P0662 Comparative effectiveness and safety of upadacitinib, tofacitinib, and filgotinib in patients with Ulcerative Colitis: analysis of whole and propensity score-matched data
Authors: Bertin L , Scarabello D , Zingone F , Savarino E V , Barberio B 
Published: January 2025

Abstract

Background
Moderate-to-severe Ulcerative Colitis (UC) often requires advanced treatments. Janus kinase (JAK) inhibitors, upadacitinib, tofacitinib, and filgotinib, have demonstrated efficacy in UC, though real-world comparisons remain limited. This retrospective, single-center study conducted at the Padua Hospital outpatient clinic compares the effectiveness and safety of these agents in patients with UC, analyzing clinical, endoscopic, and biomarker remission rates, adverse events, and therapy discontinuations using both full dataset and propensity score-matched (PSM) analyses.

Methods
We retrospectively included UC patients which started anti-JAK therapies at Padua Hospital and collected data for a follow up of 12 months. Whole data analysis was conducted first, followed by PSM based on age, sex, and disease location. Outcomes included clinical, biomarker, and endoscopic remission rates at 3 months (T1), 6 months (T2), and 1 year (T3), adverse events and discontinuation rates. Chi-square or Fisher’s exact test were used for categorical data, ANOVA for continuous data.

Results
Our study included 46 patients with UC patients (16 on upadacitinib, 23 on tofacitinib, 7 on filgotinib) treated at Padua Hospital.
In the whole dataset at T3, clinical remission was 5/15 (33.3%) for upadacitinib, 12/20 (60.0%) for tofacitinib, and 3/4 (75.0%) for filgotinib (p=0.18). Endoscopic remission at T3 was 4/15 (26.7%) for upadacitinib, 7/20 (35.0%) for tofacitinib, and 1/4 (25.0%) for filgotinib (p=0.84). Total adverse events were observed in 12/16 (75.0%) of upadacitinib, 18/23 (78.3%) of tofacitinib, and 6/7 (85.7%) of filgotinib patients (p=0.74). Discontinuations were highest for filgotinib, with 4/7 (57.1%) vs. 1/16 (6.2%) for upadacitinib and 4/23 (17.4%) for tofacitinib (p=0.01).
After matching, at T3, biomarker remission was 1/5 (20.0%) for upadacitinib, 1/5 (20.0%) for filgotinib, and 1/4 (25.0%) for tofacitinib (p=0.58). endoscopic remission at T3 was achieved by 1/5 (20.0%) for upadacitinib, 2/5 (40.0%) for filgotinib, and 1/4 (25.0%) for tofacitinib (p=0.55).Total adverse events were 3/7 (42.9%) for upadacitinib, 4/7 (57.1%) for filgotinib, and 3/7 (42.9%) for tofacitinib (p=0.67). Discontinuation rates were 2/7 (28.6%) for upadacitinib, 2/7 (28.6%) for filgotinib, and 1/7 (14.3%) for tofacitinib (p=0.81).

Conclusion
This study suggests variable effectiveness among JAK inhibitors, with tofacitinib showing higher clinical remission trends. Filgotinib showed higher discontinuation in the whole dataset but differences were less pronounced post-matching. Personalized treatment decisions may benefit UC management; larger studies are needed to confirm findings.

References
1.Honap S, Agorogianni A, Colwill MJ, Mehta SK, Donovan F, Pollok R, Poullis A, Patel K. JAK inhibitors for inflammatory bowel disease: recent advances. Frontline Gastroenterol. 2023 Sep 14;15(1):59-69. doi: 10.1136/flgastro-2023-102400. PMID: 38487554; PMCID: PMC10935522.
2.Davies SC, Hussein IM, Nguyen TM, Parker CE, Khanna R, Jairath V. Oral Janus kinase inhibitors for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2020 Jan 27;1(1):CD012381. doi: 10.1002/14651858.CD012381.pub2. PMID: 31984480; PMCID: PMC6984444.