title: Comparative efficacy of biologic therapy in biologic-naïve patients with Crohn disease: a systematic review and network meta-analysis.
abstract: OBJECTIVE
  To study the comparative efficacy of biologic therapy in the management of biologic-naïve patients with Crohn disease (CD).
  
  
  METHODS
  We conducted a systematic review of randomized controlled trials published from January 1, 1985, through September 30, 2013, comparing biologic agents (infliximab [IFX], adalimumab [ADA], certolizumab pegol, natalizumab, vedolizumab, and ustekinumab) with each other or placebo for inducing and maintaining clinical remission in adults with moderate to severe CD. To increase comparability across trials, we focused on a subset of biologic-naïve patients for the induction end point and on responders to induction therapy for the maintenance end point. We followed a Bayesian network meta-analysis approach.
  
  
  RESULTS
  We identified 17 randomized controlled trials of good methodological quality comparing 6 biologic agents with placebo, with no direct comparison of biologic agents. In network meta-analysis, we observed that IFX (relative risk [RR], 6.11; 95% credible interval [CrI], 2.49-18.29) and ADA (RR, 2.98; 95% CrI, 1.12-8.18), but not certolizumab pegol (RR, 1.48; 95% CrI, 0.76-2.93), natalizumab (RR, 1.36; 95% CrI, 0.69-2.86), vedolizumab (RR, 1.40; 95% CrI, 0.63-3.28), and ustekinumab (RR, 0.61; 95% CrI, 0.15-2.49), were more likely to induce remission than placebo. Similar results were observed for maintenance of remission. Infliximab had the highest probability of being ranked as the most efficacious agent for induction (86%) and ADA for maintenance of remission (48%).
  
  
  CONCLUSIONS
  On the basis of network meta-analysis, IFX may be most efficacious agent for inducing remission in CD in biologic-naïve patients. In the absence of head-to-head treatment comparison, the confidence in these estimates is low. Future comparative efficacy studies are warranted.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. Electronic address: singh.siddharth2@mayo.edu.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis.
authors.forename: Sushil Kumar
authors.initials: SK
authors.lastname: Garg
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
authors.forename: Darrell S
authors.initials: DS
authors.lastname: Pardi
authors.affiliation: Knowledge and Evaluation Research Unit, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Knowledge and Evaluation Research Unit, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Murad
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
authors.forename: Edward V
authors.initials: EV
authors.lastname: Loftus
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068582:Certolizumab Pegol; D003424:Crohn Disease / Q000188:drug therapy*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000069285:Infliximab; D000069442:Natalizumab; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012074:Remission Induction / Q000379:methods; D016896:Treatment Outcome; D000069549:Ustekinumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D007166:Immunosuppressive Agents; D000069442:Natalizumab; D011092:Polyethylene Glycols; C543529:vedolizumab; D000069285:Infliximab; D000069549:Ustekinumab; D000068879:Adalimumab; D000068582:Certolizumab Pegol