A Single-Arm pilot study of BRodalumab in the treatment of Primary Sclerosing Cholangitis (SABR-PSC)

Elzubeir, Amera (2025) A Single-Arm pilot study of BRodalumab in the treatment of Primary Sclerosing Cholangitis (SABR-PSC). Doctoral thesis, University of East Anglia.

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Abstract

Primary sclerosing cholangitis (PSC) is a rare, chronic, progressive fibroinflammatory cholangiopathy of unknown aetiology, frequently associated with inflammatory bowel disease (IBD). Licensed medical therapies are lacking, rendering liver transplantation as the only life-extending option and underscoring the significant unmet need for safe, effective and acceptable disease-modifying interventions. Recent basic science and translational research implicates the interleukin 17 (IL-17) pathway and T-helper 17 cells (Th-17) in PSC pathogenesis.

This thesis aimed to evaluate the safety and feasibility of brodalumab, an IL-17 receptor-targeting monoclonal antibody licensed for psoriasis, in PSC, in order to inform the design and conduct of a future adequately powered study. A single-arm, open-label pilot study (SABR-PSC) was conducted at large UK tertiary NHS centres. Secondary exploratory efficacy outcomes included change from baseline in liver biochemistry, surrogate markers of liver fibrosis, quantitative multi-parametric magnetic resonance imaging (MRI) and patient reported outcome measures (5-D Itch, CLDQ-PSC, PSC-PRO). Semi-structured interviews explored participant experiences. In parallel a systematic review and meta-analysis evaluated the safety and efficacy of advanced therapies in PSC-IBD to inform safety monitoring. Pre-trial feasibility work confirmed a limited pool of eligible PSC patients at a single centre.

Recruitment was lower than expected for SABR-PSC. A total of six participants were enrolled and received treatment with brodalumab over 13 weeks. Retention and treatment adherence were excellent (100%). Brodalumab was safe and well-tolerated in this small cohort with and without concomitant IBD, with no gastrointestinal safety signals observed.

These findings demonstrate the feasibility of delivering a trial of brodalumab in PSC and supports the rationale for a future phase 2 study. However, they also highlight the need for multicentre collaboration, careful dose selection, robust surrogate endpoints and optimised recruitment strategies to ensure success.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	Chris White
Date Deposited:	09 Apr 2026 13:20
Last Modified:	09 Apr 2026 13:20
URI:	https://ueaeprints.uea.ac.uk/id/eprint/102731
DOI:

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