Objective: To gain preliminary evidence for the safety and efficacy of B lymphocyte depletion therapy in refractory systemic lupus erythematosus (SLE).
Methods: Six female patients with active SLE, resistant to standard immunosuppressive therapy, were treated on an open-label basis. During a 2-week period, each patient received two 500-mg infusions of rituximab, two 750-mg infusions of cyclophosphamide, and high-dose oral corticosteroids.
Results: No significant adverse events were observed during followup. Patient 1 had not improved at 3 months but was then lost to followup. At 6 months, all 5 remaining patients had improved, as evidenced by improvement in British Isles Lupus Assessment Group global scores, from a median of 14 (range 9-27) at baseline to a median of 6 (range 3-8) at 6 months. Manifestations of SLE such as fatigue, arthralgia/arthritis, and serositis responded particularly well to this protocol. Hemoglobulin levels increased in patients 2, 3, 5, and 6. The erythrocyte sedimentation rate decreased in patients 2, 3, 4, and 5 and was stable in patient 1. In patients 4 and 5, the urinary protein-to-creatinine ratio decreased significantly. C3 serum levels increased in all 5 patients who had low levels at baseline; in two of these patients, patients 2 and 5, C3 values were normal at 6 months. The variation in the level of anti-double-stranded DNA antibody was different in individual patients.
Conclusion: This study provides sufficient evidence for the safety and possible efficacy of B lymphocyte depletion therapy in SLE to justify a formal controlled trial.