A Phase 3 Study Comparing 2 Doses of CP-690,550 vs. Placebo for Treatment of Rheumatoid Arthritis

Study Overview
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Brief Summary
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This Phase 3 study is intended to provide evidence of the efficacy and safety of CP 690,550 when dosed 5 mg and 10 mg twice a day as monotherapy in adult patients with moderate to severe Rheumatoid Arthritis. It is intended to confirm the benefits of CP-690,550 in improving signs and symptoms and physical function that were observed in the Phase 2 Rheumatoid Arthritis studies.

Official Title
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Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Of The Efficacy And Safety Of 2 Doses Of CP-690,550 Monotherapy In Patients With Active Rheumatoid Arthritis

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: CP-690,550
* Drug: CP-690,550
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has a diagnosis of RA based upon the American College of Rheumatology (ACR) 1987 Revised Criteria. The patient has active disease at both Screening and Baseline, as defined by both: ≥6 joints tender or painful on motion; and ≥6 joints swollen; and fulfills 1 of the following 2 criteria at Screening: 1.ESR (Westergren method) >28 mm in the local laboratory. 2. CRP >7 mg/L in the central laboratory Patient had an inadequate response to at least one DMARD (traditional or biologic) due to lack of efficacy or toxicity. No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis. Patient has washed out of all DMARDs other that antimalarials Exclusion Criteria: Blood dyscrasias including confirmed: 1. Hemoglobin <9 g/dL or Hematocrit <30%; 2. White blood cell count <3.0 x 109/L; 3. Absolute neutrophil count <1.2 x 109/L; 4. Platelet count <100 x 109/L History of any other autoimmune rheumatic disease other than Sjogren's syndrome No malignancy or history of malignancy. History of infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator, within the 6 months prior to the first dose of study drug

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active 5mg<br> | Drug: CP-690,550<br>* 5mg CP-690,550 BID PO for 6 months<br>|
| Experimental: Active 10 mg<br> | Drug: CP-690,550<br>* 10 mg CP-690,550 BID PO for 6 months<br>|
| Placebo Comparator: Placebo Sequence 1<br> | Drug: Placebo<br>* Placebo patients advance to 5mg CP-690,550 BID at Month 3 visit<br>|
| Placebo Comparator: Placebo Sequence 2<br> | Drug: Placebo<br>* Placebo patients advance to 10mg CP-690,550 BID at Month 3 visit<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 3 | ACR20 response: greater than or equal to (>=) 20 percent (%) improvement in tender joint count; >=20% improvement in swollen joint count; and >=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP). | Month 3 | 
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Month 3 | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 functional categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3, 0=least functional difficulty and 3=extreme functional difficulty. | Baseline, Month 3 | 
| Percentage of Participant With Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 at Month 3 | DAS28-4 (ESR) calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joint count, erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (PtGA) of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range:0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (=<) 3.2 implied low disease activity, greater than (>) 3.2 to 5.1 implied moderate to high disease activity and less than (<) 2.6=remission. | Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 2, Month 1 and 2 | ACR20 response: >= 20% improvement in tender joint count; >=20% improvement in swollen joint count; and >=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. | Week 2, Month 1, 2 | 
| Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 4, 5 and 6 | ACR20 response: >= 20% improvement in tender joint count; >=20% improvement in swollen joint count; and >=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. | Month 4, 5, 6 | 
| Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 2, Month 1, 2 and 3 | ACR50 response: greater than or equal to >=50% improvement in tender joint count; >=50% improvement in swollen joint count; and >=50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of HAQ); and CRP. | Week 2, Month 1, 2, 3 | 
| Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Month 4, 5 and 6 | ACR50 response: greater than or equal to >=50% improvement in tender joint count; >=50% improvement in swollen joint count; and >=50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of HAQ); and CRP. | Month 4, 5, 6 | 
| Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 2, Month 1, 2 and 3 | ACR70 response: >=70% improvement in tender joint count; >=70% improvement in swollen joint count; and >=70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of HAQ); and CRP. | Week 2, Month 1, 2, 3 | 
| Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Month 4, 5 and 6 | ACR70 response: >=70% improvement in tender joint count; >=70% improvement in swollen joint count; and >=70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of HAQ); and CRP. | Month 4, 5, 6 | 
| Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Baseline and Month 3 | DAS28-4 (ESR) calculated from SJC and TJC using 28 joint count, ESR (mm/hour) and PtGA of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range:0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) =<3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission. | Baseline, Month 3 | 
| Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Month 6 | DAS28-4 (ESR) calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joint count, erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (PtGA) of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range:0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (=<) 3.2 implied low disease activity, greater than (>) 3.2 to 5.1 implied moderate to high disease activity and less than (<) 2.6=remission. | Month 6 | 
| Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Baseline, Week 2, Month 1, 2 and 3 | DAS28-3 (CRP) was calculated from SJC and TJC using 28 joint count and CRP (milligram per liter [mg/L]). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) =<3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission. | Baseline, Week 2, Month 1, 2, 3 | 
| Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Month 4, 5 and 6 | DAS28-3 (CRP) was calculated from SJC and TJC using 28 joint count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) =<3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission. | Month 4, 5, 6 | 
| Health Assessment Questionnaire Disability Index (HAQ-DI) at Baseline, Week 2, Month 1, 2 and 3 | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 functional categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3, 0=least functional difficulty and 3=extreme functional difficulty. | Baseline, Week 2, Month 1, 2, 3 | 
| Health Assessment Questionnaire Disability Index (HAQ-DI) at Month 4, 5 and 6 | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 functional categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3, 0=least functional difficulty and 3=extreme functional difficulty. | Month 4, 5, 6 | 
| Patient Assessment of Arthritis Pain at Baseline, Week 2, Month 1, 2 and 3 | Participants assessed the severity of their arthritis pain using a 100 millimeter (mm) visual analog scale (VAS). The scale ranged from 0 (no pain) to 100 (most severe pain), measurement on a scale corresponds to the magnitude of their pain. | Baseline, Week 2, Month 1, 2, 3 | 
| Patient Assessment of Arthritis Pain at Month 4, 5 and 6 | Participants assessed the severity of their arthritis pain using a 100 mm visual analog scale (VAS). The scale ranged from 0 (no pain) to 100 (most severe pain), measurement on a scale corresponds to the magnitude of their pain. | Month 4, 5, 6 | 
| Patient Global Assessment (PtGA) of Arthritis Pain at Baseline, Week 2, Month 1, 2 and 3 | Participants answered: Considering all the ways your arthritis affects you, how are you feeling today? Participants responded by using a 0 - 100 mm Visual Analog Scale where 0 = very well and 100 = very poorly. | Baseline, Week 2, Month 1, 2, 3 | 
| Patient Global Assessment (PtGA) of Arthritis Pain at Month 4, 5 and 6 | Participants answered: Considering all the ways your arthritis affects you, how are you feeling today? Participants responded by using a 0 - 100 mm Visual Analog Scale where 0 = very well and 100 = very poorly. | Month 4, 5, 6 | 
| Physician Global Assessment (PGA) of Arthritis Pain at Baseline, Week 2, Month 1, 2 and 3 | Physician Global Assessment of Arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad. | Baseline, Week 2, Month 1, 2, 3 | 
| Physician Global Assessment (PGA) of Arthritis Pain at Month 4, 5 and 6 | Physician Global Assessment of Arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad. | Month 4, 5, 6 | 
| 36-Item Short-Form Health Survey (SF-36) at Baseline, Month 3 | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning) and is reported as 2 summary scores; Physical Component Score and Mental Component Score. Total score range for the summary scores = 0- 100, where higher score represents higher level of functioning. | Baseline, Month 3 | 
| 36-Item Short-Form Health Survey (SF-36) at Month 6 | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning) and is reported as 2 summary scores; Physical Component Score and Mental Component Score. Total score range for the summary scores = 0- 100, where higher score represents higher level of functioning. | Month 6 | 
| Medical Outcome Study Sleep Scale (MOS-SS) at Baseline and Month 3 | Participant-rated 12 item questionnaire assess constructs of sleep over past week.7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence (range:0-100); sleep quantity(range:0-24), optimal sleep(yes or no). 9 item index measures of sleep disturbance provide composite scores: sleep problem summary, overall sleep problem. Except Adequacy, Optimal, Quantity of sleep, higher scores=more impairment. Scores transformed(actual raw score minus lowest possible score divided by possible raw score range*100);total score range:0-100,higher score=more intensity of attribute. | Baseline, Month 3 | 
| Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study Sleep Scale (MOS-SS) at Baseline and Month 3 | MOS-SS: participant-rated 12 item questionnaire to assess constructs of sleep over past week. It included 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence, sleep quantity and optimal sleep. Participants responded whether their sleep was optimal or not by choosing yes or no. Number of participants with optimal sleep are reported. | Baseline, Month 3 | 
| Medical Outcome Study Sleep Scale (MOS-SS) at Month 6 | Participant-rated 12 item questionnaire assess constructs of sleep over past week.7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence (range:0-100); sleep quantity(range:0-24), optimal sleep(yes or no). 9 item index measures of sleep disturbance provide composite scores: sleep problem summary, overall sleep problem. Except Adequacy, Optimal, Quantity of sleep, higher scores=more impairment. Scores transformed(actual raw score minus lowest possible score divided by possible raw score range*100);total score range:0-100,higher score=more intensity of attribute. | Month 6 | 
| Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study Sleep Scale (MOS-SS) at Month 6 | MOS-SS: participant-rated 12 item questionnaire to assess constructs of sleep over past week. It included 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence, sleep quantity and optimal sleep. Participants responded whether their sleep was optimal or not by choosing yes or no. Number of participants with optimal sleep are reported. | Month 6 | 
| Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Baseline and Month 3 | FACIT-Fatigue is a 13-item questionnaire. Participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflected an improvement in the participant's health status. | Baseline, Month 3 | 
| Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Month 6 | FACIT-Fatigue is a 13-item questionnaire. Participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflected an improvement in the participant's health status. | Month 6 | 
| Euro Quality of Life (EQ-5D)- Health State Profile Utility Score at Baseline and Month 3 | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. | Baseline, Month 3 | 
| Euro Quality of Life (EQ-5D)- Health State Profile Utility Score at Month 6 | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. | Month 6 | 
| Work Productivity and Healthcare Resource Utilization (HCRU) at Baseline and Month 3 | Rheumatoid Arthritis (RA)-HCRU assessed healthcare usage during last 3 months for direct, indirect medical cost domains. Direct cost:visit to doctor,non-medical practitioner,nursing home,hospital,surgery,emergency room(ER) treatment,diagnostic tests, over-night stay,home healthcare services, aids/devices used. Indirect costs associated with functional disability:employment status,willingness to work,work disability due to RA,sick leave,part time work,ability to perform chores,chores done by family/friends/housekeeper. Assessment was based on 0 to 2-point scale;higher score=higher medical cost. | Baseline, Month 3 | 
| Work Productivity and Healthcare Resource Utilization (HCRU) at Month 6 | Rheumatoid Arthritis (RA)-HCRU assessed healthcare usage during last 3 months for direct, indirect medical cost domains. Direct cost:visit to doctor,non-medical practitioner,nursing home,hospital,surgery,emergency room(ER) treatment,diagnostic tests, over-night stay,home healthcare services, aids/devices used. Indirect costs associated with functional disability:employment status,willingness to work,work disability due to RA,sick leave,part time work,ability to perform chores,chores done by family/friends/housekeeper. Assessment was based on 0 to 2-point scale;higher score=higher medical cost. | Month 6 | 
| Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Baseline and Month 3 | RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any RA/non-RA related number of visits to doctor, non-medical practitioner, hospital ER treatment, hospitalizations, number of surgeries, diagnostic tests, and devices/aids used were reported. | Baseline, Month 3 | 
| Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Month 6 | RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any RA/non-RA related number of visits to doctor, non-medical practitioner, hospital ER treatment, hospitalizations, number of surgeries, diagnostic tests, and devices/aids used were reported. | Month 6 | 
| Number of Days as Assessed Using RA-HCRU at Baseline and Month 3 | RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains.Any RA or non-RA related number of days spent in hospital, nursing home, aids/devices used, on sick leave, work per week, performed part time work, performed paid work, chores done by housekeeper and chores done by family/friends. | Baseline, Month 3 | 
| Number of Days as Assessed Using RA-HCRU at Month 6 | RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains.Any RA or non-RA related number of days spent in hospital, nursing home, aids/devices used, on sick leave, work per week, performed part time work, performed paid work, chores done by housekeeper and chores done by family/friends. | Month 6 | 
| Number of Hours Per Day as Assessed RA-HCRU at Baseline and Month 3 | RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any RA or non-RA related number of hours spent per day for home healthcare services, chores done by housekeeper, chores done by family or friends, work done and work missed were reported. | Baseline, Month 3 | 
| Number of Hours Per Days as Assessed Using RA-HCRU at Month 6 | RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any RA or non-RA related number of hours spent per day for home healthcare services, chores done by housekeeper, chores done by family or friends, work done and work missed were reported. | Month 6 | 
| Work Performance in Past 3 Months on Days Bothered as Assessed Using RA-HCRU at Baseline and Month 3 | Work performance of participants on number of days bothered was based on a 0 to 10-point scale, where higher score indicated lower work performance. | Baseline, Month 3 | 
| Work Performance in Past 3 Months on Days Bothered as Assessed Using RA-HCRU at Month 6 | Work performance of participants on number of days bothered was based on a 0 to 10-point scale, where higher score indicated lower work performance. | Month 6 | 
| Work Limitations Questionnaire (WLQ) Score at Baseline and Month 3 | WLQ: participant-reported 25-item scale to evaluate degree to which health problems interfere with an ability to perform job roles along 4 dimensions: Time Management scale (5-items); Physical Demands scale (6-item); Mental-Interpersonal Demands Scale (9-items); Output Demands scale (5-items). All the scales ranged from 0 (limited none of the time) to 100 (limited all of the time). Work Loss Index, which represented percentage of lost work over time period relative to a normative population, was derived (total score:0[no loss] to 100[complete loss of work]). | Baseline, Month 3 | 
| Work Limitations Questionnaire (WLQ) Score at Month 6 | WLQ: participant-reported 25-item scale to evaluate degree to which health problems interfere with an ability to perform job roles along 4 dimensions: Time Management scale (5-items); Physical Demands scale (6-item); Mental-Interpersonal Demands Scale (9-items); Output Demands scale (5-items). All the scales ranged from 0 (limited none of the time) to 100 (limited all of the time). Work Loss Index, which represented percentage of lost work over time period relative to a normative population, was derived (total score:0[no loss] to 100[complete loss of work]). | Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antirheumatic Agents Clinical Trial