Trial of rituximab in patients with rheumatoid arthritis

INTERVENTION: Rituximab infusions CONDITION: Rheumatoid arthritis refractory to standard disease modifying agents PRIMARY OUTCOME: 1.(ACR) 20% improvement of response(ACR 20) at 24 weeks; 2.Disease activity score 28 (DAS 28) improvement at 24 weeks SECONDARY OUTCOME: 1.ACR50 and ACR70 improvement atweek 24, 1 year and 2 years ; 2.Immunological markers which include rheumatoid factor, B cells (CD 19) and T‐cell (CD3,CD27) and immunoglobulin levels (IgG,IgM,IgA) ; 3.Side effects noted with rituximab and leflunomide, particularly the rate of infections ; 4.The antibody response to tetanus toxoid and pneumococcal vaccine given at 36 weeks INCLUSION CRITERIA: 1.18‐65 years of age 2. must fulfill the revised 1987 American Rheumatism association criteria for at least 6 months 3.Swollen joint count ³4 (28 joint count) and tender joint count ³4(28 joint count at screening and baseline 4.CRP ³6 mg/L OR ESR ³28 mm/h at screening 5. Patients who used methotrexate at 15‐25 mg/wk for at least 12 weeks without response. This will include patients who failed to respond to additional treatment with either or both SSZ, chloroquine. patients who have used leflunomide will not be included 6.The doses of MTX must be stable for 4 weeks prior to baseline 7.Prednisolone <10 mg/day or equivalent glucocorticoids are permitted if dose stable for 4 weeks prior to baseline 8.Patients will be allowed to receive non‐steroidal anti‐inflammatory drugs if dose stable for ³4weeks prior to baseline 9.A negative serum pregnancy test at screening for female subjects of childbearing potential. Use of contraception in patie