Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incompleteUDCAresponse may improve outcomes

BACKGROUND: Fibrates appear to improve biochemistry in patients with primary biliary cholangitis (PBC), but it is unclear which factors predict response and whether treatment improves transplant-free survival. AIM: To evaluate biochemical profiles, liver-related outcomes and adverse events following fenofibrate therapy in PBC patients with incomplete response to ursodeoxycholic acid (UDCA). METHODS: A retrospective cohort study was performed at a tertiary centre. Cox regression was used to compare outcomes between patients treated with fibrates and UDCA (FF) or UDCA alone, adjusted for a propensity score to account for treatment selection bias. RESULTS: A total of 120 patients were included (FF group n = 46, UDCA group n = 74, median fenofibrate treatment 11 months); 41% vs. 7% met the Toronto criteria for biochemical response alkaline phosphatase ≤1.67 times the upper limit of normal in the FF and UDCA groups, respectively (P = 0.0001). Fenofibrate was also associated with improved decompensation-free and transplant-free survival hazard ratio (HR) 0.09, 95% CI 0.03-0.32, P = 0.0002. However, only fenofibrate use, not biochemical response, was independently associated with improved outcomes on multivariable analysis (HR 0.40, 95% CI 0.17-0.93, P = 0.03). Twenty-two percent discontinued fenofibrate due to adverse events (most common: abdominal pain and myalgias). In cirrhotic patients, bilirubin increased more rapidly in the FF group (P = 0.005). CONCLUSIONS: Fenofibrate therapy is associated with significant improvement in alkaline phosphatase, decompensation-free and transplant-free survival in PBC patients with incomplete UDCA response. However, fenofibrate should be used cautiously in cirrhosis, with close monitoring for clinical/biochemical decompensation. Additional studies are required to assess the validity of alkaline phosphatase as an appropriate response criteria for fibrate therapy.