Wong Emily C L, Merat Shahin, Monaco Cristina, Dulai Parambir S, Jairath Vipul, Marshall John K, Reinisch Walter, Narula Neeraj
Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
Division of Gastroenterology, Northwestern University, Chicago, IL, USA.
Dig Dis Sci. 2023 Jun;68(6):2635-2646. doi: 10.1007/s10620-023-07956-8. Epub 2023 Apr 29.
In the absence of head-to-head clinical trials, indirect comparative studies are needed to help position therapies in ulcerative colitis (UC). We aimed to compare the efficacy of infliximab vs. tofacitinib for moderate-severe UC among biologic-naïve participants at post-induction.
This was a post-hoc analysis of patient-level data from four clinical trials including 659 biologic-naïve UC participants. We compared proportions of patients achieving week 8 clinical remission (CR), endoscopic improvement, and endoscopic remission. Clinical response at week 2 was also assessed. Multiple logistic regression models were adjusted for potential confounders identified as having an association with the outcome of interest on univariate analysis. Propensity scores were calculated to create a cohort of participants with similar distribution of baseline co-variates.
Patients treated with infliximab had significantly greater odds of CR at week 8 compared to tofacitinib [88/242 (36.4%) vs. 100/417 (24.0%), aOR: 1.65 (95% CI 1.11-2.44), p = 0.013]. Endoscopic improvement at week 8 was also significantly greater among infliximab-treated patients [149/242 (61.6%) vs. 159/417 (38.1%), aOR: 2.12 (95% CI 1.45-3.10), p < 0.001]. Similar findings were observed with week 8 endoscopic remission [61/242 (25.2%) vs. 43/417 (10.3%); aOR: 2.72 (95% CI 1.66-4.46), p < 0.001]. A similar proportion of participants attained clinical response at week 2 [205/242 (84.7%) vs. 334/417 (80.1%), aOR: 1.48 (95% CI 0.93-2.37), p = 0.101]. Similar results were observed among the propensity score matched cohort.
Based on the efficacy observed in this post-hoc analysis, consideration should be given to use of infliximab over tofacitinib for treatment of moderate to severe biologic-naïve UC. However, baseline characteristic mismatches persisted despite propensity score matching, and further studies are needed to confirm our findings.
在缺乏头对头临床试验的情况下，需要进行间接比较研究以帮助确定溃疡性结肠炎（UC）治疗方法的地位。我们旨在比较初治生物制剂的中重度UC患者诱导治疗后英夫利昔单抗与托法替布的疗效。
这是一项对来自四项临床试验的患者水平数据的事后分析，包括659例初治生物制剂的UC患者。我们比较了在第8周达到临床缓解（CR）、内镜改善和内镜缓解的患者比例。还评估了第2周的临床反应。对单变量分析中确定与感兴趣结局相关的潜在混杂因素进行多因素逻辑回归模型调整。计算倾向得分以创建一组基线协变量分布相似的参与者。
与托法替布相比，接受英夫利昔单抗治疗的患者在第8周达到CR的几率显著更高[88/242（36.4%）对100/417（24.0%），调整后比值比（aOR）：1.65（95%置信区间1.11 - 2.44），p = 0.013]。在接受英夫利昔单抗治疗的患者中，第8周的内镜改善也显著更大[149/242（61.6%）对159/417（38.1%），aOR：2.12（95%置信区间1.45 - 3.10），p < 0.001]。第8周内镜缓解也有类似发现[61/242（25.2%）对43/417（10.3%）；aOR：2.72（95%置信区间1.66 - 4.46），p < 0.001]。在第2周达到临床反应的参与者比例相似[205/242（84.7%）对334/417（80.1%），aOR：1.48（95%置信区间0.93 - 2.37），p = 0.101]。在倾向得分匹配队列中观察到类似结果。
基于这项事后分析中观察到的疗效，对于初治生物制剂的中重度UC治疗，应考虑使用英夫利昔单抗而非托法替布。然而，尽管进行了倾向得分匹配，基线特征不匹配仍然存在，需要进一步研究来证实我们的发现。
