November 11, 2013

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

Alimentary Pharmacology & Therapeutics

Early View (Online Version of Record published before inclusion in an issue)

Original Article

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L. I. Backus1,2,*, P. S. Belperio1, T. A. Shahoumian1, R. Cheung3,4, L. A. Mole1

Article first published online: 10 NOV 2013

DOI: 10.1111/apt.12546

Published 2013. This article is a US Government work and is in the public domain in the USA.

Summary

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.

Introduction

The introduction of the NS3/4A protease inhibitor direct-acting anti-virals (DAA), boceprevir and telaprevir marked the beginning of a new era in hepatitis C virus (HCV) treatment. In combination with peginterferon and ribavirin, boceprevir- or telparevir-based triple therapy represents the current standard of care for those infected with HCV genotype 1.[1] Compared with clinical trials of peginterferon/ribavirin dual therapy, which showed sustained virological response (SVR) rates approximating 40%, clinical trials of these triple-drug regimens show substantially improved response rates and shortened treatment durations.[2, 3] The SVR rates were 22–31 percentage points higher with boceprevir- and telaprevir-based therapy compared with dual therapy in treatment-na├»ve patients and 23–64 percentage points higher in treatment-experienced patients.[4-7] Despite advances in efficacy, these regimens are complicated by tolerability issues, high pill burden, complex drug interactions and adverse effects, all of which may impact the effectiveness observed in routine medical practice.[1, 8]

Limited outcomes data exist from routine medical practice, where those treated with these newer agents may encompass diverse patient populations not well represented in clinical trials.[9] Historically, SVR rates in genotype 1 patients treated with peginterferon/ribavirin dual therapy in routine medical practice have been 15–25 percentage points lower than SVR rates reported in clinical trials.[2, 3, 10-14]Furthermore, no clinical trial data exist comparing the efficacy of boceprevir- to telaprevir-based regimens.

The Department of Veterans Affairs (VA) is the largest U.S. provider of healthcare to HCV-infected individuals, caring for nearly 5% of all individuals in the USA with HCV infection.[15] The VA HCV population represents a challenging population with high rates of comorbidities and historically low SVR rates with peginterferon/ribavirin dual therapy, which may benefit greatly from treatment with DAA-based therapies.[10, 11, 16, 17] In earlier work, we found that on-treatment virological response rates at 24 weeks for veterans treated with boceprevir- and telaprevir-based regimens were comparable to those reported in clinical trials. Futility and early discontinuation rates, however, were higher.[18] Our aim was to assess SVR rates, treatment discontinuation rates and haematological adverse events for boceprevir- and telaprevir-based regimens in a national cohort of U.S. veterans with HCV infection treated in routine medical practice and to compare effectiveness of these regimens.

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