PPAR agonists in PBC: Where do we go from here? Or how to choose between the new and the old.

Autor: Tanaka A; Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan. Electronic address: a-tanaka@med.teikyo-u.ac.jp., Corpechot C; Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris & Inserm UMR_S938, Saint-Antoine Research Center, Sorbonne University, Paris, France.
Jazyk: angličtina
Zdroj: Clinics and research in hepatology and gastroenterology [Clin Res Hepatol Gastroenterol] 2024 Jun; Vol. 48 (6), pp. 102358. Date of Electronic Publication: 2024 Apr 26.
DOI: 10.1016/j.clinre.2024.102358
Abstrakt: The recent phase 3 trials of peroxisome proliferator-activated receptor (PPAR) agonists in primary biliary cholangitis (PBC) patients with incomplete response to ursodeoxycholic acid (UDCA) demonstrated very promising short-term biochemical responses. However, long-term outcomes, crucial in chronic diseases like PBC, remain uncertain. While real-world data (RWD) support surrogate endpoints, there's a need to validate long-term efficacy especially with combination therapies. Bezafibrate, an off-label option with extensive RWD, demonstrated short-term response, reduced patients' pruritus, and improved long-term outcomes. Therefore, the therapeutic choice between new selective PPAR agonists and old bezafibrate poses a challenge. Undoubtedly further investigations into new PPAR agonists in terms of long-term efficacy are warranted, but prospective, randomized trials in post-approval settings are very unlikely to be successfully conducted, necessitating alternative approaches using RWD rather than traditional trial design. Finally, it will be essential to identify patients who may be intolerant and/or unresponsive to PPAR agonists.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Tanaka reports receiving consultant fees from EA Pharma, GlaxoSmithKline, Kowa Company Ltd., Abbvie and Gilead Sciences. Dr. Corpechot reports receiving grants from Arrow Generiques and Intercept France, consulting fees from Intercept France, Ipsen, Cymabay, Calliditas, GlaxoSmithKline and EchoSens, and fees for teaching from Intercept France and GlaxoSmithKline France.
(Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: