Undetectable HCV-RNA at treatment-week 8 results in high-sustained virological response in HCV G1 treatment-experienced patients with advanced liver disease: The International Italian/Spanish Boceprevir/Peginterferon/Ribavirin Name Patients Program

Bruno, S.; Bollani, S.; Zignego, A. L.; Pascasio, J. M.; Magni, C.; Ciancio, A.; Caremani, M.; Mangia, A.; Marenco, S.; Piovesan, S.; Chemello, L.; Babudieri, S.; Moretti, A.; Gea, F.; Colletta, C.; Perez-Alvarez, R.; Forns, X.; Larrubia, J. R.; Arenas, J.; Crespo, J.; Calvaruso, V.; Ceccherini Silberstein, F.; Maisonneuve, P.; Craxi, A.; Calleja, J. L.; Di Marco, V.; Monti, M.; Rizzardini, G.; Landonio, S.; Rizzetto, M.; Lapini, L. E.; Piazzolla, V.; Picciotto, A.; Alberti, A.; Cavaletto, L.; Koch, M.; Massari, M.; Muratori, L.; Cipriano, V.; Montineri, A.; Iacobello, C.; Fangazio, S.; Pirisi, M.; Colombo, A.; Bellati, G.; Mazzotta, F.; Pierotti, P.; Traverso, A.; Serviddio, G.; Russello, M.; Santantonio, T.; Drenaggi, D.; Marchionne, E.; Zuin, M.; Delliponti, M.; Farina, F.; Andreone, P.; Scuteri, A.; Galli, M.; Giannini, E. G.; Nerli, A.; Carbonai, S.; Coppola, N.; Montalbano, M.; Portelli, V.; Di Biagio, A.; Nicolini, L. A.; Mastroianni, C.; Madonia, S.; Licata, A.; Montalto, G.; Giannitrapani, L.; Mondelli, M.; Pellicelli, A.; Toniutto, P.; Borgia, G.; Gentile, I.; De Luca, M.; Di Costanzo, G. G.; Corti, G.; Sousa, M.; Delgado, M. B.; De La Revilla, J.; Navarro, J. M.; Barcena, R.; Romero-Gomez, M.; Fernandez-Rodriguez, C. M.; Narvaez, I.; Erdozain, J. C.; Molina, E.; Fernandez, I.; Cuenca, B.; Planas, R.; Garcia-Samaniego, J.; Ladero, J. M.; Gonzalez, J. M.; Serra, M. A.; Castellote, I.; Sola, R.; Anton, T.; Ryan, I.; Gonzalez, F.; Martinez, E.; Portu, J.

doi:10.1111/jvh.12342

In many countries, first-generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV-infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under-represented in clinical trials. All treatment-experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian-Spanish Name Patient Program have been included in this study. Multivariate logistic regression analysis (MLR) was used to identify baseline and on-treatment predictors of SVR and adverse events (AEs). Four hundred and sixteen patients, mean age 57.7 (range 25-78 years), 70% males, 69.5% (289/416) F4, 14% (41/289) Child-Pugh class A6, 24% (70/289) with varices and 42% (173/416) prior null responders to P/R, were analysed. Overall, SVR rate (all 381 patients who received one dose of BOC) was 49%, (58% in F3, 45% in F4, 61% in relapsers, 51% in partial, 38% in null responders, and 72% in subjects with undetectable HCV-RNA at treatment-week (TW)8. Among patients with TW8 HCV-RNA ≥ 1000 IU/L, SVR was 8% (negative predictive value = 92%). Death occurred in 3 (0.8%) patients, while decompensation and infections were observed in 2.9% and 11%, respectively. At MLR, SVR predictors were TW4 HCV-RNA ≥ 1log10-decline from baseline, undetectable TW8 HCV-RNA, prior relapse, albumin levels ≥3.5 g/dL and platelet counts ≥100 000/lL. Metavir F4, Child-Pugh A6, albumin, platelets, age and female gender were associated with serious and haematological AEs. Among treatment-experienced patients with advanced liver disease eligible for IFN-based therapy, TW8 HCV-RNA characterised the subset with either high or poor likelihood of achieving SVR. Using TW8 HCV-RNA as a futility rule, BOC/P/R appears to have a favourable benefit-risk profile.