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Lookup NU author(s): Professor David Jones
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. Background and Aims: Pruritus is a debilitating symptom for many people living with primary biliary cholangitis (PBC). In studies with seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist, patients with PBC experienced significant improvement in pruritus and reduction of serum bile acids. Interleukin-31 (IL-31) is a cytokine known to mediate pruritus, and blocking IL-31 signaling provides relief in pruritic skin diseases. This study examined the connection between seladelpar’s antipruritic effects and IL-31 and bile acid levels in patients with PBC. Approach and Results: IL-31 levels were quantified in serum samples from the ENHANCE study of patients with PBC receiving daily oral doses of placebo (n = 55), seladelpar 5 mg (n = 53) or 10 mg (n = 53) for 3 months, and for healthy volunteers (n = 55). IL-31 levels were compared with pruritus using a numerical rating scale (NRS, 0–10) and with bile acid levels. Baseline IL-31 levels closely correlated with pruritus NRS (r = 0.54, p < 0.0001), and total (r = 0.54, p < 0.0001) and conjugated bile acids (up to 0.64, p < 0.0001). Decreases in IL-31 were observed with seladelpar 5 mg (−30%, p = 0.0003) and 10 mg (−52%, p < 0.0001) versus placebo (+31%). Patients with clinically meaningful improvement in pruritus (NRS ≥ 2 decrease) demonstrated greater dose-dependent reductions in IL-31 compared to those without pruritus improvement (NRS < 2 decrease). Strong correlations were observed for the changes between levels of IL-31 and total bile acids (r = 0.63, p < 0.0001) in the seladelpar 10 mg group. Conclusions: Seladelpar decreased serum IL-31 and bile acids in patients with PBC. The reductions of IL-31 and bile acids correlated closely with each other and pruritus improvement, suggesting a mechanism to explain seladelpar’s antipruritic effects.
Author(s): Kremer AE, Mayo MJ, Hirschfield GM, Levy C, Bowlus CL, Jones DE, Johnson JD, McWherter CA, Choi Y-J
Publication type: Article
Publication status: Published
Journal: Hepatology
Year: 2024
Volume: 80
Issue: 1
Pages: 27-37
Print publication date: 01/07/2024
Acceptance date: 01/12/2023
Date deposited: 17/09/2024
ISSN (print): 0270-9139
ISSN (electronic): 1527-3350
Publisher: Lippincott Williams and Wilkins
URL: https://doi.org/10.1097/HEP.0000000000000728
DOI: 10.1097/HEP.0000000000000728
Data Access Statement: Data are available from the corresponding authors upon reasonable request.
PubMed id: 38117036
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