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

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.

Faecal biomarkers of neutrophil and eosinophil origin reflect the response to biological therapy and corticosteroids in patients with IBD

“…However, our data should be interpreted with caution because few vedolizumab-treated patients were included in our study. The association between sex and remission status at 3 months observed in our study is in line with previous findings on biological therapy ( 31 ).…”

Comparing the efficacy of vedolizumab between males and females: a post-hoc analysis of GEMINI-1 and VARSITY

“…A smaller retrospective cohort study, however, demonstrated no sex-based differences in response to infliximab [28]. Finally, a recent meta-analysis was performed and demonstrated findings in line with our study, in that men were less likely to achieve clinical and endoscopic remission compared to women after completion of the induction phase, with no differences in outcomes after treatment during maintenance [29]. With vedolizumab, one study of 265 patients addressing sex differences in outcome reported that female patients were more likely to terminate use of vedolizumab due to drug intolerance [30].…”

The 2023 Impact of Inflammatory Bowel Disease in Canada: The Influence of Sex and Gender on Canadians Living With Inflammatory Bowel Disease

“…Secondary analyses of individual studies have not generally shown consistent impacts of gender on treatment response ( 34 , 35 ). Two studies have suggested that men receiving golimumab or vedolizumab may have lower rates of response to induction therapy, but that this effect dissipates by the end of the maintenance phase ( 36 ). The reasons for this difference in speed of response are not well characterized.…”