P0591 Janus Kinase Inhibitors Improve Liver Biochemistry in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Disease: an ECCO CONFER Study.
Authors: Soriano A , Maggi D , Kagramanova A , Molnar T , Halasz R , Desmedt V , Holvoet T , Savarino E V , Barberio B , Juillerat P , Vieujean S , Zelinkova Z , Durikova D , Kubíčková K , Avni Biron I , Aratari A , Bezzio C , Bettenworth D , Clifford C , Desideri F , Felice C , Levartovsky A , Melotti L , Pugliese D , Scaldaferri F , Viganò C , Schnoy E , Teich N , Shouval D , Drobne D 
Published: January 2025

Abstract

Background
JAK inhibitors (JAKi) can induce and maintain remission in inflammatory bowel disease (IBD). Around 5% of IBD patients develop primary sclerosing cholangitis (PSC). Given the potential involvement of JAK/STAT signaling in PSC pathogenesis, JAKi may have a role in modulating IBD-related PSC. We aim to explore the course of PSC in IBD-PSC patients on JAKi for IBD.

Methods
Following a call-for-cases via ECCO CONFER (Round 10), we retrospectively collected baseline and outcome data for both PSC and IBD, before and after JAKi treatment, including laboratory tests, imaging and endoscopic findings, histopathology and adverse effects. The data were analyzed both descriptively and comparatively. A p-value of less than 0.05 was considered statistically significant.

Results
We collected data from 58 patients (53 ulcerative colitis), with a median of disease duration of 5.5 (IQR 2-9) years (Table 1). The median age at PSC diagnosis was 26 (18.25-40.5) years. Each patient had been treated with a median of 2.5 different types of drugs before starting JAKi; 57% received tofacitinib, 26% upadacitinib, 17% filgotinib. At the time of data analysis, the median time of JAKi exposure was 32 (15.75-69) weeks and we will refer to that median time of exposure when analysing each data related to JAKi exposure. At baseline, alkaline phosphatase (ALP) was elevated in 71% of patients (median, 292 U/L, 185-471). After JAKi exposure, ALP dropped to a median of 203.5 U/L (138.7-394.5), p=0.0004. Among this specific group, 30% of subjects reached normal ALP values. Gamma-glutamyl transferase (GGT) was elevated in 80% of patients (350 U/L, 164-552) and dropped to a median value of 127 U/L (95-270), p=0.0055; 13% of this specific group reached normal values of GGT after JAKi exposure. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were high in 58% and 50% of patients, respectively; following JAKi exposure, the median value of both went down significantly. After a median time of 32 weeks of JAKi treatment, 39,6% of patients had to change therapy: 23% due to primary non-response, 62% due to lack of response, 15% underwent colectomy. Patients who had to change therapy were divided into: switch group, treated with additional 40 (36-46) weeks with a different JAKi; swap group, swapped to biologic for additional 27 (24-40) weeks. Better control of liver biomarkers was observed in the switch group (Figure 1).

Conclusion
Treatment with JAKi can positively impact liver inflammation in terms of cholestasis and cytolysis indexes in patients with PSC and concomitant IBD.

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