Improvement of refractory rheumatoid arthritis after depletion of B cells

• Published in: Scandinavian journal of rheumatology 2004-03, Vol.33 (2), p.82-86
• Main Authors: Kneitz, C, Wilhelm, M, Tony, H-P
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Murine-Derived; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; B-cell depletion; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biological and medical sciences; Diseases of the osteoarticular system; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Inflammatory joint diseases; Infusions, Intravenous; Male; Medical sciences; Methotrexate - therapeutic use; Middle Aged; Pain Measurement; Prognosis; Prospective Studies; rheumatoid arthritis; Risk Assessment; Rituximab; Treatment Outcome
• ISSN: 0300-9742; 1502-7732
• DOI: 10.1080/03009740310004379

Objective: B cells are involved in the pathogenesis of rheumatoid arthritis (RA). To evaluate the effect of therapeutic B-cell depletion for treatment of RA, an open label study has been performed using the B-cell depleting anti-CD20 antibody rituximab. Methods: Five patients with refractory RA were treated weekly with four infusions of rituximab (375 mg m2) alone, or in combination with ongoing methotrexate (MTX). Patients were followed for at least 44 weeks and monitored for safety and tolerability of treatment. Results: Treatment could be performed without serious side effects and resulted in peripheral B-cell depletion lasting between 36 weeks up to >1 year. The follow-up revealed no significant treatment-associated side effects. At 22 weeks, 4 5 patients showed a significant improvement (>1.2) of the Disease Activity Score (DAS28). The mean DAS28 of all patients declined from 6.2 to 4.1. At 44 weeks there was one drop-out, another patient still had a sustained response, and three patients showed slowly increasing disease activity (mean DAS28 of the remaining four patients: Week 0: 6.0; Week 22: 3.85; Week 44: 5.6). Despite relatively constant immunoglobulin levels, rheumatoid factor levels decreased parallel to disease activity. Conclusion: In patients with refractory RA, B-cell depletion with rituximab is safe and well tolerated. A reduction of disease activity could be observed, which eventually deteriorated after B-cell repopulation. The findings give more evidence for B-cell targeted therapies in RA.