Systematic review with network meta-Analysis: The efficacy of anti-tumour necrosis factor-Alpha agents for the treatment of ulcerative colitis

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

Research output: Contribution to journalArticle

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Abstract

Summary Background Antibodies against tumour necrosis factor-Alpha (anti-TNF) are effective therapies in the treatment of ulcerative colitis (UC), but their comparative efficacy is unknown. Aim To perform a network meta-Analysis comparing the efficacy of anti-TNF agents in UC. Methods After screening 506 studies, reviewers extracted information on seven 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: 2.45, 95% CI: 1.72-3.47 and RR: 1.65, 95% CI: 1.37-1.99 respectively) as well as maintenance of remission and response (RR: 2.00, 95% CI: 1.52-2.62 and RR: 1.76, 95% CI: 1.46-2.14 respectively). Individually, infliximab, adalimumab and goliumumab resulted in a higher likelihood of induction and maintenance for both remission and response. NMA found nonsignificant trends in comparisons of the individual agents. The required sample sizes for direct head-to-head trials between infliximab and adalimumab for induction and maintenance are 174 and 204 subjects respectively. Conclusions This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis. However, network meta-Analysis demonstrates that no single agent is clinically superior to the others and therefore, other factors such as cost, safety, route of administration and patient preference should dictate our choice of anti-TNF agents. A randomised comparative efficacy trial between infliximab and adalimumab in UC is of practical size and should be performed.

Original languageEnglish (US)
Pages (from-to)660-671
Number of pages12
JournalAlimentary Pharmacology and Therapeutics
Volume39
Issue number7
DOIs
StatePublished - Apr 2014

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Ulcerative Colitis
Tumor Necrosis Factor-alpha
Antibodies
Placebos
Maintenance
Remission Induction
Sample Size
Meta-Analysis
Therapeutics
Patient Preference
Network Meta-Analysis
Safety
Costs and Cost Analysis
Infliximab
Adalimumab

ASJC Scopus subject areas

  • Pharmacology (medical)

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Systematic review with network meta-Analysis : The efficacy of anti-tumour necrosis factor-Alpha agents for the treatment of ulcerative colitis. / Stidham, R. W.; Lee, T. C H; Higgins, P. D R; Deshpande, A. R.; Sussman, D. A.; Singal, A. G.; Elmunzer, B. J.; Saini, S. D.; Vijan, S.; Waljee, A. K.

In: Alimentary Pharmacology and Therapeutics, Vol. 39, No. 7, 04.2014, p. 660-671.

Research output: Contribution to journalArticle

Stidham, RW, Lee, TCH, Higgins, PDR, Deshpande, AR, Sussman, DA, Singal, AG, Elmunzer, BJ, Saini, SD, Vijan, S & Waljee, AK 2014, 'Systematic review with network meta-Analysis: The efficacy of anti-tumour necrosis factor-Alpha agents for the treatment of ulcerative colitis', Alimentary Pharmacology and Therapeutics, vol. 39, no. 7, pp. 660-671. https://doi.org/10.1111/apt.12644
Stidham, R. W. ; Lee, T. C H ; Higgins, P. D R ; Deshpande, A. R. ; Sussman, D. 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-tumour necrosis factor-Alpha agents for the treatment of ulcerative colitis. In: Alimentary Pharmacology and Therapeutics. 2014 ; Vol. 39, No. 7. pp. 660-671.
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abstract = "Summary Background Antibodies against tumour necrosis factor-Alpha (anti-TNF) are effective therapies in the treatment of ulcerative colitis (UC), but their comparative efficacy is unknown. Aim To perform a network meta-Analysis comparing the efficacy of anti-TNF agents in UC. Methods After screening 506 studies, reviewers extracted information on seven 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: 2.45, 95{\%} CI: 1.72-3.47 and RR: 1.65, 95{\%} CI: 1.37-1.99 respectively) as well as maintenance of remission and response (RR: 2.00, 95{\%} CI: 1.52-2.62 and RR: 1.76, 95{\%} CI: 1.46-2.14 respectively). Individually, infliximab, adalimumab and goliumumab resulted in a higher likelihood of induction and maintenance for both remission and response. NMA found nonsignificant trends in comparisons of the individual agents. The required sample sizes for direct head-to-head trials between infliximab and adalimumab for induction and maintenance are 174 and 204 subjects respectively. Conclusions This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis. However, network meta-Analysis demonstrates that no single agent is clinically superior to the others and therefore, other factors such as cost, safety, route of administration and patient preference should dictate our choice of anti-TNF agents. A randomised comparative efficacy trial between infliximab and adalimumab in UC is of practical size and should be performed.",
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AU - Sussman, D. A.

AU - Singal, A. G.

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