title: Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn's disease: a network meta-analysis.
abstract: OBJECTIVE
  There is controversy regarding the best treatment for patients with Crohn's disease because of the lack of direct comparative trials. We compared therapies for induction and maintenance of remission in patients with Crohn's disease, based on direct and indirect evidence.
  
  
  METHODS
  We performed systematic reviews of MEDLINE, EMBASE, and Cochrane Central databases, through June 2014. We identified randomized controlled trials (N = 39) comparing methotrexate, azathioprine/6-mercaptopurine, infliximab, adalimumab, certolizumab, vedolizumab, or combined therapies with placebo or an active agent for induction and maintenance of remission in adult patients with Crohn's disease. Pairwise treatment effects were estimated through a Bayesian random-effects network meta-analysis and reported as odds ratios (OR) with a 95% credible interval (CrI).
  
  
  RESULTS
  Infliximab, the combination of infliximab and azathioprine (infliximab + azathioprine), adalimumab, and vedolizumab were superior to placebo for induction of remission. In pair-wise comparisons of anti-tumor necrosis factor agents, infliximab + azathioprine (OR, 3.1; 95% CrI, 1.4-7.7) and adalimumab (OR, 2.1; 95% CrI, 1.0-4.6) were superior to certolizumab for induction of remission. All treatments were superior to placebo for maintaining remission, except for the combination of infliximab and methotrexate. Adalimumab, infliximab, and infliximab + azathioprine were superior to azathioprine/6-mercaptopurine: adalimumab (OR, 2.9; 95% CrI, 1.6-5.1), infliximab (OR, 1.6; 95% CrI, 1.0-2.5), infliximab + azathioprine (OR, 3.0; 95% CrI, 1.7-5.5) for maintenance of remission. Adalimumab and infliximab + azathioprine were superior to certolizumab: adalimumab (OR, 2.5; 95% CrI, 1.4-4.6) and infliximab + azathioprine (OR, 2.6; 95% CrI, 1.3-6.0). Adalimumab was superior to vedolizumab (OR, 2.4; 95% CrI, 1.2-4.6).
  
  
  CONCLUSIONS
  Based on a network meta-analysis, adalimumab and infliximab + azathioprine are the most effective therapies for induction and maintenance of remission of Crohn's disease.
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Glen S
authors.initials: GS
authors.lastname: Hazlewood
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Ali
authors.initials: A
authors.lastname: Rezaie
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Meredith
authors.initials: M
authors.lastname: Borman
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Remo
authors.initials: R
authors.lastname: Panaccione
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Subrata
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Departmet of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Cynthia H
authors.initials: CH
authors.lastname: Seow
authors.affiliation: Departmet of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kuenzig
authors.affiliation: University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Tomlinson
authors.affiliation: Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
authors.forename: Corey A
authors.initials: CA
authors.lastname: Siegel
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Gil Y
authors.initials: GY
authors.lastname: Melmed
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Departmet of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada. Electronic address: ggkaplan@ucalgary.ca.
authors.forename: Gilaad G
authors.initials: GG
authors.lastname: Kaplan
mesh_terms: D001688:Biological Products / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D001688:Biological Products; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha
keywords: Anti-TNF Therapy; IBD; Immunosuppressive Agents; Network Meta-analysis