P821 Multi-site analysis of upadacitinib effectiveness in Crohn's Disease patients: A UK perspective

Abstract

Abstract Background Upadacitinib, a selective Janus Kinase inhibitor, is the newest advanced therapy in our armamentarium for the treatment of Crohn’s Disease (CD). It has been licensed for use in moderate-to-severely active CD. However, we have limited evidence of its effectiveness in a ‘real-world’ setting. Methods We undertook a retrospective cohort study on CD patients treated with upadacitinib in 24 UK hospitals. Clinical endpoints were reviewed at 12 weeks compared to baseline. Clinical remission was defined as Harvey-Bradshaw Index (HBI) <4 and response as HBI reduction ≥3 or sustained HBI <4. Biochemical remission using faecal calprotectin (FCal) and CRP was defined as FCal <200 µg/g and CRP ≤5, and response as FCal or CRP reduction of 50% and no increase in either parameter. Corticosteroid or exclusive enteral nutrition (EEN) use was documented. Results 170 patients (50% male) were included. The breakdown of disease location included 15% ileal, 21% colonic, 61% ileocolonic and 3% upper GI. Prior advanced therapy exposure was seen in 168 patients, with 117 having failed 3 or more agents. Clinically active disease as defined by HBI ≥4 was seen in 133 patients at baseline. Median HBI at baseline was 8 (5-10) and by week 12 this had fallen to 3 (2-6) (p<0.001). 51% received prednisolone and/ or EEN during induction. Of the 128 patients with paired clinical assessment at baseline and 12 weeks clinical remission was achieved in 41% (figure 1A), 96% of whom were in steroid free clinical remission. This also included 39% of those with 3 or more previous advanced therapy failures. A further 40% were noted to have clinical response at 12 weeks. The median faecal calprotectin reduced from 781 µg/g (354-1800) to 255 µg/g (79-655) (p<0.0001) (figure 1B). In a multivariate analysis (table 1), a higher number of previous resections (p=0.031) and use of steroids (p=0.006) increased clinical remission rate whilst disease location/ behaviour, number of prior advanced therapy failures and baseline HBI did not have an effect. There were three significant adverse events noted including: a reported malignancy, zoster reactivation (drug withdrawal required), and thrombosis. Mild lipid, liver function, and full blood count changes were noted in 29 (17%) of patients, not requiring drug withdrawal. Conclusion Upadacitinib was effective in inducing clinical response in our cohort of patients with previously refractory CD regardless of the number of previous advanced therapy failures. A higher number of prior resections may represent lower overall disease burden but further investigation into the relationship with remission is required, as well as to review real-world endoscopic response and maintenance of remission.