Elafibranor for primary biliary cholangitis: a dual PPAR agonist changing the treatment landscape

艾拉菲布拉诺用于治疗原发性胆汁性胆管炎:一种改变治疗格局的双重PPAR激动剂

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Abstract

Primary biliary cholangitis (PBC) is a chronic autoimmune disease characterized by granulomatous destruction of intrahepatic bile ducts. Current first-line treatments that delay liver damage but induce harmful side effects include ursodeoxycholic acid (UDCA), requiring lifelong administration among other complications, and obeticholic acid (OCA) associated with recurrent pruritus. In a recent breakthrough for PBC treatment, the Food and Drug Administration (FDA) granted accelerated approval for Iqirvo (elafibranor). A dual PPAR α/δ agonist, it works by decreasing bile acid synthesis and increasing bile acid export, thereby reducing liver inflammation and limiting PBC progression. Based on the promising results from the ELATIVE phase 3 trial, which show significant reduction in alkaline phosphatase (ALP) levels and normalization of bilirubin levels, its approval can position Iqirvo as an ideal second-line treatment for PBC. Apart from mild gastrointestinal side effects and moderate drug interactions, Iqirvo is found to be safe and effective with a recommended daily dosage of 80 mg, marking a crucial advancement in the treatment landscape for PBC. This perspective explores the implications of Iqirvo's approval, highlights the need for continued innovation in PBC treatment, and discusses potential future directions for therapeutic strategies, including combination therapies and personalized approaches tailored to patient needs.

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