Abstract
BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.