Samnani Sunil, Wong Emily C L, Hamam Hasan, Dulai Parambir S, Marshall John K, Jairath Vipul, Reinisch Walter, Narula Neeraj
Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, ON, Canada.
Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
J Crohns Colitis. 2025 Mar 5;19(3). doi: 10.1093/ecco-jcc/jjae151.
Inflammatory bowel disease (IBD) trials often stratify patients by prior biologic exposure, including prior biologic failure or intolerance. This study aimed to assess clinical outcomes in IBD patients with prior biologic failure vs intolerance treated with ustekinumab or vedolizumab.
A post-hoc analysis of ulcerative colitis (UC) and Crohn's disease (CD) clinical trials for ustekinumab (UNITI and UNIFI) and vedolizumab (GEMINI-1 and GEMINI-2) was performed. Clinical response, clinical remission, and endoscopic improvement (for UC) were compared among biologic naïve, biologic failure, and biologic intolerant patients. Statistical analyses, including chi-square tests and logistic regression, were performed.
A total of 1178 UC and 1439 CD patients received either ustekinumab or vedolizumab. In UC, biologic intolerant patients exhibited higher clinical response (54.7% vs 38.8%, aOR 1.87 [95% CI, 0.93-3.73]), clinical remission (25.0% vs 11.0%, aOR 2.84 [95% CI, 1.47-5.49]), and endoscopic improvement (40.6% vs 24.8%, aOR 2.76 [95% CI, 1.28-5.94]) compared to biologic failure, with outcomes similar to biologic naïve patients. In biologic intolerant CD patients, clinical response was similar between prior biologic failure and intolerance (34.2% vs 32.8%), but after adjustment for potential confounders, biologic intolerance was associated with higher odds of clinical response (aOR: 1.67, 95% CI, 1.09-2.55), with no significant difference observed for clinical remission (aOR: 1.48, 95% CI, 0.88-2.49).
Improved treatment outcomes were generally observed in patients with biologic intolerance compared to failure, especially in UC, where outcomes were similar to biologic naïve patients. Future clinical trials should meticulously differentiate prior biologic failure vs intolerance to mitigate potential bias.
炎症性肠病（IBD）试验常常根据患者既往生物制剂暴露情况进行分层，包括既往生物制剂治疗失败或不耐受。本研究旨在评估接受优特克单抗或维多珠单抗治疗的既往生物制剂治疗失败与不耐受的IBD患者的临床结局。
对优特克单抗（UNITI和UNIFI）及维多珠单抗（GEMINI - 1和GEMINI - 2）的溃疡性结肠炎（UC）和克罗恩病（CD）临床试验进行事后分析。比较了初治生物制剂、生物制剂治疗失败及生物制剂不耐受患者的临床缓解、临床应答及内镜改善情况（针对UC）。进行了包括卡方检验和逻辑回归在内的统计分析。
共有1178例UC患者和1439例CD患者接受了优特克单抗或维多珠单抗治疗。在UC中，与生物制剂治疗失败的患者相比，生物制剂不耐受的患者表现出更高的临床应答率（54.7%对38.8%，校正优势比[aOR]为1.87[95%置信区间（CI），0.93 - 3.73]）、临床缓解率（25.0%对11.0%，aOR为2.84[95%CI，1.47 - 5.49]）及内镜改善率（40.6%对24.8%，aOR为2.76[95%CI，1.28 - 5.94]），其结局与初治生物制剂的患者相似。在生物制剂不耐受的CD患者中，既往生物制剂治疗失败与不耐受患者的临床应答相似（34.2%对32.8%），但在对潜在混杂因素进行校正后，生物制剂不耐受与更高的临床应答几率相关（aOR：1.67，95%CI，1.09 - 2.55），临床缓解方面无显著差异（aOR：1.48，95%CI，0.88 - 2.49）。
与生物制剂治疗失败的患者相比，生物制剂不耐受的患者总体上观察到更好的治疗结局，尤其是在UC中，其结局与初治生物制剂的患者相似。未来的临床试验应仔细区分既往生物制剂治疗失败与不耐受情况，以减轻潜在偏倚。
