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. 2025 Jan;45(1):e16222.
doi: 10.1111/liv.16222.

Second-Line Treatment for Patients With Primary Biliary Cholangitis: A Systematic Review With Network Meta-Analysis

Edoardo G Giannini  1   2   3 , Andrea Pasta  1   2 , Francesco Calabrese  1   2 , Sara Labanca  1   2 , Simona Marenco  1   2 , Giulia Pieri  1   2 , Maria Corina Plaz Torres  1   2 , Mario Strazzabosco  3
Affiliations

Second-Line Treatment for Patients With Primary Biliary Cholangitis: A Systematic Review With Network Meta-Analysis

Edoardo G Giannini et al. Liver Int. 2025 Jan.

Abstract

Background & aims: Approximately 40% of patients with Primary Biliary Cholangitis (PBC) show incomplete response to ursodeoxycholic acid, thus needing second-line treatment to prevent disease progression. As no head-to-head comparison study is available, we used a network meta-analysis (NMA) to compare efficacy and safety of available second-line therapies.

Methods: We performed a systematic literature review including randomised, placebo-controlled trials of patients with PBC and incomplete response, or intolerance, to ursodeoxycholic acid, and compared relative risks (RRs) for primary (biochemical response at 52-week) and secondary outcomes [incidence of new-onset pruritus and serious adverse events (SAEs)].

Results: The NMA included three studies, each testing obeticholic acid (OCA), seladelpar or elafibranor versus placebo (active therapy/placebo: 379/191 patients). All treatments significantly increased the RR for biochemical response with an advantage of elafibranor versus seladelpar (RR: 4.37, 95% CI: 1.01-18.87). OCA 5-10 mg/10 mg was associated with a higher risk of new-onset pruritus compared to placebo (RR: 1.43; 95% CI: 1.09-1.88/RR: 1.79; 95% CI: 1.37-2.33), while seladelpar decreased this risk (RR: 0.30; 95% CI: 0.12-0.80). Compared to placebo, OCA 5-10 mg/10 mg was associated with an increased risk of SAE (RR: 3.82; 95% CI: 1.46-10.02/RR 2.67; 95% CI: 1.00-7.08).

Conclusions: Among second line therapies for patients with PBC, elafibranor is slightly more effective in obtaining biochemical response than seladelpar that, on the other hand, is the only drug associated with a lower incidence of pruritus. While of similar efficacy, OCA was associated with increased pruritus and SAEs. These findings may help personalise second-line treatment in patients with PBC.

Keywords: bezafibrate; elafibranor; obeticholic acid; response; seladelpar; treatment; ursodeoxycholic acid.

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Conflict of interest statement

Edoardo G. Giannini reports speaking and teaching for AbbVie, AstraZeneca, Eisai, Gilead, Roche; advising for AstraZeneca, Eisai, Gilead, Ipsen, Roche. Sara Labanca speaking and teaching for Advanz, Gilead, Ipsen. Simona Marenco speaking and teaching for Ipsen. Mario Strazzabosco advises for Engitix. Andrea Pasta, Francesco Calabrese, Giulia Pieri and Maria Corina Plaz Torres have no conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
Forest plot reporting the relative risk (A) and the risk difference (B) of biochemical response after 12‐month of treatment with the various drugs.
FIGURE 2
FIGURE 2
Forest plot showing the relative risk (A) and risk difference (B) for new‐onset pruritus within 12‐month of treatment with the various drugs.
See this image and copyright information in PMC

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