Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial
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 tri...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health/LWW
2023-03-01
|
| Series: | Hepatology Communications |
| Online Access: | http://journals.lww.com/10.1097/HC9.0000000000000057 |
| _version_ | 1811161635962748928 |
|---|---|
| author | David Jones Marco Carbone Pietro Invernizzi Nicola Little Frederik Nevens Mark G. Swain Philippe Wiesel Cynthia Levy |
| author_facet | David Jones Marco Carbone Pietro Invernizzi Nicola Little Frederik Nevens Mark G. Swain Philippe Wiesel Cynthia Levy |
| author_sort | David Jones |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T06:17:32Z |
| format | Article |
| id | doaj.art-9ce47b2b75e34bd29cbbba9a3594d8eb |
| institution | Directory Open Access Journal |
| issn | 2471-254X |
| language | English |
| last_indexed | 2024-04-10T06:17:32Z |
| publishDate | 2023-03-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj.art-9ce47b2b75e34bd29cbbba9a3594d8eb2023-03-02T06:30:57ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2023-03-0173e0057e005710.1097/HC9.0000000000000057HC90000000000000057Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trialDavid Jones0Marco Carbone1Pietro Invernizzi2Nicola Little3Frederik Nevens4Mark G. Swain5Philippe Wiesel6Cynthia Levy7 1 Newcastle University Medical School, Newcastle Upon Tyne, UK 2 Division of Gastroenterology, Department of Medicine and Surgery, Centre for Autoimmune Liver Diseases, University of Milano-Bicocca, Monza, Italy 2 Division of Gastroenterology, Department of Medicine and Surgery, Centre for Autoimmune Liver Diseases, University of Milano-Bicocca, Monza, Italy 4 Calliditas Therapeutics AB, Stockholm, Sweden 5 Department of Gastroenterology and Hepatology, University Hospital KU Leuven, Health Care Provider of the ERN RARE-LIVER, Leuven, Belgium 6 University of Calgary Liver Unit, Calgary, Alberta, Canada 7 Genkyotex, Geneva, Switzerland 8 Schiff Center for Liver Diseases, University of Miami, Florida, USABackground:. 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.http://journals.lww.com/10.1097/HC9.0000000000000057 |
| spellingShingle | David Jones Marco Carbone Pietro Invernizzi Nicola Little Frederik Nevens Mark G. Swain Philippe Wiesel Cynthia Levy Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial Hepatology Communications |
| title | Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial |
| title_full | Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial |
| title_fullStr | Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial |
| title_full_unstemmed | Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial |
| title_short | Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial |
| title_sort | impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial |
| url | http://journals.lww.com/10.1097/HC9.0000000000000057 |
| work_keys_str_mv | AT davidjones impactofsetanaxibonqualityoflifeoutcomesinprimarybiliarycholangitisinaphase2randomizedcontrolledtrial AT marcocarbone impactofsetanaxibonqualityoflifeoutcomesinprimarybiliarycholangitisinaphase2randomizedcontrolledtrial AT pietroinvernizzi impactofsetanaxibonqualityoflifeoutcomesinprimarybiliarycholangitisinaphase2randomizedcontrolledtrial AT nicolalittle impactofsetanaxibonqualityoflifeoutcomesinprimarybiliarycholangitisinaphase2randomizedcontrolledtrial AT frederiknevens impactofsetanaxibonqualityoflifeoutcomesinprimarybiliarycholangitisinaphase2randomizedcontrolledtrial AT markgswain impactofsetanaxibonqualityoflifeoutcomesinprimarybiliarycholangitisinaphase2randomizedcontrolledtrial AT philippewiesel impactofsetanaxibonqualityoflifeoutcomesinprimarybiliarycholangitisinaphase2randomizedcontrolledtrial AT cynthialevy impactofsetanaxibonqualityoflifeoutcomesinprimarybiliarycholangitisinaphase2randomizedcontrolledtrial |