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Review
. 2016 Oct 24;11(10):e0165435.
doi: 10.1371/journal.pone.0165435. eCollection 2016.

Systematic Review With Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis

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Free PMC article
Review

Systematic Review With Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis

Adrian D Vickers et al. PLoS One. .
Free PMC article

Abstract

Background: Biological therapies are increasingly used to treat ulcerative colitis (UC).

Aim: To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF) therapy.

Methods: A systematic literature review was undertaken to identify studies of biologics approved for UC. Network meta-analysis was conducted for endpoints at induction and maintenance.

Results: Seven studies were included in the meta-analysis of induction treatment for anti-TNF therapy-naïve patients. All biologics were more effective than placebo in inducing clinical response, clinical remission, and mucosal healing. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (odds ratio [OR] [95% credible interval (CrI)]: 2.19 [1.35-3.55]), clinical remission (OR [95% CrI]: 2.81 [1.49-5.49]), and mucosal healing (OR [95% CrI]: 2.23 [1.21-4.14]); there were no other significant differences between biologics for induction efficacy. Five studies were included in the meta-analysis of maintenance treatment, two studies rerandomised responder patients at end of induction, and three followed the same patients 'straight through'. To account for design differences, the number of responders at end of induction was assumed to be equivalent to the number rerandomised. Vedolizumab showed significantly different durable clinical response from comparators (OR [95% CrI] infliximab 3.18 [1.14-9.20], golimumab 2.33 [1.04-5.41], and adalimumab 3.96 [1.67-9.84]). In anti-TNF therapy-experienced patients, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were seen. During maintenance, vedolizumab showed significantly improved rates of mucosal healing versus adalimumab (OR [95% CrI]: 6.72 [1.36-41.0]).

Conclusions: This study expands the understanding of comparative efficacies of biologic treatments for UC, encompassing outcomes and populations not previously studied. All biologic treatments were effective for UC during induction. Vedolizumab demonstrated possible clinical benefits in the maintenance setting versus all comparators, irrespective of prior anti-TNF exposure and after adjusting for differences in study design.

Conflict of interest statement

Claire Ainsworth, Adrian D. Vickers and Caroline S. Ling are employees of RTI Health Solutions. Annika Bergmann, Jasmina Medjedovic and Michael Smyth are employees of Takeda Pharmaceuticals. Reema Mody was an employee of Takeda Pharmaceuticals during the conduct of the study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. PRISMA diagram: identification and selection of sources.
NA, not applicable; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Fig 2
Fig 2. Risk of bias assessment of trials included in the mixed-treatment comparison.
ITT, intent-to-treat.
Fig 3
Fig 3. Forest plot of the odds ratios for biologics vs. placebo for anti-TNF therapy-naïve patients in induction studies.
CrI, credible interval; TNF, tumour necrosis factor. Note: Adalimumab induction dose: 160 mg followed by 80 mg; vedolizumab induction dose: 300 mg; golimumab induction dose: 200 mg subcutaneous at week 0, followed by 100 mg at week 2 and then 100 mg every 4 weeks; infliximab induction dose: 5 mg/kg intravenously at week 0, followed by 5 mg/kg at 2 and 6 weeks.
Fig 4
Fig 4. Comparative efficacy of biological agents as induction therapy for anti-TNF therapy-naïve subpopulation.
CrI, credible interval; OR, odds ratio; TNF, tumour necrosis factor. Note: Treatment effect estimates come from Bayesian mixed-treatment comparison. ORs >1.0 favour the treatment in the left upper square. To obtain ORs for comparison in the opposite direction, reciprocals should be calculated.
Fig 5
Fig 5. Forest plot of the odds ratios for biologics vs. placebo for anti-TNF therapy-naïve patients in maintenance studies.
CrI, credible interval; TNF, tumour necrosis factor. Note: Adalimumab maintenance dose: 40 mg every other week; vedolizumab maintenance dose: 300 mg every 8 weeks; golimumab maintenance dose: 100 mg every 4 weeks; infliximab maintenance dose: 5 mg/kg intravenously every 8 weeks.
Fig 6
Fig 6. Comparative efficacy of biological agents as maintenance therapy for anti-TNF therapy-naïve subpopulation.
CrI, credible interval; OR, odds ratio; TNF, tumour necrosis factor. Note: Treatment effect estimates come from Bayesian mixed-treatment comparison. ORs >1.0 favour the treatment in the left upper square. To obtain ORs for comparison in the opposite direction, reciprocals should be calculated.

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Grant support

This study was conducted by RTI Health Solutions under the direction of Takeda Pharmaceuticals International Inc. The study, analysis of data, and medical writing support were performed by RTI Health Solutions. Takeda Pharmaceuticals International Inc provided funding for the research and employees of Takeda Pharmaceuticals International Inc contributed to the study protocol design, data interpretation, and manuscript development and review.
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