Evidence Grows for Upadacitinib in Managing Moderate to Severe UC

Upadacitinib continues to show sustained long-term efficacy and a consistent safety profile in patients with moderate to severe ulcerative colitis, as confirmed by both clinical trial data and real-world evidence presented at Digestive Disease Week (DDW) 2025.

Digestive Disease Week (DDW) was held in San Diego, California from May 3 to May 6, 2025. | Image credit: Aliaksandr Marko - stock.adobe.com

Upadacitinib Demonstrates Sustained Long-Term Efficacy and Safety in Ulcerative Colitis

New results from a long-term extension (LTE) study of upadacitinib reaffirmed its sustained efficacy and consistent safety profile in patients with moderately to severely active ulcerative colitis (UC).¹ This ongoing, multicenter, phase 3 LTE study is designed to evaluate the long-term impact of upadacitinib over 288 weeks. The latest efficacy and safety data, analyzed through June 30, 2024, included patients who had completed 52 weeks of maintenance therapy and then received an additional 144 weeks of open-label treatment with either upadacitinib 15 mg or upadacitinib 30 mg once daily.

Upadacitinib, an oral, selective Janus kinase inhibitor, has previously shown favorable outcomes in phase 3 trials. In the LTE, more than half of the participants maintained clinical remission per the Adapted Mayo Score through week 144 of the extension phase, demonstrating the durability of treatment benefits. Additionally, over 72% of patients achieved endoscopic improvement, and nearly half of the participants achieved endoscopic remission, regardless of whether they were receiving upadacitinib 15 mg or 30 mg. These results were achieved without the concomitant use of corticosteroids, emphasizing upadacitinib’s capacity to support steroid-free disease control in the long term.

The safety profile of upadacitinib remained consistent with earlier studies, and no new safety signals were identified. Rates of serious adverse events and treatment discontinuations due to adverse events were similar between the 15-mg and 30-mg dose groups, indicating a stable and manageable safety risk over time.

Overall, the findings from this LTE study (U-ACTIVATE) provide compelling evidence supporting the long-term use of upadacitinib in the treatment of moderate to severe UC. The sustained clinical and endoscopic benefits, coupled with a favorable safety profile over nearly 4 years of treatment, highlight upadacitinib as a viable long-term therapeutic option for patients seeking effective, steroid-free disease management.

Real-World Study Confirms Upadacitinib Efficacy, Safety in UC Through 1 Year

An interim analysis from the multinational, observational IBD-DACH study EUROPE presented at DDW 2025 offers robust real-world evidence supporting the effectiveness and safety of upadacitinib for patients with moderately to severely active UC.² This prospective analysis included 111 patients with available 52-week data and a broader safety cohort of 263 individuals treated across 73 sites.

At baseline, the median patient age was 37.6 years, with 40.5% female. Most patients had extensive disease—50.5% with pancolitis and 43.2% with left-sided colitis. Notably, 88.3% had prior exposure to advanced therapies, including tumor necrosis factor inhibitors (77.6%) and integrin inhibitors (69.4%).

Upadacitinib demonstrated strong efficacy across multiple domains. Over 75% of patients achieved symptomatic remission at weeks 8 and 52, and more than 80% reported no rectal bleeding during the same periods. Biochemical markers also improved significantly: the rate of biochemical remission (fecal calprotectin ≤ 250 μg/g and C-reactive protein < 5 mg/L) rose from 12.7% at baseline to 63.2% at week 52.

Intestinal ultrasound findings supported these outcomes, with median sigmoid bowel wall thickness (BWT) decreasing from 5 mm to 2.7 mm. The proportion of patients with pathological BWT (> 3 mm) dropped from 90.4% to 21.2% by week 52.

Safety outcomes were consistent with known profiles. Among 263 patients, the most frequent adverse events were infections (12.2%), skin disorders (11.0%), and gastrointestinal disorders (7.6%). Serious infections occurred in 1.9%, and thrombotic events in 3.0%.

These findings reinforce upadacitinib’s positive benefit-risk profile in real-world UC management.

References

1. Panaccione R, Lichtenstein G, Colombel J-F, et al. Efficacy and safety of upadacitinib after 4 years of treatment in patients with moderately to severely active ulcerative colitis: interim long-term data from the phase 3 open-label extension study (U-ACTIVATE). Presented at: Digestive Disease Week 2025; May 3-6, 2025; San Diego, CA. Poster 1841.

2. Zeissig S, Schmelz R, Helwig U, et al. Upadacitinib improves symptomatic, biochemical, and sonographic parameters in active UC patients up to one year after treatment induction – one year interim results from the IBD-DACH study EUROPE. Presented at: Digestive Disease Week 2025; May 3-6, 2025; San Diego, CA. Poster 265.