Efficacy and safety of boceprevir plus peginterferon-ribavirin in patients with HCV G1 infection and advanced fibrosis/cirrhosis

Savino Bruno, John M. Vierling, Rafael Esteban, Lisa M. Nyberg, Hugo Tanno, Zachary Goodman, Fred Poordad, Bruce Bacon, Keith Gottesdiener, Lisa D. Pedicone, Janice K. Albrecht, Clifford A. Brass, Seth Thompson, Margaret H. Burroughs

Research output: Contribution to journalArticle

52 Scopus citations

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 languageEnglish (US)
Pages (from-to)479-487
Number of pages9
JournalJournal of Hepatology
Volume58
Issue number3
DOIs
StatePublished - Mar 1 2013
Externally publishedYes

Keywords

  • Advanced fibrosis
  • Boceprevir
  • Cirrhosis
  • HCV-G1 infection
  • Triple therapy

ASJC Scopus subject areas

  • Hepatology

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    Bruno, S., Vierling, J. M., Esteban, R., Nyberg, L. M., Tanno, H., Goodman, Z., Poordad, F., Bacon, B., Gottesdiener, K., Pedicone, L. D., Albrecht, J. K., Brass, C. A., Thompson, S., & Burroughs, M. H. (2013). Efficacy and safety of boceprevir plus peginterferon-ribavirin in patients with HCV G1 infection and advanced fibrosis/cirrhosis. Journal of Hepatology, 58(3), 479-487. https://doi.org/10.1016/j.jhep.2012.11.020