The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.
Inflamm Bowel Dis. 2023 Jan 5;29(1):1-8. doi: 10.1093/ibd/izac067.
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).
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.
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.
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.
炎症性肠病（IBD）的发病机制存在性别差异，但它们对 IBD 结局的影响尚不清楚。我们确定了性别对接受肿瘤坏死因子抑制剂（TNFi）治疗的溃疡性结肠炎（UC）患者的治疗反应的影响。
我们使用耶鲁大学开放数据访问（YODA）平台从随机临床试验中提取个体参与者数据，以研究英夫利昔单抗和戈利木单抗作为中度至重度活动期 UC 的诱导和维持治疗。使用多变量逻辑回归，我们分别在每个研究和荟萃分析中检查了性别与临床缓解、黏膜愈合和临床反应终点之间的关联。
在诱导试验（溃疡性结肠炎研究方案，利用一种研究性治疗-皮下[PURSUIT-SC]，活动期溃疡性结肠炎试验[ACT]1 和 2）中纳入的 1639 例患者和维持试验（溃疡性结肠炎研究方案，利用一种研究性治疗-维持[PURSUIT-IM]，ACT1 和 2）中纳入的 1280 例患者中，分别有 696（42.5%）和 534（41.7%）例为女性。在诱导试验的荟萃分析中，治疗组临床缓解（调整后的优势比[aOR]，0.55；95%置信区间[CI]，0.31-0.97）、黏膜愈合（aOR，0.47；95%CI，0.27-0.83）和临床反应（aOR，0.51；95%CI，0.29-0.90）的调整后比值比（aOR）和安慰剂组的临床缓解（aOR，0.34；95%CI，0.15-0.82）的男性低于女性。在维持试验的荟萃分析中，治疗和安慰剂组的性别之间在结局上没有差异。
与女性相比，男性在接受 UC 的 TNFi 诱导治疗时，更不可能达到临床缓解、黏膜愈合和临床反应，但在维持阶段则不然。未来研究阐明这些观察结果背后的机制将是有益的。
