title: Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-Up.
abstract: Randomized trials of rituximab in primary membranous nephropathy (PMN) have not been conducted. We undertook a multicenter, randomized, controlled trial at 31 French hospitals (NCT01508468). Patients with biopsy-proven PMN and nephrotic syndrome after 6 months of nonimmunosuppressive antiproteinuric treatment (NIAT) were randomly assigned to 6-month therapy with NIAT and 375 mg/m2intravenous rituximab on days 1 and 8 (n=37) or NIAT alone (n=38). Median times to last follow-up were 17.0 (interquartile range, 12.5-24.0) months and 17.0 (interquartile range, 13.0-23.0) months in NIAT-rituximab and NIAT groups, respectively. Primary outcome was a combined end point of complete or partial remission of proteinuria at 6 months. At month 6, 13 (35.1%; 95% confidence interval [95% CI], 19.7 to 50.5) patients in the NIAT-rituximab group and eight (21.1%; 95% CI, 8.1 to 34.0) patients in the NIAT group achieved remission (P=0.21). Rates of antiphospholipase A2 receptor antibody (anti-PLA2R-Ab) depletion in NIAT-rituximab and NIAT groups were 14 of 25 (56%) and one of 23 (4.3%) patients at month 3 (P<0.001) and 13 of 26 (50%) and three of 25 (12%) patients at month 6 (P=0.004), respectively. Eight serious adverse events occurred in each group. During the observational phase, remission rates before change of assigned treatment were 24 of 37 (64.9%) and 13 of 38 (34.2%) patients in NIAT-rituximab and NIAT groups, respectively (P<0.01). Positive effect of rituximab on proteinuria remission occurred after 6 months. These data suggest that PLA2R-Ab levels are early markers of rituximab effect and that addition of rituximab to NIAT does not affect safety.
authors.affiliation: Department of Nephrology and Dialysis, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France; karine.dahan@aphp.fr pierre.ronco@upmc.fr.
authors.forename: Karine
authors.initials: K
authors.lastname: Dahan
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France.|Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1155, Paris, France.
authors.forename: Hanna
authors.initials: H
authors.lastname: Debiec
authors.affiliation: Department of Nephrology and Dialysis, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France.|Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France.|Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1155, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Plaisier
authors.affiliation: Department of Clinical Pharmacology and Unité de Recherche Clinique, Assistance Publique Hôpitaux de Paris, Hôpital Saint Antoine, Paris, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Cachanado
authors.affiliation: Department of Clinical Pharmacology and Unité de Recherche Clinique, Assistance Publique Hôpitaux de Paris, Hôpital Saint Antoine, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rousseau
authors.affiliation: Department of Clinical Pharmacology and Unité de Recherche Clinique, Assistance Publique Hôpitaux de Paris, Hôpital Saint Antoine, Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Wakselman
authors.affiliation: Department of Nephrology and Dialysis, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France.
authors.forename: Pierre-Antoine
authors.initials: PA
authors.lastname: Michel
authors.affiliation: Department of Nephrology and Dialysis, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Mihout
authors.affiliation: Department of Nephrology and Transplantation, Assistance Publique-Hôpitaux de Marseille, Hôpital de la Timone, Marseille, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dussol
authors.affiliation: Department of Nephrology and Transplantation, Assistance Publique Hôpitaux de Paris, Hôpital Henri Mondor, Creteil, France; and.
authors.forename: Marie
authors.initials: M
authors.lastname: Matignon
authors.affiliation: Department of Nephrology and Transplantation, Centre Hospitalier Universitaire, Dijon, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Mousson
authors.affiliation: Department of Clinical Pharmacology and Unité de Recherche Clinique, Assistance Publique Hôpitaux de Paris, Hôpital Saint Antoine, Paris, France.
authors.forename: Tabassome
authors.initials: T
authors.lastname: Simon
authors.affiliation: Department of Nephrology and Dialysis, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France; karine.dahan@aphp.fr pierre.ronco@upmc.fr.|Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France.|Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1155, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ronco
mesh_terms: D005260:Female; D005500:Follow-Up Studies; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D007155:Immunologic Factors; D000069283:Rituximab
keywords: anti-PLA2R antibody; anti-THSD7A antibody; idiopathic membranous nephropathy; randomized controlled trial; rituximab; severe adverse event