Combined treatment of budesonide and ursodeoxycholic acid for non-cirrhotic primary biliary cholangitis: a systematic review and meta-analysis.

BACKGROUND

Primary biliary cholangitis (PBC) is a chronic immune-mediated disease that may partially exhibit a poor response to the first-line treatments, such as monotherapy (MU) with ursodeoxycholic acid (UDCA). Budesonide, a widely used and readily available medication, has shown promise in previous studies as an alternative to conventional drugs when combined with UDCA (CBU) for non-cirrhotic PBC. Therefore, this study aimed to confirm the role of CBU in patients with non-cirrhotic PBC.

METHODS

We systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase databases for randomized controlled trials (RCTs) comparing CBU and MU for non-cirrhotic PBC. The certainty of evidence was assessed using the grading of the recommendation assessment, development, and evaluation (GRADE) framework. Trial sequential analysis (TSA) was applied to control for the risk of random errors and to evaluate the conclusion validity.

RESULTS

Three high-quality RCTs comprising 170 patients were included. Moderate certainty of evidence revealed that CBU showed a significantly higher percentage improvement over MU in alkaline phosphatase (ALP) [mean difference (MD) =19.97, 95% confidence interval (CI): 6.59 to 33.35, P=0.003, I2=0%], liver histology (MD =27.04, 95% CI: 1.62 to 52.46, P=0.04, I2=46%), total bilirubin (P=0.01) and immunoglobulin G (IgG, P=0.002), with no significant difference in serious adverse drug reactions (ADRs) (P=0.06). There were no significant differences for other biochemical variable outcomes; however, positive trends were observed. TSA confirmed the reliability of the ALP and IgG percentage improvements.

CONCLUSIONS

CBU might be superior to MU for non-cirrhotic PBC, possibly showing a better biochemical response and liver histology improvement with similar safety. Further large-sample studies are required in this subpopulation.