Efficacy and Safety of Obeticholic Acid as Second-Line Therapy in Primary Biliary Cholangitis: Systematic Review and...

Obeticholic acid (OCA) was conditionally approved in 2016 as a second-line therapy for patients with primary biliary cholangitis (PBC) and incomplete response to ursodeoxycholic acid (UDCA) monotherapy. We aimed to evaluate the impact of OCA add-on therapy on biochemical outcomes and safety in those patients.

We systematically searched MEDLINE, Embase, and Cochrane CENTRAL for papers published up to October 29, 2024, evaluating OCA in patients with PBC at the 12-month timepoint. Pooled analyses of liver enzymes were performed using the standard mean difference (SMD) and 95% confidence interval (CI) from the OCA baseline. Side effects and the achievement of criteria for adequate response are presented in percentages (95% CI).

We included 1285 patients from 10 studies, two of which were RCTs. The addition of OCA significantly reduced alkaline phosphatase (ALP) (SMD -0.86; -1.15 to -0.56; p < 0.001) and total bilirubin (SMD -0.29; -0.43 to -0.15; p < 0.001). Overall, 37.23% of the patients (95% CI 31.47-43.39) responded to OCA (POISE criteria). The response rate was greater in the POISE trial results compared with real-world data (46.15% vs. 30.54%, respectively; p = 0.0089). Pruritus was the most common adverse event (40.23%; 24.65-58.07). Approximately one-fifth of the patients stopped OCA (18.05%; 12.72-24.99), with pruritus being the main reason for discontinuation (47.70%; 34.15-61.60).

Adding OCA improves ALP, bilirubin, and biochemical remission rates in patients with PBC who did not respond well to UDCA monotherapy. Real-world data show an attenuated response. Pruritus is the most common side effect and the leading cause of drug discontinuation.