Background Achieving rapid symptom control is important in managing ulcerative colitis (UC). 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 UC. 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 PRO-2 response, defined as ≥50% reduction in stool frequency and rectal bleeding scores at week 2. Secondary outcomes included post-induction PRO-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 UC. At week 2, upadacitinib (65%) and infliximab (36.5%) demonstrated the highest PRO-2 response rates. In adjusted analyses compared to infliximab, upadacitinib demonstrated the highest rate of PRO-2 response [adjusted OR (aOR) 3.57 (95% CI: 2.40-6.20), p=0.029] while mirikizumab [aOR: 0.46 (95% CI 0.32–0.66), p<0.001], adalimumab [aOR: 0.67 (95% CI: 0.46–0.97), p=0.035), and ustekinumab [aOR: 0.60 (95% CI: 0.38-0.96), p=0.031] demonstrated lower odds of early response. At post-induction, all therapies except for upadacitinib demonstrated significantly lower odds of PRO-2 response compared to infliximab at week 8 (all p<0.01). A significantly lower odds of post-induction PRO-2 remission was observed for upadacitinib [aOR: 0.48 (95% CI: 0.34-0.69), p<0.001], adalimumab [aOR: 0.17 (95% CI: 0.11-0.25), p<0.001], and golimumab [aOR: 0.46 (95% CI: 0.26-0.74), p=0.001]. Conclusions Among biologic-naïve moderate to severe UC patients, upadacitinib and infliximab demonstrated the most rapid onset of action and highest post-induction clinical response. .
