Long-Term Use of Fenofibrate as Second-Line Therapy in Primary Biliary Cholangitis: A Retrospective Study

Nearly 40% of patients with primary biliary cholangitis (PBC) have an incomplete response to first-line ursodeoxycholic acid (UDCA) therapy. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, is an effective second-line treatment for PBC. Compared to the recently FDA-approved PPAR agonists, fenofibrate may provide a more cost-effective and accessible alternative. However, longitudinal data on fenofibrate use in PBC are lacking. Here, we review our experience using fenofibrate in PBC and its long-term effects on cholestatic biomarkers, prognostic scores, and fibrosis indices.

This single-centre retrospective cohort study examined PBC patients prescribed fenofibrate between 2012 and 2024 for persistent elevations in alkaline phosphatase (ALP) despite UDCA therapy. The study included 59 patients treated with fenofibrate for a mean duration of 44.8 months. The overall median time to ALP normalisation was 9.5 months. Of those who did not meet Paris II criteria prior to fenofibrate therapy, the median time to ALP normalisation was 11.2 months. GLOBE prognostic scores significantly improved with fenofibrate therapy, while UK-PBC scores and fibrosis index scores (FIB-4) remained stable. Fenofibrate was well-tolerated by most patients, with only 5% of patients discontinuing therapy due to elevated liver enzymes.

In this long-term cohort of PBC patients with insufficient response to UDCA, fenofibrate significantly improved cholestatic markers and prognostic scores over time. Given this, and its favourable safety profile, fenofibrate should be further considered as an accessible and affordable second-line therapy in PBC.