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Comparative Efficacy of Biologic Therapy in Biologic-Naïve Patients With Crohn Disease: A Systematic Review and Network Meta-analysis

Published:October 28, 2014DOI:https://doi.org/10.1016/j.mayocp.2014.08.019

      Abstract

      Objective

      To study the comparative efficacy of biologic therapy in the management of biologic-naïve patients with Crohn disease (CD).

      Patients and 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%).

      Conclusion

      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.

      Abbreviations and Acronyms:

      ADA (adalimumab), CD (Crohn disease), CDAI (Crohn’s Disease Activity Index), CrI (credible interval), CZP (certolizumab pegol), HR (hazard ratio), IBD (inflammatory bowel disease), IFX (infliximab), IL-12/23 (interleukin 12/23), NAT (natalizumab), OR (odds ratio), RCT (randomized controlled trial), RR (relative risk), TNF-α (tumor necrosis factor-α), UST (ustekinumab), VEDO (vedolizumab)
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