Higher-dose regimens of several advanced therapies for ulcerative colitis were associated with higher rates of steroid-free clinical remission at six months compared with standard dosing, according to a large real-world analysis of nearly 15,000 patients.
“Dose optimization is one of the most common and clinically important decisions we make in ulcerative colitis, yet real-world comparative data remain limited,” lead author Ahmed Salem, MD, MRCP, MSc, an internal medicine resident at Maimonides Medical Center in Brooklyn, NY, and incoming gastroenterology fellow at Cleveland Clinic Florida, told GI & Hepatology News ahead of Digestive Disease Week® (DDW) 2026, where the study was presented. “Many advanced therapies now have more than one approved dosing strategy, but clinicians often have little head-to-head evidence to guide whether a higher-dose approach translates into better outcomes outside clinical trials.”
Drawing from a US federated electronic health record network of more than 90 million patients, Dr. Salem, his mentor, Mohamed Al Omari, MD, Director of the IBD Center at the University of Arkansas for Medical Sciences, and colleagues identified adults with UC who initiated treatment with upadacitinib, tofacitinib, risankizumab, or guselkumab between 2018 and 2024 and had at least 12 months of follow-up. Higher-dose regimens were compared with standard-dose regimens within US FDA–approved labeling.
The primary outcome was steroid-free clinical remission at six months. Secondary outcomes included changes in fecal calprotectin and C-reactive protein, therapy switching, UC–related hospitalization, and colectomy. The researchers used propensity weighting to adjust for demographics, disease extent, baseline biomarkers, prior biologic exposure, corticosteroid use, and comorbidities.
Among 14,962 patients, higher-dose therapy was consistently associated with greater remission across all agents. For upadacitinib, remission occurred in 59% of patients receiving 30 mg daily vs 48% receiving 15 mg daily. For tofacitinib, rates were 45% with 10 mg twice daily vs 36% with 5 mg twice daily. For risankizumab, remission occurred in 48% of patients receiving 360 mg every eight weeks vs 40% with 180 mg. For guselkumab, rates were 39% with 200 mg every four weeks vs 33% with 100 mg every eight weeks. All differences were statistically significant (P ≤ 0.002 for all comparisons).
Biomarker outcomes also favored higher doses, with greater reductions in fecal calprotectin and C-reactive protein across all therapies (all P < 0.001). At 12 months, higher-dose regimens were associated with lower rates of therapy switching, hospitalization, and colectomy. “That gives the findings more clinical credibility because the observed benefit appears to reflect improvement in inflammatory burden, not only differences in reporting or follow-up patterns,” Dr. Salem noted.
In adjusted analyses, higher-dose therapy remained more effective across all agents. Patients receiving higher-dose upadacitinib had about 1.5 times the odds of remission and a 38% lower likelihood of hospitalization compared with standard dosing, along with reduced likelihood of switching therapy. Higher dose tofacitinib was associated with 1.4 times the odds of remission and a 32% lower likelihood of hospitalization. Risankizumab and guselkumab also showed increased odds of remission with higher dosing.
“What surprised me most was the consistency of the signal,” Dr. Salem said. “We expected some therapies to show benefit with higher dosing, but the fact that the benefit was seen across all four agents was striking.”
He acknowledged certain limitations of the study, including its observational design and reliance on electronic health record data, which may introduce residual confounding and misclassification. “The next step would be to validate these findings in additional datasets and ideally develop practical risk-stratification tools to identify which patients are most likely to benefit from higher-dose therapy,” he said.
Overall, the findings suggest that dose optimization should be considered a precision-medicine approach rather than simply increasing medication exposure. “In UC, undertreatment can carry major consequences, including persistent inflammation, steroid exposure, hospitalization, and surgery,” Dr. Salem said. “Our findings suggest that for selected patients, using the appropriate higher-dose option within the approved dosing range may help control inflammation earlier and more effectively.”
Dr. Salem reported having no relevant disclosures.
DDW is AGA’s annual meeting, jointly sponsored by AGA, AASLD, ASGE, and SSAT. Learn more at ddw.org.