Hepatitis C protease inhibitor therapy cost-effective in some circumstances

First-line hepatitis C therapy which includes a protease inhibitor can be cost-effective, investigators show in the Annals of Internal Medicine. The study showed that a triple combination of drugs, including the cheaper of the newly licensed protease inhibitors, was most cost-effective after screening for a gene mutation associated with response to hepatitis C treatment for patients with advanced fibrosis.

“Our study supports the important role of protease inhibitors in treating chronic HCV [hepatitis C virus] for patients with advanced fibrosis as part of a first-line regimen,” write the authors.

Standard therapy for hepatitis C consists of pegylated interferon and ribavirin. This achieves a cure in between 40 and 60% of patients chronically infected with hepatitis C genotype 1. Poorer response rates are seen in patients with HIV.

Two protease inhibitors have recently been approved for the treatment of hepatitis C genotype 1 infection. In clinical trials, a higher proportion of patients who received boceprevir (Victrelis) or telaprevir (Incivek / Incivo) in combination with standard therapy achieved a sustained virological response (an undetectable hepatitis C viral load six months after the completion of therapy, defined as a cure), compared to patients who received standard therapy.

However, these new drugs are expensive. Each week of treatment with boceprevir costs US$1100 and telaprevir costs $4100 per week. This expense raises important questions about the therapies’ cost-effectiveness. The presence of a mutation in the IL-28B gene has been associated with improved hepatitis C treatment responses and screening for this mutation could help target patients most likely to benefit from treatment.

Therefore a team of investigators developed a model to establish the cost of each quality-adjusted life-year (QALY) associated with the drugs.

Their model was based on the assumption that the drugs would have the same 'real world' efficacy as they demonstrated in clinical trials, and that 70% of patients would take at least 80% of their doses.

The authors’ models also took into account patient health. The cost-effectiveness of each drug was calculated according to whether individuals had mild or severe liver fibrosis.

Two different treatment strategies were included in the model. In the first, therapy was targeted at patients with the favourable IL-28B genotype; in the second, universal therapy was provided.

The model was based on the assumption that the cheaper protease inhibitor would be used and also took into account the costs of existing hepatitis C treatment.

Using a protease inhibitor was shown to have real benefits. The provision of universal triple-drug therapy for patients with advanced fibrosis increased the proportion achieving a sustained virological response to 51%, compared to the 32% rate seen with standard treatment. For patients with mild fibrosis the proportion achieving a sustained virological response increased from 38 to 61%. IL-28B-guided treatment achieved a sustained virological response in 48% of patients with advanced fibrosis and 57% of those with mild fibrosis. The improved treatment response rates achieved with the inclusion of a protease inhibitor significantly reduced the chance of decompensated liver disease, liver cancer and the need for a liver transplant.

But a substantial financial cost accompanied these improved response rates. Compared to standard treatment, the addition of a protease inhibitor increased the cost of therapy for patients with advanced fibrosis by $24,000 and for patients with mild fibrosis by $22,000.

Nevertheless, the investigators’ calculation showed that triple-drug treatment would still be cost effective in some circumstances.

For patients with advanced fibrosis, IL-28B-guided treatment cost $32, 800 per QALY. This increased to $51,500 for universal therapy. For individuals with mild fibrosis, IL-28B guided therapy had a cost of $62,900 per QALY, with universal therapy entailing a cost of $102,600 per QALY.

“Although it also increases total costs, universal triple therapy provides reasonable value for money, costing approximately $50 000 per QALY compared with IL-28B-guided therapy for patients with advanced fibrosis,” write the authors. However, the cost-effectiveness of this strategy depended on fibrosis stage. “For patients with mild fibrosis, universal triple therapy at a cost of $1100 per week is not cost-effective, even at $100,000 per QALY, but IL-28B-guided triple therapy costs $62,900 per QALY compared with standard therapy.”

Discounts could mean that the real costs were substantially lower. For instance, the Veterans Health Administration is able to purchase drugs at the Federal Supply Schedule cost.

Poor adherence to protease inhibitor therapy could reduce the cost-effectiveness of treatment. “Universal triple therapy becomes less cost-effective when the cost of protease inhibitors is higher, or when adherence rates are substantially lower for triple therapy than for standard therapy.”

The authors conclude: “Management of chronic HCV in the United States could be improved by a shift toward response-guided triple-drug strategies, provided that the price of protease inhibitors and adherence to taking them are maintained at a reasonable level.”