Efficacy and Safety of Seladelpar in Primary Biliary Cholangitis: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Document Type

Conference Proceeding

Publication Date

10-1-2024

Publication Title

Am J Gastroenterol

Abstract

Introduction: Primary biliary cholangitis (PBC) is a chronic progressive condition that causes the inflammation and destruction of bile ducts. Thus, leading to cholestatic liver disease. Although there is currently no curative treatment for PBC, medications can be utilized to slow the progression of the disease. Seladelpar is a peroxisome proliferator-activated receptor delta (PPARd) agonist that has been shown to exert beneficial effects in liver disease and reduce total bile acid levels. It also possesses anti-inflammatory activity, inhibiting the activation of macrophages and the release of inflammatory mediators. The aim of this systematic review and meta-analysis is to assess the safety and efficacy of Seladelpar in patients with PBC. Methods: We searched PubMed, EMBASE, WOS, Scopus, and Cochrane Central from inception till April 29, 2024 for randomized controlled trials (RCTs) exploring the use of Seladelpar in PBC. Data extraction included study characteristics, patient demographics, and outcomes of interest. Statistical analysis was performed using RevMan version 5.4. Heterogeneity was assessed using I2 statistics. Pooled odds ratios (OR) and mean difference (MD) were used to assess the reduction in alkaline phosphatase (ALP), bilirubin, risk of pruritus, and nausea, adopting a random-effects model. The risk of bias was assessed using Rob 2.0. Results: Three studies with 499 patients, of whom 333 received Seladelpar, were included in this meta-analysis. Our meta-analysis found a significant reduction in ALP levels in patients who received Seladelpar when compared to those who received placebo (MD: -42.32, 95% CI [-52.18 to -32.46]; P<0.00001). On the other hand, there was no significant decrease in bilirubin levels in individuals treated with Seladelpar compared to the placebo group (MD: -0.04, 95% CI [-0.13 to 0.05]; P = 0.39). The incidence of nausea in the Seladelpar group was comparable with that in the placebo group (OR 1.53, 95% CI [0.67 to -3.50]; P = 0.31). Furthermore, there was no statistically significant difference in the incidence of pruritus between the Seladelpar group and the placebo group (OR 0.53, 95% CI [0.20 to 1.40]; P = 0.20). Conclusion: Seladelpar appears to be a promising and well tolerated treatment for PBS. However, it does not seem to significantly decrease bilirubin levels. Thus, larger multicenter trials are needed to further explore and confirm the safety and efficacy of Seladelpar in PBC.

Volume

119

Issue

10

First Page

S1372

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