Combination therapy of obeticholic acid and ursodeoxycholic acid in patients with primary biliary cholangitis who respond incompletely to ursodeoxycholic acid: a systematic review

Background: Although the efficacy of ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) for primary biliary cholangitis (PBC) has been suggested by small trials, a meta-analysis to summarize the evidence has not yet been carried out. The aim of this study was to evaluate the clinical outcomes of the combination therapy of UDCA and OCA compared with UDCA monotherapy in patients with PBC.

Methods and materials: We searched the PubMed, EMBASE, the web of science, and the Cochrane Library databases for English-language studies published before September 2018. Studies were included if they were randomized controlled trials (RCTs) and reported relative risk (RR) estimates with 95% confidence intervals (CIs) or related data for the clinical outcomes of different therapies in patients with PBC.

Results: Of the 1169 titles identified, two studies meeting the inclusion criteria were included in the meta-analysis. Approximately 222 patients with PBC were included in this analysis. The results of this study indicated that combination therapy was significantly superior to monotherapy in reducing serum alanine transaminase (mean difference: -15.63 IU/L; 95% CI, -21.59 to -9.68), aspartate transaminase (mean difference: -6.63 IU/L; 95% CI, -11.03 to -2.24), gamma-glutamyl transpeptidase (mean difference: -131.30 IU/L; 95% CI, -177.52 to -85.08), and C-reactive protein (mean difference = -1.17 mg/L; 95% CI, -2.19 to -0.14), but NS in improving primary endpoints of alkaline phosphatase level with 15.0% reduction from baseline, and equal or higher than the upper limit of normal serum total bilirubin (RR = 2.75; 95% CI, 0.43-17.68), conjugated bilirubin (mean difference = -0.06 mg/dL; 95% CI, -0.28 to 0.15), IgM (mean difference = -41.18 mg/dL; 95% CI, -244.45 to 162.09), and adverse events (P > 0.05).

Conclusion: This meta-analysis demonstrated that combination therapy with UDCA and OCA provided satisfactory clinical outcomes, which may be a promising alternative for patients with PBC who had an inadequate response to UDCA therapy. Therefore, high-quality RCTs on the safety and efficacy of the combination therapy of UDCA and OCA compared with UDCA monotherapy in patients with PBC should be performed in the future.