Insufficient control of cholestatic pruritus in primary biliary cholangitis (PBC) with current therapies: preliminary baseline data from the ongoing Phase 3 GLISTEN study

Background The Phase 2b GLIMMER study that assessed linerixibat, an ileal bile acid transporter inhibitor, for treatment of cholestatic pruritus in 147 patients with PBC, demonstrated that 62% of patients experienced previous treatment failures, and 38% still experienced pruritus despite concomitant anti-pruritus therapy at baseline. This blinded preliminary analysis of baseline data from GLISTEN further explores the utilization of available pruritus therapies in a controlled PBC population.

Method GLISTEN (NCT04950127) is an ongoing Phase 3 study investigating the efficacy and safety of linerixibat in patients with PBC and moderate-severe pruritus. Pruritus severity is measured using a 0–10 numerical rating scale; stable concomitant pruritus therapy is allowed.

Results Data from 154 patients were included in this preliminary analysis. At baseline, 94% of patients were female, mean (standard deviation, SD) age was 56.0 (11.6) years, 11% had compensated cirrhosis. Mean (SD) alkaline phosphatase was 225.6 (164.4) IU/L and mean (SD) total bilirubin was 11.64 (8.0) µmol/L. 56% of patients had severe pruritus, 48% were receiving concomitant pruritus therapy: only 6% were receiving concomitant bile acid-binding resins despite being recommended as first-line therapy, while 22% were receiving fibrates, 8% selective serotonin reuptake inhibitors, 5% gabapentin, 5% antihistamines, 3% nalfurafine, 3% naltrexone, 3% rifampicin, and 1% pregabalin.

Conclusion Despite receiving licensed and/or off-label therapies, including fibrates, patients with PBC still experience moderate-severe pruritus. These data support previous findings that treating pruritus remains a high unmet need and more effective therapies are required.

Funding GSK (212620).

Publikationsverlauf

Artikel online veröffentlicht:
23. Januar 2024