Siddharth Singh1, Sushil Kumar Garg2, Darrell S Pardi3, Zhen Wang4, Mohammad Hassan Murad4, Edward V Loftus3. 1. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. Electronic address: singh.siddharth2@mayo.edu. 2. Department of Surgery, University of Minnesota, Minneapolis. 3. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. 4. Knowledge and Evaluation Research Unit, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.
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.
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.
Authors: Siddharth Singh; Herbert C Heien; Lindsey R Sangaralingham; Stephanie R Schilz; Michael D Kappelman; Nilay D Shah; Edward V Loftus Journal: Clin Gastroenterol Hepatol Date: 2016-04-04 Impact factor: 11.382
Authors: A Cholapranee; G S Hazlewood; G G Kaplan; L Peyrin-Biroulet; A N Ananthakrishnan Journal: Aliment Pharmacol Ther Date: 2017-03-22 Impact factor: 8.171
Authors: Ashwin N Ananthakrishnan; Andrew Cagan; Tianxi Cai; Vivian S Gainer; Stanley Y Shaw; Guergana Savova; Susanne Churchill; Elizabeth W Karlson; Isaac Kohane; Katherine P Liao; Shawn N Murphy Journal: Inflamm Bowel Dis Date: 2016-04 Impact factor: 5.325