Bezafibrate was found to safely improve moderate to severe pruritus in patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), according to data from a prospective randomized controlled trial published in Gastroenterology. Bezafibrate’s safety and efficacy, coupled with its antipruritic and anticholestatic properties, justify consideration of the agent as a new treatment option for patients with PSC and PBC who experience cholestasis-associated pruritus, the investigators said.
Pruritus may seriously impair quality of life in patients with cholestatic diseases such as PSC, secondary sclerosing cholangitis (SSC), and PBC, and current treatment options demonstrate limited efficacy with serious side effects. Bezafibrate is a broad peroxisome proliferator-activated receptor (PPAR) agonist that has been shown to relieve cholestasis-associated itch by alleviating hepatobiliary injury.
Researchers conducted the FITCH (The Effect of Bezafibrate on Cholestatic Itch) trial (ClinicalTrials.gov Identifier: NCT02701166) to assess the effect of bezafibrate on pruritus in patients with PSC, PBC, and SSC. The primary end point was a 50% or greater reduction of pruritus. Secondary end points included daily morning and evening pruritus visual analogue scale scores, changes in quality of life, and changes in 5-dimensional (5D) itch scale.
Patients received bezafibrate 400 mg once daily or placebo for 21 days. Most patients (70 of 74 [95%]) completed the trial (44 PSC, 24 PBC, 2 SSC). In the primary end point analysis, 45% (41% PSC, 55% PBC) of patients who received bezafibrate experienced a 50% or greater reduction in severe or moderate pruritus compared with 11% of patients who received placebo (P =.003). Regarding the trial’s secondary end points, bezafibrate reduced morning (P =.01 vs placebo) and evening (P =.007) intensity of pruritus and additionally improved the validated 5D itch scale (P = .002 vs placebo). Bezafibrate was also associated with a 35% reduction from baseline in serum alkaline phosphatase levels (P = .03 vs placebo), correlating with improved pruritus (P = .01) and suggestive of reduced biliary damage. Although serum bile acid levels and autotaxin activity remained unchanged, a mild increase in serum creatinine levels was noted compared with placebo (3% bezafibrate vs 5% placebo, P =.14).
“Bezafibrate is superior to placebo in improving moderate to severe pruritus in patients with PSC and PBC. Further prospective studies are needed to confirm long-term efficacy and safety of bezafibrate in patients with PSC, PBC, and SSC,” the authors concluded.
de Vries E, Bolier R, Goet J, et al; Netherlands Association for the Study of the Liver – Cholestasis Working Group. Fibrates for itch (FITCH) in fibrosing cholangiopathies: a double blind, randomized, placebo-controlled trial. Gastroenterology. Published online October 5, 2020. doi:10.1053/j.gastro.2020.10.001