Gender-Based Differences in Response to Tumor Necrosis Factor Inhibitor Therapies for Ulcerative Colitis: Individual Participant Data Meta-Analyses of Clinical Trials

Manasi Agrawal*, Francesca Petralia, Adam Tepler, Laura Durbin, Walter Reinisch, Jean-Frederic Colombel, Shailja C. Shah

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

5 Citations (Scopus)

Abstract

BACKGROUND: Gender-based differences are reported in inflammatory bowel diseases (IBD) pathogenesis, but their impacts on IBD outcomes are not well known. We determined gender-based differences in response to treatment with tumor necrosis factor inhibitor (TNFi) therapies in individuals with ulcerative colitis (UC).

METHODS: We used the Yale University Open Data Access (YODA) platform to abstract individual participant data from randomized clinical trials to study infliximab and golimumab as induction and maintenance therapies in moderately to severely active UC. Using multivariable logistic regression, we examined associations between gender and the endpoints of clinical remission, mucosal healing, and clinical response for each study individually and in a meta-analysis.

RESULTS: Of 1639 patients included in induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment-Subcutaneous [PURSUIT-SC], active ulcerative colitis trials [ACT] 1 and 2) and 1280 patients included in maintenance trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment-Maintenance [PURSUIT-IM], ACT 1 and 2), 696 (42.5%) and 534 (41.7%) were women, respectively. In a meta-analysis of induction trials, the adjusted odds ratios (aORs) of clinical remission (aOR, 0.55; 95% CI, 0.31-0.97), mucosal healing (aOR, 0.47; 95% CI, 0.27-0.83), and clinical response (aOR, 0.51; 95% CI, 0.29-0.90) in the treatment arm and of clinical remission in the placebo arm (aOR, 0.34; 95% CI, 0.15-0.82) were lower in men compared to women. There were no differences in outcomes by gender in the treatment and placebo arms in the meta-analysis of maintenance trials.

CONCLUSIONS: Men are less likely to achieve clinical remission, mucosal healing, and clinical response compared to women during induction treatment with TNFi for UC, but not during the maintenance phase. Future studies delineating the mechanisms underlying these observations would be informative.

Original languageEnglish
Article numberizac067
JournalInflammatory Bowel Diseases
Volume29
Issue number1
Pages (from-to)1-8
Number of pages8
ISSN1078-0998
DOIs
Publication statusPublished - 5 Jan 2023

Bibliographical note

© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. 
For permissions, please e-mail: journals.permissions@oup.com.

Keywords

  • clinical trial data
  • gender
  • individual participant data
  • meta-analysis
  • sex-based
  • therapy
  • tumor necrosis factor inhibitor
  • ulcerative colitis
  • Humans
  • Male
  • Treatment Outcome
  • Remission Induction
  • Tumor Necrosis Factor Inhibitors/therapeutic use
  • Colitis, Ulcerative/drug therapy
  • Female
  • Infliximab/therapeutic use
  • Inflammatory Bowel Diseases/drug therapy

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