Comparative effectiveness of the hepatitis C virus protease inhibitors boceprevir and telaprevir in a large U.S. cohort

Aliment Pharmacol Ther. 2014 Jan;39(1):93-103. doi: 10.1111/apt.12546. Epub 2013 Nov 10.

Abstract

Background: Limited data exist on the effectiveness of boceprevir and telaprevir in routine practice.

Aim: To assess the comparative effectiveness of boceprevir and telaprevir regimens.

Methods: In this observational, intent-to-treat cohort analysis of hepatitis C genotype 1-infected veterans initiated on peginterferon/ribavirin and boceprevir (n = 661) or telaprevir (n = 198), we determined sustained virological response (SVR), treatment discontinuation rates and adverse haematological events. Inverse probability-of-treatment weighting (IPTW) was used to estimate the effect of one drug over the other, with matched pairs and unweighted logistic regression on the entire cohort for comparison.

Results: Of 835 veterans, SVR occurred in 50% and 52% receiving boceprevir- and telaprevir-based treatment, respectively (P = 0.72). No significant differences occurred among subgroups: cirrhotics (37% vs. 39%, P = 0.94), null responders (23% vs. 18%, P = 0.81), partial responders (39% vs. 58%, P = 0.15) and relapsers (60% vs. 77%, P = 0.11). Early discontinuation rates for boceprevir and telaprevir, respectively, were 31% and 28% by week 24 (P = 0.46) and 54% and 45% by 48 weeks (in those completing at least 28 weeks) (P = 0.14). Choice of telaprevir over boceprevir was significantly associated with SVR in multivariate models (IPTW OR: 1.57, 95% CI: 1.10-2.25, P = 0.01; matched-pairs OR: 1.91, 95% CI: 1.23-3.00, P = 0.004; unweighted OR: 1.50 95% CI: 1.05-2.14, P = 0.02). Rates of haematological adverse events in boceprevir- and telaprevir-treated patients were as follows: anaemia 59% vs. 51%, P = 0.30, thrombocytopenia 41% vs. 48%, P = 0.26, neutropenia 41% vs. 27%, P = 0.04.

Conclusions: Sustained virological response was more likely with telaprevir-based regimens compared with boceprevir-based regimens in routine medical practice, after accounting for patient differences. Early discontinuation and haematological events, however, were similar.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Cohort Studies
  • Comparative Effectiveness Research
  • Female
  • Hepatitis C / drug therapy*
  • Hepatitis C / epidemiology
  • Humans
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Oligopeptides / adverse effects
  • Oligopeptides / therapeutic use*
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use
  • Proline / adverse effects
  • Proline / analogs & derivatives*
  • Proline / therapeutic use
  • Protease Inhibitors / adverse effects
  • Protease Inhibitors / therapeutic use*
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use
  • Thrombocytopenia / chemically induced
  • United States / epidemiology
  • Veterans

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Oligopeptides
  • Protease Inhibitors
  • Polyethylene Glycols
  • Ribavirin
  • telaprevir
  • 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