Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy

Fernando C. Fervenza(Columbia University Irving Medical Center), Gerald B. Appel(Columbia University Irving Medical Center), Sean J. Barbour(University of British Columbia), Brad H. Rovin(Columbia University Irving Medical Center), Richard Lafayette(Columbia University Irving Medical Center), Nabeel Aslam(Columbia University Irving Medical Center), Jonathan Ashley Jefferson(Columbia University Irving Medical Center), Patrick E. Gipson(University of Michigan), Dana V. Rizk(Columbia University Irving Medical Center), John R. Sedor(Columbia University Irving Medical Center), James F. Simon(Cleveland Clinic), Ellen T. McCarthy(Columbia University Irving Medical Center), Paul Brenchley(Columbia University Irving Medical Center), Sanjeev Sethi(Columbia University Irving Medical Center), Carmen Ávila-Casado(University Health Network), Heather Beanlands(Columbia University Irving Medical Center), John C. Lieske(Columbia University Irving Medical Center), David Philibert(Columbia University Irving Medical Center), Tingting Li(Washington University in St. Louis), Leslie F. Thomas(Columbia University Irving Medical Center), Dolly F. Green(Florida International University), Luis A. Juncos(Columbia University Irving Medical Center), Lada Beara‐Lasić(Columbia University Irving Medical Center), Samuel S. Blumenthal(Froedtert Hospital), Amy N. Sussman(University of Arizona), Stephen B. Erickson(Columbia University Irving Medical Center), Michelle Hladunewich(Sunnybrook Health Science Centre), Pietro A. Canetta(Columbia University Irving Medical Center), Lee A. Hebert(Columbia University Irving Medical Center), Nelson Leung(Columbia University Irving Medical Center), Jay Radhakrishnan(Columbia University Irving Medical Center), Heather N. Reich(University Health Network), Samir V. Parikh(Columbia University Irving Medical Center), Debbie S. Gipson(University of Michigan), Dominic K. Lee(St. Michael's Hospital), Bruno R. da Costa(St. Michael's Hospital), Peter Jüni(St. Michael's Hospital), Daniel Cattran(University Health Network)
New England Journal of Medicine
July 3, 2019
Cited by 586Open Access
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Abstract

BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. METHODS: of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. RESULTS: receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P = 0.06). CONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).


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