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Original research
Efficacy of biological therapies and small molecules in induction and maintenance of remission in luminal Crohn’s disease: systematic review and network meta-analysis
  1. Brigida Barberio1,
  2. David J Gracie2,
  3. Christopher J Black2,
  4. Alexander C Ford2,3
  1. 1Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
  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 Teaching Hospitals NHS Trust, Leeds, Leeds, UK; alexf12399{at}yahoo.com

Abstract

Objective There are numerous biological therapies and small molecules licensed for luminal Crohn’s disease (CD), but these are often studied in placebo-controlled trials, meaning relative efficacy is uncertain. We examined this in a network meta-analysis.

Design We searched the literature to 1 July 2022, judging efficacy according to induction of clinical remission, clinical response and maintenance of clinical remission, and according to previous exposure or non-exposure to biologics. We used a random effects model and reported data as pooled relative risks (RRs) with 95% CIs, ranking drugs according to p-score.

Results We identified 25 induction of remission trials (8720 patients). Based on failure to achieve clinical remission, infliximab 5 mg/kg ranked first versus placebo (RR=0.67, 95% CI 0.56 to 0.79, p-score 0.95), with risankizumab 600 mg second and upadacitinib 45 mg once daily third. However, risankizumab 600 mg ranked first for clinical remission in biologic-naïve (RR=0.66, 95% CI 0.52 to 0.85, p-score 0.78) and in biologic-exposed patients (RR=0.74, 95% CI 0.67 to 0.82, p-score 0.92). In 15 maintenance of remission trials (4016 patients), based on relapse of disease activity, upadacitinib 30 mg once daily ranked first (RR=0.61, 95% CI 0.52 to 0.72, p-score 0.93) with adalimumab 40 mg weekly second, and infliximab 10 mg/kg 8-weekly third. Adalimumab 40 mg weekly ranked first in biologic-naïve patients (RR=0.59, 95% CI 0.48 to 0.73, p-score 0.86), and vedolizumab 108 mg 2-weekly first in biologic-exposed (RR=0.70, 95% CI 0.57 to 0.86, p-score 0.82).

Conclusion In a network meta-analysis, infliximab 5 mg/kg ranked first for induction of clinical remission in all patients with luminal CD, but risankizumab 600 mg was first in biologic-naïve and biologic-exposed patients. Upadacitinib 30 mg once daily ranked first for maintenance of remission.

  • crohn's disease
  • meta-analysis

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Data availability statement

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Footnotes

  • CJB and ACF are joint senior authors.

  • Twitter @bribarberio, @DrCJBlack

  • Contributors ACF is guarantor, 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 the authorship criteria and that no others meeting the criteria have been omitted. Study concept and design: BB, DJG, CB and ACF conceived and drafted the study. BB, CB and ACF analysed and interpreted the data. BB and ACF drafted the manuscript. All authors approved the final draft of the manuscript.

  • 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.

  • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

  • 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.