Loïc Guillevin1, Christian Pagnoux, Alexandre Karras, Chahera Khouatra, Olivier Aumaître, Pascal Cohen, François Maurier, Olivier Decaux, Jacques Ninet, Pierre Gobert, Thomas Quémeneur, Claire Blanchard-Delaunay, Pascal Godmer, Xavier Puéchal, Pierre-Louis Carron, Pierre-Yves Hatron, Nicolas Limal, Mohamed Hamidou, Maize Ducret, Eric Daugas, Thomas Papo, Bernard Bonnotte, Alfred Mahr, Philippe Ravaud, Luc Mouthon. 1. From the Département de Médecine Interne, Hôpital Cochin, Université Paris Descartes, Sorbonne Paris Cité, INSERM Unité 1016, Centre de Référence pour les Maladies Auto-immunes Rares (L.G., C.P., P.C., X.P., A.M., L.M.), Unité de Néphrologie, Hôpital Européen Georges-Pompidou, Université Paris Descartes (A.K.), Hôpital Bichat, Université Paris Diderot, Service de Néphrologie, INSERM Unité 699, Département Hospitalo-Universitaire FIRE (E.D.) and Département de Médecine Interne (T.P.), and Centre d'Epidémiologie Clinique, Hôpital Hôtel-Dieu, Université Paris Descartes, INSERM Unité 738 (P.R.), Assistance Publique-Hôpitaux de Paris, Paris, Service de Pneumologie, Centre de Référence pour Maladies Pulmonaires Rares, Hôpital Universitaire Louis Pradel (C.K.), and Service de Médecine Interne, Hôpital Edouard Herriot (J.N.), Lyon, Centre Hospitalier Universitaire, Hôpital Gabriel Montpied, Clermont-Ferrand (O.A.), Service de Médecine Interne, Hôpitaux privés de Metz, Metz (F.M.), Département de Médecine Interne, Hôpitaux Universitaires de Rennes, Hôpital Sud, Université Rennes I, IGDR-UMR 6290, Rennes (O.D.), Service de Médecine Interne et Néphrologie, Hôpital Général Henri Duffaut, Avignon (P. Gobert), Département de Néphrologie and Département de Médecine Interne, Centre Hospitalier de Valenciennes, Valenciennes (T.Q.), Service de Médecine Interne, Centre Hospitalier Général de Niort, Niort (C.B.-D.), Département de Médecine Interne, Centre Hospitalier Bretagne Atlantique de Vannes, Vannes (P. Godmer), Service de Néphrologie, Dialyse et Transplantation, Centre Hospitalier Universitaire de Grenoble, Grenoble (P.-L.C.), Service de Médecine Interne, Centre National de Référence de la Sclérodermie Systémique, Hôpital Claude Huriez, Université Lille Nord de France, Centre Hospitalier Universitaire de Lille, Lille (P.-Y.H.), Service de Médecine Interne, Centre de Référence Labellisé pour la Prise en Charge des C
Abstract
BACKGROUND: The combination of cyclophosphamide and glucocorticoids leads to remission in most patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitides. However, even when patients receive maintenance treatment with azathioprine or methotrexate, the relapse rate remains high. Rituximab may help to maintain remission. METHODS:Patients with newly diagnosed or relapsing granulomatosis with polyangiitis, microscopic polyangiitis, or renal-limited ANCA-associated vasculitis in complete remission after a cyclophosphamide-glucocorticoid regimen were randomly assigned to receive either 500 mg of rituximab on days 0 and 14 and at months 6, 12, and 18 after study entry or daily azathioprine until month 22. The primary end point at month 28 was the rate of major relapse (the reappearance of disease activity or worsening, with a Birmingham Vasculitis Activity Score >0, and involvement of one or more major organs, disease-related life-threatening events, or both). RESULTS: The 115 enrolled patients (87 with granulomatosis with polyangiitis, 23 with microscopic polyangiitis, and 5 with renal-limited ANCA-associated vasculitis) receivedazathioprine (58 patients) orrituximab (57 patients). At month 28, major relapse had occurred in 17 patients in the azathioprine group (29%) and in 3 patients in the rituximab group (5%) (hazard ratio for relapse, 6.61; 95% confidence interval, 1.56 to 27.96; P=0.002). The frequencies of severe adverse events were similar in the two groups. Twenty-five patients in each group (P=0.92) had severe adverse events; there were 44 events in the azathioprine group and 45 in the rituximab group. Eight patients in the azathioprine group and 11 in the rituximab group had severe infections, and cancer developed in 2 patients in the azathioprine group and 1 in the rituximab group. Two patients in the azathioprine group died (1 from sepsis and 1 from pancreatic cancer). CONCLUSIONS: More patients with ANCA-associated vasculitides had sustained remission at month 28 with rituximab than with azathioprine. (Funded by the French Ministry of Health; MAINRITSAN ClinicalTrials.gov number, NCT00748644; EudraCT number, 2008-002846-51.).
RCT Entities:
BACKGROUND: The combination of cyclophosphamide and glucocorticoids leads to remission in most patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitides. However, even when patients receive maintenance treatment with azathioprine or methotrexate, the relapse rate remains high. Rituximab may help to maintain remission. METHODS:Patients with newly diagnosed or relapsing granulomatosis with polyangiitis, microscopic polyangiitis, or renal-limited ANCA-associated vasculitis in complete remission after a cyclophosphamide-glucocorticoid regimen were randomly assigned to receive either 500 mg of rituximab on days 0 and 14 and at months 6, 12, and 18 after study entry or daily azathioprine until month 22. The primary end point at month 28 was the rate of major relapse (the reappearance of disease activity or worsening, with a Birmingham Vasculitis Activity Score >0, and involvement of one or more major organs, disease-related life-threatening events, or both). RESULTS: The 115 enrolled patients (87 with granulomatosis with polyangiitis, 23 with microscopic polyangiitis, and 5 with renal-limited ANCA-associated vasculitis) received azathioprine (58 patients) or rituximab (57 patients). At month 28, major relapse had occurred in 17 patients in the azathioprine group (29%) and in 3 patients in the rituximab group (5%) (hazard ratio for relapse, 6.61; 95% confidence interval, 1.56 to 27.96; P=0.002). The frequencies of severe adverse events were similar in the two groups. Twenty-five patients in each group (P=0.92) had severe adverse events; there were 44 events in the azathioprine group and 45 in the rituximab group. Eight patients in the azathioprine group and 11 in the rituximab group had severe infections, and cancer developed in 2 patients in the azathioprine group and 1 in the rituximab group. Two patients in the azathioprine group died (1 from sepsis and 1 from pancreatic cancer). CONCLUSIONS: More patients with ANCA-associated vasculitides had sustained remission at month 28 with rituximab than with azathioprine. (Funded by the French Ministry of Health; MAINRITSAN ClinicalTrials.gov number, NCT00748644; EudraCT number, 2008-002846-51.).
Authors: Sebastian Unizony; Miguel Villarreal; Eli M Miloslavsky; Na Lu; Peter A Merkel; Robert Spiera; Philip Seo; Carol A Langford; Gary S Hoffman; Cg M Kallenberg; E William St Clair; David Ikle; Nadia K Tchao; Linna Ding; Paul Brunetta; Hyon K Choi; Paul A Monach; Fernando Fervenza; John H Stone; Ulrich Specks Journal: Ann Rheum Dis Date: 2015-11-30 Impact factor: 19.103