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

Foster, Graham R.; Coppola, Carmine; Derbala, Moutaz; Ferenci, Peter; Orlandini, Alessandra; Reddy, K. Rajender; Tallarico, Ludovico; Shiffman, Mitchell L.; Ahlers, Silke; Bakalos, Georgios; Hassanein, Tarek; Basho, Jovan; Shabanaj, Gentian; Harxhi, Arjan; Debzi, Nabil; Afredj, Nawel; Guessab, Nawal; Mahindad, Nadir; Mahiou, Hassene; Aissaoui, Magda; Al Qameesh, Jihad; Al Ghandoor, Zuhal; Assene, Collins; Bastens, Boris; Brixko, Christian; Cool, Mike; De Galocsy, Chantal; Delwaide, Jean; George, Christophe; Laukens, Pierre; Lefebvre, Veronique; Mulkay, Jean Pierre; Nevens, Frederik; Servais, Benoit; Van Vlierberghe, Hans; Horsmans, Yves; Henrion, Jean; Sprengers, Dirk; Michielsen, Peter; Bourgeois, Stefan; Lasser, Luc; Langlet, Philippe; Robaeys, Geert; Martinet, Jean Paul; Warzee, Philippe; Hoste, Paul; Reynaert, Hendrik; Juriens, Irène; Decaestecker, Jochen; Van Der Meersch, Filip; Janssens, Filip; Ahmetagic, Sead; Verhaz, Antonija; Bevanda, Milenko; Calkic, Lejla; Ibrahimpasic, Nevzeta; Mesihovic, Rusmir; Mello, Carlos Eduardo; Ruiz, Fernando Jose; Junior, Elson Martins; Ferraz, Maria Lucia; Silva, Giovanni; Mendes, Claudio; Lyra, Andre; Silva, Mariliza Henrique; Gomide, Geisa; Fernandes, Julio Cesar; Pereira, Patricia; Correa, Maria Cassia; Teixeira, Rosangela; Yousry, Ayman; Hanno, Abdelfatah; Gabr, Mamdouh; Omar, Ashraf; Esmat, Gamal; Karatapanis, Stilianos; Nikolopoulou, Vassiliki; Giannoulis, Grigoris; Manolakopoulos, Spilios; Elefsiniotis, Ioannis; Drakoulis, Christos; Dimitroulopoulos, Dimitrios; Kanatakis, Stilianos; Ketikoglou, Ioannis; Mimidis, Konstantinos; Evgenidis, Nikolaos; Akriviades, Euaggelos; Vafiadi Zoubouli, Irini; Tsianos, Epameinondas; Mela, Maria; Orfanou, Eleni; Mousoulis, Georgios; Karagiannis, Ioannis; Manesis, Emmanuel; Varga, Marta; Nemesánszky, Elemér; Fried, Katalin; Schuller, János; Szalay, Ferenc; Lengyel, Gabriella; Tornai, Istvan; Banyai, Tivadar; Lesch, Miklos; Nagy, Istvan; Gervain, Judit; Tusnadi, Anna; Schneider, Ferenc; Szentgyörgyi, László; Hunyady, Bela; Vincze, Aron; Tolvaj, Gyula; Varkonyi, Istvan; Makkai, Erzsébet; Enyedi, Judit; Racz, Istvan; Hausinger, Péter; Váczi, Zsuzsanna; Patai, Árpád; Ozsvár, Zsófia; Lakner, Lilla; Ribiczey, Pál; Bhalla, Ajay; Somani, Sanjay; Luaia, Rosang; Rao, Padaki; Philip, Mathew; Lawate, Parimal; Nagral, Aabha; Sood, Ajit; Parikh, Samir; Merat, Shahin; Nassiri Toosi, Mohsen; Alavian, Seyed Moayed; Zali, Mohammad Reza; Daryani, Nasser Ebrahimi; Drenaggi, Davide; ATTILI, Adolfo Francesco; Bandiera, Franco; Bassi, Paolo; Bellati, Giorgio; Bellantani, Stefano; Brunetto, Maurizia; Bruno, Savino; Castelli, Francesco; Castellacci, Roberto; Cattelan, Anna Maria; Colombo, Massimo; Craxi, Antonio; D'Angelo, Salvatore; Colombo, Silvia; Demelia, Luigi; Di Perri, Giovanni; Di Giacomo, Antonio; Ferrari, Carlo; Francisci, Daniela; Casinelli, Katia; Ganga, Roberto; Costa, Chiara; Mangia, Alessandra; Russo, Francesco Paolo; Matarazzo, Filippo; Mazzella, Giuseppe; Mazzeo, Maurizio; Memoli, Massimo; Montalbano, Marzia; Montalto, Giuseppe; Pieri, Alessandro; Passariello, Nicola; Picciotto, Antonio; Pietrangelo, Antonello; Pirisi, Mario; Quirino, Tiziana; Raimondo, Giovanni; Rapaccini, Gian Ludovico; Rizzardini, Giuliano; Rizzetto, Mario; Russello, Maurizio; Sabusco, Giuseppe; Santantonio, Teresa; Soardo, Giorgio; Amedea, Alessandri; Verucchi, Gabriella; Vinelli, Francesco; Zignego, Anna Linda; Zuin, Massimo; Ascione, Antonio; Vinci, Maria; Pigozzi, Maria Graziella; Tundo, Paolo; Saracco, Giorgio Maria; Amoroso, Pietro; Andreoni, Massimo; Colletta, Cosimo; Erne, Elke; Megna, Angelo Salomone; Biglino, Alberto; Chiriaco, Piergiorgio; Foti, Giuseppe; Spinzi, Giancarlo; D'Amico, Emilio; Paik, Seung Woon; Ahn, Sang Hoon; Lee, Yun Nah; Kim, Yoonjun; Yang, Jinmo; Han, Sang Young; Varghese, Rosh; Al Gharabally, Abeer; Askar, Haifa; Sharara, Ala; Yaghi, Cesar; Abou Rached, Antoine; Houmani, Zaher; Zaarour, Fouad; Dohaibi, Ahmad; Ivanovski, Ljubomir; Joksimovic, Nenad; Abbas, Zaigham; Memon, Sadik; Mohsin, Aftab; Masood, Siddiq; Hashmi, Zahid; Halota, Waldemar; Deron, Zbigniew; Mazur, Wlodzimierz; Flisiak, Robert; Lipczynski, Artur; Musialik, Joanna; Piekarska, Anna; Augustyniak, Krystyna; Baka Cwierz, Barbara; Simon, Krzysztof; Gietka, Andrzej; Berak, Hanna; Sieklucki, Jerzy; Radowska, Danuta; Szlauer, Bronislawa; Piekos, Tomasz; Olszok, Iwona; Jablkowski, Maciej; Orszulak, Grazyna; Warakomska, Iwona; Aleixo, Maria João; Valente, Cristina; Macedo, Guilherme; Sarmento Castro, Rui; Roxo, Fausto; Faria, Telo; Mansinho, Kamal; Velez, Jorge; Ramos, José Presa; Guerreiro, Horácio; Alberto, Sara; Monteverde, Carlos; Serejo, Fátima; Peixe, Paula; Malhado, José; Curescu, Manuela; Streinu Cercel, Adrian; Caruntu, Florin; Livia, Hara; Preotescu, Liliana; Arama, Victoria; Ancuta, Ioan; Gheorghe, Liana; Stanciu, Carol; Trifan, Anca; Acalovschi, Monica; Andreica, Vasile; Pascu, Oliviu; Lencu, Monica; Sporea, Ioan; Olteanu, Dan; Ionita Radu, Florentina; Fierbinteanu Braticevici, Carmen; Motoc, Adriana; Silaghi, Rodica; Musat, Marioara; Coman, Felicia; Stan, Marioara; Cijevschi, Cristina; Miftode, Egidia; Delic, Dragan; Jesic, Rada; Nozic, Darko; Svorcan, Petar; Fabri, Milotka; Konstantinovic, Ljiljana; Pelemis, Mijomir; Jankovic, Goran; Todorovic, Zoran; Nagorni, Aleksandar; Kupcova, Viera; Skladany, Lubomir; Szantova, Maria; Krkoska, Dusan; Jarcuska, Peter; Schreter, Ivan; Oltman, Marian; Bocakova, Jana; Bunganic, Ivan; Holoman, Jozef; Giguere, Alain; Abdou, Ahmed Mohamed Saleh

doi:10.1371/journal.pone.0151703

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.

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort / Foster, Graham R.; Coppola, Carmine; Derbala, Moutaz; Ferenci, Peter; Orlandini, Alessandra; Reddy, K. Rajender; Tallarico, Ludovico; Shiffman, Mitchell L.; Ahlers, Silke; Bakalos, Georgios; Hassanein, Tarek; Basho, Jovan; Shabanaj, Gentian; Harxhi, Arjan; Debzi, Nabil; Afredj, Nawel; Guessab, Nawal; Mahindad, Nadir; Mahiou, Hassene; Aissaoui, Magda; Al Qameesh, Jihad; Al Ghandoor, Zuhal; Assene, Collins; Bastens, Boris; Brixko, Christian; Cool, Mike; De Galocsy, Chantal; Delwaide, Jean; George, Christophe; Laukens, Pierre; Lefebvre, Veronique; Mulkay, Jean Pierre; Nevens, Frederik; Servais, Benoit; Van Vlierberghe, Hans; Horsmans, Yves; Henrion, Jean; Sprengers, Dirk; Michielsen, Peter; Bourgeois, Stefan; Lasser, Luc; Langlet, Philippe; Robaeys, Geert; Martinet, Jean Paul; Warzee, Philippe; Hoste, Paul; Reynaert, Hendrik; Juriens, Irène; Decaestecker, Jochen; Van Der Meersch, Filip; Janssens, Filip; Ahmetagic, Sead; Verhaz, Antonija; Bevanda, Milenko; Calkic, Lejla; Ibrahimpasic, Nevzeta; Mesihovic, Rusmir; Mello, Carlos Eduardo; Ruiz, Fernando Jose; Junior, Elson Martins; Ferraz, Maria Lucia; Silva, Giovanni; Mendes, Claudio; Lyra, Andre; Silva, Mariliza Henrique; Gomide, Geisa; Fernandes, Julio Cesar; Pereira, Patricia; Correa, Maria Cassia; Teixeira, Rosangela; Yousry, Ayman; Hanno, Abdelfatah; Gabr, Mamdouh; Omar, Ashraf; Esmat, Gamal; Karatapanis, Stilianos; Nikolopoulou, Vassiliki; Giannoulis, Grigoris; Manolakopoulos, Spilios; Elefsiniotis, Ioannis; Drakoulis, Christos; Dimitroulopoulos, Dimitrios; Kanatakis, Stilianos; Ketikoglou, Ioannis; Mimidis, Konstantinos; Evgenidis, Nikolaos; Akriviades, Euaggelos; Vafiadi Zoubouli, Irini; Tsianos, Epameinondas; Mela, Maria; Orfanou, Eleni; Mousoulis, Georgios; Karagiannis, Ioannis; Manesis, Emmanuel; Varga, Marta; Nemesánszky, Elemér; Fried, Katalin; Schuller, János; Szalay, Ferenc; Lengyel, Gabriella; Tornai, Istvan; Banyai, Tivadar; Lesch, Miklos; Nagy, Istvan; Gervain, Judit; Tusnadi, Anna; Schneider, Ferenc; Szentgyörgyi, László; Hunyady, Bela; Vincze, Aron; Tolvaj, Gyula; Varkonyi, Istvan; Makkai, Erzsébet; Enyedi, Judit; Racz, Istvan; Hausinger, Péter; Váczi, Zsuzsanna; Patai, Árpád; Ozsvár, Zsófia; Lakner, Lilla; Ribiczey, Pál; Bhalla, Ajay; Somani, Sanjay; Luaia, Rosang; Rao, Padaki; Philip, Mathew; Lawate, Parimal; Nagral, Aabha; Sood, Ajit; Parikh, Samir; Merat, Shahin; Nassiri Toosi, Mohsen; Alavian, Seyed Moayed; Zali, Mohammad Reza; Daryani, Nasser Ebrahimi; Drenaggi, Davide; Attili, Adolfo Francesco; Bandiera, Franco; Bassi, Paolo; Bellati, Giorgio; Bellantani, Stefano; Brunetto, Maurizia; Bruno, Savino; Castelli, Francesco; Castellacci, Roberto; Cattelan, Anna Maria; Colombo, Massimo; Craxi, Antonio; D'Angelo, Salvatore; Colombo, Silvia; Demelia, Luigi; Di Perri, Giovanni; Di Giacomo, Antonio; Ferrari, Carlo; Francisci, Daniela; Casinelli, Katia; Ganga, Roberto; Costa, Chiara; Mangia, Alessandra; Russo, Francesco Paolo; Matarazzo, Filippo; Mazzella, Giuseppe; Mazzeo, Maurizio; Memoli, Massimo; Montalbano, Marzia; Montalto, Giuseppe; Pieri, Alessandro; Passariello, Nicola; Picciotto, Antonio; Pietrangelo, Antonello; Pirisi, Mario; Quirino, Tiziana; Raimondo, Giovanni; Rapaccini, Gian Ludovico; Rizzardini, Giuliano; Rizzetto, Mario; Russello, Maurizio; Sabusco, Giuseppe; Santantonio, Teresa; Soardo, Giorgio; Amedea, Alessandri; Verucchi, Gabriella; Vinelli, Francesco; Zignego, Anna Linda; Zuin, Massimo; Ascione, Antonio; Vinci, Maria; Pigozzi, Maria Graziella; Tundo, Paolo; Saracco, Giorgio Maria; Amoroso, Pietro; Andreoni, Massimo; Colletta, Cosimo; Erne, Elke; Megna, Angelo Salomone; Biglino, Alberto; Chiriaco, Piergiorgio; Foti, Giuseppe; Spinzi, Giancarlo; D'Amico, Emilio; Paik, Seung Woon; Ahn, Sang Hoon; Lee, Yun Nah; Kim, Yoonjun; Yang, Jinmo; Han, Sang Young; Varghese, Rosh; Al Gharabally, Abeer; Askar, Haifa; Sharara, Ala; Yaghi, Cesar; Abou Rached, Antoine; Houmani, Zaher; Zaarour, Fouad; Dohaibi, Ahmad; Ivanovski, Ljubomir; Joksimovic, Nenad; Abbas, Zaigham; Memon, Sadik; Mohsin, Aftab; Masood, Siddiq; Hashmi, Zahid; Halota, Waldemar; Deron, Zbigniew; Mazur, Wlodzimierz; Flisiak, Robert; Lipczynski, Artur; Musialik, Joanna; Piekarska, Anna; Augustyniak, Krystyna; Baka Cwierz, Barbara; Simon, Krzysztof; Gietka, Andrzej; Berak, Hanna; Sieklucki, Jerzy; Radowska, Danuta; Szlauer, Bronislawa; Piekos, Tomasz; Olszok, Iwona; Jablkowski, Maciej; Orszulak, Grazyna; Warakomska, Iwona; Aleixo, Maria João; Valente, Cristina; Macedo, Guilherme; Sarmento Castro, Rui; Roxo, Fausto; Faria, Telo; Mansinho, Kamal; Velez, Jorge; Ramos, José Presa; Guerreiro, Horácio; Alberto, Sara; Monteverde, Carlos; Serejo, Fátima; Peixe, Paula; Malhado, José; Curescu, Manuela; Streinu Cercel, Adrian; Caruntu, Florin; Livia, Hara; Preotescu, Liliana; Arama, Victoria; Ancuta, Ioan; Gheorghe, Liana; Stanciu, Carol; Trifan, Anca; Acalovschi, Monica; Andreica, Vasile; Pascu, Oliviu; Lencu, Monica; Sporea, Ioan; Olteanu, Dan; Ionita Radu, Florentina; Fierbinteanu Braticevici, Carmen; Motoc, Adriana; Silaghi, Rodica; Musat, Marioara; Coman, Felicia; Stan, Marioara; Cijevschi, Cristina; Miftode, Egidia; Delic, Dragan; Jesic, Rada; Nozic, Darko; Svorcan, Petar; Fabri, Milotka; Konstantinovic, Ljiljana; Pelemis, Mijomir; Jankovic, Goran; Todorovic, Zoran; Nagorni, Aleksandar; Kupcova, Viera; Skladany, Lubomir; Szantova, Maria; Krkoska, Dusan; Jarcuska, Peter; Schreter, Ivan; Oltman, Marian; Bocakova, Jana; Bunganic, Ivan; Holoman, Jozef; Giguere, Alain; Abdou, Ahmed Mohamed Saleh. - In: PLOS ONE. - ISSN 1932-6203. - 11:3(2016), p. e0151703. [10.1371/journal.pone.0151703]