P1057 Upadacitinib as Salvage Therapy for Acute Severe Ulcerative Colitis: A Single-Center Experience

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Abstract Background Ulcerative colitis (UC) often leads to hospitalization and may be resistant to standard treatments, necessitating colectomy. Upadacitinib (UPA), an oral selective Janus kinase 1 inhibitor, offers a novel mechanism and the benefit of rapid and predictable pharmacokinetics which suggest it may be efficacious in acute severe UC (ASUC). However, there are a limited number of cases using different dosing regimens describing the potential of this treatment for ASUC. We describe the efficacy and safety of UPA in hospitalized patients with ASUC at our center. Methods We conducted an observational cohort study of patients hospitalized for ASUC treated with UPA 45 mg/d as a rescue therapy after failure or incomplete response to other therapies, including corticosteroids. Patient demographics, disease characteristics, and clinical data were collected. The Simple Clinical Colitis Activity Index (SCCAI) was used to monitor clinical response. Clinical outcomes, including loss of response and colectomy, were collected. Results Ten patients (ages 21-78, 40% female) hospitalized for ASUC were treated with UPA (population characteristics and clinical summarized in Table 1). The majority of patients (8/10) had prior exposure to two or more advanced therapies. The median SCCAI score at the time of UPA initiation was 8.5, with improvement in five patients on upadacitinib at week 2 (Figure 1). Six of 10 patients discontinued UPA, 3 of whom underwent colectomy during the same hospitalization due to inadequate response. Two patients underwent surgical intervention after discharge from the hospital. Patients who underwent colectomy had a significantly lower albumin level at the time of UPA initiation compared to patients who didn’t undergo colectomy (3.0 and 4.2 g/dL, respectively; p = 0.005), but not CRP (28.5 and 29.8 mg/L, respectively; p = 0.48). One patient had discontinuation of upadacitinib during the induction phase due to elevated liver enzymes. The median time to discontinuation was 7.5 days. Of the 4 patients on ongoing therapy with UPA after initiation in hospital, 2 have been on the maintenance dose for over 6 months with ongoing remission. Conclusion Our experience with UPA 45 mg/d for salvage therapy in ASUC patients demonstrated a higher colectomy rate than reported in earlier studies, which . Although some patients benefited from UPA with an improvement in SCCAI scores by week 2, the colectomy rate highlights the need for further research to identify which patients are most likely to benefit from UPA therapy. Our findings underscore the importance of personalized approaches to ASUC treatment and warrant further investigation in larger, controlled studies.