FibroScan-aspartate aminotransferase (FAST) score for monitoring histological improvement in non-alcoholic steatohepatitis activity during semaglutide treatment: post-hoc analysis of a randomised, double-blind, placebo-controlled, phase 2b trialResearch in context
Summary: Background: Currently, assessment of candidate pharmacotherapies in patients with non-alcoholic steatohepatitis (NASH) involves invasive liver biopsy. Non-invasive scores, such as the FibroScan-aspartate aminotransferase (FAST) score, are used to identify candidates for therapy, but their...
| मुख्य लेखकों: | , , , , , , , , , |
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| स्वरूप: | लेख |
| भाषा: | English |
| प्रकाशित: |
Elsevier
2023-12-01
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| श्रृंखला: | EClinicalMedicine |
| विषय: | |
| ऑनलाइन पहुंच: | http://www.sciencedirect.com/science/article/pii/S258953702300487X |
| _version_ | 1827687031614996480 |
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| author | Vincent Wai-Sun Wong Quentin M. Anstee Louise M. Nitze Anja Geerts Jacob George Victor Nolasco Mette S. Kjær Steen Ladelund Philip N. Newsome Vlad Ratziu |
| author_facet | Vincent Wai-Sun Wong Quentin M. Anstee Louise M. Nitze Anja Geerts Jacob George Victor Nolasco Mette S. Kjær Steen Ladelund Philip N. Newsome Vlad Ratziu |
| author_sort | Vincent Wai-Sun Wong |
| collection | DOAJ |
| description | Summary: Background: Currently, assessment of candidate pharmacotherapies in patients with non-alcoholic steatohepatitis (NASH) involves invasive liver biopsy. Non-invasive scores, such as the FibroScan-aspartate aminotransferase (FAST) score, are used to identify candidates for therapy, but their ability to assess disease progression or treatment effect is unknown. We aimed to assess the association between FAST score and histological endpoints. Methods: We conducted a post-hoc analysis using data from a prior randomised, double-blind, placebo-controlled, phase 2b trial at 143 sites across 16 countries. Patients (aged 18–75 years) with biopsy-confirmed NASH, fibrosis stage 1–3, and a Non-alcoholic fatty liver disease Activity Score (NAS) ≥4 were enrolled between January 2017 and September 2018, and randomly assigned to receive once-daily subcutaneous semaglutide 0.1, 0.2, or 0.4 mg or placebo for 72 weeks. A subgroup analysis of patients with FAST score and histological data in the pooled semaglutide treatment and placebo arms at baseline and week 72 was performed. The original trial is registered at ClinicalTrials.gov, NCT02970942. Findings: A total of 122 patients were included in this post-hoc analysis (93 received semaglutide and 29 received placebo). FAST score reduction was associated with achieving the primary endpoint of NASH resolution without worsening of fibrosis in the pooled semaglutide group (area under the receiver operating curve 0.69; 95% confidence interval [CI] 0.58, 0.81). Mean FAST score reduction from baseline to week 72 was greatest in patients who met the primary endpoint vs those who did not in both the semaglutide (−0.40 [95% CI –0.84, 0.04] vs −0.22 [95% CI –0.74, 0.30] points; p = 0.002) and placebo groups (−0.25 [95% CI –0.72, 0.23] vs 0.00 [95% CI –0.50, 0.50] points; p = 0.047). Similarly, mean reductions in FAST score at week 72 were greater in those with NAS improvement vs those without in the semaglutide and placebo groups (≥1 point, −0.36 [95% CI –0.82, 0.11] vs −0.08 [95% CI –0.53, 0.38] points [p < 0.001] and −0.25 [95% CI –0.64, 0.14] vs −0.06 [95% CI –0.40, 0.53] points [p = 0.001]; ≥2 points, −0.40 [95% CI –0.86, 0.06] vs −0.14 [95% CI –0.56, 0.28] points [p < 0.001] and −0.29 [95% CI –0.67, 0.09] vs −0.05 [95% CI –0.40, 0.50] points; [p < 0.001]). A FAST score reduction of more than 0.22 points after semaglutide treatment was associated with meeting the primary endpoint (sensitivity 78%; specificity 60%; positive likelihood ratio 1.26; negative likelihood ratio 0.25; odds ratio 4.93). Interpretation: The potential of the FAST score as a non-invasive monitoring tool to identify histological changes following treatment requires further evaluation and validation. Funding: Novo Nordisk A/S. |
| first_indexed | 2024-03-10T09:26:56Z |
| format | Article |
| id | doaj.art-be1241c16f2141948af877d3c5b51a1d |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-03-10T09:26:56Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-be1241c16f2141948af877d3c5b51a1d2023-11-22T04:48:22ZengElsevierEClinicalMedicine2589-53702023-12-0166102310FibroScan-aspartate aminotransferase (FAST) score for monitoring histological improvement in non-alcoholic steatohepatitis activity during semaglutide treatment: post-hoc analysis of a randomised, double-blind, placebo-controlled, phase 2b trialResearch in contextVincent Wai-Sun Wong0Quentin M. Anstee1Louise M. Nitze2Anja Geerts3Jacob George4Victor Nolasco5Mette S. Kjær6Steen Ladelund7Philip N. Newsome8Vlad Ratziu9Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, ChinaTranslational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United KingdomNovo Nordisk A/S, Development, Søborg, DenmarkDepartment of Gastroenterology and Hepatology, Hepatology Research Unit, Ghent University, Ghent, BelgiumStorr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, AustraliaNovo Nordisk A/S, Development, Søborg, DenmarkNovo Nordisk A/S, Development, Søborg, DenmarkNovo Nordisk A/S, Development, Søborg, DenmarkNIHR Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, United KingdomInstitute for Cardiometabolism and Nutrition, Sorbonne Université, Hôpital Pitié-Salpêtrière, APHP, INSERM UMRS 1138 CRC, Paris, France; Corresponding author. Institute for Cardiometabolism and Nutrition, Sorbonne Université, INSERM UMRS 1138 CRC, Hôpital Pitié-Salpêtrière (ICAN), 47 Bd de l'Hôpital, 75013 Paris, France.Summary: Background: Currently, assessment of candidate pharmacotherapies in patients with non-alcoholic steatohepatitis (NASH) involves invasive liver biopsy. Non-invasive scores, such as the FibroScan-aspartate aminotransferase (FAST) score, are used to identify candidates for therapy, but their ability to assess disease progression or treatment effect is unknown. We aimed to assess the association between FAST score and histological endpoints. Methods: We conducted a post-hoc analysis using data from a prior randomised, double-blind, placebo-controlled, phase 2b trial at 143 sites across 16 countries. Patients (aged 18–75 years) with biopsy-confirmed NASH, fibrosis stage 1–3, and a Non-alcoholic fatty liver disease Activity Score (NAS) ≥4 were enrolled between January 2017 and September 2018, and randomly assigned to receive once-daily subcutaneous semaglutide 0.1, 0.2, or 0.4 mg or placebo for 72 weeks. A subgroup analysis of patients with FAST score and histological data in the pooled semaglutide treatment and placebo arms at baseline and week 72 was performed. The original trial is registered at ClinicalTrials.gov, NCT02970942. Findings: A total of 122 patients were included in this post-hoc analysis (93 received semaglutide and 29 received placebo). FAST score reduction was associated with achieving the primary endpoint of NASH resolution without worsening of fibrosis in the pooled semaglutide group (area under the receiver operating curve 0.69; 95% confidence interval [CI] 0.58, 0.81). Mean FAST score reduction from baseline to week 72 was greatest in patients who met the primary endpoint vs those who did not in both the semaglutide (−0.40 [95% CI –0.84, 0.04] vs −0.22 [95% CI –0.74, 0.30] points; p = 0.002) and placebo groups (−0.25 [95% CI –0.72, 0.23] vs 0.00 [95% CI –0.50, 0.50] points; p = 0.047). Similarly, mean reductions in FAST score at week 72 were greater in those with NAS improvement vs those without in the semaglutide and placebo groups (≥1 point, −0.36 [95% CI –0.82, 0.11] vs −0.08 [95% CI –0.53, 0.38] points [p < 0.001] and −0.25 [95% CI –0.64, 0.14] vs −0.06 [95% CI –0.40, 0.53] points [p = 0.001]; ≥2 points, −0.40 [95% CI –0.86, 0.06] vs −0.14 [95% CI –0.56, 0.28] points [p < 0.001] and −0.29 [95% CI –0.67, 0.09] vs −0.05 [95% CI –0.40, 0.50] points; [p < 0.001]). A FAST score reduction of more than 0.22 points after semaglutide treatment was associated with meeting the primary endpoint (sensitivity 78%; specificity 60%; positive likelihood ratio 1.26; negative likelihood ratio 0.25; odds ratio 4.93). Interpretation: The potential of the FAST score as a non-invasive monitoring tool to identify histological changes following treatment requires further evaluation and validation. Funding: Novo Nordisk A/S.http://www.sciencedirect.com/science/article/pii/S258953702300487XBiomarkersClinical trialNon-alcoholic steatohepatitisNASHSemaglutide |
| spellingShingle | Vincent Wai-Sun Wong Quentin M. Anstee Louise M. Nitze Anja Geerts Jacob George Victor Nolasco Mette S. Kjær Steen Ladelund Philip N. Newsome Vlad Ratziu FibroScan-aspartate aminotransferase (FAST) score for monitoring histological improvement in non-alcoholic steatohepatitis activity during semaglutide treatment: post-hoc analysis of a randomised, double-blind, placebo-controlled, phase 2b trialResearch in context EClinicalMedicine Biomarkers Clinical trial Non-alcoholic steatohepatitis NASH Semaglutide |
| title | FibroScan-aspartate aminotransferase (FAST) score for monitoring histological improvement in non-alcoholic steatohepatitis activity during semaglutide treatment: post-hoc analysis of a randomised, double-blind, placebo-controlled, phase 2b trialResearch in context |
| title_full | FibroScan-aspartate aminotransferase (FAST) score for monitoring histological improvement in non-alcoholic steatohepatitis activity during semaglutide treatment: post-hoc analysis of a randomised, double-blind, placebo-controlled, phase 2b trialResearch in context |
| title_fullStr | FibroScan-aspartate aminotransferase (FAST) score for monitoring histological improvement in non-alcoholic steatohepatitis activity during semaglutide treatment: post-hoc analysis of a randomised, double-blind, placebo-controlled, phase 2b trialResearch in context |
| title_full_unstemmed | FibroScan-aspartate aminotransferase (FAST) score for monitoring histological improvement in non-alcoholic steatohepatitis activity during semaglutide treatment: post-hoc analysis of a randomised, double-blind, placebo-controlled, phase 2b trialResearch in context |
| title_short | FibroScan-aspartate aminotransferase (FAST) score for monitoring histological improvement in non-alcoholic steatohepatitis activity during semaglutide treatment: post-hoc analysis of a randomised, double-blind, placebo-controlled, phase 2b trialResearch in context |
| title_sort | fibroscan aspartate aminotransferase fast score for monitoring histological improvement in non alcoholic steatohepatitis activity during semaglutide treatment post hoc analysis of a randomised double blind placebo controlled phase 2b trialresearch in context |
| topic | Biomarkers Clinical trial Non-alcoholic steatohepatitis NASH Semaglutide |
| url | http://www.sciencedirect.com/science/article/pii/S258953702300487X |
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