Effectiveness of bezafibrate and ursodeoxycholic acid in patients with primary biliary cholangitis: a meta-analysis of randomized controlled trials

Abstract

Background Ursodeoxycholic acid (UDCA) and obeticholic acid are currently approved treatments for primary biliary cholangitis (PBC). Since some patients do not respond adequately to UDCA, other therapies, such as bezafibrate, have been developed. In this meta-analysis we evaluated the efficacy and safety of using both UDCA and bezafibrate in patients with an inadequate response to UDCA. Methods We evaluated all randomized controlled trials comparing the combination of UDCA and bezafibrate with UDCA monotherapy. Standardized mean difference (SMD) was used to assess the treatment effect of combination therapy compared with UDCA alone. Results Ten trials with a total of 369 patients were analyzed. UDCA and bezafibrate combination therapy was more effective than UDCA monotherapy in improving alanine aminotransferase (SMD-2.04, 95% confidence interval [CI]-3.30 to-0.79), alkaline phosphatase at both less than 12 months (SMD-3.63, 95%CI-6.43 to-0.84) and more than 12 months (SMD-2.33, 95%CI-4.03 to-0.63), gamma-glutamyltransferase (SMD-1.29, 95%CI-2.67 to 0.08), triglyceride (SMD-0.80, 95%CI-1.41 to-0.19), immunoglobulin M (SMD-1.48, 95%CI-2.39 to-0.56), and cholesterol (SMD-4.61, 95%CI-7.34 to-1.89). There was no difference between the 2 groups in bilirubin, aspartate aminotransferase or albumin. None of the adverse effects differed statistically between the 2 groups. Conclusion UDCA and bezafibrate combined treatment is superior to UDCA alone in UDCA non-responders with regard to decreasing liver biochemistry markers, without any significant increase in side effects in patients with PBC.

Anxiety and Depression in Patients with Primary Biliary Cholangitis: Current Insights and Impact on Quality of Life

“…Bezafibrate, a drug used to target hypercholesterolemia and hypertriglyceridemia, has also been used to treat PBC in combination with UDCA. 57 , 58 A study of 369 PBC patients showed that UDCA and bezafibrate combination therapy was effective in decreasing liver enzymes in patients non-responsive to UDCA only. 58 Another study was conducted on 22 PBC patients over a 6-month period.…”

“… 57 , 58 A study of 369 PBC patients showed that UDCA and bezafibrate combination therapy was effective in decreasing liver enzymes in patients non-responsive to UDCA only. 58 Another study was conducted on 22 PBC patients over a 6-month period. Patients taking 600mg/day of UDCA and 400mg/day of bezafibrate had significantly lower ALP levels at the end of treatment.…”

Primary biliary cholangitis as a roadmap for the development of novel treatments for cholestatic liver diseases†

“…Ten randomized clinical trials including the BEZURSO trial reported a positive effect of fibrates on cholestasis (116)). In the BEZURSO trial bezafibrate at dose of 400 mg /d improved ALP and bilirubin during a follow up of 2 years and a normalization of ALP and bilirubin was achieved in 31 % of patients vs 0% in the placebo group (117).…”

Optimal drug regimens for improving ALP biochemical levels in patients with primary biliary cholangitis refractory to UDCA: a systematic review and Bayesian network meta-analysis

“…FGF19 is an endocrine hormone induced in the gut by activation of farnesoid X receptor (FXR), which can inhibit bile acid synthesis through inhibition of CYP7A1 [ 23 ]. Several traditional meta-analyses [ 11 , 14 , 15 ] manifested that fenofibrate and bezafibrate are effective adjunctive therapies in the treatment of primary biliary cirrhosis. some single or combined therapies about obeticholic acid [ 24 – 26 ], aldafermin [ 27 ], seladelpar [ 28 , 29 ], elafibranor [ 16 ], saroglitazar [ 18 ], and budesonide [ 30 ] in the treatment of UDCA-refractory PBC patients have been studied by randomized controlled trials (RCTs).…”