Beneficial effect of bezafibrate (BZF) on symptoms and biochemical features of primary biliary cholangitis (PBC) with incomplete response to ursodeoxycholic acid (UDCA) has been reported but long-term efficacy on survival remains 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.All consecutively-registered patients of this cohort who started UDCA therapy from 2000 onwards and had a follow-up ≥ 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).Of 3908 eligible patients, 3162 (81%) received UDCA only and 746 (19%) UDCA and BZF over 17360 and 3932 patient-years, respectively. During follow-up, 183 deaths (89 liver-related) and 21 L T 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 one additional death or LT in 5, 10, and 15 years were 29 (95% CI 22 - 46), 14 (10 - 22), and 8 (6 - 15), respectively.In a large retrospective cohort study of treatment effects in patients with PBC, the addition of BZF to UDCA was associated with improved prognosis.The long-term efficacy of bezafibrate (BZF) on liver transplantation (LT) - free survival of patients with PBC with 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 lower risk in 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.
Atsushi Tanaka, Junko Hirohara, Toshiaki Nakano, Kosuke Matsumoto, Olivier Chazouillères, Hajime Takikawa, Bettina E Hansen, Fabrice Carrat, Christophe Corpechot