Comparing Onset of Efficacy of Biologic and Small Molecule Therapies in Biologic-Naïve Ulcerative Colitis: A Post-Hoc Analysis

BACKGROUND & AIMS: Achieving rapid symptom control is important in managing ulcerative colitis. However, data regarding speed of onset of therapies among these patients remains limited. We compared the onset and induction efficacy of advanced therapies in biologic-naïve patients with moderate to severe ulcerative colitis. METHODS: This post-hoc analysis utilized individual participant-level data from 11 randomized controlled trials. We evaluated biologic-naïve patients receiving standard induction doses of infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, mirikizumab, tofacitinib, or upadacitinib. The primary outcome was early Patient-Reported Outcome-2 response, defined as ≥50% reduction in stool frequency and rectal bleeding scores at week 2. Secondary outcomes included post-induction Patient-Reported Outcome-2 response and remission. Logistic regression models adjusted for baseline covariates were used with infliximab as the active comparator. RESULTS: The analysis included 3573 biologic-naïve patients with moderate to severe ulcerative colitis. At week 2, upadacitinib (65%) and infliximab (36.5%) demonstrated the highest Patient-Reported Outcome-2 response rates. In adjusted analyses compared to infliximab, upadacitinib demonstrated the highest rate of Patient-Reported Outcome-2 response (adjusted odds ratio, 3.57; 95% confidence interval, 2.40-6.20; P = .029), whereas mirikizumab (adjusted odds ratio, 0.46; 95% confidence interval, 0.32-0.66; P < .001), adalimumab (adjusted odds ratio, 0.67; 95% confidence interval, 0.46-0.97; P = .035), and ustekinumab (adjusted odds ratio, 0.60; 95% confidence interval, 0.38-0.96; P = .031) demonstrated lower odds of early response. At postinduction, all therapies except for upadacitinib demonstrated significantly lower odds of Patient-Reported Outcome-2 response compared with infliximab at week 8 (all P < .01). A significantly lower odds of postinduction Patient-Reported Outcome-2 remission was observed for upadacitinib (adjusted odds ratio, 0.48; 95% confidence interval, 0.34-0.69; P < .001), adalimumab (adjusted odds ratio, 0.17; 95% confidence interval, 0.11-0.25; P < .001), and golimumab (adjusted odds ratio, 0.46; 95% confidence interval, 0.26-0.74; P = .001). CONCLUSIONS: Among biologic-naïve patients with moderate to severe ulcerative colitis, upadacitinib and infliximab demonstrated the most rapid onset of action and highest postinduction clinical response.