Neil Canavan

December 06, 2011

December 6, 2011 (San Francisco, California) — The recently approved and highly effective hepatitis C virus (HCV) protease inhibitor telaprevir was shown not to be cost effective for the treatment of patients with HCV genotype 1 and the (CC) interleukin (IL)-28B  polymorphism, a genetic variant that predicts a favorable response to treatment with the standard dual regimen of pegylated interferon (peginterferon) and ribavirin.

This cost analysis was reported here at The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting.

"IL-28B is the strongest pretreatment predictor of sustained virologic response in genotype 1 patients," said study presenter Ziad Gellad, MD, MPH, from the Department of Medicine–Gastroenterology, Duke University Medical Center, Durham, North Carolina. "In genotype 1 patients with the favorable (CC) IL-28B polymorphism, dual therapy with peginterferon and ribavirin is effective in the majority of patients."

That said, telaprevir in combination with peginterferon plus ribavirin has demonstrated significantly increased sustained viral response rates, compared with peginterferon plus ribavirin alone in phase 3 studies of treatment-naive and treatment-experienced genotype 1 patients with HCV.

Dr. Gellad asked: Is the addition of telaprevir cost effective in the subpopulation of patients with IL-28B (CC)? The answer, he said, is no.

"One of the potential benefits of tailoring therapy is decreasing cost," Dr. Gellad said. The current wholesale cost of the 2-drug regimen is $18,336 at 24 weeks and $36,672 at 48 weeks; for the 3-drug regimen, the cost is $67,536 at 12 weeks and $85,872 at 36 weeks.

Because the addition of telaprevir more than doubles the cost of treatment, Dr. Gellad designed a cost-effectiveness model to determine whether the added expense is really worth it for a patient with the favorable genotype 1 (CC) IL-28B profile.

The model is based on a number of assumptions: that societal perspective is limited, that no patients would have a coinfection with other viruses that accelerate liver-related death or prevent treatment, "and importantly, that nonresponders or relapsers after dual therapy are retreated with a 48-week course of telaprevir."

The researchers developed a decision model that evaluated 3 treatment strategies:

  • peginterferon plus ribavirin for 48 weeks, with a 12-week stopping rule for nonresponse; patients who did not respond or who relapsed would be treated with telaprevir

  • a response-guided treatment approach with peginterferon plus ribavirin, in which those who achieved a rapid viral response (undetectable at week 4) would receive 24 weeks of dual therapy alone, and those with still-detectable viral loads at week 4 were treated for 48 weeks; nonresponsive or relapsed patients received telaprevir.

  • 12 weeks of telaprevir in combination with 24 or 48 weeks of peginterferon plus ribavirin based on the extended rapid virologic response.

Treatment outcomes generated by the model were based on outcomes data derived from the IDEAL, REALIZE, and ADVANCE clinical trials.

A theoretical cohort of patients with 10,000 iterations was performed. The end point assumed 1 of 2 health states: sustained virologic response (cure) or fibrosis progression. Dr. Gellad's team assessed the cost of each. "As patients progressed through the model, they accumulated costs, which were expressed in [quality-adjusted life-years]," Dr. Gellad explained.

"The key point is that the efficacy of all 3 strategies is similar, but when you consider point estimates, telaprevir is dominated by the interferon/ribavirin strategies, and this preference is driven by the cost of therapy," Dr. Gellad told Medscape Medical News.

Costs generated by the model were $46,785 for peginterferon plus ribavirin given as response-guided therapy, $54,931 for peginterferon plus ribavirin (not response-guided), and $68,788 for telaprevir plus peginterferon plus ribavirin.

"We then investigated the impact of the cost of telaprevir on the probability of cost effectiveness, and assumed a weekly cost of $3321 [the current cost of the drug].... If the cost dropped below $1433, a triplet with telaprevir became the preferred strategy," he reported.

Dr. Gellad concluded that in treatment-naïve patients with HCV genotype 1 and the (CC) IL-28B polymorphism, initial therapy with a telaprevir-based regimen is unlikely to be cost effective under current cost and efficacy conditions.

Comparison Shopping

"What this group from Duke did is very important because, with resources dwindling, we need to figure out whether a particular treatment is more cost effective than another," said AASLD president T. Jake Liang, MD, tenured senior investigator and chief of the Liver Diseases Branch at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. "This is somewhat related to so-called personalized medicine because it uses a genetic marker to identify patients who will respond well to a certain treatment."

Major genetic studies conducted over the past several years have indicated that (CC) IL-28B  is a genetic marker highly associated with treatment response to interferon-based therapy. "This is a great marker — probably the best genetic marker we have so far — to gauge how a person will respond to treatment," Dr. Liang said.

The analysis by Dr. Gellad's team "suggests that this could be a way to save some money for patients with the favorable IL-28B genotype," he noted. Certainly, there is excitement about the recent availability of direct-acting antivirals, such as telaprevir, which greatly enhance treatment response, "but then again, maybe not one size fits all. In the spirit of personalized medicine, this may be one way we can reduce costs and, at the same time, retain the same success rate treating patients with HCV."

Dr. Gellad reports consulting for Merck & Co and receiving grants or research support from Merck & Co and PENTAX Medical. Dr. Liang has disclosed no relevant financial relationships.

The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Abstract 118. Presented November 7, 2011.

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