Safety and Efficacy of Rituximab in Patients with Rheumatoid Arthritis Refractory to Disease Modifying Antirheumatic Drugs and Anti-Tumor Necrosis Factor-a Treatment

JEAN HIGASHIDA, TED WUN, SARA SCHMIDT, STANLEY M. NAGUWA, and JOSEPH M. TUSCANO

ABSTRACT.

Objective. To determine the safety and efficacy of rituximab treatment in patients with active seropositive rheumatoid arthritis (RA) who had experienced an inadequate response to treatment with anti-tumor necrosis factor-a agents and/or traditional disease modifying antirheumatic drugs.

Methods. Rituximab was administered to 17 patients as weekly infusions for 4 consecutive weeks. Patients continued their baseline therapy and were followed for 28 weeks.

Results. All patients were evaluable for safety, and 13 for efficacy. Profound B cell depletion occurred by 12 weeks and was sustained at 24 weeks, whereas T cell, complement, and immunoglobulin levels remained within normal ranges. Rituximab was well tolerated, with no infusion related reactions and only mild/moderate adverse events. American College of Rheumatology 20% response (ACR20) was achieved in 55% of patients by Week 5, 75% by Week 8, 50% at Week 16, and 67% at Week 28. Corresponding ACR50 and ACR70 responses were achieved in 36% and 18%, 25% and 17%, 42% and 25%, and 33% and 17% of patients at Weeks 5, 8, 16, and 28, respectively. There were significant improvements over baseline in tender and swollen joint counts (p < 0.0001), physician's global assessment of disease activity (p = 0.0001), and patient assessed pain (p = 0.0005) and disability (p = 0.0386). Erythrocyte sedimentation rate (p = 0.0361) and rheumatoid factor titers (p < 0.0001) also decreased significantly.

Conclusion. These results support the hypothesis that B cells play an important role in RA pathophysiology, and suggest that rituximab is effective and well tolerated, with a rapid onset of clinical benefit, in patients with refractory, seropositive active RA. (J Rheumatol 2005;32:2109-15)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
RITUXIMAB
TREATMENT EFFICACY
ADVERSE EFFECTS
B CELLS

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From the Sections of Rheumatology, and Hematology and Oncology, Veterans Affairs, Northern California Health Care System, Sacramento; and Division of Hematology and Oncology, University of California, Davis School of Medicine, Sacramento, California, USA.

Supported by Genentech, Inc., South San Francisco, CA, and Biogen Idec Pharmaceuticals, San Diego, CA, USA.

J. Higashida, MD, Chief of Rheumatology; S. Schmidt, PharmD, Research Pharmacist, Veterans Affairs, Northern California Health Care System; T. Wun, MD, Professor; S. Naguwa, MD, Professor; J.M. Tuscano, MD, Associate Professor, University of California, Davis School of Medicine.

Address reprint requests to Dr. J.M. Tuscano, Department of Internal Medicine, University of California, Davis Cancer Center, Sacramento, CA 95817, USA. E-mail: joseph.tuscano@ucdmc.ucdavis.edu

Accepted for publication June 24, 2005.

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