Managing Cholestatic Pruritus Itchiness with Linerixibat
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on April 20th, 2026
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Pruritus is a frequent and often debilitating symptom in patients with hepatobiliary diseases. Although treatments such as bezafibrate and seladelpar have shown some benefit, the supporting evidence remains limited. A recent study published in the Lancet evaluated the efficacy of linerixibat for managing cholestatic pruritus in patients with primary biliary cholangitis (PBC).
Funding Source(s): GlaxoSmithKline
The phase 3 clinical study enrolled 238 participants with a median age of approximately 55 years. On average, patients had experienced pruritus for about five years, and 60% were classified as having severe symptoms, defined by a Worst Itch Numerical Rating Scale (WI-NRS) score greater than 7. Participants were randomly assigned to receive either placebo or linerixibat at a dose of 40 mg twice daily. Linerixibat is an ileal bile acid transporter (IBAT) inhibitor that disrupts enterohepatic circulation by reducing bile acid reabsorption in the ileum, thereby increasing fecal excretion. This mechanism lowers bile acid accumulation in the bloodstream and skin, which is believed to reduce itch severity.
After 24 weeks of treatment, patients receiving linerixibat reported a significant 28% reduction in pruritus. On average, WI-NRS scores decreased by 2.86 points, with improvements becoming noticeable as early as the second week of therapy. Reduced itch severity was also associated with improved sleep quality. However, linerixibat was associated with a higher incidence of gastrointestinal side effects, particularly diarrhea and abdominal pain, likely due to increased bile acid excretion in the stool. These findings support linerixibat as a promising option for cholestatic pruritus, although tolerability remains an important consideration.
Funding Source(s): GlaxoSmithKline
The phase 3 clinical study enrolled 238 participants with a median age of approximately 55 years. On average, patients had experienced pruritus for about five years, and 60% were classified as having severe symptoms, defined by a Worst Itch Numerical Rating Scale (WI-NRS) score greater than 7. Participants were randomly assigned to receive either placebo or linerixibat at a dose of 40 mg twice daily. Linerixibat is an ileal bile acid transporter (IBAT) inhibitor that disrupts enterohepatic circulation by reducing bile acid reabsorption in the ileum, thereby increasing fecal excretion. This mechanism lowers bile acid accumulation in the bloodstream and skin, which is believed to reduce itch severity.
After 24 weeks of treatment, patients receiving linerixibat reported a significant 28% reduction in pruritus. On average, WI-NRS scores decreased by 2.86 points, with improvements becoming noticeable as early as the second week of therapy. Reduced itch severity was also associated with improved sleep quality. However, linerixibat was associated with a higher incidence of gastrointestinal side effects, particularly diarrhea and abdominal pain, likely due to increased bile acid excretion in the stool. These findings support linerixibat as a promising option for cholestatic pruritus, although tolerability remains an important consideration.