A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to a TNF-Blocker.

Study Overview
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Brief Summary
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This single arm study will evaluate the efficacy and safety of MabThera in patients with active rheumatoid arthritis whose current treatment with one or more TNF blocker had produced an inadequate response. Patients will receive MabThera (1g infusion) on day 1 and day 15, and will continue on their basic methotrexate therapy (10-25mg/week). The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Official Title
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An Open-label Study to Evaluate the Effect of MabThera on Treatment Response in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to Previous TNF Inhibition.

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: rituximab [MabThera/Rituxan]
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; diagnosed RA for >=3 months prior to first administration of study medication; inadequate response or intolerance to >=1 anti-TNF therapies, alone or in combination with methotrexate; if using NSAIDS, analgesics or oral corticosteroids, must be on a stable dose for >=2 weeks prior to start of study. Exclusion Criteria: other chronic inflammatory diseases; use of parental corticosteroids within 4 weeks prior to screening; severe heart failure, or severe, uncontrolled cardiac disease.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: rituximab [MabThera/Rituxan]<br>* 1g iv on days 1 and 15<br>* Other names: MabThera/Rituxan;Drug: Methotrexate<br>* 10-25mg po/week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Activity Score Based on 28-Joint Count (DAS28) | DAS28 consists of swollen joint count (SJC) and tender joint count (TJC) measurements, erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]), and Patient Global Assessment of Disease Activity (participant-rated assessment of arthritis) with transformed scores ranging from 0 to 10. Higher scores indicated greater affectation due to disease activity. DAS28 equal to or less than (≤)3.2 equals (=) low disease activity, greater than (>)3.2 to 5.1 = moderate to high disease activity. | Day 0 and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health Assessment Questionnaire - Disability Index (HAQ-DI) Scores | The HAQ-DI score consists of questions referring to 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. For each of the categories, participants reported the amount of difficulty they had in performing 2 or 3 specific subcategory items. The standard disability score was calculated from the 8 categories by dividing the sum of the individual categories by the number of categories answered, yielding a score from 0 (without any difficulty) to 3 (unable to do). | Day 0 and Week 24 | 
| Anti-cyclic Citrullinated Peptide (Anti-CCP) | Anti-CCP measured as absorbance units per milliliter (AU/mL). | Day 0 and Week 24 | 
| Vascular Endothelial Growth Factor (VEGF) | VEGF was measured as picograms per milliliter (pg/mL). | Day 0 and Week 24 | 
| Erythrocyte Sedimentation Rate (ESR) | ESR was measured in mm/hr. | Day 0 and Week 24 | 
| C-Reactive Protein (CRP) | CRP was measured in milligrams per liter (mg/L). | Day 0 and Week 24 |