Abstract
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 log10 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 × 106 IU/ml) had an overall SVR rate of 6% (2/33). For patients with a ≥1 log10 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 log10 decline at week 4, thus the 4-week PR lead-in aids in the assessment of early futility.
Original language | English (US) |
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Pages (from-to) | 479-487 |
Number of pages | 9 |
Journal | Journal of Hepatology |
Volume | 58 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2013 |
Externally published | Yes |
Keywords
- Advanced fibrosis
- Boceprevir
- Cirrhosis
- HCV-G1 infection
- Triple therapy
ASJC Scopus subject areas
- Hepatology