P1081Effectiveness of JAK inhibitors in JAK naïve Ulcerative Colitis patients: Comparative analysis of tofacitinib, filgotinib and upadacitinib in the Dutch ICC Registry

Abstract Background Comparative data on the use of Janus kinase (JAK) inhibitors in ulcerative colitis (UC) patients are limited to retrospective studies. We conducted a prospective cohort study to compare the effectiveness and safety of tofacitinib (TOFA), filgotinib (FIL) and upadacitinib (UPA) in JAK-naïve UC patients. Methods Adult UC patients who initiated TOFA, FIL or UPA treatment in routine care were enrolled in the ICC registry and prospectively followed. Patients with prior exposure to JAK inhibitors were excluded. Corticosteroid-free clinical remission (CSFR; Simple Clinical Colitis Activity Index ≤2 without corticosteroid use), biochemical remission (C-reactive protein ≤5 mg/L or faecal calprotectin ≤250 μg/g), drug persistence and frequency of adverse events (AEs) were compared after 24 weeks of treatment. Inverse probability of treatment weighting was performed to account for baseline differences and treatment selection bias. Results A total of 343 JAK-naïve UC patients were included (TOFA n = 185, FIL n = 108, UPA n = 50). Patients receiving UPA had more frequent exposure to three previous advanced treatment modalities (44% vs. 6.5% for TOFA and 24% for FIL). Among patients with clinical, biochemical or endoscopical signs of active disease at baseline (n = 323), CSFR rates at week 24 were 38%, 47% and 47% in the TOFA, FIL and UPA group, respectively. Biochemical remission was higher for UPA treated patients compared to TOFA (unadjusted OR 2.86, p = 0.012; adjusted OR 1.34, p = 0.0002) and FIL (unadjusted OR 2.21, p = 0.09; adjusted OR 1.21, p = 0.049). Drug persistence was 63%, 70% and 79% in the TOFA, FIL and UPA group, respectively. UPA treatment was associated with a lower discontinuation rate compared to TOFA in the unadjusted analysis (HR 0.49, p = 0.046), which was not confirmed in the adjusted analysis. FIL discontinuation rates did not differ statistically significantly. Infection rates per 100 patient-years were 48.6 (TOFA), 46.4 (FIL), and 60.8 (UPA). Rates of other AEs per 100 patient-years were 78.9 (TOFA), 54.6 (FIL), and 125 (UPA). The percentage of patients that stopped due to AEs was 6.4%, 2.8% and 6.0% for TOFA, FIL and UPA, respectively. Conclusion In this prospective real-world study, we compared TOFA, FIL and UPA treatment in JAK-naïve UC patients. The three treatments showed comparable CSFR rates and drug persistence, whereas UPA was associated with higher biochemical remission rates and more AEs. Conflict of interest: Ms. Naber, Myrthe: No conflict of interest Bouwknegt, Dianne G.: Speakers fees from Alfasigma Nederland B.V. and Takeda Nederland B.V. Visschedijk, Marijn: Speakers fees from Jansen-Cilag, Abbvie, Ferring, Alfasigma, Takeda. Lourens, Leonie: No conflict of interest Van der Meulen - de Jong, Andrea Elisabeth: Speaking fees from Alfasigma, Ferring and Abbvie. Advisory board fees from Abbvie, Alfasigma, Ferring, Janssen, Takeda, Vedanta and grant/research support from Alfasigma, Cablon and Norgine. Bodelier, Alexander: Participation in advisory boards of: Johnson & Johnson, Eli Lilly, Sanofi. Received unrestricted grant from Amphia research fund. Duijvestein, Marjolijn: Grant: Speaking fees from Bristol Meyers Squibb, Takeda, Galapagos, Janssen, Dr. Falk, Advisory board fees from Abbvie, Bristol Meyers Squibb, Celltrion, Galapagos/Alfasigma, Janssen, Takeda Grant/Research support: Pfizer, Bristol Meyers Squibb, Galapagos, Alfasigma, Janssen, Lilly Van Bodegraven, Adriaan Anthonie: A A van Bodegraven is working as Consultant Gastroenterology, is member of the Dutch Society of Gastroenterologists, serving as chair of the committee on Pharmacology, and has served as a consultant or speaker for AbbVie, Alfasigma SpA, Arena Pharmaceuticals, Bristol Myers Squibb, Cablon, Celltrion, Ferring, Galapagos, Janssen, Lilly, Pfizer, Takeda, Teva, Tramedico, and Dutch Ministry of Health (ZonMW) received research grants from Ferring, Pfizer, and Teva and has performed as principal investigator in studies sponsored by Abivax, AbbVie, Alfasigma SpA, Arena Pharmaceuticals, BMS, Celltrion, Galapagos, Janssen, Pfizer, Roche, TEVA and Vedanta Biosciences. De Vries, Annemarie C.: Grant: Grants, advisory boards: Pfizer, Galapagos, Takeda, Janssen Mujagic, Zlatan: Grants from ZonMw, Niels Stensen Fellowship, Maag Lever Darm Stichting (MLDS), Academische Alliantie Fonds (AAF), Top consortium for Knowledge and Innovation (TKI) and Galapagos, advisory board fees from Johnson & Johnson, Eli Lilly, Pfizer (paid to host institution) and speaker’s fees from Friso – Friesland Campina, Galapagos / Alfasigma, Eli Lilly, Takeda (paid to host institution). Pierik, Marieke: Grant: TKI, MLDS, Galapagos, Janssen-Cilag, Takeda, Pfizer Other: Financial support to institution for consultancy or lectures: Takeda, Janssen-Cilag, BMS, MSD, Abbvie, Galapagos, Ferring Verleye, Loriane: No conflict of interest West, Rachel: Speaker fees from Ferring, Pfizer and Janssen. Römkens, Tessa: Speaker or consultant fees for Ferring, Janssen, and Takeda. Jharap, Bindia: No conflict of interest van der Marel, Sander: I have participated in advisory boards for Pfizer, AbbVie, and Janssen in the context of IBD. I have provided educational contributions for Galapagos, in the context of IBD. Additionally, I participated in a documentary project supported by Takeda, a Gastro Magazine supported by AbbVie and a podcast episode supported by Janssen, also in the context of IBD. All engagements were non-recurring. van der Voorn, Michael: No conflict of interest Mensink, Peter: No conflict of interest Mares, Wout: Speaker fees from Janssen and advisory committee AbbVie, Ferring, and Takeda. Horjus Talabur Horje, Carmen Simona: No conflict of interest Jansen, Jeroen Michiel: No conflict of interest Oldenburg, Bas: Unrestricted grants: Abbvie, Takeda, Pfizer, Galapagos Advisory boards: Abbvie, Takeda, Pfizer, Lilly, Galapagos, Janssen van Schaik, Fiona: FDM van Schaik has received consultancy fees from Takeda, Galapagos and AbbVie, speaker’s honoraria from Galapagos, Lilly, AbbVie and Janssen-Cilag B.V., hospitality fees from Ferring and dr. Falk Farma and an unrestricted research grant from Takeda. Löwenberg, Mark: Consultancy/lecture fees from Abbvie, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen-Cilag, Johnson & Johnson, Medtronic, Pfizer, Takeda, Tillotts. Grants received from Alfasigma, NFU transformation deal, ZonMW and TKI.