Systematic review with network meta-analysis

The efficacy of anti-TNF agents for the treatment of Crohn's disease

R. W. Stidham, T. C H Lee, P. D R Higgins, Amar R Deshpande, Daniel A Sussman, A. G. Singal, B. J. Elmunzer, S. D. Saini, S. Vijan, A. K. Waljee

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Background Anti-tumour necrosis factor-alpha agents (anti-TNF) are effective therapies for the treatment of Crohn's disease (CD), but their comparative efficacy is unknown. Aim To perform a network meta-analysis comparing the efficacy of anti-TNF therapies in CD. Methods After screening 506 studies, reviewers extracted information on 10 studies. Traditional meta-analysis (TMA) was used to compare each anti-TNF agent to placebo. Bayesian network meta-analysis (NMA) was performed to compare the effects of anti-TNF agents to placebo. In addition, sample sizes for comparative efficacy trials were calculated. Results Compared to placebo, TMA revealed that anti-TNF agents result in a higher likelihood of induction of remission and response (RR: 1.66, 95% CI: 1.17-2.36 and RR: 1.43, 95% CI: 1.17-1.73, respectively) as well as maintenance of remission and response (RR: 1.78, 95% CI: 1.51-2.09 and RR: 1.68, 95% CI: 1.46-1.93, respectively). NMA found nonsignificant trends between infliximab and adalimumab or certolizumab pegol. Among subcutaneous therapies, NMA demonstrated superiority of adalimumab to certolizumab pegol for induction of remission (RR: 2.93, 95% CrI: 1.21-7.75). Sample size calculations suggest that adequately powered head-to-head comparative efficacy trials would require greater than 3000 patients. Conclusions All anti-TNF agents are effective for induction and maintenance of response and remission in the treatment of CD. Although adalimumab is superior to certolizumab pegol for induction of remission, there is no evidence of clinical superiority among anti-TNF agents. Head-to-head trials among the anti-TNF agents are impractical in terms of size and cost.

Original languageEnglish
Pages (from-to)1349-1362
Number of pages14
JournalAlimentary Pharmacology and Therapeutics
Volume39
Issue number12
DOIs
StatePublished - Jan 1 2014

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Crohn Disease
Tumor Necrosis Factor-alpha
Remission Induction
Placebos
Therapeutics
Sample Size
Meta-Analysis
Maintenance
Network Meta-Analysis
Costs and Cost Analysis
Adalimumab
Certolizumab Pegol

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Systematic review with network meta-analysis : The efficacy of anti-TNF agents for the treatment of Crohn's disease. / Stidham, R. W.; Lee, T. C H; Higgins, P. D R; Deshpande, Amar R; Sussman, Daniel A; Singal, A. G.; Elmunzer, B. J.; Saini, S. D.; Vijan, S.; Waljee, A. K.

In: Alimentary Pharmacology and Therapeutics, Vol. 39, No. 12, 01.01.2014, p. 1349-1362.

Research output: Contribution to journalArticle

Stidham, R. W. ; Lee, T. C H ; Higgins, P. D R ; Deshpande, Amar R ; Sussman, Daniel A ; Singal, A. G. ; Elmunzer, B. J. ; Saini, S. D. ; Vijan, S. ; Waljee, A. K. / Systematic review with network meta-analysis : The efficacy of anti-TNF agents for the treatment of Crohn's disease. In: Alimentary Pharmacology and Therapeutics. 2014 ; Vol. 39, No. 12. pp. 1349-1362.
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abstract = "Background Anti-tumour necrosis factor-alpha agents (anti-TNF) are effective therapies for the treatment of Crohn's disease (CD), but their comparative efficacy is unknown. Aim To perform a network meta-analysis comparing the efficacy of anti-TNF therapies in CD. Methods After screening 506 studies, reviewers extracted information on 10 studies. Traditional meta-analysis (TMA) was used to compare each anti-TNF agent to placebo. Bayesian network meta-analysis (NMA) was performed to compare the effects of anti-TNF agents to placebo. In addition, sample sizes for comparative efficacy trials were calculated. Results Compared to placebo, TMA revealed that anti-TNF agents result in a higher likelihood of induction of remission and response (RR: 1.66, 95{\%} CI: 1.17-2.36 and RR: 1.43, 95{\%} CI: 1.17-1.73, respectively) as well as maintenance of remission and response (RR: 1.78, 95{\%} CI: 1.51-2.09 and RR: 1.68, 95{\%} CI: 1.46-1.93, respectively). NMA found nonsignificant trends between infliximab and adalimumab or certolizumab pegol. Among subcutaneous therapies, NMA demonstrated superiority of adalimumab to certolizumab pegol for induction of remission (RR: 2.93, 95{\%} CrI: 1.21-7.75). Sample size calculations suggest that adequately powered head-to-head comparative efficacy trials would require greater than 3000 patients. Conclusions All anti-TNF agents are effective for induction and maintenance of response and remission in the treatment of CD. Although adalimumab is superior to certolizumab pegol for induction of remission, there is no evidence of clinical superiority among anti-TNF agents. Head-to-head trials among the anti-TNF agents are impractical in terms of size and cost.",
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AU - Deshpande, Amar R

AU - Sussman, Daniel A

AU - Singal, A. G.

AU - Elmunzer, B. J.

AU - Saini, S. D.

AU - Vijan, S.

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N2 - Background Anti-tumour necrosis factor-alpha agents (anti-TNF) are effective therapies for the treatment of Crohn's disease (CD), but their comparative efficacy is unknown. Aim To perform a network meta-analysis comparing the efficacy of anti-TNF therapies in CD. Methods After screening 506 studies, reviewers extracted information on 10 studies. Traditional meta-analysis (TMA) was used to compare each anti-TNF agent to placebo. Bayesian network meta-analysis (NMA) was performed to compare the effects of anti-TNF agents to placebo. In addition, sample sizes for comparative efficacy trials were calculated. Results Compared to placebo, TMA revealed that anti-TNF agents result in a higher likelihood of induction of remission and response (RR: 1.66, 95% CI: 1.17-2.36 and RR: 1.43, 95% CI: 1.17-1.73, respectively) as well as maintenance of remission and response (RR: 1.78, 95% CI: 1.51-2.09 and RR: 1.68, 95% CI: 1.46-1.93, respectively). NMA found nonsignificant trends between infliximab and adalimumab or certolizumab pegol. Among subcutaneous therapies, NMA demonstrated superiority of adalimumab to certolizumab pegol for induction of remission (RR: 2.93, 95% CrI: 1.21-7.75). Sample size calculations suggest that adequately powered head-to-head comparative efficacy trials would require greater than 3000 patients. Conclusions All anti-TNF agents are effective for induction and maintenance of response and remission in the treatment of CD. Although adalimumab is superior to certolizumab pegol for induction of remission, there is no evidence of clinical superiority among anti-TNF agents. Head-to-head trials among the anti-TNF agents are impractical in terms of size and cost.

AB - Background Anti-tumour necrosis factor-alpha agents (anti-TNF) are effective therapies for the treatment of Crohn's disease (CD), but their comparative efficacy is unknown. Aim To perform a network meta-analysis comparing the efficacy of anti-TNF therapies in CD. Methods After screening 506 studies, reviewers extracted information on 10 studies. Traditional meta-analysis (TMA) was used to compare each anti-TNF agent to placebo. Bayesian network meta-analysis (NMA) was performed to compare the effects of anti-TNF agents to placebo. In addition, sample sizes for comparative efficacy trials were calculated. Results Compared to placebo, TMA revealed that anti-TNF agents result in a higher likelihood of induction of remission and response (RR: 1.66, 95% CI: 1.17-2.36 and RR: 1.43, 95% CI: 1.17-1.73, respectively) as well as maintenance of remission and response (RR: 1.78, 95% CI: 1.51-2.09 and RR: 1.68, 95% CI: 1.46-1.93, respectively). NMA found nonsignificant trends between infliximab and adalimumab or certolizumab pegol. Among subcutaneous therapies, NMA demonstrated superiority of adalimumab to certolizumab pegol for induction of remission (RR: 2.93, 95% CrI: 1.21-7.75). Sample size calculations suggest that adequately powered head-to-head comparative efficacy trials would require greater than 3000 patients. Conclusions All anti-TNF agents are effective for induction and maintenance of response and remission in the treatment of CD. Although adalimumab is superior to certolizumab pegol for induction of remission, there is no evidence of clinical superiority among anti-TNF agents. Head-to-head trials among the anti-TNF agents are impractical in terms of size and cost.

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