apremilast
Placebo + 30 mg Apremilast
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males or females, aged ≥ 18 years at time of consent. * Have a diagnosis of Psoriatic Arthritis (PSA, by any criteria) of ≥ 6 months duration. * Meet the Classification Criteria for Psoriatic Arthritis (CASPAR) at time of screening. * Must have been inadequately treated by disease-modifying antirheumatic drugs (DMARDs) * May not have axial involvement alone * Concurrent treatment allowed with methotrexate, leflunomide, or sulfasalazine * Have ≥ 3 swollen AND ≥ 3 tender joints. * Males & Females must use contraception * Stable dose of nonsteroidal anti-inflammatory drugs (NSAIDs), narcotics and low dose oral corticosteroids allowed.
Exclusion criteria
* Pregnant or breast feeding. * History of allergy to any component of the investigational product. * Hepatitis B surface antigen and/or Hepatitis C antibody positive at screening. * Therapeutic failure on \> 3 agents for PsA or \> 1 biologic tumor necrosis factor (TNF) blocker
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16 | Baseline and Week 16 | Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an ACR 20 Response at Week 24 | Baseline and Week 24 | Percentage of participants with an American College of Rheumatology 20% (ACR20) response at Week 24. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. |
| Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24 | Baseline and Week 24 | The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. |
| Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16 | Baseline and Week 16 | The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. |
| Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16 | Baseline and Week 16 | Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from Baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from Baseline by ≥ 20 mm VAS. |
| Change From Baseline in Patient's Assessment of Pain at Week 16 | Baseline and Week 16 | The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters. |
| Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16 | Baseline and Week 16 | The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. |
| Change From Baseline in Dactylitis Severity Score at Week 16 | Baseline and Week 16 | Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. |
| Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16 | Baseline and Week 16 | The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0 to 76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: \> 2.8 and ≤ 10 Moderate Disease Activity: \> 10 and ≤ 22 High Disease Activity: \> 22. |
| Change From Baseline in the Disease Activity Score (DAS28) 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 • 28 swollen joint count, which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. |
| Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16 | Baseline and Week 16 | The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from Baseline score indicates an improvement. |
| Change From Baseline in SF-36 Physical Function 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. |
| Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24 | Baseline and Week 24 | Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: •78 tender joint count, •76 swollen joint count, •Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; •Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. |
| Change From Baseline in Patient's Assessment of Pain at Week 24 | Baseline and Week 24 | The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters. |
| Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24 | Baseline and Week 24 | The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. |
| Change From Baseline in Dactylitis Severity Score at Week 24 | Baseline and Week 24 | Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. |
| Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 | Baseline and Week 24 | The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22. |
| Change From Baseline in the Disease Activity Score (DAS28) at Week 24 | Baseline and Week 24 | The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. |
| Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 | Baseline and Week 24 | The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from Baseline score indicates an improvement. |
| Percentage of Participants With MASES Improvement ≥ 20% at Week 16 | Baseline and Week 16 | Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. |
| Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16 | Baseline and Week 16 | Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. |
| Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16 | Baseline and Week 16 | A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. |
| Percentage of Participants With MASES Improvement ≥ 20% at Week 24 | Baseline and Week 24 | Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. |
| Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24 | Baseline and Week 24 | Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. |
| Percentage of Participants With Good or Moderate EULAR Response at Week 24 | Baseline and Week 24 | EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. |
| Percentage of Participants With a ACR 50 Response at Week 16 | Baseline and Week 16 | Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. |
| Percentage of Participants With an ACR 70 Response at Week 16 | Baseline and Week 16 | Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. |
| Percentage of Participants With an ACR 50 Response at Week 24 | Baseline and Week 24 | Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. |
| Percentage of Participants With a ACR 70 Response at Week 24 | Baseline and week 24 | Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. |
| Percentage of Participants Achieving a MASES Score of Zero at Week 16 | Week 16 | Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. |
| Percentage of Participants Achieving a Dactylitis Score of Zero at Week 16 | Week 16 | Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. |
| Percentage of Participants Achieving a MASES Score of Zero at Week 24 | Week 24 | Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. |
| Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24 | Week 24 | Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. |
| Percentage of Participants With a ACR 20 Response at Week 52 | Baseline and Week 52 | Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. |
| Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52 | Baseline and Week 52 | The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. |
| Change From Baseline in the 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. |
| Percentage of Participants With a Modified PsARC Response at Week 52 | Baseline and Week 52 | Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from Baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from Baseline by ≥ 20 mm VAS. Two-sided 95% confidence interval is based on the Clopper-Pearson method. |
| Change From Baseline in the Patient Assessment of Pain at Week 52 | Baseline and Week 52 | The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters. |
| Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52 | Baseline and week 52 | The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. |
| Change From Baseline in the Dactylitis Severity Score at Week 52 | Baseline and Week 52 | Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. |
| Change From Baseline in the CDAI Score at Week 52 | Baseline and Week 52 | The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: \> 2.8 and ≤ 10 Moderate Disease Activity: \> 10 and ≤ 22 High Disease Activity: \> 22. |
| Change From Baseline in the DAS28 at Week 52 | Baseline and Week 52 | The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. |
| Change From Baseline in the FACIT-Fatigue Scale Score at Week 52 | Baseline and Week 52 | The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from Baseline score indicates an improvement. |
| Percentage of Participants With MASES Improvement ≥ 20% at Week 52 | Baseline and Week 52 | Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 52 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method. |
| Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 52 | Baseline and Week 52 | Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method. |
| Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52 | Baseline and Week 52 | A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. |
| Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 16 | Baseline and Week 16 | The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. |
| Percentage of Participants With an ACR 70 Response at Week 52 | Baseline and Week 52 | Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. |
| Percentage of Participants Achieving a MASES Score of Zero at Week 52 | Week 52 | Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method. |
| Percentage of Participants Achieving a Dactylitis Score of Zero at Week 52 | Week 52 | Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method. |
| Number of Participants With Adverse Events During the Placebo-Controlled Period | Week 0 to Week 16 for placebo participants who entered early escape at Week 16 and up to Week 24 for all other participants (placebo participants who remained on placebo through week 24 and participants randomized to the APR 20 mg BID or APR 30 mg BID) | A Treatment Emergent Adverse Event (TEAE) is an AE with a start date on or after the date of the first dose of Investigational Product (IP). An AE is any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. |
| Number of Participants With Adverse Events During the Apremilast-Exposure Period | Baseline to Week 260; median total exposure to Apremilast was 170 weeks | A TEAE is an AE with a start date on or after the date of the first dose of Investigational Product (IP) and no later than 28 days after the last dose of IP. An AE is any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. |
| Percentage of Participants With an ACR 50 Response at Week 52 | Baseline and Week 52 | Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. |
Countries
Australia, Austria, Canada, France, Germany, Hungary, New Zealand, Poland, Russia, South Africa, Spain, United Kingdom, United States
Participant flow
Recruitment details
This study was a multicenter study with 83 study sites from the US, Canada, Europe, Russia, Australia, New Zealand and South Africa.
Pre-assignment details
The study population was restricted to male and female subjects ≥ 18 years of age with moderate to severe Psoriatic Arthritis (PsA). Participants must have had a diagnosis of PsA by the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria, including peripheral joint involvement.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants initially randomized to receive placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape). | 168 |
| Apremilast 20 mg Participants initially randomized to 20 mg apremilast tablets twice daily (BID) in the placebo-controlled phase and continued to receive 20 mg apremilast tablets BID in the active treatment / long-term safety phase. After 30 mg apremilast BID was identified as the optimal dose, all active subjects originally receiving 20 mg apremilast BID were switched to the 30 mg apremilast BID dose | 168 |
| Apremilast 30 mg Participants initially randomized to 30 mg apremilast tablets twice daily (BID) in the placebo-controlled phase and continued to receive 30 mg apremilast tablets BID for up to 4.5 years in the active treatment / long-term safety phase | 168 |
| Total | 504 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Active-Treatment Phase Weeks (104-156) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Active-Treatment Phase Weeks (104-156) | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Active-Treatment Phase Weeks (104-156) | Lack of Efficacy | 0 | 4 | 2 | 0 | 0 | 0 | 0 | 2 | 2 |
| Active-Treatment Phase Weeks (104-156) | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Active-Treatment Phase Weeks (104-156) | Miscellaneious | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Active-Treatment Phase Weeks (104-156) | Withdrawal by Subject | 0 | 6 | 3 | 0 | 0 | 0 | 0 | 2 | 1 |
| Active-Treatment Phase (Weeks 156-208) | Adverse Event | 0 | 4 | 1 | 0 | 0 | 0 | 0 | 3 | 0 |
| Active-Treatment Phase (Weeks 156-208) | Lack of Efficacy | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 3 | 2 |
| Active-Treatment Phase (Weeks 156-208) | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Active-Treatment Phase (Weeks 156-208) | Miscellaneous | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Active-Treatment Phase (Weeks 156-208) | Withdrawal by Subject | 0 | 4 | 2 | 0 | 0 | 0 | 0 | 2 | 4 |
| Active-Treatment Phase (Weeks 208-260) | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 |
| Active-Treatment Phase (Weeks 208-260) | Death | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Active-Treatment Phase (Weeks 208-260) | Lack of Efficacy | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Active-Treatment Phase (Weeks 208-260) | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Active-Treatment Phase (Weeks 208-260) | Non-compliance with study drug | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Active-Treatment Phase (Weeks 208-260) | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Active-Treatment Phase (Weeks 208-260) | Withdrawal by Subject | 0 | 2 | 3 | 0 | 0 | 0 | 0 | 1 | 0 |
| Active Treatment Phase (Weeks 25-52) | Adverse Event | 0 | 2 | 5 | 1 | 1 | 2 | 0 | 0 | 0 |
| Active Treatment Phase (Weeks 25-52) | Lack of Efficacy | 0 | 4 | 7 | 3 | 1 | 3 | 0 | 0 | 0 |
| Active Treatment Phase (Weeks 25-52) | Lost to Follow-up | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Active Treatment Phase (Weeks 25-52) | Non-compliance with Study Drug | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Active Treatment Phase (Weeks 25-52) | Other | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
| Active Treatment Phase (Weeks 25-52) | Withdrawal by Subject | 0 | 5 | 1 | 2 | 2 | 9 | 1 | 0 | 0 |
| Active-Treatment Phase (Weeks 52-104) | Adverse Event | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 3 | 1 |
| Active-Treatment Phase (Weeks 52-104) | Death | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Active-Treatment Phase (Weeks 52-104) | Lack of Efficacy | 0 | 7 | 8 | 0 | 0 | 0 | 0 | 4 | 0 |
| Active-Treatment Phase (Weeks 52-104) | Lost to Follow-up | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 3 | 0 |
| Active-Treatment Phase (Weeks 52-104) | Miscellaneous | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Active-Treatment Phase (Weeks 52-104) | Missing | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Active-Treatment Phase (Weeks 52-104) | Non-compliance with Study Drug | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Active-Treatment Phase (Weeks 52-104) | Withdrawal by Subject | 0 | 10 | 8 | 0 | 0 | 0 | 0 | 5 | 2 |
| Placebo-controlled Phase (Week 0-24) | Adverse Event | 11 | 8 | 10 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo-controlled Phase (Week 0-24) | Death | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo-controlled Phase (Week 0-24) | Lack of Efficacy | 4 | 5 | 4 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo-controlled Phase (Week 0-24) | Non-compliance with Study Drug | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo-controlled Phase (Week 0-24) | Other | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo-controlled Phase (Week 0-24) | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo-controlled Phase (Week 0-24) | Withdrawal by Subject | 2 | 5 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Apremilast 20 mg | Apremilast 30 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 51.1 years STANDARD_DEVIATION 12.13 | 48.7 years STANDARD_DEVIATION 10.99 | 51.4 years STANDARD_DEVIATION 11.72 | 50.4 years STANDARD_DEVIATION 11.66 |
| Duration of psoriatic arthritis | 7.31 years STANDARD_DEVIATION 7.118 | 7.18 years STANDARD_DEVIATION 6.842 | 8.09 years STANDARD_DEVIATION 8.092 | 7.53 years STANDARD_DEVIATION 7.366 |
| Sex: Female, Male Female | 80 Participants | 83 Participants | 92 Participants | 255 Participants |
| Sex: Female, Male Male | 88 Participants | 85 Participants | 76 Participants | 249 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 43 / 168 | 69 / 168 | 80 / 168 | 150 / 245 | 17 / 87 | 169 / 245 |
| serious Total, serious adverse events | 7 / 168 | 8 / 168 | 9 / 168 | 41 / 245 | 6 / 87 | 49 / 245 |
Outcome results
Primary
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16
Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein.
Time frame: Baseline and Week 16
Population: Full analysis set consisting of all participants randomized as specified in the protocol. 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 | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16 | 19.0 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16 | 30.4 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16 | 38.1 percentage of participants |
Comparison: In order to maintain the Type 1 error at the 0.05 significance level, the Hochberg procedure was to be used. The results of the endpoint were to be considered statistically significant if both the 30 mg apremilast dose versus placebo comparison and the 20 mg versus placebo comparison were statistically significant at the 0.05 significance level, or one of the comparisons was statistically significant at the 0.025 level.p-value: 0.000195% CI: [9.7, 28.3]Cochran-Mantel-Haenszel
Comparison: In order to maintain the Type 1 error at the 0.05 significance level, the Hochberg procedure was to be used. The results of the endpoint were to be considered statistically significant if both the 30 mg apremilast dose versus placebo comparison and the 20 mg versus placebo comparison were statistically significant at the 0.05 significance level, or one of the comparisons was statistically significant at the 0.025 level.p-value: 0.016695% CI: [2.2, 20.4]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.
Time frame: Baseline and Week 16
Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included; LOCF was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16 | 1.81 units on a scale | Standard Error 0.621 |
| Apremilast 20 mg | Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16 | 3.50 units on a scale | Standard Error 0.625 |
| Apremilast 30 mg | Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16 | 4.23 units on a scale | Standard Error 0.625 |
p-value: 0.005695% CI: [0.71, 4.13]ANCOVA
p-value: 0.050495% CI: [0, 3.4]ANCOVA
Secondary
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0 to 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
Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16 | -3.84 units on a scale | Standard Error 0.929 |
| Apremilast 20 mg | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16 | -8.24 units on a scale | Standard Error 0.926 |
| Apremilast 30 mg | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16 | -8.72 units on a scale | Standard Error 0.923 |
95% CI: [-7.41, -2.34]
95% CI: [-6.92, -1.86]
Secondary
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22.
Time frame: Baseline and Week 24
Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 | -3.14 units on a scale | Standard Error 0.965 |
| Apremilast 20 mg | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 | -7.55 units on a scale | Standard Error 0.958 |
| Apremilast 30 mg | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 | -9.52 units on a scale | Standard Error 0.949 |
95% CI: [-9, -3.75]
95% CI: [-7.03, -1.79]
Secondary
Change From Baseline in Dactylitis Severity Score at Week 16
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time frame: Baseline and Week 16
Population: Full analysis set. Participants with a baseline dactylitis severity score \> 0 (i.e., pre-existing dactylitis) and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Dactylitis Severity Score at Week 16 | -1.4 units on a scale | Standard Error 0.28 |
| Apremilast 20 mg | Change From Baseline in Dactylitis Severity Score at Week 16 | -1.9 units on a scale | Standard Error 0.31 |
| Apremilast 30 mg | Change From Baseline in Dactylitis Severity Score at Week 16 | -1.7 units on a scale | Standard Error 0.28 |
95% CI: [-1.1, 0.4]
95% CI: [-1.3, 0.3]
Secondary
Change From Baseline in Dactylitis Severity Score at Week 24
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time frame: Baseline and Week 24
Population: Full analysis set. Participants with a baseline dactylitis severity score \> 0 (i.e., pre-existing dactylitis) and at least 1 postbaseline value at or prior to Week 24 are included. LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Dactylitis Severity Score at Week 24 | -1.3 units on a scale | Standard Error 0.27 |
| Apremilast 20 mg | Change From Baseline in Dactylitis Severity Score at Week 24 | -2.0 units on a scale | Standard Error 0.3 |
| Apremilast 30 mg | Change From Baseline in Dactylitis Severity Score at Week 24 | -1.8 units on a scale | Standard Error 0.27 |
95% CI: [-1.2, 0.3]
95% CI: [-1.5, 0.1]
Secondary
Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 16
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time frame: Baseline and Week 16
Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included; Last observation carried forward (LOCF) imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 16 | -0.086 units on a scale | Standard Error 0.036 |
| Apremilast 20 mg | Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 16 | -0.198 units on a scale | Standard Error 0.0364 |
| Apremilast 30 mg | Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 16 | -0.244 units on a scale | Standard Error 0.0364 |
Comparison: Pairwise comparisons (30 mg vs placebo and 20 mg vs placebo) were conducted conditional on the primary endpoint results. If the primary endpoint was statistically significant for both apremilast dose groups, pairwise comparisons for the HAQ-DI were to be evaluated at the 0.05 level using the Hochberg procedure. If only one apremilast dose was statistically significant, then only the comparison between that apremilast dose and placebo was conducted for the HAQ-DI score, at the 0.025 level.p-value: 0.001795% CI: [-0.258, -0.06]ANCOVA
Comparison: Pairwise comparisons (30 mg vs placebo and 20 mg vs placebo) were conducted conditional on the primary endpoint results. If the primary endpoint was statistically significant for both apremilast dose groups, pairwise comparisons for the HAQ-DI were to be evaluated at the 0.05 level using the Hochberg procedure. If only one apremilast dose was statistically significant, then only the comparison between that apremilast dose and placebo was conducted for the HAQ-DI score, at the 0.025 level.p-value: 0.025295% CI: [-0.211, -0.014]ANCOVA
Secondary
Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time frame: Baseline and Week 24
Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24 | -0.076 units on a scale | Standard Error 0.0369 |
| Apremilast 20 mg | Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24 | -0.211 units on a scale | Standard Error 0.0373 |
| Apremilast 30 mg | Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24 | -0.258 units on a scale | Standard Error 0.0371 |
p-value: 0.000595% CI: [-0.283, -0.08]ANCOVA
p-value: 0.009195% CI: [-0.236, -0.034]ANCOVA
Secondary
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time frame: Baseline and Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52 | -0.27 units on a scale | Standard Deviation 0.562 |
| Apremilast 20 mg | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52 | -0.29 units on a scale | Standard Deviation 0.59 |
| Apremilast 30 mg | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52 | -0.37 units on a scale | Standard Deviation 0.479 |
| Apremilast 30 mg | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52 | -0.32 units on a scale | Standard Deviation 0.547 |
Secondary
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time frame: Baseline and Week 16
Population: Full analysis set; participants with a baseline MASES \> 0 (i.e., pre-existing enthesopathy) and at least 1 postbaseline value at or prior to Week 16 are included; LOCF was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16 | -0.9 units on a scale | Standard Error 0.3 |
| Apremilast 20 mg | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16 | -1.4 units on a scale | Standard Error 0.29 |
| Apremilast 30 mg | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16 | -1.3 units on a scale | Standard Error 0.28 |
95% CI: [-1.2, 0.4]
95% CI: [-1.3, 0.3]
Secondary
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time frame: Baseline and Week 24
Population: Full analysis set; participants with a baseline MASES \> 0 (i.e., pre-existing enthesopathy) and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24 | -0.8 units on a scale | Standard Error 0.31 |
| Apremilast 20 mg | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24 | -1.6 units on a scale | Standard Error 0.3 |
| Apremilast 30 mg | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24 | -1.6 units on a scale | Standard Error 0.29 |
95% CI: [-1.6, 0]
95% CI: [-1.6, 0.1]
Secondary
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time frame: Baseline and week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a baseline value \> 0 (i.e., pre-existing enthesopathy) and a Week 52 value are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52 | -2.2 units on a scale | Standard Deviation 4.03 |
| Apremilast 20 mg | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52 | -1.9 units on a scale | Standard Deviation 3.89 |
| Apremilast 30 mg | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52 | -2.7 units on a scale | Standard Deviation 2.41 |
| Apremilast 30 mg | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52 | -1.9 units on a scale | Standard Deviation 2.93 |
Secondary
Change From Baseline in Patient's Assessment of Pain at Week 16
The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters.
Time frame: Baseline and Week 16
Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included; LOCF was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Patient's Assessment of Pain at Week 16 | -5.7 mm | Standard Error 1.83 |
| Apremilast 20 mg | Change From Baseline in Patient's Assessment of Pain at Week 16 | -11.5 mm | Standard Error 1.85 |
| Apremilast 30 mg | Change From Baseline in Patient's Assessment of Pain at Week 16 | -13.5 mm | Standard Error 1.85 |
p-value: 0.002395% CI: [-12.9, -2.8]ANCOVA
95% CI: [-10.8, -0.7]
Secondary
Change From Baseline in Patient's Assessment of Pain at Week 24
The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters.
Time frame: Baseline and Week 24
Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Patient's Assessment of Pain at Week 24 | -4.2 mm | Standard Error 1.78 |
| Apremilast 20 mg | Change From Baseline in Patient's Assessment of Pain at Week 24 | -11.2 mm | Standard Error 1.79 |
| Apremilast 30 mg | Change From Baseline in Patient's Assessment of Pain at Week 24 | -14.7 mm | Standard Error 1.77 |
95% CI: [-15.4, -5.7]
95% CI: [-12, -2.2]
Secondary
Change From Baseline in SF-36 Physical Function at 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.
Time frame: Baseline and Week 24
Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in SF-36 Physical Function at Week 24 | 1.45 units on a scale | Standard Error 0.671 |
| Apremilast 20 mg | Change From Baseline in SF-36 Physical Function at Week 24 | 3.49 units on a scale | Standard Error 0.675 |
| Apremilast 30 mg | Change From Baseline in SF-36 Physical Function at Week 24 | 5.01 units on a scale | Standard Error 0.671 |
95% CI: [1.72, 5.4]
95% CI: [0.21, 3.88]
Secondary
Change From Baseline in the CDAI Score at Week 52
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: \> 2.8 and ≤ 10 Moderate Disease Activity: \> 10 and ≤ 22 High Disease Activity: \> 22.
Time frame: Baseline and Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the CDAI Score at Week 52 | -15.00 units on a scale | Standard Deviation 11.137 |
| Apremilast 20 mg | Change From Baseline in the CDAI Score at Week 52 | -14.03 units on a scale | Standard Deviation 14.9 |
| Apremilast 30 mg | Change From Baseline in the CDAI Score at Week 52 | -15.41 units on a scale | Standard Deviation 13.039 |
| Apremilast 30 mg | Change From Baseline in the CDAI Score at Week 52 | -14.54 units on a scale | Standard Deviation 12.009 |
Secondary
Change From Baseline in the Dactylitis Severity Score at Week 52
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time frame: Baseline and Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a baseline value \> 0 (i.e., pre-existing dactylitis) and a Week 52 value are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Dactylitis Severity Score at Week 52 | -0.8 units on a scale | Standard Deviation 2.1 |
| Apremilast 20 mg | Change From Baseline in the Dactylitis Severity Score at Week 52 | -2.4 units on a scale | Standard Deviation 3.58 |
| Apremilast 30 mg | Change From Baseline in the Dactylitis Severity Score at Week 52 | -2.7 units on a scale | Standard Deviation 3.79 |
| Apremilast 30 mg | Change From Baseline in the Dactylitis Severity Score at Week 52 | -1.8 units on a scale | Standard Deviation 3.23 |
Secondary
Change From Baseline in the DAS28 at Week 52
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time frame: Baseline and Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the DAS28 at Week 52 | -1.47 units on a scale | Standard Deviation 1.103 |
| Apremilast 20 mg | Change From Baseline in the DAS28 at Week 52 | -1.15 units on a scale | Standard Deviation 1.272 |
| Apremilast 30 mg | Change From Baseline in the DAS28 at Week 52 | -1.40 units on a scale | Standard Deviation 1.125 |
| Apremilast 30 mg | Change From Baseline in the DAS28 at Week 52 | -1.31 units on a scale | Standard Deviation 1.114 |
Secondary
Change From Baseline in the Disease Activity Score (DAS28) at Week 16
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time frame: Baseline and Week 16
Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Disease Activity Score (DAS28) at Week 16 | -0.26 units on a scale | Standard Error 0.082 |
| Apremilast 20 mg | Change From Baseline in the Disease Activity Score (DAS28) at Week 16 | -0.73 units on a scale | Standard Error 0.082 |
| Apremilast 30 mg | Change From Baseline in the Disease Activity Score (DAS28) at Week 16 | -0.79 units on a scale | Standard Error 0.083 |
95% CI: [-0.76, -0.31]
95% CI: [-0.7, -0.25]
Secondary
Change From Baseline in the Disease Activity Score (DAS28) at Week 24
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time frame: Baseline and Week 24
Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Disease Activity Score (DAS28) at Week 24 | -0.20 units on a scale | Standard Error 0.087 |
| Apremilast 20 mg | Change From Baseline in the Disease Activity Score (DAS28) at Week 24 | -0.66 units on a scale | Standard Error 0.087 |
| Apremilast 30 mg | Change From Baseline in the Disease Activity Score (DAS28) at Week 24 | -0.90 units on a scale | Standard Error 0.087 |
95% CI: [-0.94, -0.46]
95% CI: [-0.7, -0.22]
Secondary
Change From Baseline in the FACIT-Fatigue Scale Score at 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.
Time frame: Baseline and Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the FACIT-Fatigue Scale Score at Week 52 | 4.33 units on a scale | Standard Deviation 8.183 |
| Apremilast 20 mg | Change From Baseline in the FACIT-Fatigue Scale Score at Week 52 | 4.15 units on a scale | Standard Deviation 11.712 |
| Apremilast 30 mg | Change From Baseline in the FACIT-Fatigue Scale Score at Week 52 | 4.27 units on a scale | Standard Deviation 8.488 |
| Apremilast 30 mg | Change From Baseline in the FACIT-Fatigue Scale Score at Week 52 | 3.67 units on a scale | Standard Deviation 9.078 |
Secondary
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16
The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from Baseline score indicates an improvement.
Time frame: Baseline and Week 16
Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16 | 1.55 units on a scale | Standard Error 0.693 |
| Apremilast 20 mg | Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16 | 1.68 units on a scale | Standard Error 0.696 |
| Apremilast 30 mg | Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16 | 3.88 units on a scale | Standard Error 0.695 |
95% CI: [0.43, 4.23]
95% CI: [-1.77, 2.03]
Secondary
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at 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.
Time frame: Baseline and Week 24
Population: Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 | 1.12 units on a scale | Standard Error 0.691 |
| Apremilast 20 mg | Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 | 1.52 units on a scale | Standard Error 0.696 |
| Apremilast 30 mg | Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 | 3.33 units on a scale | Standard Error 0.69 |
95% CI: [0.32, 4.1]
95% CI: [-1.5, 2.29]
Secondary
Change From Baseline in the Patient Assessment of Pain at Week 52
The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters.
Time frame: Baseline and Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Patient Assessment of Pain at Week 52 | -20.2 mm | Standard Deviation 26.76 |
| Apremilast 20 mg | Change From Baseline in the Patient Assessment of Pain at Week 52 | -21.0 mm | Standard Deviation 25.83 |
| Apremilast 30 mg | Change From Baseline in the Patient Assessment of Pain at Week 52 | -17.8 mm | Standard Deviation 24.5 |
| Apremilast 30 mg | Change From Baseline in the Patient Assessment of Pain at Week 52 | -20.3 mm | Standard Deviation 23.37 |
Secondary
Change From Baseline in the SF-36 Physical Functioning Domain at 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.
Time frame: Baseline and Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the SF-36 Physical Functioning Domain at Week 52 | 4.46 units on a scale | Standard Deviation 8.877 |
| Apremilast 20 mg | Change From Baseline in the SF-36 Physical Functioning Domain at Week 52 | 4.62 units on a scale | Standard Deviation 9.979 |
| Apremilast 30 mg | Change From Baseline in the SF-36 Physical Functioning Domain at Week 52 | 6.98 units on a scale | Standard Deviation 9.425 |
| Apremilast 30 mg | Change From Baseline in the SF-36 Physical Functioning Domain at Week 52 | 5.69 units on a scale | Standard Deviation 8.995 |
Secondary
Number of Participants With Adverse Events During the Apremilast-Exposure Period
A TEAE is an AE with a start date on or after the date of the first dose of Investigational Product (IP) and no later than 28 days after the last dose of IP. An AE is any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.
Time frame: Baseline to Week 260; median total exposure to Apremilast was 170 weeks
Population: Apremilast Subjects as Treated (AAT) were those who received at least 1 dose of apremilast at any time during the study. Participants were included in the treatment group corresponding to the apremilast dosing regimen they actually received, irrespective of the treatment group to which they were randomized or re-randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events During the Apremilast-Exposure Period | Treatment Emergent Adverse Events (TEAEs) | 203 participants |
| Placebo | Number of Participants With Adverse Events During the Apremilast-Exposure Period | Drug-related TEAE | 96 participants |
| Placebo | Number of Participants With Adverse Events During the Apremilast-Exposure Period | Severe TEAE | 35 participants |
| Placebo | Number of Participants With Adverse Events During the Apremilast-Exposure Period | Serious TEAE (SAE) | 41 participants |
| Placebo | Number of Participants With Adverse Events During the Apremilast-Exposure Period | Drug-related SAE | 4 participants |
| Placebo | Number of Participants With Adverse Events During the Apremilast-Exposure Period | TEAE leading to drug interruption | 47 participants |
| Placebo | Number of Participants With Adverse Events During the Apremilast-Exposure Period | TEAE leading to drug withdrawal | 27 participants |
| Placebo | Number of Participants With Adverse Events During the Apremilast-Exposure Period | TEAE leading to death | 1 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | Severe TEAE | 1 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | TEAE leading to drug withdrawal | 0 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | Serious TEAE (SAE) | 6 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | Drug-related SAE | 1 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | TEAE leading to drug interruption | 3 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | Treatment Emergent Adverse Events (TEAEs) | 39 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | Drug-related TEAE | 5 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | TEAE leading to death | 0 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | Severe TEAE | 30 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | Drug-related TEAE | 131 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | Treatment Emergent Adverse Events (TEAEs) | 131 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | Serious TEAE (SAE) | 49 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | TEAE leading to drug withdrawal | 30 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | TEAE leading to drug interruption | 49 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | Drug-related SAE | 9 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Apremilast-Exposure Period | TEAE leading to death | 2 participants |
Secondary
Number of Participants With Adverse Events During the Placebo-Controlled Period
A Treatment Emergent Adverse Event (TEAE) is an AE with a start date on or after the date of the first dose of Investigational Product (IP). An AE is any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.
Time frame: Week 0 to Week 16 for placebo participants who entered early escape at Week 16 and up to Week 24 for all other participants (placebo participants who remained on placebo through week 24 and participants randomized to the APR 20 mg BID or APR 30 mg BID)
Population: Safety population included all participants who were randomized and received at least one dose of IP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events During the Placebo-Controlled Period | Treatment Emergent Adverse Events | 81 participants |
| Placebo | Number of Participants With Adverse Events During the Placebo-Controlled Period | Drug-related TEAE | 32 participants |
| Placebo | Number of Participants With Adverse Events During the Placebo-Controlled Period | Severe TEAE | 6 participants |
| Placebo | Number of Participants With Adverse Events During the Placebo-Controlled Period | Serious TEAE (SAE) | 7 participants |
| Placebo | Number of Participants With Adverse Events During the Placebo-Controlled Period | Drug-related Serious AE) | 2 participants |
| Placebo | Number of Participants With Adverse Events During the Placebo-Controlled Period | TEAE leading to drug interruption | 9 participants |
| Placebo | Number of Participants With Adverse Events During the Placebo-Controlled Period | TEAE leading to drug withdrawal | 8 participants |
| Placebo | Number of Participants With Adverse Events During the Placebo-Controlled Period | TEAE leading to drug death | 0 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | Severe TEAE | 8 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | TEAE leading to drug withdrawal | 10 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | Serious TEAE (SAE) | 8 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | Drug-related Serious AE) | 0 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | TEAE leading to drug interruption | 10 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | Treatment Emergent Adverse Events | 101 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | Drug-related TEAE | 54 participants |
| Apremilast 20 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | TEAE leading to drug death | 1 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | Severe TEAE | 11 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | Drug-related TEAE | 70 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | Treatment Emergent Adverse Events | 103 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | Serious TEAE (SAE) | 9 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | TEAE leading to drug withdrawal | 12 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | TEAE leading to drug interruption | 17 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | Drug-related Serious AE) | 3 participants |
| Apremilast 30 mg | Number of Participants With Adverse Events During the Placebo-Controlled Period | TEAE leading to drug death | 0 participants |
Secondary
Percentage of Participants Achieving a Dactylitis Score of Zero at Week 16
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time frame: Week 16
Population: Full analysis set; participants with a baseline dactylitis severity score \> 0 (i.e., pre-existing dactylitis) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving a Dactylitis Score of Zero at Week 16 | 39.7 percentage of participants |
| Apremilast 20 mg | Percentage of Participants Achieving a Dactylitis Score of Zero at Week 16 | 42.4 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Achieving a Dactylitis Score of Zero at Week 16 | 38.2 percentage of participants |
95% CI: [-17.7, 14.8]
95% CI: [-14.8, 19.6]
Secondary
Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time frame: Week 24
Population: Full analysis set; participants with a baseline dactylitis severity score \> 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24 | 39.7 percentage of participants |
| Apremilast 20 mg | Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24 | 49.2 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24 | 45.6 percentage of participants |
95% CI: [-10.7, 22.4]
95% CI: [-8.5, 26.2]
Secondary
Percentage of Participants Achieving a Dactylitis Score of Zero at Week 52
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time frame: Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; Participants with a baseline dactylitis severity score \> 0 (i.e., pre-existing dactylitis) and who had sufficient data for a definitive determination of response status at Week 52 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving a Dactylitis Score of Zero at Week 52 | 52.2 percentage of participants |
| Apremilast 20 mg | Percentage of Participants Achieving a Dactylitis Score of Zero at Week 52 | 53.8 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Achieving a Dactylitis Score of Zero at Week 52 | 68.8 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Achieving a Dactylitis Score of Zero at Week 52 | 63.3 percentage of participants |
Secondary
Percentage of Participants Achieving a MASES Score of Zero at Week 16
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time frame: Week 16
Population: Full analysis set; participants with a baseline MASES \> 0 (i.e., pre-existing enthesopathy) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving a MASES Score of Zero at Week 16 | 15.3 percentage of participants |
| Apremilast 20 mg | Percentage of Participants Achieving a MASES Score of Zero at Week 16 | 27.2 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Achieving a MASES Score of Zero at Week 16 | 22.8 percentage of participants |
95% CI: [-2.8, 17.9]
95% CI: [0.8, 23]
Secondary
Percentage of Participants Achieving a MASES Score of Zero at Week 24
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time frame: Week 24
Population: Full analysis set; participants with a baseline MASES \> 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving a MASES Score of Zero at Week 24 | 14.3 percentage of participants |
| Apremilast 20 mg | Percentage of Participants Achieving a MASES Score of Zero at Week 24 | 31.1 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Achieving a MASES Score of Zero at Week 24 | 31.6 percentage of participants |
95% CI: [6.6, 28.2]
95% CI: [5.6, 27.9]
Secondary
Percentage of Participants Achieving a MASES Score of Zero at Week 52
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time frame: Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants with a baseline value \> 0 (i.e., pre-existing enthesopathy) and who had sufficient data for a definitive determination of response status at Week 52 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving a MASES Score of Zero at Week 52 | 33.3 percentage of participants |
| Apremilast 20 mg | Percentage of Participants Achieving a MASES Score of Zero at Week 52 | 27.8 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Achieving a MASES Score of Zero at Week 52 | 50.7 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Achieving a MASES Score of Zero at Week 52 | 38.2 percentage of participants |
Secondary
Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52
A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2.
Time frame: Baseline and Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants who had sufficient data for a definitive determination of response status at Week 52 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52 | 82.8 percentage of participants |
| Apremilast 20 mg | Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52 | 70.0 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52 | 75.0 percentage of participants |
| Apremilast 30 mg | Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52 | 74.4 percentage of participants |
Secondary
Percentage of Participants With a ACR 20 Response at Week 52
Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein.
Time frame: Baseline and Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population consists of all participants who were randomized or re-randomized to apremilast at any time during the study. Only those participants who had sufficient data for a definitive determination of response status at Week 52 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a ACR 20 Response at Week 52 | 53.1 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With a ACR 20 Response at Week 52 | 50.0 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With a ACR 20 Response at Week 52 | 63.0 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With a ACR 20 Response at Week 52 | 54.6 percentage of participants |
Secondary
Percentage of Participants With a ACR 50 Response at Week 16
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein.
Time frame: Baseline and Week 16
Population: Full analysis set; Participants who discontinued early, or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a ACR 50 Response at Week 16 | 6.0 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With a ACR 50 Response at Week 16 | 15.5 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With a ACR 50 Response at Week 16 | 16.1 percentage of participants |
95% CI: [3.7, 16.8]
95% CI: [3, 16]
Secondary
Percentage of Participants With a ACR 70 Response at Week 24
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein.
Time frame: Baseline and week 24
Population: Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a ACR 70 Response at Week 24 | 0.6 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With a ACR 70 Response at Week 24 | 5.4 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With a ACR 70 Response at Week 24 | 10.1 percentage of participants |
95% CI: [4.8, 14.2]
95% CI: [1.2, 8.3]
Secondary
Percentage of Participants With a Modified PsARC Response at Week 52
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from Baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from Baseline by ≥ 20 mm VAS. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time frame: Baseline and Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants who had sufficient data for a definitive determination of response status at Week 52 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Modified PsARC Response at Week 52 | 73.8 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With a Modified PsARC Response at Week 52 | 71.2 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With a Modified PsARC Response at Week 52 | 77.5 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With a Modified PsARC Response at Week 52 | 73.6 percentage of participants |
Secondary
Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from Baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from Baseline by ≥ 20 mm VAS.
Time frame: Baseline and Week 16
Population: Full analysis set; Participants who discontinued early, or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16 | 29.8 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16 | 38.7 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16 | 46.4 percentage of participants |
p-value: 0.001795% CI: [6.6, 26.8]Cochran-Mantel-Haenszel
95% CI: [-1.2, 18.9]
Secondary
Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: •78 tender joint count, •76 swollen joint count, •Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; •Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS.
Time frame: Baseline and Week 24
Population: Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24 | 18.5 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24 | 31.0 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24 | 42.9 percentage of participants |
95% CI: [15.2, 34]
95% CI: [3.4, 21.5]
Secondary
Percentage of Participants With an ACR 20 Response at Week 24
Percentage of participants with an American College of Rheumatology 20% (ACR20) response at Week 24. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein.
Time frame: Baseline and Week 24
Population: Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an ACR 20 Response at Week 24 | 13.1 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With an ACR 20 Response at Week 24 | 25.6 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With an ACR 20 Response at Week 24 | 35.1 percentage of participants |
p-value: <0.000195% CI: [13.4, 30.9]Cochran-Mantel-Haenszel
p-value: 0.003895% CI: [4.2, 20.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With an ACR 50 Response at Week 24
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein.
Time frame: Baseline and Week 24
Population: Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an ACR 50 Response at Week 24 | 4.2 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With an ACR 50 Response at Week 24 | 14.3 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With an ACR 50 Response at Week 24 | 19.0 percentage of participants |
95% CI: [8.3, 21.5]
95% CI: [4, 16.1]
Secondary
Percentage of Participants With an ACR 50 Response at Week 52
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time frame: Baseline and Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants who had sufficient data for a definitive determination of response status at Week 52 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an ACR 50 Response at Week 52 | 25.4 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With an ACR 50 Response at Week 52 | 27.9 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With an ACR 50 Response at Week 52 | 24.8 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With an ACR 50 Response at Week 52 | 24.6 percentage of participants |
Secondary
Percentage of Participants With an ACR 70 Response at Week 16
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein.
Time frame: Baseline and Week 16
Population: Full analysis set; Participants who discontinued early, or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an ACR 70 Response at Week 16 | 1.2 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With an ACR 70 Response at Week 16 | 6.0 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With an ACR 70 Response at Week 16 | 4.2 percentage of participants |
95% CI: [-0.4, 6.5]
95% CI: [0.8, 8.7]
Secondary
Percentage of Participants With an ACR 70 Response at Week 52
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time frame: Baseline and Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants who had sufficient data for a definitive determination of response status at Week 52 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an ACR 70 Response at Week 52 | 4.8 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With an ACR 70 Response at Week 52 | 14.8 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With an ACR 70 Response at Week 52 | 15.4 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With an ACR 70 Response at Week 52 | 13.8 percentage of participants |
Secondary
Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time frame: Baseline and Week 16
Population: Full analysis set; participants with a baseline dactylitis severity score \> 0 (i.e., pre-existing dactylitis) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16 | 57.4 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16 | 66.1 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16 | 60.3 percentage of participants |
95% CI: [-13.4, 19.3]
95% CI: [-9.1, 24.6]
Secondary
Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time frame: Baseline and Week 24
Population: Full analysis set; participants with a baseline dactylitis severity score \> 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24 | 60.3 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24 | 69.5 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24 | 69.1 percentage of participants |
95% CI: [-6.8, 24.6]
95% CI: [-8.7, 24.2]
Secondary
Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 52
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time frame: Baseline and Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; Participants with a baseline dactylitis severity score \> 0 (i.e., pre-existing dactylitis) and who had sufficient data for a definitive determination of response status at Week 52 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 52 | 65.2 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 52 | 73.1 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 52 | 85.4 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 52 | 77.6 percentage of participants |
Secondary
Percentage of Participants With Good or Moderate EULAR Response at Week 24
EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2.
Time frame: Baseline and Week 24
Population: Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Good or Moderate EULAR Response at Week 24 | 16.1 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With Good or Moderate EULAR Response at Week 24 | 30.4 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With Good or Moderate EULAR Response at Week 24 | 42.3 percentage of participants |
95% CI: [17.1, 35.5]
95% CI: [5.4, 23.1]
Secondary
Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16
A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2.
Time frame: Baseline and Week 16
Population: Full analysis set; Participants who discontinued early, or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16 | 29.8 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16 | 46.4 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16 | 48.8 percentage of participants |
95% CI: [9, 29.3]
95% CI: [6.4, 26.8]
Secondary
Percentage of Participants With MASES Improvement ≥ 20% at Week 16
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time frame: Baseline and Week 16
Population: Full analysis set; participants with a baseline MASES \> 0 (i.e., pre-existing enthesopathy) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With MASES Improvement ≥ 20% at Week 16 | 49.0 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With MASES Improvement ≥ 20% at Week 16 | 56.3 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With MASES Improvement ≥ 20% at Week 16 | 52.6 percentage of participants |
95% CI: [-10.1, 16.7]
95% CI: [-6.5, 21.1]
Secondary
Percentage of Participants With MASES Improvement ≥ 20% at Week 24
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time frame: Baseline and Week 24
Population: Full analysis set; participants with a baseline MASES \> 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With MASES Improvement ≥ 20% at Week 24 | 46.9 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With MASES Improvement ≥ 20% at Week 24 | 58.3 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With MASES Improvement ≥ 20% at Week 24 | 60.5 percentage of participants |
95% CI: [-0.1, 26.5]
95% CI: [-2.4, 25]
Secondary
Percentage of Participants With MASES Improvement ≥ 20% at Week 52
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 52 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time frame: Baseline and Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants with a baseline MASES \> 0 (i.e., pre-existing enthesopathy) and who had sufficient data for a definitive determination of response status at Week 52 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With MASES Improvement ≥ 20% at Week 52 | 69.4 percentage of participants |
| Apremilast 20 mg | Percentage of Participants With MASES Improvement ≥ 20% at Week 52 | 55.6 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With MASES Improvement ≥ 20% at Week 52 | 84.1 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With MASES Improvement ≥ 20% at Week 52 | 75.3 percentage of participants |