Treatment with bezafibrate proved superior to placebo in a small randomized trial for short-term relief of moderate to severe cholestasis-associated pruritus in patients with fibrosing cholangiopathies.
The primary endpoint of a more than 50% reduction in severe or moderate pruritus at 21 days was achieved by 45% of patients in the arm given the lipid-lowering drug bezafibrate versus 11% in those receiving placebo (P=0.003), according to Ulrich Beuers, MD, of the Tytgat Institute for Liver and Intestinal Research at Amsterdam University Medical Center in the Netherlands, and colleagues.
As reported in Gastroenterology, for secondary endpoints, bezafibrate reduced the intensity of both morning (P=0.01) and evening (P=0.007) pruritus versus placebo on a visual analog scale (VAS) and also improved scores (P=0.002) on a validated itch scale questionnaire of five dimensions (degree, duration, direction, disability, and distribution).
The researchers explained that in patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), bezafibrate can be considered a new treatment option for cholestasis-associated pruritus due to its anti-pruritic and anticholestatic properties and favorable safety profile. Further prospective studies, however, are needed to confirm the long-term efficacy and safety.
As the authors pointed out, pruritus can seriously impair quality of life in patients with cholestatic diseases, and pharmacological strategies have shown limited efficacy and sometimes serious side effects.
“We hypothesized that bezafibrate, a broad peroxisome proliferator-activated receptor agonist, relieves cholestasis-associated itch by alleviating hepatobiliary injury,” the investigators wrote.
Suthat Liangpunsakul, MD, MPH, of Indiana University School of Medicine in Indianapolis, who was not involved with the study, called the results promising for this common but difficult-to-treat condition. “Once cholestasis develops, effective therapies, either to treat underlying liver disease or itching, are limited,” he told MedPage Today.
“Overall, this study provides us a new insight into the possible role of bezafibrate as part of a treatment algorithm for pruritus in patients with cholestatic liver disease. This compound may also be beneficial for improving underlying cholestasis and hepatobiliary damage, though this is a speculation,” he continued.
The major limiting factor, Liangpunsakul said, was the treatment’s short duration, with the severity of itching rebounding at day 35, 2 weeks after the end of bezafibrate therapy. “Therefore, I would view this as a pilot proof-of-concept study on the use of this drug for pruritis. Long-term treatment intervention to further evaluate its safety profile and efficacy is certainly needed,” he said.
For the study, called Fibrates for Itch (FITCH), patients at least 18 years old with severe or moderate pruritus from cholestasis caused by PBC, PSC, or secondary sclerosing cholangitis (SSC) (as defined by European Association for the Study of the Liver clinical practice guidelines) were recruited from 2016 to 2019 at one Spanish and seven Dutch academic hospitals.
Eligible participants twice reported an itch intensity on VAS of at least 5 out of 10 (0 = no itch, 10 = worst itch possible) within the week before inclusion.
Of 74 patients randomized to once-daily bezafibrate at