Combination therapy shows superior clinical benefits over ursodeoxycholic acid monotherapy for primary biliary cholangitis patients with inadequate response to ursodeoxycholic acid alone.

The study sought to determine the comparative efficacy of medications like fibroblast growth factor 19 (FGF19) analogs, peroxisome proliferator-activated receptor (PPAR) agonists, and Farnesoid X receptor (FXR) agonists as supplementary therapy for individuals with cholangitis who have not responded adequately to ursodeoxycholic acid (UDCA), specifically in terms of enhancing alkaline phosphatase (ALP) levels.

For this systematic review and Bayesian network meta-analysis, a thorough search of Cochrane Library, Web of Science, Embase, and PubMed was carried out for relevant studies. The analysis incorporated case-control studies, cohort studies, and randomized controlled trials that investigated the efficiency of various combination treatments with UDCA monotherapy in people suffering from UDCA-refractory primary biliary cholangitis. Utilizing cumulative probability, treatment rankings were determined.

The network meta-analysis comprised 23 eligible articles. In the context of ameliorating ALP levels, combination therapies such as Bezafibrate with UDCA (Mean difference [MD] 104.49, 95% Confidence Interval [CI] 60.41, 161.92), Fenofibrate with UDCA (MD 87.81, 95% CI (52.34, 129.79), Obeticholic acid with UDCA (MD 65.21, 95% CI 8.99, 121.80), Seladelpar with UDCA (MD 117.39, 95% CI 19.97, 213.95), Elafibranor with UDCA (MD 140.73, 95% CI 74.34, 209.98), and Saroglitazar with UDCA (MD 132.09, 95% CI 13.99, 247.04) illustrated superior efficacy compared to UDCA monotherapy. Notably, Elafibranor combined with UDCA emerged as the most promising regimen, with a 32% likelihood of being the optimal therapy.

In the context of second-line therapy for UDCA-refractory primary biliary cholangitis, PPAR agonists exhibited greater effectiveness in boosting ALP levels compared to alternative drugs with differing mechanisms, with Elafibranor showing the highest effectiveness.