Efficacy and Safety of Bezafibrate Alone or in Combination with Ursodeoxycholic Acid in Primary Biliary Cholangitis: Systematic Review and Meta-Analysis.

BACKGROUND: Bezafibrate (BZF) alone or in combination with ursodeoxycholic acid (UDCA) has been used to slow disease progression in patients with primary biliary cholangitis (PBC). We performed a systematic review and meta-analysis to assess the efficacy and harms of BZF monotherapy or combination therapy. METHODS: We performed a systematic search of PubMed, EMBASE, Cochrane Library, Scopus, ClinicalTrials.gov, and WHO ICTRP from inception until January 2020, for randomized controlled clinical trials assessing BZF + UDCA versus UDCA monotherapy or BZF monotherapy versus UDCA monotherapy in PBC patients. Additionally, we systematically evaluated data on harms using seven observational studies. Pooled effect estimates were calculated for the outcomes of interest. The certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: We identified 7 randomized controlled trials with a total of 279 participants. Comparing BZF + UDCA to UDCA alone, a clinically significant improvement was observed in serum ALP with a mean difference (MD) of - 159.04 U/L (95% CI - 186.45 to - 131.62) and a reduction in gamma-glutamyltransferase (GGT) (MD - 106.94 IU/L; 95% CI - 151.99 to - 61.89), but not in total bilirubin (TB) or IgM levels. A statistically significant reduction in ALP levels was also noticed with BZF monotherapy compared to UDCA monotherapy. The effect of BZF + UDCA versus UDCA on mortality remains unclear. Across 5 observational studies including 106 patients, one death was reported due to advanced liver disease in an incomplete responder getting treatment with BZF + UDCA. Analysis of observational studies demonstrated improvement in pruritus intensity with BZF. CONCLUSIONS: Use of BZF alone or in combination with UDCA improved liver biochemistries in patients with PBC, but its effect on mortality, liver-related complications or quality of life remains unknown.