Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial

by Selleckchem | May 27 2023

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.

Comments：

In this study, the researchers aimed to evaluate the potential impact of setanaxib, an inhibitor of NADP oxidase 1/4, on the quality of life of patients with primary biliary cholangitis (PBC). A total of 111 PBC patients with inadequate response or intolerance to ursodeoxycholic acid were recruited and administered either oral placebo, setanaxib 400 mg once daily, or setanaxib 400 mg twice daily for 24 weeks in addition to ursodeoxycholic acid. Quality of life was assessed using the PBC-40 questionnaire, and patients were stratified by baseline fatigue severity.

The results showed that patients treated with setanaxib 400 mg twice daily reported greater absolute reductions in fatigue domain score compared to those receiving setanaxib 400 mg once daily or placebo. Similar improvements were observed across all PBC-40 domains except itch. Patients with moderate-to-severe fatigue at baseline had a greater reduction in mean fatigue score at week 24 than those with mild fatigue in the setanaxib 400 mg twice daily arm. The reduction in fatigue was also correlated with emotional, social, symptom, and cognitive improvements.

These findings suggest that setanaxib may be a potential treatment option for PBC patients, especially those with clinically significant fatigue. However, further investigation is required to confirm these results and to determine the safety and efficacy of setanaxib as a treatment for PBC.