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Positive predictive value of sustained virologic response 4 weeks posttreatment for achieving sustained virologic response 12 weeks posttreatment in patients receiving glecaprevir/pibrentasvir in Phase 2 and 3 clinical trials
Sustained virologic response at posttreatment Week 12 (SVR12) is the widely accepted efficacy endpoint for direct‐acting antiviral agents. Those with hepatitis C virus (HCV) are presenting younger with milder liver disease, potentially reducing need for long‐term liver posttreatment monitoring. This...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292745/ https://www.ncbi.nlm.nih.gov/pubmed/34448313 http://dx.doi.org/10.1111/jvh.13600 |
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author | Gane, Edward de Ledinghen, Victor Dylla, Douglas E. Rizzardini, Giuliano Shiffman, Mitchell L. Barclay, Stephen T. Calleja, Jose Luis Xue, Zhenyi Burroughs, Margaret Gutierrez, Julio A. |
author_facet | Gane, Edward de Ledinghen, Victor Dylla, Douglas E. Rizzardini, Giuliano Shiffman, Mitchell L. Barclay, Stephen T. Calleja, Jose Luis Xue, Zhenyi Burroughs, Margaret Gutierrez, Julio A. |
author_sort | Gane, Edward |
collection | PubMed |
description | Sustained virologic response at posttreatment Week 12 (SVR12) is the widely accepted efficacy endpoint for direct‐acting antiviral agents. Those with hepatitis C virus (HCV) are presenting younger with milder liver disease, potentially reducing need for long‐term liver posttreatment monitoring. This analysis aimed to determine the positive predictive value (PPV) of SVR at posttreatment Week 4 (SVR4) for achieving SVR12 in patients with HCV, without cirrhosis or with compensated cirrhosis, receiving glecaprevir/pibrentasvir (G/P) in clinical trials. An integrated dataset from 20 Phase 2 and 3 clinical trials of G/P was evaluated in patients with 8‐, 12‐ or 16‐week treatment duration consistent with the current label (label‐consistent group), and in all patients regardless of treatment duration consistency with the current label (overall group). Sensitivity analyses handled missing data either by backward imputation or were excluded. SVR4 PPV, negative predictive value (NPV), sensitivity and specificity were calculated for achieving SVR12 in both groups, and by treatment duration in the label‐consistent group. SVR was defined as HCV ribonucleic acid <lower limit of quantification. The label‐consistent group and overall group included 2890 and 4390 patients, respectively. PPV of SVR4 for SVR12 was >99% in both groups regardless of treatment duration. Not achieving SVR4 had 100% NPV and sensitivity for all groups. SVR4 measure had 79.5% specificity for identifying patients who did not achieve SVR12. Across 20 Phase 2/3 clinical trials of G/P, SVR4 was highly predictive of SVR12. Long‐term follow‐up to confirm SVR may not be necessary for certain populations of patients with HCV. |
format | Online Article Text |
id | pubmed-9292745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92927452022-07-20 Positive predictive value of sustained virologic response 4 weeks posttreatment for achieving sustained virologic response 12 weeks posttreatment in patients receiving glecaprevir/pibrentasvir in Phase 2 and 3 clinical trials Gane, Edward de Ledinghen, Victor Dylla, Douglas E. Rizzardini, Giuliano Shiffman, Mitchell L. Barclay, Stephen T. Calleja, Jose Luis Xue, Zhenyi Burroughs, Margaret Gutierrez, Julio A. J Viral Hepat Original Articles Sustained virologic response at posttreatment Week 12 (SVR12) is the widely accepted efficacy endpoint for direct‐acting antiviral agents. Those with hepatitis C virus (HCV) are presenting younger with milder liver disease, potentially reducing need for long‐term liver posttreatment monitoring. This analysis aimed to determine the positive predictive value (PPV) of SVR at posttreatment Week 4 (SVR4) for achieving SVR12 in patients with HCV, without cirrhosis or with compensated cirrhosis, receiving glecaprevir/pibrentasvir (G/P) in clinical trials. An integrated dataset from 20 Phase 2 and 3 clinical trials of G/P was evaluated in patients with 8‐, 12‐ or 16‐week treatment duration consistent with the current label (label‐consistent group), and in all patients regardless of treatment duration consistency with the current label (overall group). Sensitivity analyses handled missing data either by backward imputation or were excluded. SVR4 PPV, negative predictive value (NPV), sensitivity and specificity were calculated for achieving SVR12 in both groups, and by treatment duration in the label‐consistent group. SVR was defined as HCV ribonucleic acid <lower limit of quantification. The label‐consistent group and overall group included 2890 and 4390 patients, respectively. PPV of SVR4 for SVR12 was >99% in both groups regardless of treatment duration. Not achieving SVR4 had 100% NPV and sensitivity for all groups. SVR4 measure had 79.5% specificity for identifying patients who did not achieve SVR12. Across 20 Phase 2/3 clinical trials of G/P, SVR4 was highly predictive of SVR12. Long‐term follow‐up to confirm SVR may not be necessary for certain populations of patients with HCV. John Wiley and Sons Inc. 2021-09-08 2021-11 /pmc/articles/PMC9292745/ /pubmed/34448313 http://dx.doi.org/10.1111/jvh.13600 Text en © 2021 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Gane, Edward de Ledinghen, Victor Dylla, Douglas E. Rizzardini, Giuliano Shiffman, Mitchell L. Barclay, Stephen T. Calleja, Jose Luis Xue, Zhenyi Burroughs, Margaret Gutierrez, Julio A. Positive predictive value of sustained virologic response 4 weeks posttreatment for achieving sustained virologic response 12 weeks posttreatment in patients receiving glecaprevir/pibrentasvir in Phase 2 and 3 clinical trials |
title | Positive predictive value of sustained virologic response 4 weeks posttreatment for achieving sustained virologic response 12 weeks posttreatment in patients receiving glecaprevir/pibrentasvir in Phase 2 and 3 clinical trials |
title_full | Positive predictive value of sustained virologic response 4 weeks posttreatment for achieving sustained virologic response 12 weeks posttreatment in patients receiving glecaprevir/pibrentasvir in Phase 2 and 3 clinical trials |
title_fullStr | Positive predictive value of sustained virologic response 4 weeks posttreatment for achieving sustained virologic response 12 weeks posttreatment in patients receiving glecaprevir/pibrentasvir in Phase 2 and 3 clinical trials |
title_full_unstemmed | Positive predictive value of sustained virologic response 4 weeks posttreatment for achieving sustained virologic response 12 weeks posttreatment in patients receiving glecaprevir/pibrentasvir in Phase 2 and 3 clinical trials |
title_short | Positive predictive value of sustained virologic response 4 weeks posttreatment for achieving sustained virologic response 12 weeks posttreatment in patients receiving glecaprevir/pibrentasvir in Phase 2 and 3 clinical trials |
title_sort | positive predictive value of sustained virologic response 4 weeks posttreatment for achieving sustained virologic response 12 weeks posttreatment in patients receiving glecaprevir/pibrentasvir in phase 2 and 3 clinical trials |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292745/ https://www.ncbi.nlm.nih.gov/pubmed/34448313 http://dx.doi.org/10.1111/jvh.13600 |
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