Bezafibrate normalizes indicators of biliary cholangitis in some patients

Last Updated: 2018-06-06

By Gene Emery

NEW YORK (Reuters Health) - Bezafibrate added to conventional ursodeoxycholic acid therapy dramatically restores normal levels of bilirubin and other indicators in patients with primary biliary cholangitis who have an inadequate response to ursodeoxycholic acid alone, according to a randomized trial of 100 patients.

The rare autoimmune disease, seen in about 1 in 2,860 people in the United States, leads to the slow destruction of the liver's bile ducts, causing a backup of bile in the liver and, in some cases, cirrhosis.

The new study, known as BEZURSO and published online June 6 in the New England Journal of Medicine, was conducted at 21 centers in France. It was designed to see if a daily dose of 400 mg of bezafibrate might augment standard ursodeoxycholic acid therapy.

After 24 months of bezafibrate or placebo treatment, in addition to continued ursodeoxycholic acid (UDCA) therapy, 31% in the experimental group had a complete biochemical response consisting of normal levels of total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and albumin, in addition to a normal prothrombin time.

None of the patients in the control group met that primary end point (P<0.001).

"Since bezafibrate is pretty safe and inexpensive, future strategies promoting the UDCA-bezafibrate combination therapy as a first-line treatment deserves consideration with the aim to reducing the proportion of patients with an incomplete response," chief author Dr. Christophe Corpechot of Saint-Antoine University Hospital in Paris told Reuters Health by email.

Dr. Corpechot said that as a result of the findings, most physicians will probably start prescribing bezafibrate as a replacement for obeticholic acid (OCA) in cases where UDCA isn't working.

Fifty-four of the 100 volunteers were in the advanced stage of the disease.

People with a total bilirubin level above 3 mg/dL and/or features of autoimmune hepatitis were excluded from the trial.

On individual measures, total bilirubin decreased 14% with bezafibrate and rose 18% in the control group. Alkaline phosphatase levels dropped 60% with bezafibrate and didn't change in the placebo group. Alanine aminotransferase levels dropped 36% in the experimental group and remained unchanged at the 24-month mark in the control group.

Bezafibrate therapy also produced an increase in creatinine levels.

"Like with UDCA or OCA, bezafibrate protects the liver against the accumulation of toxic bile acids (cholestasis) in hepatic cells and as a result reduces inflammation and fibrosis development," said Dr. Corpechot. "So, bezafibrate simply stops or at least limits the progression of liver damage."

After the trial ended, levels of total bilirubin, gamma-glutamyltransferase, alkaline phosphatase and aminotransferases got worse among the bezafibrate recipients.

"These treatments should be considered as life-long therapies," Dr. Corpechot said. "All these treatments target cholestasis and inflammation, which are the consequences but not the cause of the disease. The cause remains unknown."

Members of both treatment groups reported comparable quality of life scores.

Serious adverse events occurred in 14 patients taking bezafibrate and 12 in the control group. At the 24-month mark, four volunteers in the bezafibrate group and six who got placebo had stage 2 chronic kidney disease.

"Stage 3 chronic kidney disease developed during treatment with bezafibrate in one patient in this trial, who had diabetes and hypertension. As a precaution, bezafibrate use should be evaluated taking kidney function into consideration, especially in patients with diabetes, hypertension, or any known renal disease," the researchers said

SOURCE: https://bit.ly/2J8P16G

N Engl J Med 2018.