S1630 Upadacitinib as Salvage Therapy for Acute Severe Ulcerative Colitis: A Multi-Center Experience

Introduction: In patients with acute severe ulcerative colitis (ASUC), approximately one-third will not respond to corticosteroids, with up to 20% ultimately requiring colectomy. There has been increasing interest in the use of upadacitinib (UPA), a selective Janus Kinase 1 Inhibitor (JAKi), for rescue therapy in these patients. Data on its use in ASUC remains limited warranting further investigation. Methods: We performed a retrospective review of all patients aged 16 years or older who were admitted to Mayo Clinic Rochester or Arizona with a diagnosis of ASUC and treated with UPA from February 2023 through April 2025. Data were captured during admission and 90 days post discharge. Primary outcomes were inpatient clinical response to UPA at day 3 (≥50% reduction in stool frequency, reduction in bleeding) and 90-day colectomy free survival. Secondary endpoints included 90-day clinical remission rates and adverse events. Results: A total of 10 patients were admitted for ASUC during this time frame and received UPA 45 mg daily. All patients were tumor-necrosis factor inhibitor (TNFi)-exposed (80% IFX, 20% adalimumab) with 60% having been exposed to 2 or more advanced therapies. On admission, median CRP was 61.7 mg/L (interquartile range [IQR], 23.2-86.3). By day 3, 60% of patients achieved clinical response. Median CRP at day 3 was reduced to 29.9 mg/L (IRQ, 12.4-38.6), with 50% (4/8) of patients achieving 50% reduction in CRP from baseline. The 90-day colectomy rate was 20%. Ninety-day clinical remission was achieved in 50% (3/6) of patients who continued UPA following hospital discharge. Adverse events (AE) were reported in 30% (3/10) of patients, including acne (20%) and drug-related fever (10%), the latter being the only AE resulting in discontinuation of UPA. No patients developed thromboembolic complications. Conclusion: UPA appears to be an effective and safe option for rescue therapy in patients admitted with ASUC, all of whom were previously exposed to a TNFi. With a substantial proportion of patients achieving clinical response and avoiding colectomy after 90 days of follow-up, this is important given that prior to the availability of JAKi these are patients were more likely to proceed to colectomy. AE leading to discontinuation of UPA were minimal with no thromboembolic events. Further prospective studies are needed to evaluate the efficacy and safety of UPA in this population.