A Study of RoActemra/Actemra (Tocilizumab) in Combination With DMARDs Versus Current Best Practice DMARD Therapy in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This randomized, open-label, parallel-group study will assess the effect on disease remission of RoActemra/Actemra (tocilizumab) in combination with disease-modifying antirheumatic drugs (DMARDs) versus current best practice non-biologic DMARD therapy in patients with moderate-to-severe active rheumatoid arthritis. Patients who are randomly assigned to the RoActemra/Actemra treatment group will receive 8 mg/kg RoActemra/Actemra intravenously every 4 weeks. The anticipated time on study treatment is 12 months.

Official Title
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A Pragmatic, Randomized, Parallel Group Study of the Effect on Disease Remission, Work Productivity and Tolerability of Tocilizumab in Combination With DMARDs and Individually Designed Best Practice DMARD Therapy in Patients With Early, Moderate to Severe Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: tocilizumab [RoActemra/Actemra]
* Drug: DMARD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, over the age of 18 years Diagnosis of moderate-to-severe active early rheumatoid arthritis (RA) of less than 2 years duration DAS28 >3.2 Swollen joint count (SJC) >/=6 (66 joint count), and tender joint count (TJC) >/=6 (68 joint count) Patients who have received DMARDs (including methotrexate) for 3-7 months Exclusion Criteria: Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after baseline Rheumatic autoimmune disease other than rheumatoid arthritis (secondary Sjögrens syndrome or nodulosis with RA is permitted) Functional class III or IV as defined by ACR Classification of Functional Status in Rheumatoid Arthritis Prior history of or current inflammatory joint disease other than RA

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: tocilizumab [RoActemra/Actemra]<br>* 8 mg/kg intravenously every 4 weeks plus background DMARDs (including methotrexate)<br>|
| Active Comparator: 2<br> | Drug: DMARD<br>* Non-biologic DMARDs (including methotrexate) according to current best practice<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Disease Remission at Month 12 Assessed Using the Disease Activity Score Based on 28-Joint Count (DAS28) | The DAS28 is a combined index for measuring disease activity in Rheumatoid Arthritis (RA). The index includes swollen and tender joint counts (SJC and TJC), acute phase response, and general health status. For this study Erythrocyte sedimentation Rate (ESR) was to be used to calculate DAS28 score. The DAS28, which uses a 28 joint count, is derived from the original DAS which includes a 44 swollen joint count. The DAS28 has been validated in RA. The index is calculated using the following formula: DAS28 equals (=) 0.56 times (×) square root of √(TJC) plus (+) 0.28 × √(SJC) + 0.70 × ln(ESR) + 0.014 × GH Where, TJC28 = tender joint count on 28 joints, SJC28 = swollen joint count on 28 joints, ln = natural log, ESR measured as millimeters per hour (mm/hr), and GH = general health, which is participant's global assessment of disease activity (100-mm Visual Analog Scale [VAS]). DAS28 less than/equal to (≤) 2.6 defined remission. | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Hours Absent From Work | Work productivity measures include absence from work (participant reported and registries), permanent work disability (pension, participant reported and registries), presenteeism (Quantity and Quality instrument, QQ). | Baseline and 6 and 12 months | 
| Percentage of Participants Achieving Disease Remission at Month 6 Assessed Using DAS28 | The DAS28 is a combined index for measuring disease activity in RA. The index includes SJC and TJC, acute phase response, and general health status. For this study ESR was to be used to calculate DAS28 score. The DAS28, which uses a 28 joint count, is derived from the original DAS which includes a 44 swollen joint count. The DAS28 has been validated in RA. The index is calculated using the following formula: DAS28 = 0.56 × √(TJC) + 0.28 × √(SJC) + 0.70 × ln(ESR) + 0.014 × GH Where, TJC28 = tender joint count on 28 joints, SJC28 = swollen joint count on 28 joints, ln = natural log, ESR measured as millimeters per hour (mm/hr), and GH = general health, which is participant's global assessment of disease activity (100-mm VAS). DAS28 ≤ 2.6 defined remission. | Month 6 | 
| Percentage of Participants Achieving Responses According to American College of Rheumatology (ACR) Criteria | The ACR definition of response includes tender and swollen joint counts, VAS scales for pain, participant and investigator global assessment of disease activity, participant-assessed disability using Health Assessment Questionnaire (HAQ) and acute phase response. | Months 6 and 12 | 
| Percentage of Participants Achieving Remission at Months 6 and 12 Assessed Using Clinical Activity Disease Index (CDAI) | The CDAI is a purely clinical index to measure disease activity. The index includes swollen and tender joint counts, participant global assessment of disease activity, and evaluator global assessment of disease activity (EGA). | Months 6 and 12 | 
| Change From Baseline to Months 6 and 12 in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT F) Scores | The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. FACIT-F is a 13-item questionnaire. Participants 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 participants 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). Clinically relevant improvement is defined as a ≥5-point change from Baseline. | Baseline and Months 6 and 12 | 
| Change From Baseline to Months 6 and 12 in European Quality of Life-5D (EQ-5D) Score | EQ-5D is a 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 and Months 6 and 12 | 
| Change From Baseline to Months 6 and 12 in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Overall score was computed as the sum of the domain scores and divided by the number of domains answered. Total possible score range was 0-3 where 0=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. | Baseline and Months 6 and 12 |