Author information

• ¹Newcastle University Medical School, Newcastle Upon Tyne, UK.
• ²Division of Gastroenterology, Department of Medicine and Surgery, Centre for Autoimmune Liver Diseases, University of Milano-Bicocca, Monza, Italy.
• ³European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.
• ⁴Calliditas Therapeutics AB, Stockholm, Sweden.
• ⁵Department of Gastroenterology and Hepatology, University Hospital KU Leuven, Health Care Provider of the ERN RARE-LIVER, Leuven, Belgium.
• ⁶University of Calgary Liver Unit, Calgary, Alberta, Canada.
• ⁷Genkyotex, Geneva, Switzerland.
• ⁸Schiff Center for Liver Diseases, University of Miami, Florida, USA.

Abstract

Background: There is a real unmet need for primary biliary cholangitis (PBC) treatments that can improve quality of life impacting symptoms. In this post hoc analysis, we evaluated potential effects of the NADP oxidase 1/4 inhibitor, setanaxib, on patient-reported quality of life from a phase 2 trial in PBC.

Patients and methods: The underpinning double-blind, randomized, placebo-controlled trial (NCT03226067) recruited 111 patients with PBC and inadequate response/intolerance to ursodeoxycholic acid. Patients self-administered oral placebo (n=37), setanaxib 400 mg once daily (OD; n=38), or setanaxib 400 mg twice daily (BID; n=36), in addition to ursodeoxycholic acid for 24 weeks. Quality of life outcomes were assessed using the validated PBC-40 questionnaire. Patients were stratified post hoc by baseline fatigue severity.

Results: At week 24, patients treated with setanaxib 400 mg BID reported greater mean (SE) absolute reductions from baseline in PBC-40 fatigue domain score [-3.6 (1.3)] versus those receiving setanaxib 400 mg OD [-0.8 (1.0)]) or placebo [0.6 (0.9)]. Similar observations were made across all PBC-40 domains except itch. In the setanaxib 400 mg BID arm, patients with moderate-to-severe fatigue at baseline had a greater reduction in mean fatigue score at week 24 [-5.8 (2.1)] versus those with mild fatigue [-0.6 (0.9)]; results were similar across all domains. Reduced fatigue was correlated with emotional, social, symptom, and cognitive improvements.

Conclusions: These results support further investigation of setanaxib as a treatment for patients with PBC, particularly for those with clinically significant fatigue.