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; Hassanein, T; Bakalos, G; Ahlers, S; Shiffman, Ml; Tallarico, L; Reddy, Kr; Orlandini, A; Ferenci, P; Derbala, M; Coppola, C; Foster, Gr; 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 JP; Nevens F; Servais B; Van Vlierberghe H; Horsmans Y; Henrion J; Sprengers D; Michielsen P; Bourgeois S; Lasser L; Langlet P; Robaeys G; Martinet JP; 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 CE; Ruiz FJ; Martins Junior E; Ferraz ML; Silva G; Mendes C; Lyra A; Silva MH; Gomide G; Fernandes JC; Pereira P; Correa MC; 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; Nemesánszky E; Fried K; Schuller J; Szalay F; Lengyel G; Tornai I; Banyai T; Lesch M; Nagy I; Gervain J; Tusnadi A; Schneider F; Szentgyörgyi L; Hunyady B; Vincze A; Tolvaj G; Varkonyi I; Makkai E; Enyedi J; Racz I; Hausinger P; Váczi Z; Patai Á; Ozsvár 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 SM; Zali MR; Daryani NE; Drenaggi D; Attili AF; Bandiera F; Bassi P; Bellati G; Bellantani S; BRUNETTO, MAURIZIA ROSSANA; Bruno S; Castelli F; Castellacci R; Cattelan AM; Colombo M; Coppola C; 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 FP; 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 GL; Rizzardini G; Rizzetto M; Russello M; Sabusco G; Santantonio T; Soardo G; Tallarico L; Amedea A; Verucchi G; Vinelli F; Zignego AL; Zuin M; Ascione A; Vinci M; Pigozzi MG; Tundo P; Saracco GM; Amoroso P; Andreoni M; Colletta C; Erne E; Megna AS; Biglino A; Chiriaco P; Foti G; Spinzi G; D'amico E; Paik SW; Ahn SH; Lee YN; Kim Y; Yang J; Han SY; Varghese R; Al Gharabally A; Askar H; Sharara A; Yaghi C; Rached AA; 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 MJ; Valente C; Macedo G; Sarmento Castro R; Roxo F; Faria T; Mansinho K; Velez J; Ramos JP; Guerreiro H; Alberto S; Monteverde C; Serejo F; Peixe P; Malhado J; Derbala M; 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 M; Krkoska D; Jarcuska P; Schreter I; Oltman M; Bocakova J; Bunganic I; Holoman J; Giguere A; Abdou A.M.

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 peginterferon alfa-2a/ribavirin.