BACKGROUND & AIMS: We assessed the safety and efficacy of boceprevir (BOC) plus peginterferon-ribavirin (PR) in patients with HCV-G1 infection and advanced fibrosis/cirrhosis (Metavir F3/F4). METHODS: In two randomized controlled studies of previously untreated and previous treatment failures, patients received a 4-week lead-in of PR followed by PR plus placebo for 44 weeks (PR48); PR plus BOC using response guided therapy (BOC/RGT); or PR plus BOC for 44 weeks (BOC/PR48). RESULTS: The trials enrolled 178 patients with F3/4. HCV RNA levels at week 4 and 8 were highly predictive of response. No patient with F3/4 in the PR48 arm with a <1 log(10) decline in HCV RNA at week 4 achieved SVR, whereas those randomized to BOC/RGT or BOC/PR48 had SVR rates of 11-33% (F3) and 10-14% (F4). In these latter groups, patients with high baseline viral load (>2 × 10(6)IU/ml) had an overall SVR rate of 6% (2/33). For patients with a ≥1 log(10) decline at week 4, SVR rates in the BOC/PR48 arm of SPRINT-2 and RESPOND-2, respectively, were 77% and 87% vs. 18% and 50% for PR48; SVR rates in early responders (undetectable HCV RNA at week 8) were 90-93% in the BOC/PR48 arm. Neutropenia and thrombocytopenia were more common in cirrhotics than non-cirrhotics. CONCLUSIONS:BOC improves SVR rates in patients with F3/4, and longer treatment duration provides the most benefit. With triple therapy, SVR rates are modest in F4 patients with a <1 log(10) decline at week 4, thus the 4-week PR lead-in aids in the assessment of early futility.
RCT Entities:
BACKGROUND & AIMS: We assessed the safety and efficacy of boceprevir (BOC) plus peginterferon-ribavirin (PR) in patients with HCV-G1 infection and advanced fibrosis/cirrhosis (Metavir F3/F4). METHODS: In two randomized controlled studies of previously untreated and previous treatment failures, patients received a 4-week lead-in of PR followed by PR plus placebo for 44 weeks (PR48); PR plus BOC using response guided therapy (BOC/RGT); or PR plus BOC for 44 weeks (BOC/PR48). RESULTS: The trials enrolled 178 patients with F3/4. HCV RNA levels at week 4 and 8 were highly predictive of response. No patient with F3/4 in the PR48 arm with a <1 log(10) decline in HCV RNA at week 4 achieved SVR, whereas those randomized to BOC/RGT or BOC/PR48 had SVR rates of 11-33% (F3) and 10-14% (F4). In these latter groups, patients with high baseline viral load (>2 × 10(6)IU/ml) had an overall SVR rate of 6% (2/33). For patients with a ≥1 log(10) decline at week 4, SVR rates in the BOC/PR48 arm of SPRINT-2 and RESPOND-2, respectively, were 77% and 87% vs. 18% and 50% for PR48; SVR rates in early responders (undetectable HCV RNA at week 8) were 90-93% in the BOC/PR48 arm. Neutropenia and thrombocytopenia were more common in cirrhotics than non-cirrhotics. CONCLUSIONS:BOC improves SVR rates in patients with F3/4, and longer treatment duration provides the most benefit. With triple therapy, SVR rates are modest in F4 patients with a <1 log(10) decline at week 4, thus the 4-week PR lead-in aids in the assessment of early futility.
Authors: Javier Salmerón; Carmen Vinaixa; Rubén Berenguer; Juan Manuel Pascasio; Juan José Sánchez Ruano; Miguel Ángel Serra; Ana Gila; Moisés Diago; Manuel Romero-Gómez; José María Navarro; Milagros Testillano; Conrado Fernández; Dolores Espinosa; Isabel Carmona; José Antonio Pons; Francisco Jorquera; Francisco Javier Rodriguez; Ramón Pérez; José Luis Montero; Rafael Granados; Miguel Fernández; Ana Belén Martín; Paloma Muñoz de Rueda; Rosa Quiles Journal: World J Gastroenterol Date: 2015-08-14 Impact factor: 5.742
Authors: Ya-Chi Chen; Coen Bernaards; Rohit Kulkarni; Sebastian Moreira; Yonghong Zhu; Anna Chan; Ethan Badman; Andrew Ackrill; James Thommes; Patrick F Smith Journal: Br J Clin Pharmacol Date: 2014-09 Impact factor: 4.335
Authors: Stefan Zeuzem; Vicente Soriano; Tarik Asselah; Edward J Gane; Jean-Pierre Bronowicki; Peter Angus; Ansgar W Lohse; Felix Stickel; Beat Müllhaupt; Stuart Roberts; Marcus Schuchmann; Michael Manns; Marc Bourlière; Maria Buti; Jerry O Stern; John-Paul Gallivan; Florian Voss; John P Sabo; Wulf Böcher; Federico J Mensa Journal: Antimicrob Agents Chemother Date: 2014-12-15 Impact factor: 5.191
Authors: Antonio Ascione; Luigi Elio Adinolfi; Pietro Amoroso; Angelo Andriulli; Orlando Armignacco; Tiziana Ascione; Sergio Babudieri; Giorgio Barbarini; Michele Brogna; Francesco Cesario; Vincenzo Citro; Ernesto Claar; Raffaele Cozzolongo; Giuseppe D'Adamo; Emilio D'Amico; Pellegrino Dattolo; Massimo De Luca; Vincenzo De Maria; Massimo De Siena; Giuseppe De Vita; Antonio Di Giacomo; Rosanna De Marco; Giorgio De Stefano; Giulio De Stefano; Sebastiano Di Salvo; Raffaele Di Sarno; Nunzia Farella; Laura Felicioni; Basilio Fimiani; Luca Fontanella; Giuseppe Foti; Caterina Furlan; Francesca Giancotti; Giancarlo Giolitto; Tiziana Gravina; Barbara Guerrera; Roberto Gulminetti; Angelo Iacobellis; Michele Imparato; Angelo Iodice; Vincenzo Iovinella; Antonio Izzi; Alfonso Liberti; Pietro Leo; Gennaro Lettieri; Ileana Luppino; Aldo Marrone; Ettore Mazzoni; Vincenzo Messina; Roberto Monarca; Vincenzo Narciso; Lorenzo Nosotti; Adriano Maria Pellicelli; Alessandro Perrella; Guido Piai; Antonio Picardi; Paola Pierri; Grazia Pietromatera; Francesco Resta; Luca Rinaldi; Mario Romano; Angelo Rossini; Maurizio Russello; Grazia Russo; Rodolfo Sacco; Vincenzo Sangiovanni; Antonio Schiano; Antonio Sciambra; Gaetano Scifo; Filomena Simeone; Annarita Sullo; Pierluigi Tarquini; Paolo Tundo; Alfredo Vallone Journal: World J Hepatol Date: 2016-08-08