Successful Treatment of Refractory Pruritus in Primary Sclerosing Cholangitis with Upadacitinib: A Case Report

Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease that is often complicated by severe pruritus, which can profoundly impair quality of life. In select cases, intractable pruritus is an independent indication for liver transplantation (LT) even in the absence of advanced liver disease, recurrent cholangitis, or malignancy. Conventional pharmacological and endoscopic therapies frequently provide only partial or transient relief, highlighting the need for mechanism-based treatments.

We report the case of a 32-year-old man with long-standing PSC and Crohn's disease (CD) who developed severe treatment-refractory pruritus despite multiple conventional pharmacologic therapies and endoscopic biliary interventions. In the absence of advanced liver disease or malignancy, he underwent LT evaluation primarily due to debilitating pruritus significantly impairing quality of life, with secondary consideration given to medically and endoscopically challenging but manageable recurrent dominant common bile duct stricture and episodes of acute cholangitis. Upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, was initiated for a CD flare, after which pruritus completely resolved within 48-72 h. Maintenance therapy with upadacitinib 30 mg daily has sustained symptom-free status for over 27 months, markedly improving quality of life and allowing the patient to remain inactive on the liver transplant waitlist.

This case demonstrates the rapid and durable resolution of PSC-associated pruritus with JAK1 inhibition. Effective symptom control allowed deferral of LT driven primarily by quality-of-life impairment, with the patient remaining inactive on the waitlist. To our knowledge, this is the first reported case of successful treatment of PSC-associated pruritus with upadacitinib, supporting further investigation of JAK1 inhibition as a potential therapeutic strategy for cholestatic pruritus.