AMSTERDAM — Patients with an incomplete response to first-line therapy for primary biliary cholangitis are significantly more likely to achieve a complete biochemical response with bezafibrate adjunctive therapy than with placebo, a new trial reveals.
Ursodeoxycholic acid is the universal first-line treatment, "but there is inadequate biochemical response to this drug for 30% to 40% of patients, and they are at increased risk for liver transplantation or death," Christophe Corpechot, MD, from the Reference Center for Inflammatory Biliary Diseases in Paris, said during a news conference here at the International Liver Congress 2017.
Obeticholic acid (Ocaliva, Intercept Pharmaceuticals) was approved as a second-line treatment for primary biliary cholangitis by the US Food and Drug Administration in May 2016. It is indicated for use in combination with ursodeoxycholic acid or as a single agent in patients who cannot tolerate the drug. The "combination of fibrates with ursodeoxycholic acid may be an alternative option," said Dr Corpechot. However, evidence to date comes from small, nonrandomized studies.
To find out more, he and his colleagues assessed 100 patients in the 2-year double-blind, multicenter, placebo-controlled Bezafibrate in Combination With Ursodeoxycholic Acid in Primary Biliary Cirrhosis (BEZURSO) trial. All patients had an inadequate response to first-line ursodeoxycholic acid.
BEZURSO Trial
All patients received ursodeoxycholic acid 13 to 15 mg/kg per day. In addition, 50 patients were randomized to daily bezafibrate 400 mg and 50 to placebo. Slightly more than half the patients in each group had advanced disease.
The primary outcome — a complete biochemical response at 2 years — was defined as normal levels of total bilirubin, alkaline phosphatase, amino transferases, albumin, and other parameters. This was achieved by significantly more patients in the bezafibrate group than in the placebo group (30% vs 0%; P < .001).
The change in itch score was also significantly different in the two groups — with a 75% decrease in the bezafibrate group from baseline to 2 years, and no change in the placebo group (P < .01). This is clinically relevant, Dr Corpechot pointed out, because obeticholic acid can generate pruritus, "and in routine practice, it is a difficult task to explain to patients that we have a treatment that can increase their symptoms."
Improvements in many biochemical parameters — secondary outcomes — also favored bezafibrate over placebo, he reported.
Table. Changes in Biochemical Parameters During the 2-Year Study
| Parameter | Bezafibrate Group, % | Placebo Group | P Value |
| Total bilirubin, % | –14 | 18 | <.0001 |
| Alkaline phosphatase, % | –60% | 0% | <.0001 |
| Aspartate transaminase (AST) | –8 | +8 | =.06 |
| Alanine transaminase (ALT) | –36 | 0 | <.0001 |
| Albumin | 0 | –3 | <.05 |
| Immunoglobulin M | –21 | –2 | =.25 |
| Cholesterol | –16 | 0 | <.0001 |
Two patients in each group developed end-stage liver complications, so that rate was identical in the two groups. Rates of serious adverse events did not differ between groups, and no patients died.
"In primary biliary cholangitis patients with inadequate biochemical response to ursodeoxycholic acid, adjuvant therapy with bezafibrate is safe, improves pruritus, normalizes biochemical prognostic markers, and prevents liver stiffness progression," Dr Corpechot said. "This supports use of bezafibrate in combination with ursodeoxycholic acid as an effective second-line therapy for primary biliary cholangitis."
This is the first time a randomized, placebo-controlled, prospective study has shown "that bezafibrate has a place as a second-line therapy in primary biliary cholangitis," said Frank Tacke, MD, PhD, from University Hospital Aachen in Germany, who is vice-secretary of the European Association for the Study of the Liver.
However, "we don't know yet if the bezafibrate is doing better or worse than the obeticholic acid," Dr Tacke told Medscape Medical News. "We probably need to have a head-to-head comparison of the two second-line therapies."
In addition to less itching, the self-reported fatigue often associated with primary biliary cholangitis improved with bezafibrate, "which is encouraging," he said.
Dr Corpechot is a consultant for Intercept Pharma France and provides sponsored lectures for GlaxoSmithKline France. Dr Tacke has disclosed no relevant financial relationships.
International Liver Congress (ILC) 2017: Late breaker abstract 1. Presented April 22, 2017.
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Cite this: Comparison Backs Bezafibrate for Biliary Cholangitis - Medscape - Apr 25, 2017.
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