A Pharmacokinetic and Pharmacodynamic Study of MabThera (Rituximab) Plus Methotrexate in Patients With Rheumatoid Arthritis (RA)

An Open-label, Exploratory Study of the Pharmacokinetic and Pharmacodynamic Activity of MabThera in Combination With Methotrexate in Synovial Tissue and in Peripheral Blood of Patients With Active Rheumatoid Arthritis.

This single arm study will investigate the pattern of B cell depletion in synovial tissue and peripheral blood of patients with active RA, after MabThera (1000mg iv x 2 on days 1 and 15) + methotrexate (10-25mg/week po) treatment. The clinical efficacy and pharmacokinetic profile of MabThera after treatment and retreatment will also be investigated. The anticipated time on study treatment is 2+ years, and the target sample size is <100 individuals.

Inclusion Criteria:

• adult patients 18-80 years of age;
• RA for >=3 months;
• receiving outpatient treatment;
• failed treatment with >=1 DMARD (but not anti TNF or other biologic therapy);
• inadequate response to methotrexate, having taken and tolerated it for >=12 weeks, with a stable dose for >=4 weeks.

Exclusion Criteria:

• rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA;
• history of, or current, inflammatory joint disease other than RA, or other systemic autoimmune disorder;
• diagnosis of RA before the age of 16;
• bone/joint surgery within 12 weeks of study;
• prior use of anti-TNF or other biologic therapy, an anti-alpha 4 integrin, or any cell-depleting therapies.