Fenofibrate discontinuation and the association with clinical outcomes in primary biliary cholangitis patients receiving combination therapy

INTRODUCTION: Fenofibrate serves as a second-line therapy in combination with ursodeoxycholic acid (UDCA) for patients with primary biliary cholangitis (PBC). However, a substantial proportion of patients discontinue treatment in clinical practice. AIM: To characterize the biochemical and clinical associations of fenofibrate discontinuation and the changes observed upon re-initiation in PBC patients. METHOD: Patients receiving combination therapy with UDCA and fenofibrate were consecutively enrolled between January 2011 and March 2025. Fenofibrate discontinuation was treated as a time-dependent covariate: patients were classified as being in the continuation group from fenofibrate initiation until the date of first discontinuation. Treatment adherence was quantified using the medication possession ratio (MPR). The composite endpoint included decompensated cirrhosis, liver transplantation, and death. RESULTS: Among 161 patients analyzed, 46 (28.6%) discontinued fenofibrate, and 31 of these later re-initiated treatment during follow-up. Patients were stratified into continuation and discontinuation groups, and no significant difference in the incidence of adverse events was observed. Discontinuation was associated with rapid biochemical relapse, with alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels significantly increasing within one month and the biochemical response rates declining from 59 to 25% at 12 months. Re-initiation of fenofibrate effectively reversed this deterioration. Time-dependent Cox analysis showed fenofibrate discontinuation was associated with a higher risk of clinical endpoint events (HR 2.57, 95% CI 1.12-5.91, P = 0.026). MPR showed an independent association with the risk of endpoint events and can be used to monitor patient medication adherence. CONCLUSION: Discontinuation of fenofibrate in patients with PBC is associated with rapid biochemical relapse and a trend toward unfavorable long-term outcomes. Maintaining treatment adherence is crucial, whereas timely re-initiation of therapy can effectively restore biochemical control.