S1427 A Single Center Experience of Upadacitinib Treatment for Acute Severe Ulcerative Colitis

Introduction: Acute severe ulcerative colitis (ASUC) affects many patients with ulcerative colitis and requires intensive management, including prolonged inpatient care and surgical intervention. Standard of care for ASUC includes intravenous steroids with escalation to biologics and surgery in refractory cases. Recently, there has been increased interest in using upadacitinib, a Janus kinase 1 inhibitor, as salvage therapy in ASUC. While early studies have shown promising results, sample sizes are limited. Given these encouraging early findings, we studied the use of upadactinib for ASUC at our own institution, tracking patient outcomes including need for surgery, steroid-free remission, and adverse medication events. Methods: Patients hospitalized for ASUC flares and started on upadacitinib during 2023 were eligible for inclusion. Retrospective chart review was used to compile data on pre-admission demographics, comorbidities, ulcerative colitis disease history, inpatient laboratory values, colonoscopy data, hospital course, and post-discharge outcomes at 90 days. Results: Fourteen patients met inclusion criteria, 50% of whom were male, with a median age of 30 years. Mean admission hemoglobin was 11.0 g/dl, albumin 3.1 g/dl, C-reactive protein 64.5 mg/L and fecal calprotectin 1981 μg/g. Admission sigmoidoscopy showed Mayo 3 colitis in 9 patients. All patients were treated with standard dosing of upadacitinib (45mg/day) in addition to intravenous methylprednisolone (60mg/day). Median total length of stay (LOS) was 9.5 days, with 3 patients undergoing colectomy or diverting loop ileostomy within 90 days of discharge. Median length of stay after initiation of upadacitinib was 1.5 days. At 90-day follow-up, all nonsurgical patients remained on upadacitinib and 90% were steroid-free. There were no venous thromboembolisms or major adverse cardiovascular events; 2 patients contracted coronavirus disease 2019, one of whom also had norovirus. Conclusion: Upadacitinib in patients with ASUC was associated with rapid clinical improvement and high rates of successful steroid discontinuation, without a significant burden of adverse events. Rates of surgery were slightly higher than those documented in the literature on ASUC, but this likely reflects selection bias towards sicker, more refractory patients. While future studies are required to delineate optimal dosing and long-term safety of upadactinib, this study adds to the growing literature on its efficacy, not only for outpatient treatment of ulcerative colitis but for severe flares of disease requiring admission (see Table 1). Table 1. - Demographics, disease history, inpatient data, and 90-day post-discharge outcomes of patients with acute severe ulcerative colitis treated with upadacitinib Characteristic Total Patients 14 Male (%) 7 (50%) Age (median, IQR) 30 (25.5, 36) Duration (months) of UC (median, IQR) 72 (14, 180) Location of UC disease Proctitis 2 (14%) Left-sided 2 (14%) Pancolitis 10 (71%) Biologic exposure prior to index admission On biologic at admission 10 (71%) Biologic naive 2 (14%) Previously on 1 biologic 1 (7%) Previously on ≥2 biologics 1 (7%) Hospital Course (n=14) Admission CRP (mean ± SD) 64.5 ± 64.7 Admission hemoglobin (mean ± SD) 11.0 ± 1.9 Admission albumin (mean ± SD) 3.1 ± 0.7 Received steroids on admission 14 (100%) Time from admission to upadacitinib, days (median, IQR) 3.5 (2, 8) LOS, days (median, IQR) 9.5 (5, 13) Time from upadacitinib initiation to discharge, days (median, IQR) 3.4 (0.25, 6) Colectomy during admission 1 (7%) 90-day outcomes (n=13) Colectomy or diversion loop ileostomy within 90 days 3 (23%) Steroid-free at 90 days (non-surgical patients only) 9 (90%) VTE within 90 days 0 Adverse events 2 Readmission within 90 days 2 (15%)