Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-Up
Karine Dahan, Hanna Debiec, Emmanuelle Plaisier, Marine Cachanado, Alexandra Rousseau, Laura Wakselman, Pierre-Antoine Michel, Fabrice Mihout, Bertrand Dussol, Marie Matignon, Christiane Mousson, Tabassome Simon, Pierre Ronco, GEMRITUX Study Group, Vincent Audard, Pierre Bataille, Yvon Berland, Jean-Jacques Boffa, Nicolas Bouvier, Laura Braun, Frank Bridoux, Stéphane Burtey, Déborah Chaintreuil, Cindy Castrale, Gabriel Choukroun, Christian Combe, Eric Daugas, Michel Delahousse, Ariane Duval-Sabatier, Marie Essig, Isabelle Etienne, Hélène François, Denis Fouque, Denis Glotz, Michel Godin, Bertrand Gondouin, Morgane Gosselin, Maryvonne Hourmant, Aurélie Hummel, Corinne Isnard-Bagnis, Charlotte Jouzel, Bruno Hurault de Ligny, Alexandre Karras, Thomas Kofman, Philippe Lang, Sandrine Lemoine, Anne-Sophie Librez Verhoeven, Rafik Mesbah, Laurent Mesnard, Bruno Moulin, Jean-Noël Ottavioli, Marie-Noelle Péraldi, Evangeline Pillebout, Claire Pouteil-Noble, Philippe Rieu, Claire Rigothier, Jean-Philippe Ryckelynck, Djillali Sahali, Zaara Soltani, Marc Souid, Thomas Stehlé, Maxime Touzot, Pierre Trolliet, Philippe Vanhille, Céline Lebas, David Verhelst, Cecile Vigneau, Laurence Vrigneaud, François Vrtosvnik, Karine Dahan, Hanna Debiec, Emmanuelle Plaisier, Marine Cachanado, Alexandra Rousseau, Laura Wakselman, Pierre-Antoine Michel, Fabrice Mihout, Bertrand Dussol, Marie Matignon, Christiane Mousson, Tabassome Simon, Pierre Ronco, GEMRITUX Study Group, Vincent Audard, Pierre Bataille, Yvon Berland, Jean-Jacques Boffa, Nicolas Bouvier, Laura Braun, Frank Bridoux, Stéphane Burtey, Déborah Chaintreuil, Cindy Castrale, Gabriel Choukroun, Christian Combe, Eric Daugas, Michel Delahousse, Ariane Duval-Sabatier, Marie Essig, Isabelle Etienne, Hélène François, Denis Fouque, Denis Glotz, Michel Godin, Bertrand Gondouin, Morgane Gosselin, Maryvonne Hourmant, Aurélie Hummel, Corinne Isnard-Bagnis, Charlotte Jouzel, Bruno Hurault de Ligny, Alexandre Karras, Thomas Kofman, Philippe Lang, Sandrine Lemoine, Anne-Sophie Librez Verhoeven, Rafik Mesbah, Laurent Mesnard, Bruno Moulin, Jean-Noël Ottavioli, Marie-Noelle Péraldi, Evangeline Pillebout, Claire Pouteil-Noble, Philippe Rieu, Claire Rigothier, Jean-Philippe Ryckelynck, Djillali Sahali, Zaara Soltani, Marc Souid, Thomas Stehlé, Maxime Touzot, Pierre Trolliet, Philippe Vanhille, Céline Lebas, David Verhelst, Cecile Vigneau, Laurence Vrigneaud, François Vrtosvnik
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/m2 intravenous 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.
Keywords: anti-PLA2R antibody; anti-THSD7A antibody; idiopathic membranous nephropathy; randomized controlled trial; rituximab; severe adverse event.
Copyright © 2016 by the American Society of Nephrology.
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Source: PubMed