Effectiveness and tolerability of bezafibrate in primary biliary cholangitis – a nationwide real-world study

Abstract

Introduction: 

Off-label bezafibrate is increasingly used for primary biliary cholangitis (PBC) following randomized evidence of clinical efficacy. Evaluate the real-world experience with bezafibrate in PBC in relation to tolerability, response and long-term outcome.

Methods: 

All patients initiating off-label bezafibrate in the Dutch PBC Cohort Study (DPCS) – a retrospective cohort study– were evaluated. Biochemical changes (Δ) during the first year of treatment were assessed, expressed in upper limits of normal (ULN). Dichotomous response was evaluated with the Paris II criteria and normal alkaline phosphatase (ALP).

Results: 

In total, 317 individuals (290 [91.5%] females) initiated bezafibrate therapy. Median baseline ALP was 2.30 (IQR 1.52–3.36) and median TB 0.58 (IQR 0.41–0.92). At 12 months, the cumulative cessation rate was 24.6% (95%CI 19.7–29.5); the minimal cessation rate due to side effects was 12.9%. The overall on-treatment median ΔALP and ΔTB at 12 months were -1.00xULN (IQR -1.50 to -0.49) and -0.06xULN (IQR -0.20 to 0.05). Normal ALP increased from 6% at baseline to 40% at one year, and Paris II fulfilment from 19% to 48% (p<0.001 both). The ΔALP at one year was 0.83 (IQR -1.25 to -0.53) in complete responders and -1.16 (IQR -2.34 to -0.45) in incomplete responders (p=0.078). Multivariable logistic regression showed that ALP (OR 0.52, 95%CI 0.34 – 0.80) and AST (OR 0.22, 95%CI 0.10 – 0.51) were negatively associated with the Paris II response. Ln(ALP in ULN) during bezafibrate treatment were associated with decompensation, liver transplantation or death (HR 3.29, 95%CI 1.76-6.16, p<0.001).

Discussion: 

In this real-world nationwide study, the one-year fibrate discontinuation rate was substantial. However off-label use of bezafibrate was associated with reductions in the biochemical markers of cholestasis in PBC, which were associated with clinical outcome in this setting of second line therapy.

Copyright © 2025 The American College of Gastroenterology. The American Journal of Gastroenterology.

Note: Obeticholic acid, marketed under the brand name Ocaliva^® for the treatment of primary biliary cholangitis (PBC), was voluntarily withdrawn from the US market by Intercept Pharmaceuticals following a request from the US Food and Drug Administration (FDA) on 11/14/2025