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Review
. 2025 Sep 30.
doi: 10.1111/jgh.70094. Online ahead of print.

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

Eliabe S Abreu  1 , Gabriel Prusch Fernandes  1 , Henrique de Carvalho Lacerda  2 , Pedro Henrique Reginato  3 , Henrique Alexsander Ferreira Neves  3 , Carlos Danilo Sanchez Gonzalez  1 , John E Eaton  1 , Guilherme Grossi Lopes Cançado  4   5
Affiliations
Review

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

Eliabe S Abreu et al. J Gastroenterol Hepatol. .

Abstract

Background: 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.

Methods: 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).

Results: 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).

Conclusion: 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.

Keywords: add‐on therapy; obeticholic acid; primary biliary cholangitis.

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References

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