Research Article
Should we await IFN-free regimens to treat HCV genotype 1 treatment-naive patients? A cost-effectiveness analysis (ANRS 95141)

https://doi.org/10.1016/j.jhep.2014.03.011Get rights and content

Background & Aims

In treatment-naive patients mono-infected with genotype 1 chronic HCV, treatments with telaprevir/boceprevir (TVR/BOC)-based triple therapy are standard-of-care. However, more efficacious direct-acting antivirals (IFN-based new DAAs) are available and interferon-free (IFN-free) regimens are imminent (2015).

Methods

A mathematical model estimated quality-adjusted life years, cost and incremental cost-effectiveness ratios of (i) IFN-based new DAAs vs. TVR/BOC-based triple therapy; and (ii) IFN-based new DAAs initiation strategies, given that IFN-free regimens are imminent. The sustained virological response in F3–4/F0–2 was 71/89% with IFN-based new DAAs, 85/95% with IFN-free regimens, vs. 64/80% with TVR/BOC-based triple therapy. Serious adverse events leading to discontinuation were taken as: 0–0.6% with IFN-based new DAAs, 0% with IFN-free regimens, vs. 1–10% with TVR/BOC-based triple therapy. Costs were €60,000 for 12 weeks of IFN-based new DAAs and two times higher for IFN-free regimens.

Results

Treatment with IFN-based new DAAs when fibrosis stage ⩾F2 is cost-effective compared to TVR/BOC-based triple therapy (€37,900/QALY gained), but not at F0–1 (€103,500/QALY gained). Awaiting the IFN-free regimens is more effective, except in F4 patients, but not cost-effective compared to IFN-based new DAAs. If we decrease the cost of IFN-free regimens close to that of IFN-based new DAAs, then awaiting the IFN-free regimen becomes cost-effective.

Conclusions

Treatment with IFN-based new DAAs at stage ⩾F2 is both effective and cost-effective compared to TVR/BOC triple therapy. Awaiting IFN-free regimens and then treating regardless of fibrosis is more efficacious, except in F4 patients; however, the cost-effectiveness of this strategy is highly dependent on its cost.

Introduction

In patients infected with genotype 1 (G1) chronic hepatitis C virus (HCV), the current standard-of-care is triple therapy combining a protease inhibitor, telaprevir (TVR) or boceprevir (BOC), peg-interferon and ribavirin [1], [2], [3]. These combinations are more effective in treatment-naive patients than previous dual therapy combining peg-interferon and ribavirin [4], [5]. However, TVR/BOC-based triple therapy slightly increases the rate of severe adverse events compared to dual therapy [4], [5]. Moreover, these triple therapy combinations are associated with higher cost (around €33,000/patient in France vs. €7500–15,000 with dual therapy) [6]. Despite higher cost and adverse events, TVR/BOC-based triple therapy has been shown to be cost-effective compared to dual therapy [7], [8], [9].

Numerous other more effective and better tolerated direct-acting antiviral (DAA)-based regimens are being evaluated, including interferon (IFN)-based new DAAs and IFN-free regimens [10]. As a result, the issues currently facing clinicians are: Should we start IFN-based new DAAs to treat HCV G1 treatment-naive patients or wait for IFN-free regimens? Should all patients be treated with these new DAAs regardless of fibrosis stage, or only patients at ⩾F2?

The objective of this study in treatment-naive patients was, first, to assess the cost-effectiveness of IFN-based new DAAs compared to TVR/BOC-based triple therapy, and second, to compare different IFN-based new DAA initiation strategies, given that IFN-free regimens will soon be available.

Section snippets

Study design

We designed a decision analysis model to simulate the trajectory of chronic G1 HCV-mono-infected patients, from HCV diagnosis in 2014 to death. We used this model to compare life expectancy, quality-adjusted life years (QALYs), lifetime cost, and the incremental cost-effectiveness ratio (ICER) of different treatment initiation strategies based on fibrosis stage at diagnosis and available treatment combinations (TVR/BOC-based triple therapy, and IFN-based new DAAs at the present time, and

Baseline analysis (Table 4)

For patients at stage F0–1 at diagnosis, treatment with IFN-based new DAAs when at stage ⩾F2 was cost-effective compared to TVR/BOC-based triple therapy (€37,900/QALY gained). Immediate treatment with IFN-based new DAAs, although more effective, was not cost-effective at the current estimated cost of IFN-based new DAAs (€103,500/QALY gained compared to treatment with IFN-based new DAAs at stage ⩾F2). Awaiting IFN-free regimens and then treating regardless of fibrosis was more effective, but was

Discussion

This model-based analysis demonstrates, first, that in treatment-naive G1 HCV-mono-infected patients, treatment with IFN-based new DAAs for fibrosis ⩾F2 is both effective and cost-effective. Second, treating with IFN-based new DAAs when fibrosis is F0/F1, or awaiting the arrival of IFN-free regimens, is not cost-effective. However, results were sensitive to the presence of co-morbidities and the cost of IFN-based new DAAs and IFN-free regimens.

We showed that treating with IFN-based new DAAs

Financial support

This work was supported by the Agence nationale de Recherches sur le Sida et les Hépatites virales (ANRS, http://www.anrs.fr/) Grant No. 95141.

Conflict of interest

Sylvie Deuffic-Burban has received unrestricted research grants from Roche, Janssen and Schering-Plough/Merck, lecture fees from Cellestis and consultancy honoraria from Abbott/Abbvie, Bristol-Myers Squibb, Gilead, Schering-Plough/Merck and Glaxo Smith Kline. Vincent Mallet has received consultancy honoraria from Gilead, Schering-Plough/Merck, Janssen and Novartis, lecture fees from Bristol-Myers Squibb, Gilead, Roche, Schering-Plough/Merck and Abbott/Abbvie and research grants from Janssen,

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