A long-term extension (LTE) study, presented at the American College of Gastroenterology, evaluated the efficacy and safety of upadacitinib (UPA), an oral Janus kinase inhibitor, as maintenance therapy for moderately to severely active Crohn's disease (CD).

The U-ENDURE LTE substudy included patients who had completed a 52-week UPA maintenance study, continuing their treatment at either 15 mg (UPA15) or 30 mg (UPA30) once daily. Efficacy outcomes were assessed over a 48-week period in terms of clinical remission, endoscopic response, and endoscopic remission using as observed (AO) and nonresponder imputation (NRI) methods. Safety outcomes were assessed from the start of maintenance treatment, with up to 5 years of cumulative UPA exposure.

Results indicated stable efficacy rates from LTE week 0 to week 48. Clinical remission based on stool frequency/abdominal pain score (SF/APS) ranged from 78.3% to 82.9% for UPA15 and from 84.7% to 76.6% for UPA30. Remission rates based on the CD Activity Index (CDAI) were 81.3% to 83.1% for UPA15 and 86.1% to 86.8% for UPA30. Endoscopic response rates were also consistent, from 59.6% to 67.1% (UPA15) and 71.2% to 69.6% (UPA30), with endoscopic remission maintained from 42.4% to 45.1% (UPA15) and from 53.0% to 56.3% (UPA30). Inflammatory markers high-sensitivity C-reactive protein (hs-CRP) and fecal calprotectin (FCP) showed stable reductions, confirming the sustained anti-inflammatory effects of UPA.

The safety profile remained consistent, with no new safety signals. Higher rates of COVID-19 infection, herpes zoster, and lymphopenia were noted in the UPA30 group compared to UPA15. Overall, UPA maintenance therapy demonstrated sustained efficacy in achieving clinical, endoscopic, and inflammatory remission for up to 2 years in CD, with manageable safety outcomes.

Reference
D'Haens GR, Louis E, Loftus EV, et al. Efficacy and safety of upadacitinib maintenance treatment in patients with moderately to severely active crohn’s disease: two-year results from the U-ENDURE long-term extension study. Presented at: American College of Gastroenterology. October 25-30, 2024; Philadelphia, PA.