title: 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.
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 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.affiliation: 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.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Sautenet
authors.forename: Gilles
authors.initials: G
authors.lastname: Blancho
authors.forename: Mathias
authors.initials: M
authors.lastname: Büchler
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Morelon
authors.forename: Olivier
authors.initials: O
authors.lastname: Toupance
authors.forename: Benoit
authors.initials: B
authors.lastname: Barrou
authors.forename: Didier
authors.initials: D
authors.lastname: Ducloux
authors.forename: Valérie
authors.initials: V
authors.lastname: Chatelet
authors.forename: Bruno
authors.initials: B
authors.lastname: Moulin
authors.forename: Caroline
authors.initials: C
authors.lastname: Freguin
authors.forename: Marc
authors.initials: M
authors.lastname: Hazzan
authors.forename: Philippe
authors.initials: P
authors.lastname: Lang
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.forename: Pierre
authors.initials: P
authors.lastname: Merville
authors.forename: Georges
authors.initials: G
authors.lastname: Mourad
authors.forename: Christine
authors.initials: C
authors.lastname: Mousson
authors.forename: Claire
authors.initials: C
authors.lastname: Pouteil-Noble
authors.forename: Raj
authors.initials: R
authors.lastname: Purgus
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Rerolle
authors.forename: Johnny
authors.initials: J
authors.lastname: Sayegh
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Westeel
authors.forename: Philippe
authors.initials: P
authors.lastname: Zaoui
authors.forename: Hedia
authors.initials: H
authors.lastname: Boivin
authors.forename: Amélie
authors.initials: A
authors.lastname: Le Gouge
authors.forename: Yvon
authors.initials: Y
authors.lastname: Lebranchu
mesh_terms: D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005602:France; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006084:Graft Rejection / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020127:Recovery of Function; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003404:Creatinine