Changes in serum bile acid levels associated with bezafibrate add-on therapy in patients with primary biliary cholangitis and inadequate biochemical response to ursodeoxycholic acid: results from the BEZURSO trial (NCT01654731) - Sorbonne Université Access content directly
Conference Poster Year : 2017

Changes in serum bile acid levels associated with bezafibrate add-on therapy in patients with primary biliary cholangitis and inadequate biochemical response to ursodeoxycholic acid: results from the BEZURSO trial (NCT01654731)

Christophe Corpechot

Abstract

Background and aim: We recently reported the results of a 2-year, multicenter, double-blind, randomized, placebo-controlled trial of bezafibrate (BZF) add-on therapy in patients with primary biliary cholangitis (PBC) and inadequate biochemical response to ursodeoxycholic acid (UDCA) [1]. These results showed that a combination of BZF with UDCA is associated with a significant improvement in the symptoms, standard biochemical liver tests, and prognostic markers of the disease. Here, we report the changes in serum BA concentrations and profiles associated with these therapeutic effects. Methods: Fasting serum BAs were assessed from serum samples collected at baseline (M0), month-12 (M12), and month-24 (M24, end of trial). The concentrations of total, primary and secondary (i.e. endogenous) BAs, and UDCA were determined using a high-performance liquid chromatography-mass spectrometry method. Concentrations, proportions, and relative changes in BA species were compared between the BZF and placebo (PLB) groups, and according to the biochemical response to BZF using nonparametric tests. Analyses were performed on the intent-to- treat population. Results: Of the 100 patients participating in the trial, M0, M12, and M24 serum samples were available in 91, 82, and 79, respectively. Eighty-one patients had at least 2 consecutive samples including M0. At baseline, both the BZF (n=45) and PLB (n=46) groups were similar for total and individual BA concentrations and profiles. While the overall changes in total BAs at M24 did not differ significantly between the 2 groups, the % of endogenous BAs was significantly reduced in the BZF than in the PLB group both at M12 (21% vs. 29%; p=0.009) and M24 (17% vs. 25%; p=0.0260). In addition, the % reductions in both endogenous BA concentration and percentage from M0 to M24 were significantly higher in the patients who achieved a complete biochemical response (i.e. normal total bilirubin, alkaline phosphatases, transaminases, albumin and prothrombin time) as opposed to the others (-50% vs. +10%, p=0.0173, and -50% vs. -10%, p=0.0244, respectively). Complete responders had significantly lower % of endogenous BAs at baseline than non-complete responders (22% vs. 34%, p=0.05). Conclusions: The beneficial effect of BZF add-on therapy in patients with PBC and inadequate biochemical response to UDCA is associated with a decrease in both concentration and % of endogenous BAs. This decrease is higher in the patients with a lower % of endogenous BA at baseline, who are more likely to achieve a complete biochemical response. Serum BA determination may help to predict biochemical response to BZF therapy in PBC.
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Dates and versions

hal-03972631 , version 1 (20-02-2023)

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  • HAL Id : hal-03972631 , version 1

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Christophe Corpechot. Changes in serum bile acid levels associated with bezafibrate add-on therapy in patients with primary biliary cholangitis and inadequate biochemical response to ursodeoxycholic acid: results from the BEZURSO trial (NCT01654731). AASLD, Oct 2017, Washington, United States. ⟨hal-03972631⟩
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