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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 languageEnglish
Article numbere0151703
JournalPloS one
Volume11
Issue number3
DOIs
Publication statusPublished - 2016 Mar

Fingerprint

Hepatitis C virus
Viruses
Hepacivirus
Ribavirin
Safety
dosage
Patient treatment
Sustained Virologic Response
Pulmonary diseases
chronic hepatitis C
antiviral agents
safety factor
Antiviral Agents
Chronic Hepatitis C
Virus Diseases
physicians
respiratory tract diseases
Lung Diseases
body mass index
RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

@article{4b3e29e3b16240559c2543876faebd58,
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 {Van Der Meersch}, Filip",
year = "2016",
month = "3",
doi = "10.1371/journal.pone.0151703",
language = "English",
volume = "11",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

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.

In: PloS one, Vol. 11, No. 3, e0151703, 03.2016.

Research output: Contribution to journalArticle

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 - Van Der Meersch, Filip

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 - http://www.scopus.com/inward/record.url?scp=84962170784&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962170784&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0151703

DO - 10.1371/journal.pone.0151703

M3 - Article

C2 - 27018988

AN - SCOPUS:84962170784

VL - 11

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e0151703

ER -