Maralixibat offers clinically meaningful pruritus reductions in PSC

With decreases in serum bile acid levels also observed, Adrielly Martins (Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Florida, USA) and colleagues say that the results “suggest a potential role for IBAT inhibitors for the treatment of pruritus in PSC.”

Pruritus is present in up to 91% of PSC patients, the authors note, and while 49% of patients report using at least two antipruritic medications, 75% say they experience only partial or no symptom relief.

Maralixibat reduces enterohepatic bile acid recirculation and has been shown to significantly reduce pruritus and serum bile acids, which led to its approval for the treatment of cholestatic pruritus in Alagille syndrome, as well as in progressive familial intrahepatic cholestasis.

For the current study, the researchers sought to examine the real-world experience with the drug in PSC, via an analysis of eight patients from seven tertiary referral hospitals. Pruritus was assessed using the 5-point Clinician Scratch Scale (CSS), on which a reduction in scores of at least 1 point is considered clinically meaningful.

Half of the patients were women, and the median age at initiation of maralixibat was 34 years, more than 10 years since the initial PSC diagnosis. The majority (63%) of patients had previously taken antihistamines for their pruritus, while 50% had tried cholestyramine, and 25% rifampicin. All patients were on ursodeoxycholic acid.

The median duration of maralixibat treatment was 7.5 months. All patients had a complete or near-complete resolution of their pruritus, with seven of the eight patients experiencing a reduction in CSS scores of at least 2 points. Six out of eight patients also had reductions in serum bile acid levels, from a median of 142 µmol/L at baseline to 37 µmol/L at final follow-up.

The researchers note that two patients had diarrhea, which was moderate to severe in one case and required dose adjustments and, later, discontinuation of treatment. Mild increases in liver enzymes were observed. “Although increases in liver enzymes have been reported with IBAT inhibitors,” they say, “this effect is thought to be unrelated to direct toxicity, given their minimal systemic absorption.”