A Placebo-controlled Trial of Bezafibrate in Primary Biliary Cholangitis
Abstract
BACKGROUND
Patients with primary biliary cholangitis (PBC) who inadequately respond to ursodeoxycholic acid (UDCA) therapy are at high risk of disease progression. Fibrates, which are agonists of peroxisome proliferator-activated receptors, in combination with UDCA, have shown potential benefit in this condition.
METHODS
In this 24-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 100 patients who had an inadequate response to UDCA according to the Paris-2 criteria to receive bezafibrate, at a daily dose of 400 mg (n=50), or placebo (n=50), in addition to continued treatment with UDCA. The primary outcome was a complete biochemical response defined as normal levels at 24 months of all of the following: total bilirubin, alkaline phosphatase (ALP), aminotransferases, albumin, and prothrombin index.
RESULTS
The primary outcome occurred in 30% of patients with bezafibrate and 1% with placebo (difference [95%CI] = 29% [16% ; 43%]; P < 0.001). Normalization of ALP occurred in 67% of patients with bezafibrate and 2% with placebo. Changes in pruritus, fatigue, and non-invasive markers of liver fibrosis, including liver stiffness measurement and Enhanced Liver Fibrosis score, were consistent with the primary outcome. Two patients in each group experienced end-stage liver complications. Creatinine level increased 5% in the bezafibrate group and decreased 3% in the placebo group. Myalgia was experienced by 20% in bezafibrate and 10% in placebo group.
CONCLUSIONS
Bezafibrate administered with UDCA in patients with PBC who had inadequate response to UDCA alone resulted in a significantly higher rate of complete biochemical response than placebo with UDCA. (Funded by the Assistance Publique–Hôpitaux de Paris with support from Arrow Génériques; BEZURSO ClinicalTrials.gov number, NCT01654731).
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