title: Long-Term Outcomes Among Participants in the WEGENT Trial of Remission-Maintenance Therapy for Granulomatosis With Polyangiitis (Wegener's) or Microscopic Polyangiitis.
abstract: OBJECTIVE
  Findings from the WEGENT trial and other short-term studies have suggested that azathioprine (AZA) or methotrexate (MTX) could effectively maintain remission of granulomatosis with polyangiitis (Wegener's) (GPA) or microscopic polyangiitis (MPA). This study was undertaken to examine whether differences in rates of relapse or adverse events would appear after discontinuation of these 2 maintenance regimens, when assessed over a longer followup period.
  
  
  METHODS
  Long-term outcomes in patients enrolled in the WEGENT trial were analyzed according to their randomized treatment group (AZA or MTX). Parameters at trial entry were evaluated as potential prognostic factors for death, relapse, or damage in multivariate models.
  
  
  RESULTS
  Data from 10 years of followup were available for 112 (88.8%) of the 126 original trial participants. The median followup time was 11.9 years (95% confidence interval [95% CI] 11.3-12.5 years). In patients receiving AZA and those receiving MTX, the 10-year overall survival rates were 75.1% (95% CI 64.8-86.9%) and 79.9% (95% CI 70.3-90.8%) (P = 0.56), respectively, and relapse-free survival rates were 26.3% (95% CI 17.3-40.1%) and 33.5% (95% CI 23.5-47.7%) (P = 0.29), respectively. No between-treatment differences were observed with regard to rates of relapse, adverse events, damage, survival without severe side effects, and survival without relapse and severe side effects. In analyses limited to the 97 patients with GPA, no between-treatment differences in survival rates were observed. The 10-year relapse-free survival rate was lower in patients with GPA than in patients with MPA. However, in the multivariate analysis, anti-proteinase 3 antineutrophil cytoplasmic antibody (ANCA) positivity, and not GPA, was retained as being independently associated with the relapse rate.
  
  
  CONCLUSIONS
  The results of this long-term analysis confirm that AZA and MTX are comparable treatment options for maintaining remission of GPA or MPA. Despite achieving good overall survival with these treatments, relapse rates, adverse events, and damage remain matters of concern and further studies are needed to reduce their frequency in these ANCA-associated vasculitides.
authors.affiliation: Université Paris Descartes and Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Puéchal
authors.affiliation: Université Paris Descartes and Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Pagnoux
authors.affiliation: Hôpital Hôtel-Dieu, Paris, France.
authors.forename: Élodie
authors.initials: É
authors.lastname: Perrodeau
authors.affiliation: Hôpital Hôtel-Dieu, Nantes, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hamidou
authors.affiliation: Hôpital Tenon, Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Boffa
authors.affiliation: Centre Hospitalier de Valenciennes, Valenciennes, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Kyndt
authors.affiliation: Centre Hospitalier de Dax, Dax, France.
authors.forename: François
authors.initials: F
authors.lastname: Lifermann
authors.affiliation: Hôpital Bichat-Claude Bernard, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Papo
authors.affiliation: Centre Hospitalier de Compiègne, Compiègne, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Merrien
authors.affiliation: Hôpital Nord, Amiens, France.
authors.forename: Amar
authors.initials: A
authors.lastname: Smail
authors.affiliation: Hôpital Sud, Rennes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delaval
authors.affiliation: Hôpital de la Cavale Blanche, Brest, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Hanrotel-Saliou
authors.affiliation: Centre Hospitalier Universitaire de Grenoble, Grenoble, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Imbert
authors.affiliation: Hôpital Louis-Pradel, Lyon, France.
authors.forename: Chahéra
authors.initials: C
authors.lastname: Khouatra
authors.affiliation: Centre Hospitalier Régional Universitaire de Lille, Lille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lambert
authors.affiliation: Centre Hospitalier de Cholet, Cholet, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Leské
authors.affiliation: Hôpital Dupuytren, Limoges, France.
authors.forename: Kim H
authors.initials: KH
authors.lastname: Ly
authors.affiliation: Hôpital René-Dubos, Pontoise, France.
authors.forename: Edouard
authors.initials: E
authors.lastname: Pertuiset
authors.affiliation: Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Roblot
authors.affiliation: Hôpital d'Estaing, Clermont-Ferrand, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Ruivard
authors.affiliation: Centre Hospitalier Universitaire d' Angers, Angers, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Subra
authors.affiliation: Hôpital Haut Lévêque, Pessac, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Viallard
authors.affiliation: Université Paris Descartes and Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Terrier
authors.affiliation: Université Paris Descartes and Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Cohen
authors.affiliation: Université Paris Descartes and Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Mouthon
authors.affiliation: Université Paris Descartes and Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Le Jeunne
authors.affiliation: Hôpital Hôtel-Dieu, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravaud
authors.affiliation: Université Paris Descartes and Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Guillevin
mesh_terms: D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055953:Microscopic Polyangiitis / Q000188:drug therapy* / Q000401:mortality; D015999:Multivariate Analysis; D011379:Prognosis; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D001379:Azathioprine; D008727:Methotrexate