麻豆传媒

AMSTERDAM -- A long-standing agent mainly used to treat hyperlipidemia might turn out to have an important role in primary biliary cholangitis (PBC), a researcher said here.

The standard treatment for PBC is ursodeoxycholic acid (UDCA) but between 30% and 40% of patients do not have an adequate response to the drug, according to Christophe Corpechot, MD, of the Hôpital Saint-Antoine in Paris.

But adding the lipid-lowering bezafibrate (introduced to market in 1977) overcame the failure in patients who had not responded to UDCA, Corpechot reported at the International Liver Congress, the annual meeting of the European Association for the Study of the Liver (EASL).

In the first randomized, prospective trial of a fibrate in PBC, the drug, combined with UCDA, led to a complete biochemical response in 30% of patients after 24 weeks of therapy. In contrast, none of the patients on UCDA alone had such a response, Corpechot said.

"We have shown for the first time that treatment with a fibrate can improve surrogate markers and especially prevent liver stiffness progression," Corpechot told reporters in an EASL media briefing.

Fibrates "have been around for a very, very long time," commented Frank Tacke, MD, PhD, of University Hospital Aachen in Germany, who was not part of the study but who moderated the EASL media briefing.

"Lots of people have been using them," he told 麻豆传媒, but the resulting data have represented a "handful of cases" rather than a robust clinical trial. "What we have now is randomized, prospective trial for a long period of time, so I think this is a big step forward."

Bezafibrate, he noted, is cheap and seems to be both effective and safe, but added that PBC treatment remains an off-label use "so we have to be cautious."

Bezafibrate has often been tested in patients with PBC, Corpechot said, but always in a small, non-randomized, and uncontrolled fashion. To help fill the gap, his group randomly assigned 100 people who had failed previous UCDA therapy to get a 2-year course of UCDA at 13 to 15 mg/kg per day with bezafibrate at 400 mg a day or to get the same dose of UCDA plus a matching placebo.

The primary endpoint was the proportion of patients in each arm who had a complete biochemical response at month 24, which the investigators defined as normal levels of total bilirubin, alkaline phosphatase, aminotransferases, albumin, and prothrombin time.

But the analysis also looked at other factors, including safety and tolerability, effect on PBC symptoms, and effect on prognostic markers, Corpechot said.

The drug met the primary endpoint, Corpechot said, but also significantly improved other biochemical markers, including gamma-glutamyl transferase and cholesterol.

One of the main symptoms of PCB is intense and unrelenting pruritis; treatment with bezafibrate lowered the itch score by median of 75%, but there was no change in the placebo arm over the 24 months, Corpechot reported.

The drug also prevented and reversed liver stiffness: Over the 24 months, liver stiffness in the placebo arm increased by a median of 14%, while it fell by a median of 10% in the bezafibrate arm.

Two patients in each arm had end-stage liver complications: One patient in the placebo arm had ascites and one had elevated bilirubin, while one patient in the bezafibrate arm had a liver transplant and another was placed on the transplant waiting list.

Most patients did not report any serious adverse events, and there was no significant difference between arms in the proportion that did, Corpechot reported.

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