Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

GUARD-C Study Group Investigators

doi:10.1371/journal.pone.0151703

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

GUARD-C Study Group Investigators

Division of Gastroenterology

Queen Mary University of London
Unità Operativa Epatologia ed Ecografia Interventistica Ospedale Gragnano
Hamad Medical Corporation
Medical University of Vienna
University of Parma
University of Pennsylvania
Ospedale Elena d'Aosta
Bon Secours Health System
Prometris GmbH
F. Hoffmann-La Roche AG
University of California at San Diego

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin.

Original language	English
Article number	e0151703
Journal	PLoS ONE
Volume	11
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0151703
State	Published - Mar 2016

Bibliographical note

Publisher Copyright:
© 2016 Foster et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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SDG 3 Good Health and Well-being

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10.1371/journal.pone.0151703

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@article{2c9315b6c53e4e01a16a6eb95c5600c7,

title = "Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort",

abstract = "Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 \% (754/1634), 77.1\% (279/362), 68.0\% (514/756), and 51.3\% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9\% and 21.8\% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9\% vs. 54.4\%; P = 0.0046) and Week 12 (41.7\% vs. 55.3\%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin.",

author = "\{GUARD-C Study Group Investigators\} and Foster, \{Graham R.\} and Carmine Coppola and Moutaz Derbala and Peter Ferenci and Alessandra Orlandini and Reddy, \{K. Rajender\} and Ludovico Tallarico and Shiffman, \{Mitchell L.\} and Silke Ahlers and Georgios Bakalos and Tarek Hassanein and Jovan Basho and Gentian Shabanaj and Arjan Harxhi and Nabil Debzi and Nawel Afredj and Nawal Guessab and Nadir Mahindad and Hassene Mahiou and Magda Aissaoui and \{Al Qameesh\}, Jihad and \{Al Ghandoor\}, Zuhal and Collins Assene and Boris Bastens and Christian Brixko and Mike Cool and \{De Galocsy\}, Chantal and Jean Delwaide and Christophe George and Pierre Laukens and Veronique Lefebvre and Mulkay, \{Jean Pierre\} and Frederik Nevens and Benoit Servais and \{Van Vlierberghe\}, Hans and Yves Horsmans and Jean Henrion and Dirk Sprengers and Peter Michielsen and Stefan Bourgeois and Luc Lasser and Philippe Langlet and Geert Robaeys and Martinet, \{Jean Paul\} and Philippe Warzee and Paul Hoste and Hendrik Reynaert and Ir{\`e}ne Juriens and Jochen Decaestecker and Jinmo Yang",

note = "Publisher Copyright: {\textcopyright} 2016 Foster et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2016",

month = mar,

doi = "10.1371/journal.pone.0151703",

language = "English",

volume = "11",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "3",

}

TY - JOUR

T1 - Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients

T2 - Results from the GUARD-C Cohort

AU - GUARD-C Study Group Investigators

AU - Foster, Graham R.

AU - Coppola, Carmine

AU - Derbala, Moutaz

AU - Ferenci, Peter

AU - Orlandini, Alessandra

AU - Reddy, K. Rajender

AU - Tallarico, Ludovico

AU - Shiffman, Mitchell L.

AU - Ahlers, Silke

AU - Bakalos, Georgios

AU - Hassanein, Tarek

AU - Basho, Jovan

AU - Shabanaj, Gentian

AU - Harxhi, Arjan

AU - Debzi, Nabil

AU - Afredj, Nawel

AU - Guessab, Nawal

AU - Mahindad, Nadir

AU - Mahiou, Hassene

AU - Aissaoui, Magda

AU - Al Qameesh, Jihad

AU - Al Ghandoor, Zuhal

AU - Assene, Collins

AU - Bastens, Boris

AU - Brixko, Christian

AU - Cool, Mike

AU - De Galocsy, Chantal

AU - Delwaide, Jean

AU - George, Christophe

AU - Laukens, Pierre

AU - Lefebvre, Veronique

AU - Mulkay, Jean Pierre

AU - Nevens, Frederik

AU - Servais, Benoit

AU - Van Vlierberghe, Hans

AU - Horsmans, Yves

AU - Henrion, Jean

AU - Sprengers, Dirk

AU - Michielsen, Peter

AU - Bourgeois, Stefan

AU - Lasser, Luc

AU - Langlet, Philippe

AU - Robaeys, Geert

AU - Martinet, Jean Paul

AU - Warzee, Philippe

AU - Hoste, Paul

AU - Reynaert, Hendrik

AU - Juriens, Irène

AU - Decaestecker, Jochen

AU - Yang, Jinmo

N1 - Publisher Copyright: © 2016 Foster et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2016/3

Y1 - 2016/3

N2 - Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin.

AB - Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin.

UR - https://www.scopus.com/pages/publications/84962170784

U2 - 10.1371/journal.pone.0151703

DO - 10.1371/journal.pone.0151703

M3 - Article

C2 - 27018988

AN - SCOPUS:84962170784

SN - 1932-6203

VL - 11

JO - PLoS ONE

JF - PLoS ONE

IS - 3

M1 - e0151703

ER -

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Abstract

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