One-year Results of the Effects of Rituximab on Acute Antibody-Mediated Rejection in Renal Transplantation: RITUX ERAH, a Multicenter Double-blind Randomized Placebo-controlled Trial.

Bénédicte Sautenet (1, 2) , Gilles Blancho (3) , Matthias Buchler (1, 2) , Emmanuel Morelon (4) , Olivier Toupance (5) , Benoit Barrou (6) , Didier Ducloux (7) , Valérie Châtelet (8) , Bruno Moulin (9) , Caroline Freguin (10) , Marc Hazzan (11) , Philippe Lang (12) , Christophe Legendre (13) , Pierre Merville (14) , Georges Mourad (15, 16, 17) , Christine Mousson (18) , Claire Pouteil-Noble (19) , Raj Purgus (20) , Jean-Philippe Rerolle (21) , Johnny Sayegh (22) , Pierre-François Westeel (23) , Philippe Zaoui (24) , Hedia Boivin (1) , Amélie Le Gouge (25) , Yvon Lebranchu (1, 2)

1 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
2 Université Francois Rabelais [Tours]
3 ITUN - Institut de transplantation urologie-néphrologie
4 Hôpital Edouard Herriot [CHU - HCL]
5 Hôpital Maison Blanche
6 CHU Pitié-Salpêtrière [AP-HP]
7 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
8 Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen]
9 Service de néphrologie et hémodialyse [CHU de Strasbourg]
10 Service de Néphrologie [Rouen]
11 Service de Néphrologie et Transplantation rénale [CHRU-lille]
12 Service de néphrologie et transplantation
13 Service de néphrologie adultes [CHU Necker]
14 Service de Néphrologie-transplantation-dialyse [Bordeaux]
15 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
16 AIDMP - Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415
17 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
18 Service de néphrologie (CHU de Dijon)
19 HCL - Hospices Civils de Lyon
20 Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM]
21 Service de Néphrologie, Dialyse, Transplantations [CHU Limoges]
22 CHU Angers - Centre Hospitalier Universitaire d'Angers
23 CHU Amiens-Picardie
24 Service de néphrologie, dialyse, aphérèses et transplantation
25 CIC - Centre d’Investigation Clinique [Tours] CIC 1415

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.

Domaines: Immunologie; Chirurgie

Bénédicte Sautenet, Gilles Blancho, Matthias Buchler, Emmanuel Morelon, Olivier Toupance, et al.. One-year Results of the Effects of Rituximab on Acute Antibody-Mediated Rejection in Renal Transplantation: RITUX ERAH, a Multicenter Double-blind Randomized Placebo-controlled Trial.. Transplantation, 2016, 100 (2), pp.391 - 399. ⟨10.1097/TP.0000000000000958⟩. ⟨hal-01886920⟩