PARIS, France—Although a trial of rituximab (Rituxan®, Genentech-Biogen Idec) in systemic lupus erythematosus (SLE) reported last year was disappointing, the anti-B-cell antibody is being widely used by clinicians treating severe lupus nephritis, and a study reported by French researchers in the Clinical Journal of the American Society of Nephrology supports that use.1

Catherine Melander, MD, and colleagues at 11 French hospitals treated 20 patients with active class IV or class V lupus nephritis with rituximab and were able to induce complete or partial remissions in 12/20 patients (60%).

Senior author Fadi Fakhouri, MD, told MSKreport.com, “I was surprised by the high percentage of partial and complete remission in these highly resistant lupus nephritis patients and by the reduction in steroids doses achieved with rituximab. This raises the question of the feasibility of rituximab regimen without steroids.” Dr. Fakhouri is now at the Molecular Genetics and Rheumatology Section at the Imperial College, London, Faculty of Medicine.

Rituximab effective in refractory or relapsed lupus nephritis

The patients in this study had lupus nephritis refractory to standard treatment (12 cases), relapsing disease (6 cases), or were given rituximab as first-line treatment for lupus nephritis (2 cases). Three patients received cyclophosphamide plus rituximab. Ten patients had repeat injection of rituximab as maintenance therapy once remission was achieved.

Rituximab was given weekly for 4 weeks at 375 mg/sqm except for 2 patients, who received 3 rather than 4 injections.

After a median follow-up of 22 months, 7 patients had complete renal remission and 5 patients had partial renal remission.

Remissions occurred less than 6 months after rituximab in 6 patients, at 12 months in 5 patients, and at 26 months in 1 patient.

Ten of the 15 class IV (proliferative) lupus nephritis patients responded to rituximab, including 5 complete remissions, and only 1 responder relapsed.

Median dose of oral corticosteroids dropped from 0.7 mg/kg/day to 0.1 mg/kg/day (P =.0001). In responders the steroid sparing was clinically significant, decreasing from 1 mg/kg/day to 0.1 mg/kg/day.

However, response is dependent on prompt achievement of B-cell depletion. The authors reported, “Depletion failure was significantly associated with black ethnicity...and with hypoalbuminemia.”

The main side effects were 5 infections and 4 moderate neutropenias.

Rituximab for lupus nephritis: Translating research into practice

Dr. Fakhouri said that there are 3 messages for clinicians to remember from this study.

“Consider using rituximab in selected patients resistant to conventional therapy,” Dr. Fakhouri said. “Remember that if B cells are not depleted by week 4 of treatment you should switch your patient to another drug. And remember that one main issue in treating lupus nephritis is to spare steroids. Rituximab may help in avoiding high doses of steroids in severe patients.”

Dr. Fakhouri added, “Even though LUNAR results were negative (due in part to the study design), rituximab is still a interesting option in highly resistant lupus nephritis.”

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