P821 Multi-site analysis of upadacitinib effectiveness in Crohn's Disease patients: A UK perspective
Authors: Radia C , Danso Y , Kok K , Samaan M , Kent A J , Pavlidis P , Patel K , Harrow P , Yeung K , Hussain M A , Dong C , Morris T , Patel C , Cummings J F , Hale M , Pillay L , Walsh A , Sebastian S , Trodden-Mittnacht H , Davis E , Yeo J H , Campbell R , Mehta S , Sethi-Arora K , Fraser A , George B , Harvey P , Sawan N J , Hicks L , Allah-Ditta M , Johnston E , Dhar A , Al-zarrad D , Kumar R , Young D , Butler K , Raine T , Rice J , Hewitt A , Selinger C 
Published: January 2024

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) &lt;4 and response as HBI reduction ≥3 or sustained HBI &lt;4. Biochemical remission using faecal calprotectin (FCal) and CRP was defined as FCal &lt;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&lt;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&lt;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.