Bénédicte Sautenet1, Gilles Blancho, Mathias Büchler, Emmanuel Morelon, Olivier Toupance, Benoit Barrou, Didier Ducloux, Valérie Chatelet, Bruno Moulin, Caroline Freguin, Marc Hazzan, Philippe Lang, Christophe Legendre, Pierre Merville, Georges Mourad, Christine Mousson, Claire Pouteil-Noble, Raj Purgus, Jean-Philippe Rerolle, Johnny Sayegh, Pierre-François Westeel, Philippe Zaoui, Hedia Boivin, Amélie Le Gouge, Yvon Lebranchu. 1. 1 Service de Néphrologie-Immunologie Clinique, CHU Bretonneau, Tours, France. 2 Université François-Rabelais, Tours, France. 3 Institut de Transplantation, Urologie-Néphrologie (ITUN), CHU, Nantes, France. 4 Université François-Rabelais, Tours, France. 5 Service de Néphrologie, CHU Edouard Herriot, Lyon, France. 6 Service de Néphrologie, CHU Maison Blanche, Reims, France. 7 Service d'Urologie, CHU Pitié Salpêtrière, Paris, France. 8 Service de Néphrologie, CHU Jean Minjoz, Besançon, France. 9 Service de Néphrologie, CHU, Caen, France. 10 Service de Néphrologie, CHU Civil, Strasbourg, France. 11 Service de Néphrologie, CHU, Rouen, France. 12 Service de Néphrologie, CHU, Lille, France. 13 Service de Néphrologie, CHU Henri Mondor, Paris, France. 14 Service de Néphrologie, CHU Necker, Paris, France. 15 Service de Néphrologie-Transplantation-Dialyse, CHU Pellegrin, Bordeaux, France. 16 Service de Néphrologie, CHU, Montpellier, France. 17 Service de Néphrologie, CHU, Dijon, France. 18 Service de Néphrologie, CHU, Lyon, France. 19 Service de Néphrologie, CHU, Marseille, France. 20 Service de Néphrologie, CHU, Limoges, France. 21 Service de Néphrologie-Dialyse-Transplantation, CHU, Angers, France. 22 Service de Néphrologie, CHU, Amiens, France. 23 Service de Néphrologie, CHU, Grenoble, France. 24 Service de Pharmacologie Clinique, CHU Bretonneau, Tours, France. 25 INSERM, CIC 1415, CHU Bretonneau, Tours, France.
Abstract
BACKGROUND: Treatment of acute antibody-mediated rejection (AMR) is based on a combination of plasma exchange (PE), IVIg, corticosteroids (CS), and rituximab, but the place of rituximab is not clearly specified in the absence of randomized trials. METHODS: In this phase III, multicenter, double-blind, placebo-controlled trial, we randomly assigned patients with biopsy-proven AMR to receiverituximab (375 mg/m) or placebo at day 5. All patients received PE, IVIg, and CS. The primary endpoint was a composite of graft loss or no improvement in renal function at day 12. RESULTS: Among the 38 patients included, at 1 year, no deaths occurred, but 1 graft loss occurred in each group. The primary endpoint frequency was 52.6% (10/19) and 57.9% (11/19) in the rituximab and placebo groups, respectively (P = 0.744). Renal function improved in both groups, as soon as day 12 with no difference in serum creatinine level and proteinuria at 1, 3, 6, and 12 months. Supplementary administration of rituximab and total number of IVIg and PE treatments did not differ between the 2 groups. Both groups showed improved histological features of AMR and Banff scores at 1 and 6 months, with no significant difference between groups but with a trend in favor of the rituximab group. Both groups showed decreased mean fluorescence intensity of donor-specific antibodies as soon as day 12, with no significant difference between them but with a trend in favor of the rituximab group at 12 months. CONCLUSIONS: After 1 year of follow-up, we observed no additional effect of rituximab in patients receiving PE, IVIg, and CS for AMR. Nevertheless, our study was underpowered and important differences between groups may have been missed. Complementary trials with long-term follow-up are needed.
RCT Entities:
BACKGROUND: Treatment of acute antibody-mediated rejection (AMR) is based on a combination of plasma exchange (PE), IVIg, corticosteroids (CS), and rituximab, but the place of rituximab is not clearly specified in the absence of randomized trials. METHODS: In this phase III, multicenter, double-blind, placebo-controlled trial, we randomly assigned patients with biopsy-proven AMR to receive rituximab (375 mg/m) or placebo at day 5. All patients received PE, IVIg, and CS. The primary endpoint was a composite of graft loss or no improvement in renal function at day 12. RESULTS: Among the 38 patients included, at 1 year, no deaths occurred, but 1 graft loss occurred in each group. The primary endpoint frequency was 52.6% (10/19) and 57.9% (11/19) in the rituximab and placebo groups, respectively (P = 0.744). Renal function improved in both groups, as soon as day 12 with no difference in serum creatinine level and proteinuria at 1, 3, 6, and 12 months. Supplementary administration of rituximab and total number of IVIg and PE treatments did not differ between the 2 groups. Both groups showed improved histological features of AMR and Banff scores at 1 and 6 months, with no significant difference between groups but with a trend in favor of the rituximab group. Both groups showed decreased mean fluorescence intensity of donor-specific antibodies as soon as day 12, with no significant difference between them but with a trend in favor of the rituximab group at 12 months. CONCLUSIONS: After 1 year of follow-up, we observed no additional effect of rituximab in patients receiving PE, IVIg, and CS for AMR. Nevertheless, our study was underpowered and important differences between groups may have been missed. Complementary trials with long-term follow-up are needed.
Authors: James H Lan; David Gjertson; Ying Zheng; Stephanie Clark; Elaine F Reed; Michael J Cecka Journal: Am J Transplant Date: 2018-05-09 Impact factor: 8.086
Authors: Scott Davis; Jane Gralla; Patrick Klem; Suhong Tong; Gina Wedermyer; Brian Freed; Alexander Wiseman; James E Cooper Journal: Am J Transplant Date: 2017-10-24 Impact factor: 8.086