From the Journals

Bezafibrate shows promise as second-line option for PBC

 

Key clinical point: Primary biliary cholangitis patients who took bezafibrate showed decreases in alkaline phosphatase levels and total bilirubin.

Major finding: A total of 31% of patients who took bezafibrate achieved normal levels of disease biomarkers after 24 months compared with 0% of placebo patients.

Study details: The data come from a double-blind, placebo-controlled trial of 100 adults with primary biliary cholangitis at 21 medical centers in France.

Disclosures: Programme Hospitalier de Recherche Clinique 2010 (Ministry of Health) and Arrow Génériques supported the study. Dr. Corpechot disclosed relationships with companies including Intercept France, Inventiva Pharma, and GlaxoSmithKline.

Source: Corpechot C et al. N Engl J Med. 2018 June 6. doi: 10.1056/NEJMoa1714519.

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Trial offers hope for patients with limited options

The BEZURSO study findings “merit cautious excitement,” Elizabeth J. Carey, MD, wrote in an editorial.

“This pivotal trial effectively doubles the limited options for second-line therapy of primary biliary cholangitis,” she said.

Approximately 40% of primary biliary cholangitis patients fail to respond adequately to ursodeoxycholic acid, the first-line therapy, and they remain at risk for progression of liver disease and liver failure, wrote Dr. Carey. Bezafibrate is the first drug to generate improvement in these patients not only in measures of biochemical markers, but also measures of fibrosis and disease symptoms, she said. Patient reports of reduced itching and lower levels of fatigue are worth noting, although they were not the primary outcomes, said Dr. Carey.

“Improvement in patient-reported outcomes prompts the question of whether there is a role for the use of bezafibrate for the management of fatigue or pruritus, even in patients who have a biochemical response to ursodeoxycholic acid,” she noted (N Engl J Med. 2018 June 6. doi: 10.1056/NEJMe1804945).

Despite the promising results, challenges remain for primary biliary cholangitis patients, as approximately 70% did not meet the primary outcome, and those with more severe disease were less likely to respond, Dr. Carey said. However, she added, any agent “that both delays disease progression and alleviates symptoms is a potential boon for patients with the debilitating symptoms of primary biliary cholangitis.”

Dr. Carey is affiliated with the Mayo Clinic in Phoenix, Ariz. Disclosure forms provided by the author are available at NEJM.org.


 

FROM NEW ENGLAND JOURNAL OF MEDICINE

Nearly one-third of patients with primary biliary cholangitis treated with bezafibrate showed clinical improvement after 24 months, according to data from a randomized trial of 100 adults.

Ursodeoxycholic acid remains the standard first-line therapy for primary biliary cholangitis (PBC), but many patients have an incomplete response to the treatment, and consequently their long-term survival is limited, wrote Christophe Corpechot, MD, of Sorbonne University, Paris, and his colleagues. PBC is also known as primary biliary cirrhosis.

In the BEZURSO trial (Bezafibrate in Combination with Ursodeoxycholic Acid in Primary Biliary Cirrhosis), published in the New England Journal of Medicine, the researchers randomized 100 primary PBC patients with an inadequate response to ursodeoxycholic acid to receive 400 mg per day of bezafibrate or a placebo for 24 months. Inadequate response was defined as “a serum level of alkaline phosphatase or aspartate aminotransferase more than 1.5 times the upper limit of the normal range or an abnormal total bilirubin level, assessed after at least 6 months of treatment with ursodeoxycholic acid,” the researchers said.

Baseline demographics were not significantly different between the groups. The average age of the patients was 53 years, and 95% were white women.

After 24 months, 31% of the patients in the treatment group met the primary outcome, which was the achievement of normal levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin, plus a normal prothrombin index. By contrast, none of the patients in the placebo group achieved the primary outcome.

In particular, bezafibrate patients showed a 60% reduction in alkaline phosphatase levels from baseline to 3 months, and a 14% decrease in total bilirubin from baseline during the course of the study.

Clinical outcomes were similar between the groups; 20% of the bezafibrate group and 18% of the placebo group developed portal hypertension, and two patients in each group developed liver complications. No deaths occurred in either group during the study. Approximately half of the patients in each group reported adverse events. Serious adverse events occurred in 14 bezafibrate patients and 12 placebo patients.

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