Safety and efficacy of boceprevir/peginterferon/ribavirin for HCV G1 compensated cirrhotics: meta-analysis of 5 trials

J Hepatol. 2014 Aug;61(2):200-9. doi: 10.1016/j.jhep.2014.03.022. Epub 2014 Apr 18.

Abstract

Background & aims: HCV-infected cirrhotics may urgently need therapy but are often under-represented in clinical trials resulting in limited data to guide their management. We performed a meta-analysis of well-compensated cirrhotic patients from five Phase 3 trials.

Methods: Patients received P/R (peginterferon/ribavirin; 4 weeks) followed by BOC (boceprevir)/P/R or P/R for 24, 32, or 44 weeks. Sustained virologic response (SVR) rates were calculated by Metavir score. Multivariate logistic regression (MLR) models identified baseline and on-treatment predictors of SVR. Safety was evaluated by adverse-event (AE) reporting and laboratory monitoring.

Results: Pooled meta-estimates for SVR rates (95% confidence interval) in 212 F4 (cirrhotic) patients were 55% (43, 66) with BOC/P/R vs.17% (0, 41) with P/R. MLR identified 4 predictors of SVR in F3/F4 patients: undetectable HCV-RNA at treatment week (TW) 8; ⩾ 1 log10 decline in HCV-RNA from baseline at TW4; male; and baseline HCV-RNA ⩽ 800,000 IU/ml. SVR rate was 89% (65/73) in F4 patients who were HCV-RNA undetectable at TW8. No F3 (0/5) or F4 (0/17) patients with <3 log10 decline and detectable HCV-RNA at TW8 achieved SVR. Anemia and diarrhea occurred more frequently in cirrhotic than non-cirrhotic patients. Serious AEs, discontinuations due to an AE, interventions to manage anemia, infections, and thrombocytopenia occurred more frequently in cirrhotics with BOC/P/R than P/R. Potential hepatic decompensation and/or sepsis were identified in 2 P/R and 3 BOC/P/R recipients.

Conclusions: BOC/P/R appears to have a generally favorable benefit-risk profile in compensated cirrhotic patients. SVR rates were particularly high in cirrhotic patients with undetectable HCV-RNA at TW8.

Keywords: Chronic HCV; Cirrhosis; Hepatitis C.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / administration & dosage*
  • Clinical Trials, Phase III as Topic
  • Drug Therapy, Combination
  • Female
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-alpha / administration & dosage*
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / etiology
  • Logistic Models
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Proline / administration & dosage
  • Proline / analogs & derivatives*
  • RNA, Viral / analysis
  • Recombinant Proteins / administration & dosage
  • Retrospective Studies
  • Ribavirin / administration & dosage*

Substances

  • Antiviral Agents
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • 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
  • Proline
  • peginterferon alfa-2a