Efficacy and Safety of Bezafibrate 400 mg and Bezafibrate 200 mg as Adjunctive Treatments in Patients With Primary Biliary Cholangitis and Non-optimal Biochemical Response to Ursodeoxycholic Acid Therapy

Efficacy and Safety of Bezafibrate 400 mg and Bezafibrate 200 mg as Adjunctive Treatments in Patients With Primary Biliary Cholangitis and Non-optimal Biochemical Response to Ursodeoxycholic Acid Therapy: a 12-month, Double-blind, Randomized, Placebo-controlled Trial With a 12-month, Double-blind, Placebo-free Extension Phase.

Promoteur : Assistance Publique - Hôpitaux de Paris

Titre et résumé fournis en anglais par le registre source, reproduits sans traduction ni interprétation.

Primary biliary cholangitis (PBC) is a rare chronic, progressive, cholestatic liver disease that leads to cirrhosis and its life-threatening complications if undertreated. Ursodeoxycholic acid (UDCA) is the standard-of-care therapy for PBC. However, patients with an inadequate biochemical response to UDCA according to the Paris-2 criteria are still at high-risk of poor clinical outcome. In this situation of biochemical resistance to UDCA, bezafibrate 400 mg/d given in association with UDCA has been shown to improve the symptoms, biochemical response (BEZURSO study), histologic features, and possibly long-term clinical outcome. However, it has been shown that even patients with an adequate response to UDCA but persistent elevation in biochemical markers of cholestasis or liver inflammation, including alkaline phosphatases (ALP), gamma-glutamyl transpeptidase (GGT), transaminases, or total bilirubin (i.e., non-optimal biochemical response) have still an increased risk of death or liver transplantation in the long term, thus defining the complete normalization of these markers as the new clinically-relevant target for PBC treatment. In parallel to these findings, bezafibrate 400 mg/d as a second-line therapy for PBC could be associated with potentially dose-related, muscle, kidney, or liver toxic effects, and whether bezafibrate 200 mg/d could have a better benefit/risk ratio in this disease-setting remains to be determined. Therefore, our aim is to evaluate the efficacy and safety of bezafibrate 400 mg and bezafibrate 200 mg as adjunctive treatments in PBC patients with non-optimal biochemical response to UDCA.