Effectiveness and Tolerability of Bezafibrate in Primary Biliary Cholangitis: A Nationwide Real-World Study

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

All patients initiating off-label bezafibrate in the Dutch PBC Cohort Study-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).

In total, 317 individuals (290 [91.5%] females) initiated bezafibrate therapy. Median baseline ALP was 2.30 (interquartile range [IQR] 1.52-3.36) and median total bilirubin (TB) 0.58 (IQR 0.41-0.92). At 12 months, the cumulative cessation rate was 24.6% (95% confidence interval [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 -1.00 × ULN (IQR -1.50 to -0.49) and -0.06 × ULN (IQR -0.20 to 0.05), respectively. Normal ALP increased from 6% at baseline to 40% at 1 year, and Paris II fulfilment from 19% to 48% ( P < 0.001 both). The ΔALP at 1 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 (odds ratio 0.52, 95% CI 0.34-0.80) and AST (odds ratio 0.22, 95% CI 0.10-0.51) were negatively associated with the Paris II response. Ln(ALP in ULN) during bezafibrate treatment was associated with decompensation, liver transplantation, or death (hazard ratio 3.29, 95% CI 1.76-6.16, P < 0.001).

In this real-world nationwide study, the 1-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.