title: Non-biologic remission maintenance therapy in adult patients with ANCA-associated vasculitis: a systematic review and network meta-analysis.
abstract: OBJECTIVE
  To determine the comparative efficacy of non-biologic treatments for remission maintenance in ANCA-associated vasculitis.
  
  
  METHODS
  We identified all randomized trials comparing leflunomide, azathioprine, methotrexate or mycophenolate mofetil in adult patients with granulomatosis with polyangiitis or microscopic polyangiitis. Relapse-free survival was compared through hazard ratios (HR) using a Bayesian fixed-effects network meta-analysis. Multiple sensitivity analyses were performed to explore biases identified in one trial using original trial data.
  
  
  RESULTS
  Three trials were available (leflunomide-methotrexate, methotrexate- azathioprine, azathioprine-mycophenolate). Mycophenolate was inferior to all treatments, although the 95% credible interval (CrI) of the HR relative to methotrexate crossed 1. Leflunomide was superior to azathioprine (HR 0.43 [95% CrI: 0.14-1.3]) and methotrexate (HR 0.47 [95% CrI: 0.18-1.2]), although the 95% CrI also crossed 1. There was a 90% probability that leflunomide was the best treatment. After down weighting the effect of leflunomide vs. methotrexate for early trial termination and slow MTX dose escalation, there remained a 55% probability leflunomide was best.
  
  
  CONCLUSIONS
  Based on indirect evidence, leflunomide is effective in maintaining remission in granulomatosis with polyangiitis or microscopic polyangiitis relative to other non-biologic treatments. Further randomized trials of leflunomide are needed for confirmation.
authors.affiliation: Department of Internal Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, Alberta, T2N1N1 Canada. Electronic address: glenhazlewood@gmail.com.
authors.forename: Glen S
authors.initials: GS
authors.lastname: Hazlewood
authors.affiliation: University of Lubeck, Bad Branstedy, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Metzler
authors.affiliation: University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, ON, Canada.
authors.forename: George A
authors.initials: GA
authors.lastname: Tomlinson
authors.affiliation: Medical University at Lubeck, Lubeck, Germany.
authors.forename: Wolfgang L
authors.initials: WL
authors.lastname: Gross
authors.affiliation: The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, Canada.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Feldman
authors.affiliation: Department of Internal Medicine, Cochin Hospital, Assistance publique-Hôpitaux de Paris, université Paris-Descartes, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France.
authors.forename: Loic
authors.initials: L
authors.lastname: Guillevin
authors.affiliation: Mount Sinai Hospital, University of Toronto, 60 Murray Street, 2nd Floor, Room 222, Toronto, Ontario, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Pagnoux
mesh_terms: D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy*; D001379:Azathioprine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007555:Isoxazoles / Q000627:therapeutic use; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D007555:Isoxazoles; D000077339:Leflunomide; D009173:Mycophenolic Acid; D001379:Azathioprine; D008727:Methotrexate
keywords: Anti-neutrophil cytoplasm antibody-associated vasculitis; Azathioprine; Leflunomide; Meta-analysis; Methotrexate; Mycophenolic acid