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

Inflamm Bowel Dis. 2023 Jan 5;29(1):1-8. doi: 10.1093/ibd/izac067.

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.

Keywords: clinical trial data; gender; individual participant data; meta-analysis; sex-based; therapy; tumor necrosis factor inhibitor; ulcerative colitis.

Plain language summary

In our meta-analysis of individual patient data from 4 ulcerative colitis clinical trials, the odds of clinical remission, mucosal healing, and clinical response with tumor necrosis factor inhibitors were lower among men compared to women during induction therapy, but not during maintenance therapy.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • Colitis, Ulcerative* / drug therapy
  • Female
  • Humans
  • Inflammatory Bowel Diseases* / drug therapy
  • Infliximab / therapeutic use
  • Male
  • Remission Induction
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors / therapeutic use

Substances

  • Tumor Necrosis Factor Inhibitors
  • Infliximab