P724 Upadacitinib is Effective and Safe in Tofacitinib-Experienced Patients with Ulcerative Colitis: A Prospective Real-World Experience

Abstract

Background The development and availability of Janus kinus inhibitors (JAKinibs) for moderately to severely active ulcerative colitis (UC) provides new therapeutic options with both novel mechanisms and unique pharmacodynamic benefits. Tofacitinib (tofa) is a non-selective pan-JAKinib that received FDA approval for UC in 2018 and upadacitinib (upa) is a JAK-1 selective inhibitor, that received FDA approval for UC in 2022. It is unknown whether patients who do not respond to tofa will subsequently respond to upa. We report our real-world experience with upa in UC patients with primary or secondary non-response to tofa. Methods We performed a prospective analysis of clinical outcomes on upa in patients with UC and Crohn’s disease (CD) using pre-determined intervals at weeks 0, 2, 4, and 8 as part of a formalized treatment protocol at our institution. We used the SCCAI and HBI, as well as CRP and fecal calprotectin (FCP) to assess efficacy and recorded treatment-related adverse events and serious adverse events (AEs). Here we report our experience in patients treated with upa who have been previously treated with tofa. Results 26 patients (18=UC, 8=CD) with primary or secondary non-response to tofa received upa. (Table 1) In addition to tofa, all of these patients failed at least two biologics prior to upa treatment. In UC: by week 2 60% (6/10) achieved clinical response, and 40% (4/10) achieved clinical remission. By week 4 87.5% (7/8) achieved clinical remission, and 87.5% (6/8) achieved steroid-free remission; FCP decreased by a mean of 649.2 μg/g from baseline (+/- 772.7). At week 8: 100% (8/8) of patients achieved clinical response, 87.5% (7/8) achieved clinical remission, and of all of these (7/7) achieved steroid-free remission; FCP decreased by a mean of 180 μg/g (+/- 721.8) from baseline. One patient had follow-up to week 12 and continued to be in steroid-free remission. (Table 2) In CD: by week 2 2 of 2 patients achieved clinical remission, by week 4 3 of 3 were in clinical remission, 2 of 3 achieved steroid-free remission, and one patient had follow-up to week 8 and he remained in steroid-free remission. (Table 2). 6 patients experienced AEs, with the most common being acne (19.2%). No infections, MACE, or VTE occurred. Conclusion In this prospective real-world experience in medically-resistant patients with UC and CD who previously failed treatment with tofa and at least two biologics, we describe that upa is rapidly effective, inducing both clinical, steroid-free, and biochemical remission with no serious AEs.