Psoriatic Arthritis
Conditions
Keywords
psoriasis, Arthritis, Psoriatic 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 who have not been previously treated with DMARDs. Apremilast is proposed to improve signs and symptoms of psoriatic arthritis (tender and swollen joints, pain, physical function) in treated patients.
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 20mg twice daily, orally
DRUGApremilast 30mg
Apremilast 30mg twice daily, orally
DRUGPlacebo
Placebo
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
Subjects must satisfy the following criteria to be enrolled in the study: 1. Male or female, aged ≥ 18 years at time of consent. 2. Must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted. 3. Able to adhere to the study visit schedule and other protocol requirements. 4. Have a documented diagnosis of Psoriatic Arthritis (PsA, by any criteria) of ≥ 3 months duration. 5. Meet the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for PsA at time of screening. 6. Have ≥ 3 swollen AND ≥ 3 tender joints. 7. Have not been previously treated with disease-modifying antirheumatic drugs (DMARDS) (small molecules or biologics) 8. Be receiving treatment on an outpatient basis. 9. If taking oral corticosteroids, must be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 1 month prior to screening. 10. If taking nonsteroidal anti-inflammatory drugs (NSAIDs) or narcotic analgesics, must be on stable dose for at least 2 weeks prior to screening and until they have completed the Week 24 study visit. 11. Low potency topical corticosteroids (Appendix M or locally available equivalent) will be allowed as background therapy for treatment of psoriasis on the face, axillae and groin in accordance with the manufacturers' suggested usage during the course of the study. Subjects with scalp psoriasis will be permitted to use coal tar shampoo and/or salicylic acid scalp preparations on scalp lesions. A non-medicated skin emollient (eg, Eucerin cream) will also be permitted for body lesions only. Subjects must not use these treatments within 24 hours prior to the clinic visit. 12. Meet the following laboratory criteria: * White blood cell count ≥ 3000/mm3 (≥ 3.0 x 109/L) and \< 14,000/mm3 (\< 14 x 109/L) * Platelet count ≥ 100,000/mm3 (≥ 100 x 109/L) * Serum creatinine ≤ 1.5 mg/dL(≤ 132.6 μmol/L) * Aspartate aminotransferase/Serum glutamic oxaloacetic transaminase (AST/SGOT) and Alanine aminotransferase/Serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2 x upper limit of normal (ULN) * Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L) * Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L) * Hemoglobin A1c ≤ 9.0% 13. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex condom or any nonlatex condom NOT made out of natural \[animal\] membrane \[eg, polyurethane\]) while on IP and for at least 28 days after the last dose of IP. 14. Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use 2 forms of contraception while on investigational product (IP) and for at least 28 days after the last dose of IP: one highly effective form (ie, hormonal, intrauterine device \[IUD\], tubal ligation, vasectomized partner) and one additional form (latex condom or any nonlatex condom NOT made out of natural \[animal\] membrane \[eg, polyurethane\], diaphragm, sponge). If one highly effective form of contraception cannot be used, then 2 forms of barrier contraception must be used, ie, latex condom or any nonlatex condom NOT made out of natural (animal) membrane (eg, polyurethane) with either of the following: sponge with spermicide or diaphragm with spermicide.
Exclusion criteria
1. History of clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major uncontrolled disease. 2. Any condition, including the presence of laboratory abnormalities that places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. 3. Clinically significant abnormality on 12-lead electrocardiography (ECG) at Screening. 4. Pregnant or breast feeding. 5. History of allergy to any component of the IP. 6. Hepatitis B surface antigen positive at screening. 7. Hepatitis C antibody positive at screening. 8. AST/SGOT and/or ALT/SGPT \> 1.5 x ULN and total bilirubin \> ULN or albumin \< lower limit of normal (LLN). 9. History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease). 10. Active tuberculosis or a history of incompletely treated tuberculosis. 11. Clinically significant abnormality based upon chest radiograph with at least PA view (radiograph must be taken within 12 weeks prior to Screening or during the Screening visit). An additional lateral view is strongly recommended but not required. 12. Active substance abuse or a history of substance abuse within 6 months prior to Screening. 13. Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening. Any treatment for such infections must have been completed at least 4 weeks prior to Screening. 14. Malignancy or history of malignancy (except for treated \[ie, cured\] basal cell or squamous cell in situ skin carcinomas and treated \[ie, cured\] cervical intraepithelial neoplasia \[CIN\] or carcinoma in situ of the cervix). 15. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization. 16. Erythrodermic, guttate, or pustular psoriasis. 17. Topical therapy for psoriasis, except as noted in the Inclusion Criteria, within 2 weeks of randomization (including but not limited to topical corticosteroids, topical retinoids or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin). 18. Rheumatic autoimmune disease other than PsA, including systemic lupus erythematosis (SLE), mixed connective tissue disease (MCTD), scleroderma, or polymyositis. 19. Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis (Appendix Q). 20. Prior history of or current inflammatory joint disease other than PsA (eg, gout, reactive arthritis, RA, ankylosing spondylitis, Lyme disease). 21. Prior use of disease modifying antirheumatic drugs (DMARDS; small molecules or biologics). 22. Use of the following systemic therapy(ies) within 4 weeks of randomization, including but not limited to corticosteroids (except as noted in inclusion criteria), oral retinoids and fumaric acid esters. 23. Use of phototherapy within 4 weeks of randomization (ie, UVB, PUVA). 24. Previous treatment with any cell depleting therapies, including investigational agents (eg, rituximab, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20). 25. Treatment with intravenous gamma globulin, plasmapheresis, or Prosorba® column within 6 months of baseline. 26. Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation. 27. Prior treatment with apremilast. 28. Use of any investigational drug within 4 weeks of randomization, or 5 pharmacokinetic/ pharmacodynamic half lives, if known (whichever is longer).
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 | 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. A participant was a responder if the following 3 criteria for improvement from baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. |
| Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 24 | Baseline and Week 24 | The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative changes from Baseline in the overall score indicate improvement in functional ability. |
| Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16 | Baseline and Week 16 | The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). SF-36 domain scores were first calculated to range from 0 to100 and then transformed to norm-based scores (the norm-based scores in the US general population have an average of 50 and a standard deviation of 10). Norm-based scores were used in analyses, with higher scores indicating a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement. |
| Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16 | Baseline and Week 16 | Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. |
| Change From Baseline in Patient's Assessment of Pain at Week 16 | Baseline and Week 16 | The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters. |
| Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16 | Baseline and Week 16 | The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. |
| Change From Baseline in Dactylitis Severity Score at Week 16 | Baseline to Week 16 | Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. |
| Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16 | Baseline and Week 16 | The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: \> 2.8 and ≤ 10 Moderate Disease Activity: \> 10 and ≤ 22 High Disease Activity: \> 22 |
| Change From Baseline in the Disease Activity Score (DAS28) After 16 Weeks of Treatment | Baseline and Week 16 | The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. |
| Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16 | Baseline and Week 16 | The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement. |
| Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 24 | Baseline and Week 24 | The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). SF-36 domain scores were first calculated to range from 0 to100 and then transformed to norm-based scores (the norm-based scores in the US general population have an average of 50 and a standard deviation of 10). Norm-based scores were used in analyses, with higher scores indicating a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement. |
| Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24 | Baseline and Week 24 | Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. |
| Change From Baseline in Participants Assessment of Pain at Week 24 | Baseline and Week 24 | The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters. |
| Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24 | Baseline and Week 24 | The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. |
| Change From Baseline in Dactylitis Severity Score at Week 24 | Baseline and Week 24 | Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. |
| Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 | Baseline and Week 24 | The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22. |
| Change From Baseline in Disease Activity Score (DAS 28) at Week 24 | Baseline and Week 24 | The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. |
| Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 | Baseline and Week 24 | The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement. |
| Percentage of Participants With ≥ 20% Improvement in Maastricht Ankylosing Spondylitis Entheses Score at Week 16 | Baseline and Week 16 | Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. |
| Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16 | Baseline and Week 16 | Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. |
| Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16 | Baseline and Week 16 | The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2 |
| 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 |
| Percentage of Participants With MASES Improvement ≥ 20% at Week 24 | Baseline and Week 24 | Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. |
| Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24 | Baseline and Week 24 | Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. |
| Percentage of Participants With Good or Moderate EULAR Response at Week 24 | Baseline and Week 24 | The EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on th DAS-28. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2 A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. |
| Percentage of Participants With a ACR 50 Response at Week 16 | Baseline and Week 16 | Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. |
| Percentage of Participants With a ACR 70 Response at Week 16 | Baseline and Week 16 | Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. |
| Percentage of Participants With a ACR 50 Response at Week 24 | Baseline and Week 24 | Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. |
| Percentage of Participants With a ACR 70 Response at Week 24 | Baseline and Week 24 | Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. |
| Percentage of Participants With Pre-existing Enthesopathy Whose Maastricht Ankylosing Spondylitis Entheses Score Improves to 0 at Week 16 | Baseline and Week 16 | Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. |
| Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves to 0 at Week 16 | Baseline and Week 16 | Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. |
| Percentage of Participants Achieving a MASES Score of Zero at Week 24 | Baseline and Week 24 | Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. |
| Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24 | Baseline and Week 24 | Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. |
| Percentage of Participants With a ACR 20 Response at Week 52 | Baseline and Week 52 | Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 20% improvement in 78 tender joint count; ≥ 20% improvement in 76 swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. |
| Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52 | Baseline and Week 52 | The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative changes from Baseline in the overall score indicate improvement in functional ability. |
| Change From Baseline in the SF-36v2 Physical Functioning Scale Score at Week 52 | Baseline and Week 52 | The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. |
| Percentage of Participants With a Modified PsARC Response at Week 52 | Baseline and Week 52 | Measure Description: Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. Two-sided 95% confidence interval is based on the Clopper-Pearson method. |
| Change From Baseline in the Participants Assessment of Pain Using the Visual Analog Scale at Week 52 | Baseline and Week 52 | The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters. |
| Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52 | Baseline and Week 52 | The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. |
| Change From Baseline in the CDAI Score at Week 52 | Baseline and Week 52 | The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: 28 tender joint count (TJC), 28 swollen joint count (SJC), Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: \> 2.8 and ≤ 10 Moderate Disease Activity: \> 10 and ≤ 22 High Disease Activity: \> 22. |
| Change From Baseline in the DAS28 at Week 52 | Baseline and Week 52 | The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. |
| Change From Baseline in the FACIT-Fatigue Scale Score at Week 52 | Baseline and Week 52 | The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement. |
| Percentage of Participants With MASES Improvement ≥ 20% at Week 52 | Baseline and Week 52 | Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 52 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method. |
| Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline by ≥ 1 at Week 52 | Baseline and Week 52 | Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method. |
| Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52 | Baseline and Week 52 | The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. A Good response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 A Moderate Response is defined as either: an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. Two-sided 95% confidence interval is based on the Clopper-Pearson method |
| Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 16 | Baseline and Week 16 | The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative changes from baseline in the overall score indicate improvement in functional ability. |
| Percentage of Participants With an ACR 70 Response at Week 52 | Baseline and Week 52 | A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 70% improvement in 78 tender joint count; ≥ 70% improvement in 76 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. |
| Percentage of Participants With Pre-existing Enthesopathy Whose MASES Improves From Baseline to 0 at Week 52 | Baseline and Week 52 | Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval was based on the Clopper-Pearson method. |
| Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline to 0 at Week 52 | Baseline and Week 52 | Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit and ranges from 0 to 20. Two-sided 95% confidence interval is based on the Clopper-Pearson method. |
| Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants (placebo participants who remained on placebo through week 24 and participants randomized to the APR 20 mg BID or APR 30 mg BID) | A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE is any AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or constitutes an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale: Mild: asymptomatic or with mild symptoms, Moderate: symptoms causing moderate discomfort or Severe: symptoms causing severe discomfort or pain. |
| Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Week 0 to Week 260; median duration of exposure to apremilast 20 mg BID was 168.93 weeks and 229.36 weeks for apremilast 30 mg BID | A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE is any AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or constitutes an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale: Mild: asymptomatic or with mild symptoms, Moderate: symptoms causing moderate discomfort or Severe: symptoms causing severe discomfort or pain. |
| Percentage of Participants With an ACR 50 Response at Week 52 | Baseline and Week 52 | Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 50% improvement in 78 tender joint count; ≥ 50% improvement in 76 swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: o Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. |
Countries
Australia, Belgium, Bulgaria, Canada, Czechia, Estonia, France, Hungary, Italy, Lithuania, New Zealand, Poland, Romania, Russia, South Korea, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted in 16 countries including the United States, Canada, Europe, New Zealand, Australia and Russia.
Pre-assignment details
This study consisted of a 24-week randomized, double-blind, placebo-controlled phase, a 28-week randomized, double-blind active treatment phase and a 4-year open-label safety phase, for an overall study duration of 5 years.
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). | 176 |
| Apremilast 20mg Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase. | 175 |
| Apremilast 30mg Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase. | 176 |
| Total | 527 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Active Treatment Phase (Week 25-52) | Adverse Event | 0 | 3 | 2 | 2 | 2 | 0 | 0 | 0 | 0 |
| Active Treatment Phase (Week 25-52) | Lack of Efficacy | 0 | 5 | 5 | 3 | 1 | 0 | 0 | 0 | 0 |
| Active Treatment Phase (Week 25-52) | Lost to Follow-up | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Active Treatment Phase (Week 25-52) | Non-compliance with Study Drug | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Active Treatment Phase (Week 25-52) | Other | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Active Treatment Phase (Week 25-52) | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Active Treatment Phase (Week 25-52) | Withdrawal by Subject | 0 | 11 | 2 | 0 | 0 | 1 | 1 | 0 | 0 |
| Long-term Safety Phase (Year 2) | Adverse Event | 0 | 2 | 7 | 0 | 0 | 0 | 0 | 1 | 1 |
| Long-term Safety Phase (Year 2) | Lack of Efficacy | 0 | 7 | 5 | 0 | 0 | 0 | 0 | 4 | 3 |
| Long-term Safety Phase (Year 2) | Miscellaneous | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Long-term Safety Phase (Year 2) | Noncompliance with study drug | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Long-term Safety Phase (Year 2) | Withdrawal by Subject | 0 | 13 | 12 | 0 | 0 | 0 | 0 | 3 | 2 |
| Long-term Safety Phase (Year 3) | Adverse Event | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 3 | 4 |
| Long-term Safety Phase (Year 3) | Lack of Efficacy | 0 | 2 | 4 | 0 | 0 | 0 | 0 | 1 | 2 |
| Long-term Safety Phase (Year 3) | Lost to Follow-up | 0 | 2 | 3 | 0 | 0 | 0 | 0 | 1 | 1 |
| Long-term Safety Phase (Year 3) | Miscellaneous | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Long-term Safety Phase (Year 3) | Noncompliance with Study Drug | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Long-term Safety Phase (Year 3) | Withdrawal by Subject | 0 | 2 | 8 | 0 | 0 | 0 | 0 | 2 | 4 |
| Long-term Safety Phase (Year 4) | Adverse Event | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Long-term Safety Phase (Year 4) | Lack of Efficacy | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Long-term Safety Phase (Year 4) | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Long-term Safety Phase (Year 4) | Miscellaneous | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Long-term Safety Phase (Year 4) | Withdrawal by Subject | 0 | 5 | 4 | 0 | 0 | 0 | 0 | 1 | 4 |
| Long-term Safety Phase (Year 5) | Adverse Event | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Long-term Safety Phase (Year 5) | Lack of Efficacy | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Long-term Safety Phase (Year 5) | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Long-term Safety Phase (Year 5) | Miscellaneous | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 1 | 1 |
| Long-term Safety Phase (Year 5) | Withdrawal by Subject | 0 | 6 | 2 | 0 | 0 | 0 | 0 | 0 | 1 |
| Placebo-controlled Phase (Week 0 - 24) | Adverse Event | 4 | 4 | 6 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo-controlled Phase (Week 0 - 24) | Lack of Efficacy | 1 | 3 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo-controlled Phase (Week 0 - 24) | Lost to Follow-up | 5 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo-controlled Phase (Week 0 - 24) | Non-compliance with Study Drug | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo-controlled Phase (Week 0 - 24) | Other | 1 | 2 | 0 | 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) | Randomization Error | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo-controlled Phase (Week 0 - 24) | Withdrawal by Subject | 8 | 4 | 10 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Apremilast 20mg | Apremilast 30mg | Total |
|---|---|---|---|---|
| Age, Continuous | 50.5 years STANDARD_DEVIATION 11.58 | 49.2 years STANDARD_DEVIATION 12 | 48.4 years STANDARD_DEVIATION 12.52 | 49.4 years STANDARD_DEVIATION 12.05 |
| Duration of Psoriatic Arthritis | 3.42 years STANDARD_DEVIATION 5.103 | 3.19 years STANDARD_DEVIATION 4.706 | 3.62 years STANDARD_DEVIATION 5.041 | 3.41 years STANDARD_DEVIATION 4.947 |
| Sex: Female, Male Female | 86 Participants | 95 Participants | 96 Participants | 277 Participants |
| Sex: Female, Male Male | 90 Participants | 80 Participants | 80 Participants | 250 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 | 30 / 176 | 51 / 175 | 65 / 175 | 121 / 252 | 24 / 122 | 141 / 252 |
| serious Total, serious adverse events | 5 / 176 | 3 / 175 | 1 / 175 | 35 / 252 | 5 / 122 | 36 / 252 |
Outcome results
Primary
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16
A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: -Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); -Patient's global assessment of disease activity (measured on a 100 mm VAS); -Physician's global assessment of disease activity (measured on a 100 mm VAS); -Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); -C-Reactive Protein.
Time frame: Baseline and Week 16
Population: Full analysis set consisting of all participants randomized as specified in the protocol; one participant randomized in error and not receiving any dose of investigational product was excluded. Participants who withdrew early or did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16 | 15.9 percentage of participants |
| Apremilast 20mg | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16 | 28.0 percentage of participants |
| Apremilast 30mg | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16 | 30.7 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: 0.006295% CI: [3.5, 20.7]Chi-squared
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: 0.00195% CI: [6.1, 23.5]Chi-squared
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). SF-36 domain scores were first calculated to range from 0 to100 and then transformed to norm-based scores (the norm-based scores in the US general population have an average of 50 and a standard deviation of 10). Norm-based scores were used in analyses, with higher scores indicating a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.
Time frame: Baseline and Week 16
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 | 0.01 units on a scale | Standard Error 0.588 |
| Apremilast 20mg | Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16 | 2.39 units on a scale | Standard Error 0.586 |
| Apremilast 30mg | Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16 | 3.19 units on a scale | Standard Error 0.59 |
p-value: 0.004395% CI: [0.75, 4.01]ANCOVA
p-value: 0.000295% CI: [1.55, 4.82]ANCOVA
Secondary
Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain 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). SF-36 domain scores were first calculated to range from 0 to100 and then transformed to norm-based scores (the norm-based scores in the US general population have an average of 50 and a standard deviation of 10). Norm-based scores were used in analyses, with higher scores indicating a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.
Time frame: Baseline and Week 24
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 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 24 | 0.16 units on a scale | Standard Error 0.609 |
| Apremilast 20mg | Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 24 | 2.13 units on a scale | Standard Error 0.605 |
| Apremilast 30mg | Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 24 | 3.88 units on a scale | Standard Error 0.611 |
95% CI: [0.28, 3.65]
95% CI: [2.02, 5.41]
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 0-76 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 | -1.98 units on a scale | Standard Error 0.77 |
| Apremilast 20mg | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16 | -6.89 units on a scale | Standard Error 0.763 |
| Apremilast 30mg | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16 | -7.63 units on a scale | Standard Error 0.768 |
95% CI: [-7.04, -2.78]
95% CI: [-7.78, -3.51]
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 | -2.23 units on a scale | Standard Error 0.807 |
| Apremilast 20mg | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 | -7.30 units on a scale | Standard Error 0.803 |
| Apremilast 30mg | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 | -7.36 units on a scale | Standard Error 0.81 |
95% CI: [-7.31, -2.84]
95% CI: [-7.38, -2.89]
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 to 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 | -1.0 units on a scale | Standard Error 0.25 |
| Apremilast 20mg | Change From Baseline in Dactylitis Severity Score at Week 16 | -1.9 units on a scale | Standard Error 0.25 |
| Apremilast 30mg | Change From Baseline in Dactylitis Severity Score at Week 16 | -1.7 units on a scale | Standard Error 0.26 |
95% CI: [-1.6, -0.2]
95% CI: [-1.4, 0]
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 | -1.0 units on a scale | Standard Error 0.26 |
| Apremilast 20mg | Change From Baseline in Dactylitis Severity Score at Week 24 | -2.0 units on a scale | Standard Error 0.26 |
| Apremilast 30mg | Change From Baseline in Dactylitis Severity Score at Week 24 | -1.7 units on a scale | Standard Error 0.27 |
95% CI: [-1.7, -0.3]
95% CI: [-1.4, 0.1]
Secondary
Change From Baseline in Disease Activity Score (DAS 28) 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 Disease Activity Score (DAS 28) at Week 24 | -0.22 units on a scale | Standard Error 0.084 |
| Apremilast 20mg | Change From Baseline in Disease Activity Score (DAS 28) at Week 24 | -0.69 units on a scale | Standard Error 0.084 |
| Apremilast 30mg | Change From Baseline in Disease Activity Score (DAS 28) at Week 24 | -0.68 units on a scale | Standard Error 0.084 |
p-value: <0.000195% CI: [-0.7, -0.23]ANCOVA
p-value: 0.000195% CI: [-0.69, -0.22]ANCOVA
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 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 | 0.012 units on a scale | Standard Error 0.035 |
| Apremilast 20mg | Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 16 | -0.156 units on a scale | Standard Error 0.0349 |
| Apremilast 30mg | Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 16 | -0.205 units on a scale | Standard Error 0.035 |
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: 0.000895% CI: [-0.265, -0.071]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: <0.000195% CI: [-0.314, -0.12]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 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 | 0.012 units on a scale | Standard Error 0.037 |
| Apremilast 20mg | Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 24 | -0.156 units on a scale | Standard Error 0.0368 |
| Apremilast 30mg | Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 24 | -0.207 units on a scale | Standard Error 0.0369 |
p-value: 0.001495% CI: [-0.271, -0.065]ANCOVA
p-value: <0.000195% CI: [-0.322, -0.117]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 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 | -0.21 units on a scale | Standard Deviation 0.45 |
| Apremilast 20mg | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52 | -0.25 units on a scale | Standard Deviation 0.533 |
| Apremilast 30mg | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52 | -0.32 units on a scale | Standard Deviation 0.559 |
| Apremilast 30 mg | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52 | -0.39 units on a scale | Standard Deviation 0.567 |
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 Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time frame: Baseline and Week 16
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 | -0.5 units on a scale | Standard Error 0.24 |
| Apremilast 20mg | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16 | -0.5 units on a scale | Standard Error 0.24 |
| Apremilast 30mg | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16 | -1.5 units on a scale | Standard Error 0.25 |
p-value: 0.769695% CI: [-0.8, 0.6]ANCOVA
p-value: 0.003895% CI: [-1.7, -0.3]ANCOVA
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 Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time frame: Baseline and Week 24
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 | -0.6 units on a scale | Standard Error 0.25 |
| Apremilast 20mg | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24 | -0.9 units on a scale | Standard Error 0.25 |
| Apremilast 30mg | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24 | -1.5 units on a scale | Standard Error 0.26 |
95% CI: [-1, 0.4]
95% CI: [-1.6, -0.2]
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 Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time frame: Baseline and Week 52
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 | -1.7 units on a scale | Standard Deviation 2.38 |
| Apremilast 20mg | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52 | -1.8 units on a scale | Standard Deviation 2.34 |
| Apremilast 30mg | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52 | -1.5 units on a scale | Standard Deviation 2.62 |
| Apremilast 30 mg | Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52 | -1.8 units on a scale | Standard Deviation 3.03 |
Secondary
Change From Baseline in Participants 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 Participants Assessment of Pain at Week 24 | -3.8 mm | Standard Error 1.83 |
| Apremilast 20mg | Change From Baseline in Participants Assessment of Pain at Week 24 | -9.4 mm | Standard Error 1.82 |
| Apremilast 30mg | Change From Baseline in Participants Assessment of Pain at Week 24 | -9.6 mm | Standard Error 1.83 |
95% CI: [-10.6, -0.5]
95% CI: [-10.8, -0.7]
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 | -2.6 mm | Standard Error 1.81 |
| Apremilast 20mg | Change From Baseline in Patient's Assessment of Pain at Week 16 | -7.7 mm | Standard Error 1.79 |
| Apremilast 30mg | Change From Baseline in Patient's Assessment of Pain at Week 16 | -10.5 mm | Standard Error 1.8 |
p-value: 0.048595% CI: [-10, 0]ANCOVA
p-value: 0.002295% CI: [-12.8, -2.8]ANCOVA
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 | -11.0 units on a scale | Standard Deviation 10.288 |
| Apremilast 20mg | Change From Baseline in the CDAI Score at Week 52 | -14.67 units on a scale | Standard Deviation 11.943 |
| Apremilast 30mg | Change From Baseline in the CDAI Score at Week 52 | -14.32 units on a scale | Standard Deviation 11.128 |
| Apremilast 30 mg | Change From Baseline in the CDAI Score at Week 52 | -13.98 units on a scale | Standard Deviation 10.541 |
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 | -2.2 units on a scale | Standard Deviation 1.89 |
| Apremilast 20mg | Change From Baseline in the Dactylitis Severity Score at Week 52 | -2.9 units on a scale | Standard Deviation 2.47 |
| Apremilast 30mg | Change From Baseline in the Dactylitis Severity Score at Week 52 | -2.2 units on a scale | Standard Deviation 4.09 |
| Apremilast 30 mg | Change From Baseline in the Dactylitis Severity Score at Week 52 | -2.9 units on a scale | Standard Deviation 3.55 |
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 | -1.08 units on a scale | Standard Deviation 1.113 |
| Apremilast 20mg | Change From Baseline in the DAS28 at Week 52 | -1.28 units on a scale | Standard Deviation 1.044 |
| Apremilast 30mg | Change From Baseline in the DAS28 at Week 52 | -1.37 units on a scale | Standard Deviation 1.128 |
| Apremilast 30 mg | Change From Baseline in the DAS28 at Week 52 | -1.39 units on a scale | Standard Deviation 0.97 |
Secondary
Change From Baseline in the Disease Activity Score (DAS28) After 16 Weeks of Treatment
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time frame: Baseline and Week 16
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) After 16 Weeks of Treatment | -0.15 units on a scale | Standard Error 0.076 |
| Apremilast 20mg | Change From Baseline in the Disease Activity Score (DAS28) After 16 Weeks of Treatment | -0.61 units on a scale | Standard Error 0.076 |
| Apremilast 30mg | Change From Baseline in the Disease Activity Score (DAS28) After 16 Weeks of Treatment | -0.68 units on a scale | Standard Error 0.075 |
p-value: <0.000195% CI: [-0.67, -0.25]ANCOVA
p-value: <0.000195% CI: [-0.74, -0.32]ANCOVA
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 | 6.03 units on a scale | Standard Deviation 8.787 |
| Apremilast 20mg | Change From Baseline in the FACIT-Fatigue Scale Score at Week 52 | 4.27 units on a scale | Standard Deviation 9.461 |
| Apremilast 30mg | Change From Baseline in the FACIT-Fatigue Scale Score at Week 52 | 2.39 units on a scale | Standard Deviation 10.197 |
| Apremilast 30 mg | Change From Baseline in the FACIT-Fatigue Scale Score at Week 52 | 5.89 units on a scale | Standard Deviation 10.471 |
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 | 0.07 units on a scale | Standard Error 0.631 |
| Apremilast 20mg | Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16 | 1.19 units on a scale | Standard Error 0.629 |
| Apremilast 30mg | Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16 | 2.62 units on a scale | Standard Error 0.0633 |
95% CI: [-0.63, 2.87]
95% CI: [0.8, 4.31]
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 | 0.25 units on a scale | Standard Error 0.652 |
| Apremilast 20mg | Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 | 1.37 units on a scale | Standard Error 0.648 |
| Apremilast 30mg | Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 | 2.58 units on a scale | Standard Error 0.655 |
95% CI: [-0.68, 2.93]
95% CI: [0.52, 4.15]
Secondary
Change From Baseline in the Participants Assessment of Pain Using the Visual Analog Scale 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 Participants Assessment of Pain Using the Visual Analog Scale at Week 52 | -13.1 mm | Standard Deviation 25.57 |
| Apremilast 20mg | Change From Baseline in the Participants Assessment of Pain Using the Visual Analog Scale at Week 52 | -18.9 mm | Standard Deviation 24.28 |
| Apremilast 30mg | Change From Baseline in the Participants Assessment of Pain Using the Visual Analog Scale at Week 52 | -15.6 mm | Standard Deviation 27.29 |
| Apremilast 30 mg | Change From Baseline in the Participants Assessment of Pain Using the Visual Analog Scale at Week 52 | -14.2 mm | Standard Deviation 28.14 |
Secondary
Change From Baseline in the SF-36v2 Physical Functioning Scale Score 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-36v2 Physical Functioning Scale Score at Week 52 | 7.76 units on a scale | Standard Deviation 8.236 |
| Apremilast 20mg | Change From Baseline in the SF-36v2 Physical Functioning Scale Score at Week 52 | 6.87 units on a scale | Standard Deviation 7.241 |
| Apremilast 30mg | Change From Baseline in the SF-36v2 Physical Functioning Scale Score at Week 52 | 5.68 units on a scale | Standard Deviation 8.467 |
| Apremilast 30 mg | Change From Baseline in the SF-36v2 Physical Functioning Scale Score at Week 52 | 5.87 units on a scale | Standard Deviation 8.008 |
Secondary
Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period
A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE is any AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or constitutes an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale: Mild: asymptomatic or with mild symptoms, Moderate: symptoms causing moderate discomfort or Severe: symptoms causing severe discomfort or pain.
Time frame: Week 0 to Week 260; median duration of exposure to apremilast 20 mg BID was 168.93 weeks and 229.36 weeks for apremilast 30 mg BID
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 (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any TEAE | 188 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any Drug-Related TEAE | 89 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any Severe TEAE | 24 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any Serious TEAE (SAE) | 35 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Drug-Related (SAE) | 6 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any TEAE Leading to Drug Interruption | 41 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any TEAE Leading to Drug Wirhdrawal | 22 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any TEAE Leading to Death | 0 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any Severe TEAE | 3 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any TEAE Leading to Drug Wirhdrawal | 2 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any Serious TEAE (SAE) | 5 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Drug-Related (SAE) | 1 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any TEAE Leading to Drug Interruption | 5 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any TEAE | 60 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any Drug-Related TEAE | 16 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any TEAE Leading to Death | 0 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any Severe TEAE | 23 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any Drug-Related TEAE | 113 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any TEAE | 204 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any Serious TEAE (SAE) | 36 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any TEAE Leading to Drug Wirhdrawal | 26 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any TEAE Leading to Drug Interruption | 36 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Drug-Related (SAE) | 6 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period | Any TEAE Leading to Death | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase
A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE is any AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or constitutes an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale: Mild: asymptomatic or with mild symptoms, Moderate: symptoms causing moderate discomfort or Severe: symptoms causing severe discomfort or pain.
Time frame: Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants (placebo participants who remained on placebo through week 24 and participants randomized to the APR 20 mg BID or APR 30 mg BID)
Population: Safety population included participants who were randomized and received at least one dose of IP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any TEAE | 73 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any Drug-Related TEAE | 25 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any Severe TEAE | 6 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any Serious TEAE (SAE) | 5 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Drug-Related (SAE) | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any TEAE Leading to Drug Interruption | 8 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any TEAE Leading to Drug Withdrawal | 4 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any TEAE Leading to Death | 0 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any Severe TEAE | 4 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any TEAE Leading to Drug Withdrawal | 4 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any Serious TEAE (SAE) | 3 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Drug-Related (SAE) | 0 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any TEAE Leading to Drug Interruption | 11 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any TEAE | 87 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any Drug-Related TEAE | 40 Participants |
| Apremilast 20mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any TEAE Leading to Death | 0 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any Severe TEAE | 2 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any Drug-Related TEAE | 58 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any TEAE | 99 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any Serious TEAE (SAE) | 1 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any TEAE Leading to Drug Withdrawal | 6 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any TEAE Leading to Drug Interruption | 9 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Drug-Related (SAE) | 1 Participants |
| Apremilast 30mg | Number of Participants With Treatment Emergent Adverse Events During the Placebo Controlled Phase | Any TEAE Leading to Death | 0 Participants |
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: 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 Achieving a Dactylitis Score of Zero at Week 24 | 35.6 percentage of participants |
| Apremilast 20mg | Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24 | 46.1 percentage of participants |
| Apremilast 30mg | Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24 | 40.5 percentage of participants |
95% CI: [-3.8, 24.8]
95% CI: [-9.5, 19.3]
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 Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time frame: Baseline and Week 24
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 | 22.6 percentage of participants |
| Apremilast 20mg | Percentage of Participants Achieving a MASES Score of Zero at Week 24 | 29.1 percentage of participants |
| Apremilast 30mg | Percentage of Participants Achieving a MASES Score of Zero at Week 24 | 37.8 percentage of participants |
95% CI: [-4.8, 17.7]
95% CI: [3.4, 27.1]
Secondary
Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52
The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. A Good response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 A Moderate Response is defined as either: an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. Two-sided 95% confidence interval is based on the Clopper-Pearson method
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 | 64.5 Percentage of Participants |
| Apremilast 20mg | Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52 | 73.5 Percentage of Participants |
| Apremilast 30mg | Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52 | 75.4 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52 | 79.0 Percentage of Participants |
Secondary
Percentage of Participants With ≥ 20% Improvement in Maastricht Ankylosing Spondylitis Entheses Score 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 Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time frame: Baseline and Week 16
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 ≥ 20% Improvement in Maastricht Ankylosing Spondylitis Entheses Score at Week 16 | 46.1 percentage of participants |
| Apremilast 20mg | Percentage of Participants With ≥ 20% Improvement in Maastricht Ankylosing Spondylitis Entheses Score at Week 16 | 48.7 percentage of participants |
| Apremilast 30mg | Percentage of Participants With ≥ 20% Improvement in Maastricht Ankylosing Spondylitis Entheses Score at Week 16 | 63.1 percentage of participants |
95% CI: [-10.2, 15.5]
95% CI: [4.2, 29.8]
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. 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 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 | 59.7 Percentage of Participants |
| Apremilast 20mg | Percentage of Participants With a ACR 20 Response at Week 52 | 56.7 Percentage of Participants |
| Apremilast 30mg | Percentage of Participants With a ACR 20 Response at Week 52 | 53.4 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants With a ACR 20 Response at Week 52 | 58.7 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 | 4.5 Percentage of participants |
| Apremilast 20mg | Percentage of Participants With a ACR 50 Response at Week 16 | 11.4 Percentage of participants |
| Apremilast 30mg | Percentage of Participants With a ACR 50 Response at Week 16 | 11.4 Percentage of participants |
95% CI: [1.3, 12.5]
95% CI: [1.2, 12.4]
Secondary
Percentage of Participants With a 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 a ACR 50 Response at Week 24 | 6.3 percentage of participants |
| Apremilast 20mg | Percentage of Participants With a ACR 50 Response at Week 24 | 16.0 percentage of participants |
| Apremilast 30mg | Percentage of Participants With a ACR 50 Response at Week 24 | 12.5 percentage of participants |
95% CI: [3.2, 16.3]
95% CI: [0.2, 12.3]
Secondary
Percentage of Participants With a 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 a ACR 70 Response at Week 16 | 1.1 percentage of participants |
| Apremilast 20mg | Percentage of Participants With a ACR 70 Response at Week 16 | 4.0 percentage of participants |
| Apremilast 30mg | Percentage of Participants With a ACR 70 Response at Week 16 | 4.0 percentage of participants |
95% CI: [-0.4, 6.2]
95% CI: [-0.4, 6.1]
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 | 4.0 percentage of participants |
| Apremilast 20mg | Percentage of Participants With a ACR 70 Response at Week 24 | 4.0 percentage of participants |
| Apremilast 30mg | Percentage of Participants With a ACR 70 Response at Week 24 | 4.5 percentage of participants |
95% CI: [-4.1, 4.1]
95% CI: [-3.7, 4.8]
Secondary
Percentage of Participants With a Modified PsARC Response at Week 52
Measure Description: Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
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 20mg | Percentage of Participants With a Modified PsARC Response at Week 52 | 79.1 Percentage of Participants |
| Apremilast 30mg | Percentage of Participants With a Modified PsARC Response at Week 52 | 75.6 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants With a Modified PsARC Response at Week 52 | 75.9 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=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS.
Time frame: Baseline and Week 16
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 | 24.4 percentage of participants |
| Apremilast 20mg | Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16 | 38.9 percentage of participants |
| Apremilast 30mg | Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16 | 45.5 percentage of participants |
p-value: 0.003795% CI: [4.8, 24]Chi-squared
p-value: <0.000195% CI: [11.3, 30.7]Chi-squared
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=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS.
Time frame: Baseline and Week 24
Population: Full analysis set; Participants who discontinued early, escaped early at Week 16, or who did not have sufficient data for a determination of response status at Week 24 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24 | 17.0 percentage of participants |
| Apremilast 20mg | Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24 | 36.6 percentage of participants |
| Apremilast 30mg | Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24 | 35.2 percentage of participants |
95% CI: [10.5, 28.6]
95% CI: [9.2, 27.2]
Secondary
Percentage of Participants With an ACR 20 Response at Week 24
Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein.
Time frame: Baseline and Week 24
Population: Full analysis set; Participants who discontinued early, escaped at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an ACR 20 Response at Week 24 | 13.1 percentage of participants |
| Apremilast 20mg | Percentage of Participants With an ACR 20 Response at Week 24 | 29.1 percentage of participants |
| Apremilast 30mg | Percentage of Participants With an ACR 20 Response at Week 24 | 24.4 percentage of participants |
p-value: 0.000295% CI: [7.7, 24.4]Chi-squared
p-value: 0.006395% CI: [3.3, 19.4]Chi-squared
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: o Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time frame: Baseline and Week 52
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 an ACR 50 Response at Week 52 | 30.6 Percentage of Participants |
| Apremilast 20mg | Percentage of Participants With an ACR 50 Response at Week 52 | 25.4 Percentage of Participants |
| Apremilast 30mg | Percentage of Participants With an ACR 50 Response at Week 52 | 27.1 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants With an ACR 50 Response at Week 52 | 31.9 Percentage of Participants |
Secondary
Percentage of Participants With an ACR 70 Response at Week 52
A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 70% improvement in 78 tender joint count; ≥ 70% improvement in 76 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
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 | 8.2 Percentage of Participants |
| Apremilast 20mg | Percentage of Participants With an ACR 70 Response at Week 52 | 10.3 Percentage of Participants |
| Apremilast 30mg | Percentage of Participants With an ACR 70 Response at Week 52 | 13.7 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants With an ACR 70 Response at Week 52 | 18.1 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 | 60.0 percentage of participants |
| Apremilast 20mg | Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16 | 66.3 percentage of participants |
| Apremilast 30mg | Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16 | 61.9 percentage of participants |
95% CI: [-7.8, 20.4]
95% CI: [-12.6, 16.4]
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 | 57.8 percentage of participants |
| Apremilast 20mg | Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24 | 69.7 percentage of participants |
| Apremilast 30mg | Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24 | 63.1 percentage of participants |
95% CI: [-2.1, 25.9]
95% CI: [-9.2, 19.8]
Secondary
Percentage of Participants With Good or Moderate EULAR Response at Week 24
The EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on th DAS-28. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2 A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2.
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 | 17.0 percentage of participants |
| Apremilast 20mg | Percentage of Participants With Good or Moderate EULAR Response at Week 24 | 34.9 percentage of participants |
| Apremilast 30mg | Percentage of Participants With Good or Moderate EULAR Response at Week 24 | 28.4 percentage of participants |
95% CI: [8.8, 26.8]
95% CI: [2.7, 20]
Secondary
Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16
The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2
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 | 25.0 percentage of participants |
| Apremilast 20mg | Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16 | 41.1 percentage of participants |
| Apremilast 30mg | Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16 | 44.3 percentage of participants |
95% CI: [6.4, 25.8]
95% CI: [9.6, 29.1]
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 Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time frame: Baseline and Week 24
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 | 48.7 percentage of participants |
| Apremilast 20mg | Percentage of Participants With MASES Improvement ≥ 20% at Week 24 | 54.7 percentage of participants |
| Apremilast 30mg | Percentage of Participants With MASES Improvement ≥ 20% at Week 24 | 66.7 percentage of participants |
95% CI: [-6.8, 18.8]
95% CI: [5.3, 30.6]
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 Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time frame: Baseline and Week 52
Population: The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a baseline MASES \> 0 (i.e., pre-existing enthesopathy) and who had sufficient data for a definitive determination of response status at Week 52 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With MASES Improvement ≥ 20% at Week 52 | 70.7 Percentage of Participants |
| Apremilast 20mg | Percentage of Participants With MASES Improvement ≥ 20% at Week 52 | 81.0 Percentage of Participants |
| Apremilast 30mg | Percentage of Participants With MASES Improvement ≥ 20% at Week 52 | 65.9 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants With MASES Improvement ≥ 20% at Week 52 | 69.4 Percentage of Participants |
Secondary
Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline by ≥ 1 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 Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline by ≥ 1 at Week 52 | 93.8 Percentage of Participants |
| Apremilast 20mg | Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline by ≥ 1 at Week 52 | 94.7 Percentage of Participants |
| Apremilast 30mg | Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline by ≥ 1 at Week 52 | 87.1 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline by ≥ 1 at Week 52 | 85.9 Percentage of Participants |
Secondary
Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline to 0 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 and ranges from 0 to 20. 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 Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline to 0 at Week 52 | 75.0 Percentage of Participants |
| Apremilast 20mg | Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline to 0 at Week 52 | 78.9 Percentage of Participants |
| Apremilast 30mg | Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline to 0 at Week 52 | 68.6 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline to 0 at Week 52 | 68.8 Percentage of Participants |
Secondary
Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves to 0 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: 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 Pre-existing Dactylitis Whose Dactylitis Severity Score Improves to 0 at Week 16 | 33.3 percentage of participants |
| Apremilast 20mg | Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves to 0 at Week 16 | 42.7 percentage of participants |
| Apremilast 30mg | Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves to 0 at Week 16 | 40.5 percentage of participants |
95% CI: [-4.8, 23.5]
95% CI: [-7.2, 21.5]
Secondary
Percentage of Participants With Pre-existing Enthesopathy Whose Maastricht Ankylosing Spondylitis Entheses Score Improves to 0 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 Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time frame: Baseline and Week 16
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 Pre-existing Enthesopathy Whose Maastricht Ankylosing Spondylitis Entheses Score Improves to 0 at Week 16 | 19.1 percentage of participants |
| Apremilast 20mg | Percentage of Participants With Pre-existing Enthesopathy Whose Maastricht Ankylosing Spondylitis Entheses Score Improves to 0 at Week 16 | 21.4 percentage of participants |
| Apremilast 30mg | Percentage of Participants With Pre-existing Enthesopathy Whose Maastricht Ankylosing Spondylitis Entheses Score Improves to 0 at Week 16 | 36.9 percentage of participants |
95% CI: [-8.1, 12.6]
95% CI: [6.3, 29.3]
Secondary
Percentage of Participants With Pre-existing Enthesopathy Whose MASES Improves From Baseline to 0 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 Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval was based on the Clopper-Pearson method.
Time frame: Baseline and Week 52
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 With Pre-existing Enthesopathy Whose MASES Improves From Baseline to 0 at Week 52 | 39.0 percentage of participants |
| Apremilast 20mg | Percentage of Participants With Pre-existing Enthesopathy Whose MASES Improves From Baseline to 0 at Week 52 | 61.9 percentage of participants |
| Apremilast 30mg | Percentage of Participants With Pre-existing Enthesopathy Whose MASES Improves From Baseline to 0 at Week 52 | 39.6 percentage of participants |
| Apremilast 30 mg | Percentage of Participants With Pre-existing Enthesopathy Whose MASES Improves From Baseline to 0 at Week 52 | 45.9 percentage of participants |