A Phase 2 interventional study of Apremilast 30 mg and Apremilast 20 mg in Rheumatoid Arthritis, sponsored by Amgen. Terminated at 50 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-05-08.
Sponsored by Amgen · Phase 2, Interventional, and Treatment
The purpose of this study is to determine whether Apremilast is safe and effective in the treatment of patients with rheumatoid arthritis, specifically in improving signs and symptoms of rheumatoid arthritis (tender and swollen joints, pain, physical function and structure) in treated patients who have had an inadequate response to Methotrexate.
3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.
This study's enrollment of 237 is above the median of 90 across 2,377 interventional studies indexed under Arthritis.
Browse Arthritis studies →Amgen is the lead sponsor of 1,015 studies on the registry; 49 are open to participants now.
Of its 245 completed or terminated interventional studies of FDA-regulated products, 159 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Must have active disease despite current methotrexate treatment as defined below:
≥ 6 tender joints (68 tender joint count)
-. Must meet at least one of the four lab requirements below:
For participants participating in the Magnetic Resonance Imaging (MRI) assessment:
Must have been treated with methotrexate for at least 4 months prior to randomization, and must be on stable dose. Participants will be required to maintain their stable dose through Week 52 of the study. Oral folate (folic acid) supplementation is required with a minimum dose of 5 mg/week, or instead leucovorin may be used up to 10 mg/week orally.
Must meet the following laboratory criteria at screening:
Exclusion Criteria:
For Magnetic Resonance Imaging (MRI) Only:
Drug: Apremilast 30 mg
Drug: Apremilast 20 mg · Drug: Placebo
Drug: Placebo
30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Also known as: CC-10004
20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Oral Placebo tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in active treatment / active treatment extension phase. Participants who are nonresponders will advance early to 20 mg Apremilast BID at Week 16.
Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 16
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein.
Time frame: Baseline and Week 16
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time frame: Baseline and Week 16
Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 24
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein
Time frame: Baseline and Week 24
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 24
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time frame: Baseline and Week 24
Change From Baseline in the Medical Outcome Study Short Form 36-item (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). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.
Time frame: Baseline and Week 16
Change From Baseline in the 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), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22
Time frame: Baseline and Week 16
Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 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), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22
Time frame: Baseline and Week 16
Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Week 16
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count (TJC28) * 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; * C-reactive protein (CRP) * Subject's global assessment of disease activity (SGA ) DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time frame: Baseline and Week 16
Percentage Change From Baseline in the Tender Joint Count at Week 16
Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time frame: Baseline and Week 16
Percentage Change From Baseline in the Swollen Joint Count at Week 16
Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time frame: Baseline and Week 16
Percentage Change From Baseline in the Subject Assessment of Pain at Week 16
The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time frame: Baseline and Week 16
Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 16
The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time frame: Baseline and Week 16
Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 16
The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time frame: Baseline and Week 16
Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 16
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time frame: Baseline and Week 16
Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 16
C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.
Time frame: Baseline and Week 16
Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 16
The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.
Time frame: Baseline and Week 16
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Time frame: Baseline and Week 16
Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time frame: Baseline and Week 16
Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 16
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Time frame: Baseline and Week 16
Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 16
EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2
Time frame: Baseline and Week 16
Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 16
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[(HAQ-DI)\]); C-Reactive Protein.
Time frame: Baseline and Week 16
Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 16
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein
Time frame: Baseline and Week 16
Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 24
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[(HAQ-DI)\]); C-Reactive Protein.
Time frame: Baseline and Week 24
Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 24
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[(HAQ-DI)\]); C-Reactive Protein.
Time frame: Baseline and Week 24
Change From Baseline in the Medical Outcome Study Short Form 36-item (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). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.
Time frame: Baseline and Week 24
Change From Baseline in the 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), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity.The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22
Time frame: Baseline and Week 24
Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 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), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity.The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22
Time frame: Baseline and Week 24
Change From Baseline in Disease Activity Score 28 (DAS28) Using CRP 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) * Subject's Global Assessment of Disease Activity. DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time frame: Baseline and Week 24
Percentage Change From Baseline in the Tender Joint Count at Week 24
Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time frame: Baseline and Week 24
Percentage Change From Baseline in the Swollen Joint Count at Week 24
Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time frame: Baseline and Week 24
Percentage Change From Baseline in the Subject Assessment of Pain at Week 24
The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time frame: Baseline and Week 24
Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 24
The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time frame: Baseline and Week 24
Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 24
The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time frame: Baseline and Week 24
Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time frame: Baseline and Week 24
Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 24
C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.
Time frame: Baseline and Week 24
Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24
The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.
Time frame: Baseline and Week 24
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Time frame: Baseline and Week 24
Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time frame: Baseline and Week 24
Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 24
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
Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 24
EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2
Time frame: Baseline and Week 24
Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 52
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein.
Time frame: Baseline and Week 52
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time frame: Baseline and Week 52
Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 52
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.
Time frame: Baseline and Week 52
Change From Baseline in the Clinical Disease Activity Index (CDAI) 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), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22
Time frame: Baseline and Week 52
Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 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), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS),, where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22
Time frame: Baseline and Week 52
Change From Baseline in the Disease Activity Score 28 (DAS 28) Using CRP 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 (TJC28) * 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; * C-reactive protein (CRP) * Subject's global assessment of disease activity (SGA). DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time frame: Baseline and Week 52
Percentage Change From Baseline in the Tender Joint Count at Week 52
Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time frame: Baseline and Week 52
Percentage Change From Baseline in the Swollen Joint Count at Week 52
Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time frame: Baseline and Week 52
Percentage Change From Baseline in the Subject Assessment of Pain at Week 52
The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time frame: Baseline and Week 52
Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 52
The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time frame: Baseline and Week 52
Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 52
The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time frame: Baseline and Week 52
Percentage Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 52
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time frame: Baseline and Week 52
Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 52
C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.
Time frame: Baseline and Week 52
Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52
The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.
Time frame: Baseline and Week 52
Change From Baseline in the FACIT-Fatigue Scale Score at Week 52
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Time frame: Baseline and Week 52
Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 52
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time frame: Baseline and Week 52
Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 52
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[(HAQ-DI)\]); C-Reactive Protein.
Time frame: Baseline and Week 52
Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 52
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein
Time frame: Baseline and Week 52
Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Week 52
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
Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP 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. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2
Time frame: Baseline and Week 52
Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Year 2
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time frame: Baseline and Year 2
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Year 2
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time frame: Baseline and Year 2
Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Year 2
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) was a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time frame: Baseline and Year 2
Change From Baseline in the Clinical Disease Activity Index (CDAI) at Year 2
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: \> 2.8 and ≤ 10 Moderate Disease Activity: \> 10 and ≤ 22 High Disease Activity: \> 22 The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time frame: Baseline and Year 2
Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Year 2
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: \> 2.8 and ≤ 10 Moderate Disease Activity: \> 10 and ≤ 22 High Disease Activity: \> 22 The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time frame: Baseline and Year 2
Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Year 2
The DAS 28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count (TJC28) * 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; * C-reactive protein (CRP) * Subject's global assessment of disease activity (SGA ). A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time frame: Baseline and Year 2
Percentage Change From Baseline in the Individual American College of Rheumatology Components at Year 2
The Individual ACR Components were defined as follows: 1. Tender Joint Count (out of 68 joints) 2. Swollen Joint Count (out of 66 joints) 3. Subject Assessment of Pain (0 to 100 mm VAS) 4. Subject Global Assessment of Disease Activity (0 to 100 mm VAS) 5. Physician Global Assessment of Disease Activity (0 to 100 mm VAS) 6. HAQ-DI Score 7. Acute Phase Reactant High Sensitivity C-Reactive Protein (hsCRP, mg/dL) Erythrocyte Sedimentation Rate (ESR) The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time frame: Baseline and Year 2
Change From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Year 2
The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time frame: Baseline and Year 2
Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Year 2
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time frame: Baseline and Year 2
Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Year 2
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[(HAQ-DI)\]); C-Reactive Protein. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time frame: Baseline and Year 2
Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Year 2
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time frame: Baseline and Year 2
Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Year 2
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time frame: Baseline and Year 2
Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Year 2
EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2 The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time frame: Baseline and Year 2
A total of 302 subjects were screened for inclusion in this study, and 237 participants randomized in parallel in a 1:1:1 ratio to treatment groups. The first participant was enrolled on 27 December 2010; the last participant completed week 24 visit on 23 February 2012.
| Milestone | Placebo | Apremilast 20 mg | Apremilast 30 mg | Placebo/Apremilast 20mg EE | Placebo / Apremilast 20 mg XO |
|---|---|---|---|---|---|
| Started | 79 | 82 | 76 | 0 | 0 |
| Completed | 70 | 67 | 61 | 0 | 0 |
| Not completed | 9 | 15 | 15 | 0 | 0 |
| Withdrew: Adverse event | 3 | 4 | 6 | 0 | 0 |
| Withdrew: Lack of efficacy | 1 | 7 | 3 | 0 | 0 |
| Withdrew: Non-compliance | 1 | 0 | 2 | 0 | 0 |
| Withdrew: Withdrawal by subject | 3 | 3 | 2 | 0 | 0 |
| Withdrew: Lost to follow-up | 0 | 1 | 1 | 0 | 0 |
| Withdrew: Other | 1 | 0 | 1 | 0 | 0 |
| Milestone | Placebo | Apremilast 20 mg | Apremilast 30 mg | Placebo/Apremilast 20mg EE | Placebo / Apremilast 20 mg XO |
|---|---|---|---|---|---|
| Started | 0 | 63 | 60 | 27 | 42 |
| Completed | 0 | 31 | 34 | 17 | 23 |
| Not completed | 0 | 32 | 26 | 10 | 19 |
| Withdrew: Adverse event | 0 | 2 | 3 | 0 | 2 |
| Withdrew: Lack of efficacy | 0 | 4 | 3 | 1 | 0 |
| Withdrew: Withdrawal by subject | 0 | 3 | 0 | 2 | 2 |
| Withdrew: Study termination by sponsor | 0 | 21 | 19 | 6 | 15 |
| Withdrew: Other | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Non-compliance | 0 | 1 | 1 | 1 | 0 |
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein.
| percentage of participants | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 16 | 35.4 | 28 (-27.7 to 7.0) | 34.2 (-16.2 to 13.8) |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
| units on a scale | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16 | -0.106 ± 0.4173 | -0.114 ± 0.5036 | -0.209 ± 0.4469 |
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein
| percentage of participants | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 24 | 24.1 | 19.5 | 27.6 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
| units on a scale | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 24 | -0.069 ± 0.4328 | -0.080 ± 0.4653 | -0.227 ± 0.4910 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.
| units on a scale | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 16 | 1.48 ± 6.937 | 1.64 ± 7.036 | 3.33 ± 6.970 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22
| units on a scale | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 16 | -11.52 ± 14.850 | -9.49 ± 12.998 | -11.38 ± 13.230 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22
| percentage of participants | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 16 | 17.7 | 12.2 | 10.5 |
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count (TJC28) * 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; * C-reactive protein (CRP) * Subject's global assessment of disease activity (SGA ) DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
| units on a scale | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Week 16 | -0.90 ± 1.272 | -0.73 ± 1.079 | -0.90 ± 1.168 |
Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in the Tender Joint Count at Week 16 | -33.08 ± 5.154 | -26.92 ± 5.058 | -33.68 ± 5.221 |
Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in the Swollen Joint Count at Week 16 | -36.96 ± 5.432 | -34.38 ± 5.328 | -40.22 ± 5.502 |
The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in the Subject Assessment of Pain at Week 16 | 30.50 ± 16.584 | -5.03 ± 16.369 | -7.87 ± 16.800 |
The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 16 | 10.84 ± 10.004 | -3.50 ± 9.872 | 11.19 ± 10.131 |
The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 16 | -28.82 ± 4.478 | -28.22 ± 4.440 | -32.66 ± 4.540 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 16 | -9.43 ± 5.307 | -3.50 ± 5.234 | -10.20 ± 5.416 |
C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 16 | 41.99 ± 30.559 | 46.69 ± 30.027 | 100.04 ± 31.127 |
The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 16 | 6.81 ± 10.633 | 13.98 ± 10.522 | -9.39 ± 10.681 |
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
| units on a scale | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16 | 2.7 ± 0.96 | 1.5 ± 0.96 | 2.6 ± 0.98 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
| percentage of participants | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16 | 39.2 | 35.4 | 52.6 |
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
| percentage of participants | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 16 | 39.2 | 35.4 | 42.1 |
EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2
| percentage of participants | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 16 | 46.8 | 41.5 | 44.7 |
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[(HAQ-DI)\]); C-Reactive Protein.
| percentage of participants | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 16 | 11.4 | 4.9 | 9.2 |
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein
| percent of participants | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 16 | 2.5 | 1.2 | 0.0 |
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[(HAQ-DI)\]); C-Reactive Protein.
| percentage of participants | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 24 | 6.3 | 4.9 | 15.8 |
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[(HAQ-DI)\]); C-Reactive Protein.
| percentage of participants | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 24 | 3.8 | 2.4 | 5.3 |
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.
| units on a scale | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 24 | 1.78 ± 0.849 | 1.66 ± 0.850 | 3.76 ± 0.865 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity.The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22
| units on a scale | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 24 | -10.40 ± 1.597 | -9.46 ± 1.571 | -11.63 ± 1.602 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity.The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22
| percentage of participants | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 24 | 16.5 | 12.2 | 21.1 |
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count * 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; * C-reactive protein (CRP) * Subject's Global Assessment of Disease Activity. DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
| units on a scale | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Change From Baseline in Disease Activity Score 28 (DAS28) Using CRP at Week 24 | -0.82 ± 0.139 | -0.78 ± 0.137 | -0.91 ± 0.141 |
Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in the Tender Joint Count at Week 24 | -30.81 ± 5.909 | -26.21 ± 5.800 | -27.80 ± 5.987 |
Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in the Swollen Joint Count at Week 24 | -34.41 ± 5.876 | -32.56 ± 5.764 | -41.43 ± 5.952 |
The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in the Subject Assessment of Pain at Week 24 | 28.16 ± 16.111 | -6.66 ± 15.902 | -9.66 ± 16.320 |
The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 24 | 15.04 ± 8.566 | 0.70 ± 8.453 | 2.54 ± 8.675 |
The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 24 | -29.98 ± 4.740 | -24.13 ± 4.700 | -31.78 ± 4.805 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 | -6.59 ± 5.171 | -5.01 ± 5.100 | -12.30 ± 5.277 |
C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 24 | 39.14 ± 30.504 | 47.43 ± 29.972 | 106.22 ± 31.071 |
The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.
| percent change | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24 | -0.06 ± 9.531 | 11.99 ± 9.431 | -6.60 ± 9.573 |
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
| units on a scale | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 | 1.7 ± 1.01 | 0.5 ± 1.01 | 3.4 ± 1.03 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
| percentage of participants | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24 | 20.3 | 25.6 | 32.9 |
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 | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 24 | 26.6 | 14.6 | 26.3 |
EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2
| percentage of participants | Placebo | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|
| Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 24 | 40.5 | 29.3 | 35.5 |
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein.
| percentage of participants | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 52 | 47.8 (26.8 to 69.4) | 51.3 (34.8 to 67.6) | 30.9 (19.1 to 44.8) | 38.2 (25.4 to 52.3) |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
| units on a scale | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52 | -0.219 ± 0.4287 | -0.192 ± 0.4728 | -0.155 ± 0.5501 | -0.277 ± 0.4281 |
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.
| units on a scale | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 52 | 2.11 ± 6.959 | 3.50 ± 10.146 | 2.56 ± 9.978 | 5.23 ± 10.227 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22
| units on a scale | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 52 | -16.22 ± 8.722 | -20.70 ± 14.253 | -14.77 ± 14.220 | -17.68 ± 13.331 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS),, where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22
| percentage of participants | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 52 | 16.7 (4.7 to 37.4) | 41.0 (25.6 to 57.9) | 25.0 (14.4 to 38.4) | 27.3 (16.1 to 41.0) |
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count (TJC28) * 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; * C-reactive protein (CRP) * Subject's global assessment of disease activity (SGA). DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
| units on a scale | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Change From Baseline in the Disease Activity Score 28 (DAS 28) Using CRP at Week 52 | -1.18 ± 0.717 | -1.68 ± 1.243 | -1.10 ± 1.290 | -1.38 ± 1.264 |
Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
| percent change | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Percentage Change From Baseline in the Tender Joint Count at Week 52 | -55.47 ± 24.072 | -62.70 ± 38.785 | -43.88 ± 38.728 | -54.03 ± 43.200 |
Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
| percent change | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Percentage Change From Baseline in the Swollen Joint Count at Week 52 | -59.40 ± 28.088 | -67.73 ± 42.431 | -57.31 ± 45.480 | -66.74 ± 30.277 |
The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
| percent change | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Percentage Change From Baseline in the Subject Assessment of Pain at Week 52 | 44.63 ± 184.396 | 15.78 ± 176.601 | -11.69 ± 42.608 | -3.73 ± 98.150 |
The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
| percent change | Placebo/Apremilast 20 EE | Placebo / Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 52 | 14.20 ± 76.243 | 33.31 ± 186.069 | -5.20 ± 73.593 | 8.22 ± 83.321 |
The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
| percent change | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 52 | -41.30 ± 35.683 | -49.10 ± 45.037 | -41.19 ± 47.417 | -44.85 ± 41.822 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
| percent change | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Percentage Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 52 | -13.32 ± 35.634 | -10.53 ± 49.600 | -8.20 ± 44.369 | -22.46 ± 31.856 |
C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.
| percent change | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 52 | 13.34 ± 90.641 | 82.14 ± 226.455 | 104.25 ± 210.138 | 79.33 ± 205.501 |
The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.
| percent change | Placebo/Apremilast 20 EE | Placebo / Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52 | -6.28 ± 40.585 | 17.15 ± 244.497 | 4.83 ± 51.294 | -15.99 ± 53.892 |
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
| units on a scale | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Change From Baseline in the FACIT-Fatigue Scale Score at Week 52 | 3.50 ± 11.085 | 3.18 ± 9.236 | 2.87 ± 9.650 | 3.47 ± 11.115 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
| percentage of participants | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 52 | 58.3 (36.6 to 77.9) | 43.6 (27.8 to 60.4) | 40.0 (27.0 to 54.1) | 58.2 (44.1 to 71.3) |
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[(HAQ-DI)\]); C-Reactive Protein.
| percentage of participants | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 52 | 3.4 (0.1 to 17.8) | 11.9 (4.0 to 25.6) | 4.9 (1.3 to 12.0) | 5.3 (1.5 to 12.9) |
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein
| percentage of participants | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 52 | 0.0 (0.0 to 14.2) | 5.0 (0.6 to 16.9) | 7.1 (2.0 to 17.3) | 5.5 (1.1 to 15.1) |
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 | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Week 52 | 41.7 (22.1 to 63.4) | 61.5 (44.6 to 76.6) | 45.5 (32.0 to 59.4) | 40.0 (27.0 to 54.1) |
The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2
| percentage of participants | Placebo/Apremilast 20mg EE | Placebo/Apremilast 20 mg XO | Apremilast 20 mg | Apremilast 30 mg |
|---|---|---|---|---|
| Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 52 | 69.6 (47.0 to 86.8) | 82.1 (66.5 to 92.5) | 63.0 (48.7 to 75.7) | 65.5 (51.4 to 77.8) |
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
No measurements were reported for this outcome.
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
No measurements were reported for this outcome.
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) was a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
No measurements were reported for this outcome.
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: \> 2.8 and ≤ 10 Moderate Disease Activity: \> 10 and ≤ 22 High Disease Activity: \> 22 The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
No measurements were reported for this outcome.
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: \> 2.8 and ≤ 10 Moderate Disease Activity: \> 10 and ≤ 22 High Disease Activity: \> 22 The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
No measurements were reported for this outcome.
The DAS 28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count (TJC28) * 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; * C-reactive protein (CRP) * Subject's global assessment of disease activity (SGA ). A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
No measurements were reported for this outcome.
The Individual ACR Components were defined as follows: 1. Tender Joint Count (out of 68 joints) 2. Swollen Joint Count (out of 66 joints) 3. Subject Assessment of Pain (0 to 100 mm VAS) 4. Subject Global Assessment of Disease Activity (0 to 100 mm VAS) 5. Physician Global Assessment of Disease Activity (0 to 100 mm VAS) 6. HAQ-DI Score 7. Acute Phase Reactant High Sensitivity C-Reactive Protein (hsCRP, mg/dL) Erythrocyte Sedimentation Rate (ESR) The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
No measurements were reported for this outcome.
The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
No measurements were reported for this outcome.
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
No measurements were reported for this outcome.
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[(HAQ-DI)\]); C-Reactive Protein. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
No measurements were reported for this outcome.
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
No measurements were reported for this outcome.
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
No measurements were reported for this outcome.
EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2 The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
No measurements were reported for this outcome.
Collected over All AEs were recorded by the Investigator from the time the participant signed the informed consent to 28 days after the last dose of investigational product.. Non-serious events are listed at a 5.0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Week 24: Placebo | — | 1/79 (1.3%) | 15/79 (19%) |
| Week 24: Apremilast 20 mg | — | 6/82 (7.3%) | 26/82 (31.7%) |
| Week 24: Apremilast 30 mg | — | 4/76 (5.3%) | 23/76 (30.3%) |
| Study Termination: Apremilast 20 mg | — | 16/153 (10.5%) | 49/153 (32%) |
| Study Termination: Apremilast 30 mg | — | 7/76 (9.2%) | 29/76 (38.2%) |
| Event | Week 24: Placebo | Week 24: Apremilast 20 mg | Week 24: Apremilast 30 mg | Study Termination: Apremilast 20 mg | Study Termination: Apremilast 30 mg |
|---|---|---|---|---|---|
| CellulitisInfections and infestations | 0/79 | 0/82 | 1/76 | 0/153 | 1/76 |
| Staphylococcal abscessInfections and infestations | 0/79 | 0/82 | 1/76 | 0/153 | 1/76 |
| AppendicitisInfections and infestations | 0/79 | 1/82 | 0/76 | 1/153 | 1/76 |
| Lung neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/79 | 0/82 | 1/76 | 0/153 | 1/76 |
| Bipolar disorderPsychiatric disorders | 0/79 | 0/82 | 1/76 | 0/153 | 1/76 |
| Suicidal ideationPsychiatric disorders | 0/79 | 0/82 | 1/76 | 0/153 | 1/76 |
| Acute respiratory failureRespiratory, thoracic and mediastinal disorders | 0/79 | 0/82 | 1/76 | 0/153 | 1/76 |
| EmpyemaInfections and infestations | 0/79 | 0/82 | 1/76 | 0/153 | 1/76 |
| Rheumatoid vasculitisVascular disorders | 0/79 | 0/82 | 0/76 | 0/153 | 1/76 |
| PeritonitisGastrointestinal disorders | 0/79 | 0/82 | 0/76 | 0/153 | 1/76 |
| Event | Week 24: Placebo | Week 24: Apremilast 20 mg | Week 24: Apremilast 30 mg | Study Termination: Apremilast 20 mg | Study Termination: Apremilast 30 mg |
|---|---|---|---|---|---|
| NauseaGastrointestinal disorders | 6/79 | 7/82 | 10/76 | 13/153 | 10/76 |
| HeadacheNervous system disorders | 1/79 | 9/82 | 7/76 | 12/153 | 8/76 |
| Upper respiratory tract infecetionInfections and infestations | 2/79 | 3/82 | 5/76 | 9/153 | 7/76 |
| DiarrhoeaGastrointestinal disorders | 2/79 | 7/82 | 6/76 | 14/153 | 6/76 |
| NasopharyngitisInfections and infestations | 4/79 | 6/82 | 3/76 | 11/153 | 6/76 |
| Abdominal pain upperGastrointestinal disorders | 3/79 | 3/82 | 5/76 | 3/153 | 5/76 |
| VomitingGastrointestinal disorders | 1/79 | 1/82 | 3/76 | 3/153 | 5/76 |
| HypertensionVascular disorders | 0/79 | 2/82 | 0/76 | 9/153 | 1/76 |
| Decreased appetiteMetabolism and nutrition disorders | 0/79 | 2/82 | 4/76 | 4/153 | 4/76 |
Full Analysis Set (FAS) The FAS consisted of all participants who were randomized as specified per protocol during the placebo controlled period.
| Age, Continuous(years) | Placebo | Apremilast 20 mg | Apremilast 30 mg | Total |
|---|---|---|---|---|
| Mean | 56.5 ± 12.45 | 58.6 ± 11.84 | 52.6 ± 11.87 | 56.0 ± 12.26 |
| Sex: Female, Male(Participants) | Placebo | Apremilast 20 mg | Apremilast 30 mg | Total |
|---|---|---|---|---|
| Female | 62 | 65 | 55 | 182 |
| Male | 17 | 17 | 21 | 55 |
| Duration of Rheumatoid Arthritis Diagnosis(years) | Placebo | Apremilast 20 mg | Apremilast 30 mg | Total |
|---|---|---|---|---|
| Mean | 11.98 ± 12.104 | 8.46 ± 6.856 | 7.76 ± 7.833 | 9.41 ± 9.351 |
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