Comparative efficacy of biologic therapy in biologic-naïve patients with Crohn disease: A systematic review and network meta-analysis

Siddharth Singh, Sushil Kumar Garg, Darrell S. Pardi, Zhen Wang, Mohammad H Murad, Edward Vincent Loftus, Jr

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1621-1635
Number of pages15
JournalMayo Clinic Proceedings
Volume89
Issue number12
DOIs
StatePublished - Dec 1 2014

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Biological Therapy
Biological Products
Crohn Disease
Biological Factors
Placebos
Maintenance
Randomized Controlled Trials
Network Meta-Analysis
Infliximab
Therapeutics
Adalimumab

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Comparative efficacy of biologic therapy in biologic-naïve patients with Crohn disease : A systematic review and network meta-analysis. / Singh, Siddharth; Garg, Sushil Kumar; Pardi, Darrell S.; Wang, Zhen; Murad, Mohammad H; Loftus, Jr, Edward Vincent.

In: Mayo Clinic Proceedings, Vol. 89, No. 12, 01.12.2014, p. 1621-1635.

Research output: Contribution to journalArticle

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abstract = "Objective To study the comparative efficacy of biologic therapy in the management of biologic-na{\"i}ve 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-na{\"i}ve 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-na{\"i}ve patients. In the absence of head-to-head treatment comparison, the confidence in these estimates is low. Future comparative efficacy studies are warranted.",
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N2 - 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.

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