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

Articolo
Data di Pubblicazione:
2016
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 peginterferon alfa-2a/ribavirin.
Tipologia CRIS:
1.1 Articolo in rivista
Keywords:
Adult; Aged; Anemia; Antiviral Agents; Asthenia; Cohort Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Hepacivirus; Hepatitis C, Chronic; Host-Pathogen Interactions; Humans; Interferon-alpha; Male; Middle Aged; Neutropenia; Outcome Assessment (Health Care); Polyethylene Glycols; Proportional Hazards Models; RNA, Viral; Recombinant Proteins; Ribavirin; Withholding Treatment
Elenco autori:
Foster, G. R.; Coppola, C.; Derbala, M.; Ferenci, P.; Orlandini, A.; Reddy, K. R.; Tallarico, L.; Shiffman, M. L.; Ahlers, S.; Bakalos, G.; Hassanein, T.; Basho, J.; Shabanaj, G.; Harxhi, A.; Debzi, N.; Afredj, N.; Guessab, N.; Mahindad, N.; Mahiou, H.; Aissaoui, M.; Al Qameesh, J.; Al Ghandoor, Z.; Assene, C.; Bastens, B.; Brixko, C.; Cool, M.; De Galocsy, C.; Delwaide, J.; George, C.; Laukens, P.; Lefebvre, V.; Mulkay, J. -P.; Nevens, F.; Servais, B.; Van Vlierberghe, H.; Horsmans, Y.; Henrion, J.; Sprengers, D.; Michielsen, P.; Bourgeois, S.; Lasser, L.; Langlet, P.; Robaeys, G.; Martinet, J. -P.; Warzee, P.; Hoste, P.; Reynaert, H.; Juriens, I.; Decaestecker, J.; Van Der Meersch, F.; Janssens, F.; Ahmetagic, S.; Verhaz, A.; Bevanda, M.; Calkic, L.; Ibrahimpasic, N.; Mesihovic, R.; Mello, C. E.; Ruiz, F. J.; Junior, E. M.; Ferraz, M. L.; Silva, G.; Mendes, C.; Lyra, A.; Silva, M. H.; Gomide, G.; Fernandes, J. C.; Pereira, P.; Correa, M. C.; Teixeira, R.; Yousry, A.; Hanno, A.; Gabr, M.; Omar, A.; Esmat, G.; Karatapanis, S.; Nikolopoulou, V.; Giannoulis, G.; Manolakopoulos, S.; Elefsiniotis, I.; Drakoulis, C.; Dimitroulopoulos, D.; Kanatakis, S.; Ketikoglou, I.; Mimidis, K.; Evgenidis, N.; Akriviades, E.; Vafiadi-Zoubouli, I.; Tsianos, E.; Mela, M.; Orfanou, E.; Mousoulis, G.; Karagiannis, I.; Manesis, E.; Varga, M.; Nemesanszky, E.; Fried, K.; Schuller, J.; Szalay, F.; Lengyel, G.; Tornai, I.; Banyai, T.; Lesch, M.; Nagy, I.; Gervain, J.; Tusnadi, A.; Schneider, F.; Szentgyorgyi, L.; Hunyady, B.; Vincze, A.; Tolvaj, G.; Varkonyi, I.; Makkai, E.; Enyedi, J.; Racz, I.; Hausinger, P.; Vaczi, Z.; Patai, A.; Ozsvar, Z.; Lakner, L.; Ribiczey, P.; Bhalla, A.; Somani, S.; Luaia, R.; Rao, P.; Philip, M.; Lawate, P.; Nagral, A.; Sood, A.; Parikh, S.; Merat, S.; Nassiri-Toosi, M.; Alavian, S. -M.; Zali, M. R.; Daryani, N. E.; Drenaggi, D.; Attili, A. F.; Bandiera, F.; Bassi, P.; Bellati, G.; Bellantani, S.; Brunetto, M.; Bruno, S.; Castelli, F.; Castellacci, R.; Cattelan, A. M.; Colombo, M.; Craxi, A.; D'Angelo, S.; Colombo, S.; Demelia, L.; Di Perri, G.; Di Giacomo, A.; Ferrari, C.; Francisci, D.; Casinelli, K.; Ganga, R.; Costa, C.; Mangia, A.; Russo, F. P.; Matarazzo, F.; Mazzella, G.; Mazzeo, M.; Memoli, M.; Montalbano, M.; Montalto, G.; Pieri, A.; Passariello, N.; Picciotto, A.; Pietrangelo, A.; Pirisi, M.; Quirino, T.; Raimondo, G.; Rapaccini, G. L.; Rizzardini, G.; Rizzetto, M.; Russello, M.; Sabusco, G.; Santantonio, T.; Soardo, G.; Amedea, A.; Verucchi, G.; Vinelli, F.; Zignego, A. L.; Zuin, M.; Ascione, A.; Vinci, M.; Pigozzi, M. G.; Tundo, P.; Saracco, G. M.; Amoroso, P.; Andreoni, M.; Colletta, C.; Erne, E.; Megna, A. S.; Biglino, A.; Chiriaco, P.; Foti, G.; Spinzi, G.; D'Amico, E.; Paik, S. W.; Ahn, S. -H.; Lee, Y. N.; Kim, Y.; Yang, J.; Han, S. Y.; Varghese, R.; Al Gharabally, A.; Askar, H.; Sharara, A.; Yaghi, C.; Abou Rached, A.; Houmani, Z.; Zaarour, F.; Dohaibi, A.; Ivanovski, L.; Joksimovic, N.; Abbas, Z.; Memon, S.; Mohsin, A.; Masood, S.; Hashmi, Z.; Halota, W.; Deron, Z.; Mazur, W.; Flisiak, R.; Lipczynski, A.; Musialik, J.; Piekarska, A.; Augustyniak, K.; Baka-Cwierz, B.; Simon, K.; Gietka, A.; Berak, H.; Sieklucki, J.; Radowska, D.; Szlauer, B.; Piekos, T.; Olszok, I.; Jablkowski, M.; Orszulak, G.; Warakomska, I.; Aleixo, M. J.; Valente, C.; Macedo, G.; Sarmento-Castro, R.; Roxo, F.; Faria, T.; Mansinho, K.; Velez, J.; Ramos, J. P.; Guerreiro, H.; Alberto, S.; Monteverde, C.; Serejo, F.; Peixe, P.; Malhado, J.; Curescu, M.; Streinu-Cercel, A.; Caruntu, F.; Livia, H.; Preotescu, L.; Arama, V.; Ancuta, I.; Gheorghe, L.; Stanciu, C.; Trifan, A.; Acalovschi, M.; Andreica, V.; Pascu, O.; Lencu, M.; Sporea, I.; Olteanu, D.; Ionita-Radu, F.; Fierbinteanu-Braticevici, C.; Motoc, A.; Silaghi, R.; Musat, M.; Coman, F.; Stan, M.; Cijevschi, C.; Miftode, E.; Delic, D.; Jesic, R.; Nozic, D.; Svorcan, P.; Fabri, M.; Konstantinovic, L.; Pelemis, M.; Jankovic, G.; Todorovic, Z.; Nagorni, A.; Kupcova, V.; Skladany, L.; Szantova
Autori di Ateneo:
CASTELLI FRANCESCO
Link alla scheda completa:
https://iris.unibs.it/handle/11379/518644
Pubblicato in:
PLOS ONE
Journal
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