Efficacy of Janus Kinase Inhibitors (JAKi) in the treatment of biologic-naive and biologic-experienced patients with ulcerative colitis

Abstract Introduction Janus kinase inhibitors (JAKi) are an orally available treatment for patients with moderately to severe ulcerative colitis (UC). There are currently 3 JAKi for UC: tofacitinib, filgotinib and upadacitinib with variable selectivity to JAK-11. There is limited data comparing the outcomes between biologic-naive and biologic-experienced patients. This study describes the effectiveness of JAKi according to biologic exposure. Aim To investigate the effectiveness of 3 the JAKi’s, tofacitinib, filgotinib and upadacitinib according to biologic exposure. Method We undertook a retrospective study of UC patients treated with JAKi within a tertiary hospital. Clinical endpoints were assessed at week 8-12. Baseline disease activity, previous advanced therapies and use of corticosteroids were documented. Clinical response was defined as reduction in SCCAI score by ≥3 points from baseline or a sustained score of <2.5. Clinical remission was defined as a SCCAI score of < 2.5, and/ or a calprotectin level of <250 mg/g with a CRP of < 5mg/L. Ethical approval has been granted by HRA and Health and Care Research Wales (HCRW) (REC ref: 24/HRA/1198) Results 52 patients were reviewed at week 8-12 following their first dose. 15, 15 and 22 patients were on tofacitinib, filgotinib, and upadacitinib respectively. 3 (20%) of patient in the tofacitinib group were exposed to at least 3 biologics prior to initiating the JAK Inhibitor, followed by upadacitinib which was 3 (14%) of patients. In the tofacitinib group, most patients were exposed to 2 previous biologics (n=7, 47%), whereas majority of patients on filgotinib and upadacitinib had exposure to 1 previous biologic, 7 (47%) and 8 (36%) patients respectively. For the patient group exposed to 3 or more biologics (n=7, 14%), 100% patients on tofacitinib (n=3) and upadacitinib (n=3) achieved clinical remission by week 8-12, whereas none of the patients on filgotinib achieve clinical remission. In biologic naïve patients, filgotinib demonstrated the greatest improvement in calprotectin score with a reduction in 30% from baseline (n=2, 100%). In patients exposed to ≥3 biologics, upadacitinib achieved higher rates of improvement in faecal calprotectin score (n=2, 100%). Conclusion Our observations suggest that patients exposed to at least 3 biologics, tofacitinib and upadacitinib were the most effective, whereas filgotinib seems to be more effective in biologic naïve patients. Our patient cohort is small. We will continue to collect data and undertake further statistical analysis to examine the significance of the observations and factors associated with effectiveness. Reference 1. Goetsch, A et al. Advances in pharmacotherapy for ulcerative colitis: a focus on JAK1 inhibitors. Expert Opinion on Pharmacotherapy, 2023, 24(7), 849–861.