A Study of MabThera/Rituxan (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis and Inadequate Response to DMARD Therapy

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of MabThera/Rituxan plus methotrexate in patients with active rheumatoid arthritis who have had an inadequate response to at least 1 DMARD treatment. All patients will receive MabThera (1000mg iv infusion) on days 1 and 15, and methotrexate (10-25mg po) weekly. The anticipated time on study treatment is 3-12 months.

Official Title
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An Open-label Study to Evaluate the Effect of MabThera in Combination With Methotrexate on Disease Activity in Patients With Active Rheumatoid Arthritis After DMARD Treatment Failure

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: rituximab [MabThera/Rituxan]
* Drug: methotrexate
* Drug: methylprednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, 18-80 years of age; rheumatoid arthritis after inadequate response to >=1 DMARD treatment; active disease; DMARDs other than methotrexate withdrawn for at least 4 weeks prior to start of study treatment. Exclusion Criteria: autoimmune disease other than rheumatoid arthritis; bone/joint surgery within 8 weeks prior to screening, or joint surgery planned within 24 weeks of MabThera infusion; concurrent treatment with any DMARD or antiTNF-alfa; intra-articular or parenteral corticosteroids within 4 weeks prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MabThera/Rituxan<br> | Drug: rituximab [MabThera/Rituxan]<br>* 1000 mg iv Days 1 and 15<br>Drug: methotrexate<br>* 10 - 25 mg/week<br>Drug: methylprednisolone<br>* iv administration on Day 1 and 15 prior to MabThera/Rituxan infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Disease Activity Score Based on 28-Joint Count (DAS28) at Week 24 | DAS28 was calculated from the number of swollen joints and painful joints using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (PGA) of disease activity (participant-rated arthritis activity assessment using visual analog scale [VAS]) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 less than or equal to (≤)3.2 equals (=) low disease activity, DAS28 greater than (>)3.2 to 5.1 = moderate to high disease activity. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health Assessment Questionnaire-Disability Index (HAQ-DI) | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 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 where 0 = least difficulty and 3 = extreme difficulty. | Baseline, Week 24 |