DAY 3 - Benefit of Upadacitinib Therapy Is Long-Lasting for Individuals With Inflammatory Bowel Disease

Findings from two long-term studies presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania showed that people treated with upadacitinib for Crohn’s Disease (CD) and ulcerative colitis (UC) maintained clinical and endoscopic improvements over several years of maintenance therapy.

Upadacitinib (Rinvoq), a selective Janus kinase 1 inhibitor, has emerged as a novel, promising therapy for moderate to severe UC and CD, demonstrating sustained efficacy and a favorable safety profile in phase 3 clinical trials.
 
In the U-ENDURE maintenance substudy, upadacitinib therapy, administered in 15 mg or 30 mg daily doses, showed greater efficacy than placebo in maintaining clinical and endoscopic improvements achieved in patients with moderately to severely active CD over a period of 52 weeks.

A long-term extension (LTE) substudy was designed to assess the efficacy and safety of upadacitinib maintenance therapy in individuals who completed the 52-week treatment, over a period of up to 204 weeks. Edward Loftus, MD, Professor of Gastroenterology at the Mayo Clinic College of Medicine and Science in Rochester, Minnesota, who presented the findings of the long-term study in a plenary session, reported that the improvements seen in the initial trial and in the 52-week maintenance phase were maintained with both doses of upadacitinib. “Sustained efficacy for clinical, endoscopic, and inflammatory biomarkers was observed in patients who completed up to 2 years of upadacitinib maintenance therapy,” Loftus said. “No new safety signals were identified in patients who received upadacitinib therapy for at least 2 years, and up to 5 years, in the ongoing U-ENDURE LTE substudy.”

These results were mirrored by an interim analysis from the U-ACTIVATE trial, an ongoing, 288-week, multicenter phase 3 long-term extension study designed to assess the efficacy of upadacitinib in patients with moderately to severely active UC. Lead author Remo Panaccione, MD, Director of the Inflammatory Bowel Disease Unit at the University of Calgary in Calgary, Canada, reported that patients enrolled in the extension trial sustained clinical and endoscopic improvements of UC over a period of 3 years.

Clinical and endoscopic improvements were observed in a majority of patients treated with both doses of upadacitinib. Approximately 75% of patients treated with upadacitinib achieved clinical remission by week 96 of the LTE study. A similar proportion of patients maintained the response with the 15 mg dose at week 96, with a slightly higher response rate observed with the higher dose. Almost half of the treated participants achieved endoscopic remission, with more than half of those maintaining remission status through week 96. Response rates were slightly better with the higher dose of upadacitinib, the author said.

“The long-term safety profile for upadacitinib treatment through 3 years was consistent with previous analyses,” Panaccione added. “These data provide further evidence of the positive benefit-risk profile of upadacitinib in patients with moderately to severely active ulcerative colitis, and support the continued use of upadacitinib in these patients.”