Systematic review with network meta‐analysis: comparative assessment of tofacitinib and biological therapies for moderate‐to‐severe ulcerative colitis

• Published in: Alimentary pharmacology & therapeutics Vol. 47; no. 4; pp. 454 - 465
• Main Authors: Bonovas, S., Lytras, T., Nikolopoulos, G., Peyrin‐Biroulet, L., Danese, S.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-02-2018
• Subjects: Adult; Antagonists; Biological Products - therapeutic use; Biological Therapy - adverse effects; Clinical trials; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - pathology; Double-Blind Method; Enzyme inhibitors; Humans; Immunotherapy; Inflammatory bowel disease; Infliximab; Janus kinase; Meta-analysis; Monoclonal antibodies; Mucosa; Network Meta-Analysis; Piperidines - therapeutic use; Pyrimidines - therapeutic use; Pyrroles - therapeutic use; Randomization; Remission; Severity of Illness Index; Systematic review; Tumor necrosis factor-α; Ulcerative colitis
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/apt.14449

Summary
Background
Biological therapies have improved the care of patients with ulcerative colitis (UC). Tofacitinib, an oral small‐molecule Janus kinase inhibitor, is potentially a new treatment option.
Aim
To comparatively assess efficacy and harm of tofacitinib and biologics (infliximab, adalimumab, golimumab and vedolizumab) in adult patients not previously exposed to TNF antagonists.
Methods
We performed a comprehensive search of PubMed, Embase, Scopus, clinical trial registries, regulatory authorities' websites and major conference proceedings, through August 2017, to identify randomised, placebo‐controlled or head‐to‐head trials assessing tofacitinib or biologics as induction and/or maintenance therapy in moderate‐to‐severe UC. Two reviewers independently extracted study data and outcomes, and investigated each trial's risk‐of‐bias. We used conventional meta‐analysis to synthesise direct evidence, and network meta‐analysis for adjusted indirect treatment comparisons.
Results
Fifteen randomised, double‐blind, placebo‐controlled trials (n = 3130) contributed data for induction: All treatments are superior to placebo. Indirect treatment comparisons showed that infliximab is better than adalimumab (OR: 2.01, 95% CI: 1.36‐2.98) and golimumab (1.67, 1.08‐2.59) in clinical response, better than adalimumab (2.10, 1.21‐3.64) in clinical remission, and better than adalimumab (1.87, 1.26‐2.79) and golimumab (1.75, 1.13‐2.73) in mucosal healing. No indirect comparisons between tofacitinib and biologics reached statistical significance. Nine studies (n = 1776) contributed maintenance data showing that all treatments have higher clinical efficacy than placebo. Safety analyses indicated no increased rates of adverse events for the treatments under evaluation (except for infliximab), while vedolizumab may have an advantage regarding the occurrence of serious adverse events.
Conclusions
Tofacitinib and biologics are efficacious and safe for UC. Further high‐quality research is warranted to establish the best therapeutic option.
Linked Content
This article is linked to Tsai and Bonovas et al papers. To view these articles visit https://doi.org/10.1111/apt.14480 and https://doi.org/10.1111/apt.14486.