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Original research
Efficacy of biological therapies and small molecules in moderate to severe ulcerative colitis: systematic review and network meta-analysis
  1. Nicholas E Burr1,2,
  2. David J Gracie2,
  3. Christopher J Black2,
  4. Alexander C Ford2,3
  1. 1Department of Gastroenterology, Mid Yorkshire Hospitals NHS Trust, Wakefield, UK
  2. 2Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  3. 3Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
  1. Correspondence to Professor Alexander C Ford, Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, Leeds, UK; alexf12399{at}yahoo.com

Abstract

Objective Biological therapies and small molecules continue to be evaluated in moderate to severely active ulcerative colitis, but are often studied in placebo-controlled trials, meaning their relative efficacy and safety is unknown. We examined this in a network meta-analysis.

Design We searched the literature to October 2021 to identify eligible trials. We judged efficacy using clinical remission, endoscopic improvement, or clinical response, and according to previous exposure or non-exposure to antitumour necrosis factor (TNF)-α therapy. We also assessed safety. We used a random effects model and reported data as pooled relative risks (RRs) with 95% CIs. Interventions were ranked according to their P-score.

Results We identified 28 trials (12 504 patients). Based on failure to achieve clinical remission, upadacitinib 45 mg once daily ranked first versus placebo (RR 0.73; 95% CI 0.68 to 0.80, P-score 0.98), with infliximab 5 mg/kg and 10 mg/kg second and third, respectively. Upadacitinib ranked first for clinical remission in both patients naïve to anti-TNF-α drugs (RR 0.69; 95% CI 0.61 to 0.78, P-score 0.99) and previously exposed (RR 0.78; 95% CI 0.72 to 0.85, P-score 0.99). Upadacitinib was superior to almost all other drugs in these analyses. Based on failure to achieve endoscopic improvement infliximab 10 mg/kg ranked first (RR 0.61; 95% CI 0.51 to 0.72, P-score 0.97), with upadacitinib 45 mg once daily, second, and infliximab 5 mg/kg third. Upadacitinib was more likely to lead to adverse events, but serious adverse events were no more frequent, and withdrawals due to adverse events were significantly lower than with placebo. Infections were significantly more likely with tofacitinib than placebo (RR 1.41; 95% CI 1.03 to 1.91).

Conclusion In a network meta-analysis, upadacitinib 45 mg once daily ranked first for clinical remission in all patients, patients naïve to anti-TNF-α drugs and patients previously exposed. Infliximab 10 mg/kg ranked first for endoscopic improvement. Most drugs were safe and well tolerated.

  • ulcerative colitis
  • meta-analysis

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Footnotes

  • CJB and ACF are joint last authors.

  • Twitter @Nick_Burr1, @DrCJBlack

  • Contributors Guarantor: ACF is guarantor. He accepts full responsibility for the work and the conduct of the study, had access to the data and controlled the decision to publish. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Specific author contributions: Study concept and design: NEB, CB, DJG and ACF conceived and drafted the study. NEB, CB and ACF analysed and interpreted the data. ACF drafted the manuscript. All authors have approved the final draft of the manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.