Primary biliary cholangitis (PBC) is a chronic intrahepatic cholestasis disease of unknown cause. PBC is more common in middle-aged and elderly women. The most common clinical manifestations are fatigue and skin itching. Its pathological characteristics are progressive, non-suppurative, and destructive intrahepatic cholangitis, which can eventually develop into liver cirrhosis.
Currently, ursodeoxycholic acid (UDCA) is still the only drug proven to be safe and effective in the treatment of this disease through randomized controlled clinical trials. However, long-term survival remains limited in patients with inadequate response to UDCA. Therefore, patients with inadequate response to UDCA require additional treatment options.
Bezafibrate is a pan-agonist of peroxisome proliferator-activated receptors, which may be used to alleviate biochemical indicators and reduce symptoms and inflammation in patients with PBC. Researchers from France’s Sorbonne University conducted a placebo-controlled phase III trial (BEZURSO), which included 100 PBC patients with inadequate response to UDCA and evaluated the efficacy and safety of fibrates in such patients. and adverse reactions.
Patients were randomly assigned to the placebo group combined with UDCA group (n=50) or bezafibrate 400 mg/day combined with UDCA treatment group (n=50). The follow-up period was 24 months, with follow-up visits every 3 months. Liver ultrasound and liver stiffness measurements were performed at baseline, 12 months, and 24 months (liver stiffness less than 6 kPa was considered normal). The primary study outcome was the proportion of patients achieving a complete biochemical response, defined as normal levels of total bilirubin, alkaline phosphatase, transaminases, albumin, and prothrombin index at 24 months.
Research results
1. Main research results:
31% of patients in the bezafibrate group achieved a complete biochemical response, while no patients in the placebo group achieved a biochemical response (P<0.001).
2. Secondary research results:
① Biochemical index measurement: specific for total bilirubin, alkaline phosphatase, γ-glutamyl transferase, alanine aminotransferase, albumin, total cholesterol and low-density lipoprotein cholesterol levels and platelet count Sexual changes were consistent with the results of the main study.
② Patient-reported outcomes, liver fibrosis: skin itching, fatigue, and non-invasive liver fibrosis diagnosis including liver stiffness and enhanced liver fibrosis score results were consistent with the main study results.
③Clinical outcomes: 2 patients in both groups developed complications related to end-stage liver disease.
3. Safety and adverse events:
Creatinine levels increased by 5% in the bezafibrate group and decreased by 3% in the placebo group. The incidence of myalgia was 20% in the bezafibrate group and 10% in the placebo group.
Research conclusion
Overall, for PBC patients with insufficient response to UDCA alone, the biochemical response rate of the UDCA combined with bezafibrate treatment regimen was significantly better than that of placebo combined with UDCA. Future longer-term and larger studies are still needed to evaluate the impact of bezafibrate on clinical outcomes in PC patients.
Reference materials
Corpechot C, Chazouillères O, et al. A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis. N Engl J Med. 2018 Jun 7;378(23):2171-2181. doi: 10.1056/NEJMoa1714519.
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