Long-term efficacy and safety of rituximab in refractory and relapsing systemic lupus erythematosus

Background. Systemic lupus erythematosus is a relapsing autoimmune disease. Conventional therapy increases the risk of infection and malignancies; furthermore, a minority of patients suffer from refractory disease. B-cell depletion with the chimeric \anti-CD20 monoclonal antibody, rituximab, is an alternative therapy for relapsing and refractory systemic lupus erythematosus. We sought to assess the long-term efficacy and safety of rituximab in this patient subgroup. Methods. Thirty-one sequential patients with relapsing or refractory systemic lupus erythematosus, 11 of whom had active lupus nephritis, received rituximab [either 375 mg/m(2)/week x 4 (n = 16) or 1000 mg x 2 (n = 15)]. The median follow-up was 30 months. Results. Thirty of 31 (97%) patients had depleted peripheral B cells. Twenty-seven of 31 (87%) patients achieved remission (17 complete, 10 partial). Renal response occurred in 10/11 patients (4 complete, 6 partial) with active glomerulonephritis. Clinical improvement was reflected by reductions of disease activity, proteinuria and daily prednisolone dose. Eighteen of 27 (67%) patients relapsed after a median of 11 months. Relapses occurred on or after the return of circulating B cells in 10 but in the absence of B-cell return in 8. Re-treatment with rituximab was effective. Infusion reactions were common (18/31; 58%), and infections occurred in 8/31 (26%) patients. Conclusions. Rituximab had a high rate of efficacy in relapsing or refractory systemic lupus erythematosus with or without renal involvement. Although relapse was common, it responded to re-treatment. The contribution of rituximab to infection risk was uncertain in view of the complex disease course and concomitant therapy of the patients studied.