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Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct‐acting antiviral treatment

Although direct‐acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection have demonstrated high rates of sustained virologic response, virologic failure may still occur, potentially leading to the emergence of viral resistance, which can decrease the effectiveness of subsequent...

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Autores principales: Poordad, Fred, Felizarta, Franco, Asatryan, Armen, Sulkowski, Mark S., Reindollar, Robert W., Landis, Charles S., Gordon, Stuart C., Flamm, Steven L., Fried, Michael W., Bernstein, David E., Lin, Chih‐Wei, Liu, Ran, Lovell, Sandra S., Ng, Teresa I., Kort, Jens, Mensa, Federico J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573922/
https://www.ncbi.nlm.nih.gov/pubmed/28128852
http://dx.doi.org/10.1002/hep.29081
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author Poordad, Fred
Felizarta, Franco
Asatryan, Armen
Sulkowski, Mark S.
Reindollar, Robert W.
Landis, Charles S.
Gordon, Stuart C.
Flamm, Steven L.
Fried, Michael W.
Bernstein, David E.
Lin, Chih‐Wei
Liu, Ran
Lovell, Sandra S.
Ng, Teresa I.
Kort, Jens
Mensa, Federico J.
author_facet Poordad, Fred
Felizarta, Franco
Asatryan, Armen
Sulkowski, Mark S.
Reindollar, Robert W.
Landis, Charles S.
Gordon, Stuart C.
Flamm, Steven L.
Fried, Michael W.
Bernstein, David E.
Lin, Chih‐Wei
Liu, Ran
Lovell, Sandra S.
Ng, Teresa I.
Kort, Jens
Mensa, Federico J.
author_sort Poordad, Fred
collection PubMed
description Although direct‐acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection have demonstrated high rates of sustained virologic response, virologic failure may still occur, potentially leading to the emergence of viral resistance, which can decrease the effectiveness of subsequent treatment. Treatment options for patients who failed previous DAA‐containing regimens, particularly those with nonstructural protein 5A inhibitors, are limited and remain an area of unmet medical need. This phase 2, open‐label study (MAGELLAN‐1) evaluated the efficacy and safety of glecaprevir (GLE) + pibrentasvir (PIB) ± ribavirin (RBV) in HCV genotype 1–infected patients with prior virologic failure to HCV DAA‐containing therapy. A total of 50 patients without cirrhosis were randomized to three arms: 200 mg GLE + 80 mg PIB (arm A), 300 mg GLE + 120 mg PIB with 800 mg once‐daily RBV (arm B), or 300 mg GLE + 120 mg PIB without RBV (arm C). By intent‐to‐treat analysis, sustained virologic response at posttreatment week 12 was achieved in 100% (6/6, 95% confidence interval 61‐100), 95% (21/22, 95% confidence interval 78‐99), and 86% (19/22, 95% confidence interval 67‐95) of patients in arms A, B, and C, respectively. Virologic failure occurred in no patients in arm A and in 1 patient each in arms B and C (two patients were lost to follow‐up in arm C). The majority of adverse events were mild in severity; no serious adverse events related to study drug and no relevant laboratory abnormalities in alanine aminotransferase, total bilirubin, or hemoglobin were observed. Conclusion: The combination of GLE and PIB was highly efficacious and well tolerated in patients with HCV genotype 1 infection and prior failure of DAA‐containing therapy; RBV coadministration did not improve efficacy. (Hepatology 2017;66:389–397).
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spelling pubmed-55739222017-09-15 Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct‐acting antiviral treatment Poordad, Fred Felizarta, Franco Asatryan, Armen Sulkowski, Mark S. Reindollar, Robert W. Landis, Charles S. Gordon, Stuart C. Flamm, Steven L. Fried, Michael W. Bernstein, David E. Lin, Chih‐Wei Liu, Ran Lovell, Sandra S. Ng, Teresa I. Kort, Jens Mensa, Federico J. Hepatology Original Articles Although direct‐acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection have demonstrated high rates of sustained virologic response, virologic failure may still occur, potentially leading to the emergence of viral resistance, which can decrease the effectiveness of subsequent treatment. Treatment options for patients who failed previous DAA‐containing regimens, particularly those with nonstructural protein 5A inhibitors, are limited and remain an area of unmet medical need. This phase 2, open‐label study (MAGELLAN‐1) evaluated the efficacy and safety of glecaprevir (GLE) + pibrentasvir (PIB) ± ribavirin (RBV) in HCV genotype 1–infected patients with prior virologic failure to HCV DAA‐containing therapy. A total of 50 patients without cirrhosis were randomized to three arms: 200 mg GLE + 80 mg PIB (arm A), 300 mg GLE + 120 mg PIB with 800 mg once‐daily RBV (arm B), or 300 mg GLE + 120 mg PIB without RBV (arm C). By intent‐to‐treat analysis, sustained virologic response at posttreatment week 12 was achieved in 100% (6/6, 95% confidence interval 61‐100), 95% (21/22, 95% confidence interval 78‐99), and 86% (19/22, 95% confidence interval 67‐95) of patients in arms A, B, and C, respectively. Virologic failure occurred in no patients in arm A and in 1 patient each in arms B and C (two patients were lost to follow‐up in arm C). The majority of adverse events were mild in severity; no serious adverse events related to study drug and no relevant laboratory abnormalities in alanine aminotransferase, total bilirubin, or hemoglobin were observed. Conclusion: The combination of GLE and PIB was highly efficacious and well tolerated in patients with HCV genotype 1 infection and prior failure of DAA‐containing therapy; RBV coadministration did not improve efficacy. (Hepatology 2017;66:389–397). John Wiley and Sons Inc. 2017-04-10 2017-08 /pmc/articles/PMC5573922/ /pubmed/28128852 http://dx.doi.org/10.1002/hep.29081 Text en © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://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
Poordad, Fred
Felizarta, Franco
Asatryan, Armen
Sulkowski, Mark S.
Reindollar, Robert W.
Landis, Charles S.
Gordon, Stuart C.
Flamm, Steven L.
Fried, Michael W.
Bernstein, David E.
Lin, Chih‐Wei
Liu, Ran
Lovell, Sandra S.
Ng, Teresa I.
Kort, Jens
Mensa, Federico J.
Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct‐acting antiviral treatment
title Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct‐acting antiviral treatment
title_full Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct‐acting antiviral treatment
title_fullStr Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct‐acting antiviral treatment
title_full_unstemmed Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct‐acting antiviral treatment
title_short Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct‐acting antiviral treatment
title_sort glecaprevir and pibrentasvir for 12 weeks for hepatitis c virus genotype 1 infection and prior direct‐acting antiviral treatment
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573922/
https://www.ncbi.nlm.nih.gov/pubmed/28128852
http://dx.doi.org/10.1002/hep.29081
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