Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies

The FITCH trial investigated the efficacy of bezafibrate, a broad peroxisome proliferator-activated receptor (PPAR) agonist, in alleviating moderate to severe pruritus in patients with fibrosing cholangiopathies, including primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), and secondary sclerosing cholangitis (SSC). Conducted between 2016 and 2019 as a multicenter, double-blind, randomized, placebo-controlled trial, it enrolled 74 adults with pruritus ≥5/10 on a visual analog scale (VAS). Patients received either bezafibrate 400 mg daily or placebo for 21 days.

The primary endpoint, a ≥50% reduction in itch intensity, was achieved by 45% of bezafibrate-treated patients compared to 11% in the placebo group (P=0.003). Secondary measures, including daily VAS scores and pruritus questionnaires (5D-Itch, Liver Disease Symptom Index 2.0), confirmed significant improvements in itch severity, sleep quality, and daily functioning. Bezafibrate also reduced serum alkaline phosphatase (ALP) by 35% versus a 6% increase in the placebo group (P=0.03), correlating strongly with pruritus relief. Gamma-glutamyl transferase (GGT) and ALT levels improved, while bile acids and autotaxin levels remained unchanged, suggesting the antipruritic effect was independent of these pathways.

Bezafibrate was effective across PSC, PBC, and varying pruritus severities, with comparable benefits in cirrhotic and non-cirrhotic patients. It was well-tolerated, with mild side effects such as transient mouth pain and back pain. The study concluded that bezafibrate offers a promising short-term treatment for cholestatic pruritus, with its antipruritic and anticholestatic effects likely mediated through PPAR activation. Long-term studies are needed to confirm its sustained efficacy and safety.