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