title: 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.
abstract: 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/μL. 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.
authors.affiliation: AO Fatebenefratelli e Oftalmico, Milano, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bruno
authors.forename: S
authors.initials: S
authors.lastname: Bollani
authors.forename: A L
authors.initials: AL
authors.lastname: Zignego
authors.forename: J M
authors.initials: JM
authors.lastname: Pascasio
authors.forename: C
authors.initials: C
authors.lastname: Magni
authors.forename: A
authors.initials: A
authors.lastname: Ciancio
authors.forename: M
authors.initials: M
authors.lastname: Caremani
authors.forename: A
authors.initials: A
authors.lastname: Mangia
authors.forename: S
authors.initials: S
authors.lastname: Marenco
authors.forename: S
authors.initials: S
authors.lastname: Piovesan
authors.forename: L
authors.initials: L
authors.lastname: Chemello
authors.forename: S
authors.initials: S
authors.lastname: Babudieri
authors.forename: A
authors.initials: A
authors.lastname: Moretti
authors.forename: F
authors.initials: F
authors.lastname: Gea
authors.forename: C
authors.initials: C
authors.lastname: Colletta
authors.forename: R
authors.initials: R
authors.lastname: Perez-Alvarez
authors.forename: X
authors.initials: X
authors.lastname: Forns
authors.forename: J R
authors.initials: JR
authors.lastname: Larrubia
authors.forename: J
authors.initials: J
authors.lastname: Arenas
authors.forename: J
authors.initials: J
authors.lastname: Crespo
authors.forename: V
authors.initials: V
authors.lastname: Calvaruso
authors.forename: F
authors.initials: F
authors.lastname: Ceccherini Silberstein
authors.forename: P
authors.initials: P
authors.lastname: Maisonneuve
authors.forename: A
authors.initials: A
authors.lastname: Craxì
authors.forename: J L
authors.initials: JL
authors.lastname: Calleja
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007558:Italy; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood*; D012254:Ribavirin / Q000627:therapeutic use*; D013030:Spain; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D012254:Ribavirin; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline
keywords: IFN-based therapy; boceprevir; cirrhosis; first-generation protease inhibitors; hepatitis C