Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial.
Journal
Hepatology communications
ISSN: 2471-254X
Titre abrégé: Hepatol Commun
Pays: United States
ID NLM: 101695860
Informations de publication
Date de publication:
01 03 2023
01 03 2023
Historique:
received:
02
09
2022
accepted:
04
12
2022
entrez:
22
2
2023
pubmed:
23
2
2023
medline:
25
2
2023
Statut:
epublish
Résumé
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. 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. 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. These results support further investigation of setanaxib as a treatment for patients with PBC, particularly for those with clinically significant fatigue.
Sections du résumé
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.
Identifiants
pubmed: 36809195
doi: 10.1097/HC9.0000000000000057
pii: 02009842-202303010-00020
pmc: PMC9949832
doi:
Substances chimiques
Ursodeoxycholic Acid
724L30Y2QR
setanaxib
45II35329V
Banques de données
ClinicalTrials.gov
['NCT03226067']
Types de publication
Randomized Controlled Trial
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0057Subventions
Organisme : Medical Research Council
ID : MR/L001489/1
Pays : United Kingdom
Informations de copyright
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.
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