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. 2017 May;45(10):1291-1302.
doi: 10.1111/apt.14030. Epub 2017 Mar 22.

Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis controlled trials

A Cholapranee  1 , G S Hazlewood  2   3 , G G Kaplan  2 , L Peyrin-Biroulet  4 , A N Ananthakrishnan  5
Affiliations

Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis controlled trials

A Cholapranee et al. Aliment Pharmacol Ther. 2017 May.

Abstract

Background: Mucosal healing is an important therapeutic endpoint in the management of Crohn's disease (CD) and ulcerative colitis (UC). Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome.

Aim: To perform a systematic review and meta-analysis of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis.

Methods: We performed a systematic review and meta-analysis of randomised controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumour necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC. Pooled effect sizes for induction and maintenance of mucosal healing were calculated and pairwise treatment comparisons evaluated using a Bayesian network meta-analysis.

Results: A total of 12 RCTs were included in the meta-analysis (CD - 2 induction, 4 maintenance; UC - 8 induction, 5 maintenance). Duration of follow-up was 6-12 weeks for induction and 32-54 weeks for maintenance trials. In CD, anti-TNFs were more effective than placebo for maintaining mucosal healing [28% vs. 1%, Odds ratio (OR) 19.71, 95% confidence interval (CI) 3.51-110.84]. In UC, anti-TNFs and anti-integrins were more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). In network analysis, adalimumab therapy was inferior to infliximab [OR 0.45, 95% credible interval (CrI) 0.25-0.82] and combination infliximab-azathioprine (OR 0.32, 95% CrI 0.12-0.84) for inducing mucosal healing in UC. There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC.

Conclusions: Anti-TNF and anti-integrin biological agents are effective in inducing mucosal healing in UC, with adalimumab being inferior to infliximab or combination therapy. Infliximab and adalimumab were similar in CD.

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Conflict of interest statement

Conflicts of interest/Financial support: Dr. Cholapranee has no conflicts of interest to declare.

Dr. Hazlewood has received fellowship funding partially supported by UCB Pharma, honorariums and travel expenses from Abbott, and honorariums from UCB Pharma and has participated in an advisory board meeting for Amgen.

Dr. Kaplan is supported through a New Investigator Award from the Canadian Institute of Health Research and a Population Health Investigator Award from Alberta-Innovates Health-Solutions. Dr. Kaplan has served as a speaker for Janssen and Abbvie. He has participated in advisory board meetings for Abbvie, Janssen, and Shire. Dr. Kaplan has received research support from Abbvie, Shire, and GlaxoSmithKline.

Dr. Peyrin-Biroulet has received consulting fees from Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, Therakos, Pharmacosmos, Pilège, BMS, UCB-pharma, Hospira, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, Pfizer, HAC-Pharma, Index Pharmaceuticals, Amgen, Sandoz, Forward Pharma GmbH, Celgene, Biogen, Lycera, Samsung Bioepis. Lecture fees from Merck, Abbvie, Takeda, Janssen, Takeda, Ferring, Norgine, Tillots, Vifor, Therakos, Mitsubishi, HAC-pharma.

Dr. Ananthakrishnan has received funding from the US National Institutes of Health, served on scientific advisory boards for Abbvie, Cubist and Exact Sciences, and received research funding from Merck and Amgen.

Figures

Figure 1
Figure 1
Algorithm for selection of studies
Figure 2
Figure 2. Effectiveness of biologics in attaining mucosal healing in Crohn’s disease compared to placebo
(a) Induction trials IFX – infliximab; ADA - adalimumab (b) Maintenance trials IFX – infliximab; ADA - adalimumab
Figure 2
Figure 2. Effectiveness of biologics in attaining mucosal healing in Crohn’s disease compared to placebo
(a) Induction trials IFX – infliximab; ADA - adalimumab (b) Maintenance trials IFX – infliximab; ADA - adalimumab
Figure 3
Figure 3. Effectiveness of biologics in attaining mucosal healing in ulcerative colitis compared to placebo
(a) Induction trials IFX – infliximab; ADA – adalimumab; GLM – golimumab; VEDO - vedolizumab (b) Maintenance trials IFX – infliximab; ADA – adalimumab; GLM – golimumab; VEDO - vedolizumab
Figure 3
Figure 3. Effectiveness of biologics in attaining mucosal healing in ulcerative colitis compared to placebo
(a) Induction trials IFX – infliximab; ADA – adalimumab; GLM – golimumab; VEDO - vedolizumab (b) Maintenance trials IFX – infliximab; ADA – adalimumab; GLM – golimumab; VEDO - vedolizumab
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References

    1. Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142:46–54 e42. quiz e30. - PubMed
    1. Burisch J, Jess T, Martinato M, et al. The burden of inflammatory bowel disease in Europe. J Crohns Colitis. 2013;7:322–37. - PubMed
    1. Ananthakrishnan AN, Korzenik JR, Hur C. Can mucosal healing be a cost-effective endpoint for biologic therapy in Crohn’s disease? A decision analysis. Inflamm Bowel Dis. 2013;19:37–44. - PubMed
    1. Froslie KF, Jahnsen J, Moum BA, et al. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007;133:412–22. - PubMed
    1. Rutgeerts P, Vermeire S, Van Assche G. Mucosal healing in inflammatory bowel disease: impossible ideal or therapeutic target? Gut. 2007;56:453–5. - PMC - PubMed

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