Key takeaways:
- A post-hoc analysis of 11 trials found upadacitinib and infliximab had the highest symptom improvement rates at 2 weeks among biologic-naive patients with UC.
- Other advanced therapies had a more gradual onset.
Among biologic-naive patients with moderate to severe ulcerative colitis, upadacitinib and infliximab had the quickest onset and highest postinduction response of eight advanced therapies, according to results of a post-hoc analysis.
The other therapies had a more gradual onset but exhibited strong efficacy by the end of induction.
“We have all these great new therapies for ulcerative colitis, but their clinical trials used completely different timelines and endpoints, making it impossible to compare them head-to-head,” study author Neeraj Narula, MD, MPH, director of the IBD clinic at McMaster University, told Healio. “Our study pooled individual patient data from 11 major trials to look at them on a more-level playing field.”
Diarrhea, urgency and rectal bleeding significantly impair quality of life for patients with moderate to severe UC, and delayed treatment onset can increase risk for complications, according to study background. Achieving symptom relief quickly is a primary treatment goal, but data detailing the speed of onset for available therapies are limited.
Narula and colleagues evaluated onset and induction efficacy for eight advanced therapies using data from 3,573 biologic-naive patients (mean age, 40.8 years; 59.2% women; mean disease duration, 6.6 years) treated with standard induction doses for moderate to severe UC.
Therapies included adalimumab (n = 338), golimumab (n = 149), infliximab (n = 241), mirikizumab (n = 542), tofacitinib (n = 193), upadacitinib (n = 300), ustekinumab (n = 156) and vedolizumab (n = 431). Researchers also included a placebo group (n = 1,223).
Patient-reported outcome-2 (PRO-2) response, defined as at least a 50% reduction in rectal bleeding and stool frequency at 2 weeks, served as the primary outcome. Secondary outcomes included postinduction PRO-2 response and PRO-2 remission at week 2 and at the end of induction.
Results showed upadacitinib (65%) and infliximab (36.5%) exhibited the highest week 2 PRO-2 response rates.
“It was fascinating to see the high week 2 response rate from upadacitinib,” Narula said. “Its speed of onset may suggest it should have a role in management of hospitalized colitis patients, although we need more prospective [randomized controlled trial] data vs. infliximab to fully understand its role in this setting.”
When compared with infliximab in adjusted analysis, upadacitinib demonstrated significantly higher odds of PRO-2 response (aOR = 3.57; 95% CI, 2.4-6.2).
Other therapies appeared significantly less likely than infliximab to demonstrate PRO-2 response at week 2, including mirikizumab (aOR = 0.46; 95% CI, 0.32-0.66), ustekinumab (aOR = 0.6; 95% CI, 0.38-0.96) and adalimumab (aOR = 0.67; 95% CI, 0.46-0.97).
“Clinicians can use this data to tailor treatment directly to how urgent a patient’s situation is,” Narula said. “If a patient is suffering severely and we need to keep them out of the hospital right now, upadacitinib or infliximab are the go-to options; if their disease is more stable, we can comfortably opt for therapies with a more gradual onset but perhaps a different safety or convenience profile.”
By the end of induction at week 8, upadacitinib (79%) and infliximab (72.6%) continued to demonstrate the highest rates of PRO-2 response. The other therapies had significantly lower odds of postinduction PRO-2 response compared with infliximab (P < .001).
PRO-2 remission rates were highest at week 2 for infliximab (34.9%), golimumab (26.9%) and tofacitinib (25.9%). At week 8, ustekinumab (53.9%), infliximab (51.9%) and adalimumab (45.9%) had the highest rates of PRO-2 remission.
“There’s a clear hierarchy when it comes to how fast these drugs provide symptom relief,” Narula said. “Upadacitinib and infliximab are the clear frontrunners for rapid onset, showing significant patient-reported improvement by week 2, though many other therapies definitely catch up by the end of induction.”
Study limitations stem from the individual trials, which varied in methodology, duration of induction and assessment intervals. The trials’ strict inclusion criteria also may limit the generalizability of these findings.
“Moving forward, we really need prospective, real-world studies to see if these speed-of-onset differences directly translate into other meaningful IBD-related outcomes, such as fewer hospitalizations and less corticosteroid use,” Narula said.
For more information:
Neeraj Narula, MD, MPH, who also serves as associate professor of medicine at McMaster University and staff gastroenterologist at Hamilton Health Sciences, can be reached at gastroenterology@healio.com.
Sources/Disclosures
Source:
Wong ECL, et al. Clin Gastroenterol Hepatol. 2026;doi:10.1016/j.cgh.2026.05.020.
Disclosures:
Narula reports honoraria from AbbVie, Amgen, Eli Lilly & Co., Ferring Pharmaceuticals, Fresenius Kabi, Innomar Strategies, Iterative Health, Janssen, Novartis, Organon, Pfizer, Sandoz and Takeda Pharmaceuticals. Please see the study for all other authors’ relevant financial disclosures.
Ask a clinical question and tap into Healio AI’s knowledge base.
- PubMed, enrolling/recruiting trials, guidelines
- Clinical Guidance, Healio CME, FDA news
- Healio’s exclusive daily news coverage of clinical data
