P0519 Upadacitinib in Acute Severe Ulcerative Colitis among previously anti-TNFa exposed patients
Authors: Manti M , Kamperidis N , Toskas A , Misra R , Arebi N 
Published: January 2025

Abstract

Background
25% of patients with ulcerative colitis (UC) experience acute severe UC (ASUC), with 40% risk of urgent colectomy1. Standard rescue therapy following intravenous steroids includes infliximab (IFX). Many admitted patients are previous non-responders to IFX. JAK inhibitors (JAKi) have a rapid onset of action and may have a role in ASUC. In earlier studies, results were based on heterogenous induction doses2 with patients previously exposed to anti-integrin α4β7, but not anti-TNFα agents3. The aim of our study was to report outcomes with an alternative JAKi, Upadacitinib, using a standard induction dose only among patients previously exposed to anti-TNF agents.

Methods
This retrospective study from February 2023 to October 2024, in a tertiary UK centre. Identified anti-TNF experienced patients admitted with ASUC fulfilling Truelove and Witts’ criteria. All patients treated with Upadacitinib were included. Outcomes were length of stay, colectomy rates and clinical response with biochemical markers (CRP and faecal calprotectin), simple Clinical Colitis Activity Index (SCCAI) score and endoscopic remission rates. Adverse events were also recorded.

Results
Ten patients received Upadacitinib 45 mg daily. The mean age of the patients was 39.7 years (±11.7) and 75% were male. Figure 1 shows previous exposure to biologics and immunomodulators.
The mean follow-up period was 56 days, with no major side effects reported. The mean length of hospital stay was 6.5 days (±4.0) and the mean time from admission to Upadacitinib initiation was 6.5 days (± 2.8). Biochemical and clinical responses are shown in table 1. Biochemically, the median CRP levels at admission demonstrated statistically significant drop when compared to CRP levels at discharge (p = 0.008). The median drop in calprotectin levels was not statistically significant between admission and discharge (p = 0.225). Regarding clinical remission, the mean SCCAI score was 10.5 ± 2.55 prior to Upadacitinib, while it was 2.2± 2.0 on discharge (p= 0.005). The results are summarised in Table 1.
Finally, endoscopic remission was observed in 3 patients who underwent surveillance colonoscopy at 3 months. There were no colectomies during 4-week follow-up.Upadacitinib offers promise as an alternative for treating ASUC in previously anti-TNFα exposed patients. None of our patients underwent colectomy with clinical and biochemical response. A randomised controlled study is warranted to confirm the findings.

Conclusion
Upadacitinib offers promise as an alternative for treating ASUC in previously anti-TNFα exposed patients. None of our patients underwent colectomy with clinical and biochemical response. A randomised controlled study is warranted to confirm the findings.

References
1.Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD. ACG Clinical Guideline: Ulcerative Colitis in Adults. Am J Gastroenterol. 2019;114(3):384-413. doi:10.14309/ajg.0000000000000152
2.Berinstein JA, Karl T, Patel A, et al. Effectiveness of Upadacitinib for Patients With Acute Severe Ulcerative Colitis: A Multicenter Experience. Am J Gastroenterol. 2024;119(7):1421-1425. doi:10.14309/ajg.0000000000002674
3.Ali NM, Shehab MA. Upadacitinib as a Rescue Therapy in Acute Severe Ulcerative Colitis: A Case Report and Review of the Literature. Am J Case Rep. 2023;24. doi:10.12659/AJCR.940966