Association of bezafibrate with transplant-free survival in patients with primary biliary cholangitis

Background & Aims: A beneficial effect of bezafibrate (BZF) on symptoms and biochemical features of primary biliary cholangitis (PBC) has been reported in patients with an incomplete response to ursodeoxycholic acid (UDCA), but long-term effects on survival remain unknown. In Japan, BZF has been used as a de facto second-line therapy for PBC since 2000. Herein, we compared the survival rates between patients treated with and those without BZF in a large nationwide Japanese PBC cohort. Methods: All consecutively registered patients of this cohort who started UDCA therapy from 2000 onwards and had a followup >-1 year were included. Association between BZF exposure and mortality or need for liver transplantation (LT) was assessed using time-dependent, multivariable-and propensity score adjusted Cox proportional hazards models. Clinical benefit was quantified using the number needed to treat (NNT). Results: Of 3,908 eligible patients, 3,162 (81%) received UDCA only and 746 (19%) UDCA and BZF over 17,360 and 3,932 patient years, respectively. During follow-up, 183 deaths (89 liver related) and 21 LT were registered. Exposure to combination therapy was associated with a significant decrease in all-cause and liver-related mortality or need for LT (adjusted hazard ratios: 0.3253, 95% CI 0.1936-0.5466 and 0.2748, 95% CI 0.1336-0.5655, respectively; p <0.001 for both). This association was consistent across various risk groups at baseline. The NNTs with combination therapy to prevent 1 additional death or LT over 5,10, and 15 years were 29 (95% CI 22-46), 14 (10-22), and 8 (6-15), respectively. Conclusions: In a large retrospective cohort study of treatment effects in patients with PBC, the addition of BZF to UDCA was associated with improved prognosis. Lay summary: The long-term efficacy of bezafibrate (BZF) on liver transplantation (LT) - free survival in patients with PBC and an incomplete response to ursodeoxycholic acid (UDCA) remains to be determined. In this Japanese nationwide retrospective cohort study, the use of UDCA-BZF combination therapy, compared to UDCA alone, was associated with a lower risk of all cause and liver-related mortality or need for LT. These results indicate that BZF is so far the only drug in PBC to have demonstrated efficacy in improving symptoms, biochemical markers, and long-term outcomes. (C) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Automated summary

The addition of bezafibrate to ursodeoxycholic acid in patients with primary biliary cholangitis was associated with improved prognosis, as evident from a large retrospective cohort study. The combination therapy showed a significant decrease in all-cause and liver-related mortality or need for liver transplantation, indicating the potential benefits of this treatment approach.