Cholestatic liver diseases are characterized by jaundice, pruritus, and elevated levels of alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT). Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) represent the major autoimmune-driven entities within this category. Without effective intervention, these conditions may progress to liver failure and even death. Ursodeoxycholic acid (UDCA), the first-line therapy for PBC, has been shown to improve prognosis; however, 20%-40% of patients exhibit an inadequate biochemical response. For PSC, no clearly effective pharmacologic agent is currently available. In refractory patients, pruritus often progressively worsens, severely impairing quality of life and treatment adherence, underscoring an urgent need for novel therapeutic approaches that simultaneously address disease control and itch relief.
Autoimmune-associated cholangitis frequently coexists with atopic dermatitis, and in a subset of patients, pruritus may be compounded by dermatologic factors. The pruritus of atopic dermatitis involves the JAK-STAT signaling pathway, which not only serves as a convergent node for pruritic signals but also constitutes a key downstream hub in the immune dysregulation characteristic of cholangitis. Inhibition of this pathway is therefore hypothesized to alleviate pruritus and modulate aberrant immune responses. Case reports have suggested that upadacitinib, a selective JAK inhibitor, may improve biochemical parameters in refractory PBC and exhibit potential anti-fibrotic effects.
To this end, investigators plan to conduct an exploratory clinical study to systematically evaluate the safety and efficacy of upadacitinib in patients with atopic dermatitis complicated by moderate-to-severe pruritus and refractory autoimmune-associated cholangitis.
Aged ≥18 and ≤70 years, of either sex.
Criteria for Atopic Dermatitis (AD)
Presence of symmetrical eczema with a disease duration of more than 6 months.
Personal and/or first-degree family history of atopic diseases (e.g., eczema, allergic rhinitis, asthma, allergic conjunctivitis, etc.).
Known concurrent or history of other hepatobiliary diseases, including but not limited to: active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection; complete biliary obstruction; acute cholecystitis or symptomatic cholelithiasis; suspected or confirmed hepatocellular carcinoma (HCC) or cholangiocarcinoma.
Child-Pugh Class C cirrhosis; evidence of end-stage liver disease, including: history of liver transplantation or being on the liver transplant waiting list; Model for End-Stage Liver Disease (MELD) score >20; severe portal hypertension complications (including severe gastric or esophageal varices, refractory or diuretic-resistant ascites, history of variceal bleeding); or other serious cirrhosis-related complications (spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome).
Total bilirubin >10 × upper limit of normal (ULN).
Serum creatinine ≥1.5 × ULN and creatinine clearance <60 mL/min.