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Cited by 37Liver Diseases and ImmunityPediatric Hepatobiliary Diseases and TreatmentsDrug-Induced Hepatotoxicity and Protection

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

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Jones, David, Carbone, Marco, Invernizzi, Pietro, Little, Nicola, Nevens, Frederik, Swain, Mark G., Wiesel, Philippe, Levy, Cynthia·2023·Hepatology Communications
DOI 10.1097/hc9.0000000000000057PMC PMC9949832
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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.

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  • In a phase 2 study of setanaxib, after 24 weeks, changes in the PBC-40 fatigue domain score were +2.4 for placebo, +0.3 for setanaxib 400 mg daily, and -9.9 for 400 mg twice daily (p=0.027).

    “After 24 weeks of treatment, the changes in the primary biliary cholangitis with a -40 fatigue domain score were encouraging: +2•4 for placebo, +0•3 for setanaxib 400 mg daily, and -9•9 for 400 mg twice daily groups (p=0•027).116,117”

    From Primary biliary cholangitis. (2024) · cites this paper as [117]

    The Abstract’s Results report different week-24 PBC-40 fatigue-score changes for all three groups: +0.6 for placebo, −0.8 for setanaxib 400 mg once daily, and −3.6 for 400 mg twice daily. The paper describes these quality-of-life analyses as descriptive; it does not report the claimed p=0.027 for these changes. (LLM, conf=0.90)

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Authors
Jones, D., Carbone, M., Invernizzi, P., Little, N., Nevens, F., Swain, M. G., Wiesel, P., & Levy, C.
Affiliations
  • Newcastle University (GB)
  • Azienda Ospedaliera San Gerardo (IT)
  • Calliditas Therapeutics AB (Sweden) (SE)
  • KU Leuven (BE)
  • University of Calgary (CA)
  • Genkyotex (Switzerland) (CH)
  • University of Miami (US)
Corresponding author
Jones, David
ORCID
Venue
Hepatology Communications
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2023-02-20
Volume
7
Issue
3
Pages
e0057-e0057
ISSN
2471-254X (ISSN-L)
DOI
10.1097/hc9.0000000000000057
PMC
PMC9949832
OpenAlex
W4321443507
Cited by
37
References
8
Citations by year
2026: 8 · 2025: 17 · 2024: 11 · 2023: 1
FWCI
6.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Hepatology Communications (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Lirias (KU Leuven) (submittedVersion, cc-by-nc-nd)
  • BOA (University of Milano-Bicocca) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Pfizer
  • Gilead Sciences
  • Intercept Pharmaceuticals
  • National Institute for Health and Care Research (NIHR200243, NF-SI-0513-10091)
  • Ministero dell’Istruzione, dell’Università e della Ricerca
  • American Medical Association Foundation
  • Medical Research Council (MR/L001489/1)
Topics
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
  • Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
primary biliary cirrhosis, quality of life, fatigue, ursodeoxycholic acid, dose comparison, pruritus, patient-reported outcomes
MeSH terms
Fatigue, Humans, Liver Cirrhosis, Biliary, Pyridones, Quality of Life, Ursodeoxycholic Acid, Pyrazolones

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