PROFUNDUS: Real-World Outcomes With Upadacitinib in Ulcerative Colitis, With Remo Panaccione, MD

New interim data from the ongoing PROFUNDUS study, presented at the European Crohn’s and Colitis Organisation Congress, provide important real-world insight into the effectiveness and safety of upadacitinib (Rinvoq) in patients with moderate-to-severe ulcerative colitis (UC).

While randomized controlled trials established the drug’s efficacy under tightly controlled conditions, the PROFUNDUS findings help clarify how those results translate into everyday clinical practice.

In an interview with HCPLive, Remo Panaccione, MD, director of the inflammatory bowel disease unit at the University of Calgary, explained that randomized controlled trials rely on strict inclusion and exclusion criteria, often excluding the complex patients physicians routinely encounter. Real-world studies like PROFUNDUS, by contrast, include patients with diverse comorbidities, varied steroid tapering approaches, and heterogeneous prior treatment histories.

“When we complement those findings from the randomized controlled trials with real world evidence, if we see that the response rates and remission rates that we're seeing in the clinical trials hold up in the real world in these complex settings, it gives us a lot more confidence that the trial results are valid and that they can be translated into our clinical practice,” Panaccione explained. “Plus, it gives us that experience in those patients that are not necessarily included in the clinical trials.”

The interim analysis evaluated 494 of the first 500 eligible adult patients (aged 18-79 years) with moderate-to-severe UC who initiated once-daily upadacitinib across 16 countries, per investigator discretion and according to the local label. Induction was initiated with the first dose of upadacitinib 45 mg at the beginning of the study. Maintenance was initiated with the start of upadacitinib 15 mg or upadacitinib 30 mg after completion of the induction phase.

Assessed endpoints included clinical response per Partial Adapted Mayo Score (PAMS), corticosteroid (CS)-free response per PAMS, clinical remission per Partial Mayo Score (PMS), absence of abdominal pain, and absence of bowel urgency at week 26.

Among the overall population at week 26, with any upadacitinib dose, 81.8% of patients achieved clinical response, 72.4% clinical remission, 66.3% no abdominal pain, and 71.9% no bowel urgency. Among those on baseline CS, 64.4% attained CS-free response. Of note, similar results were observed for all endpoints, regardless of advanced therapy status.

Among patients treated with upadacitinib induction/maintenance) at either 45/15 mg, 45/30 mg, or any upadacitinib dose, adverse event (AE) were 66.0%, 50.8%, and 51.4%, respectively. Serious AEs were 3.8%, 4.6%, and 5.7%, and severe AEs were 5.7%, 4.0%, and 5.5%. Within the subgroup of patients who experienced TEAEs potentially related to upadacitinib, as assessed by the study investigator, exhibited serious and severe AEs at 3.6%, 6.3%, 6.9%, and 7.1%, 5.4%, 6.9%, respectively.

Panaccione called attention to the consistency of the results across advanced therapy–naïve and experienced populations. Of note, in October 2025, the US Food and Drug Administration approved an updated indication statement for upadacitinib for the treatment of adults with moderately to severely active UC and moderately to severely active Crohn's disease (CD), allowing the use of upadacitinib for patients with moderately to severely active UC or CD after they have received ≥ 1 approved systemic therapy in the event tumor necrosis factor (TNF) blockers are clinically inadvisable. Previously upadacitinib was only indicated for adults who had an inadequate response or intolerance to ≥ 1 blockers.

“This data from the real world studies allows physicians to feel very confident that they can position upadacidinib in different patient populations,” Panaccione said.

Editors’ Note: Panaccione reports relevant disclosures with Abbott, AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Janssen, Lilly, Novartis, Takeda, and others.

References

1. R Panaccione, M Fumery, D Bettenworth, S Danese, P Morisset, M Mallick, S H Chen, J Kim, S Suravaram, G Parkes, P1073 Real-World Effectiveness, Symptomatic Improvement, and Safety of Upadacitinib in Patients With Moderate-to-Severe Ulcerative Colitis: Interim Findings From the PROFUNDUS Study, Journal of Crohn's and Colitis, Volume 20, Issue Supplement_1, January 2026, jjaf231.1254, https://doi.org/10.1093/ecco-jcc/jjaf231.1254

2. Brooks A. FDA Approves Updated Indication for Upadacitinib (Rinvoq) in IBD. HCPLive. October 13, 2025. Accessed February 20, 2026. https://www.hcplive.com/view/fda-approves-updated-indication-for-upadacitinib-rinvoq-in-ibd