AASLD: Antiviral Likely Too Costly for Initial HCV Tx

AASLD: Antiviral Likely Too Costly for Initial HCV Tx

By Charles Bankhead, Staff Writer, MedPage Today
Published: November 11, 2011
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

Action Points
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Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Explain that a study using decision modeling found that the protease inhibitor telaprevir was unlikely to be cost-effective as first-line therapy for genotype 1 hepatitis C virus (HCV) infection with the favorable CC IL28B polymorphism when compared to pegylated interferon-alfa plus ribavirin.

Note that the CC IL28B polymorphism has been identified as the strongest pretreatment predictor of sustained virologic response in genotype 1 HCV.


SAN FRANCISCO -- First-line treatment with the direct-acting antiviral agent telaprevir appeared unlikely to be cost-effective for hepatitis C virus (HCV) infection in patients with the favorable CC IL28B polymorphism, according to a decision modeling analysis.

Telaprevir-based treatment resulted in a clinical benefit comparable to that of two different regimens of pegylated interferon alfa plus ribavirin, but use of the agent increased the estimated cost by 27% to 47% compared with the other two regimens.

The combination of pegylated interferon and ribavirin proved dominant versus telaprevir, and the dominance was driven by the cost difference, Ziad Gellad, MD, reported here at the American Association for the Study of Liver Diseases meeting.

"In treatment-naïve genotype 1 patients with the CC IL28B polymorphism, initial therapy with a telaprevir-based regimen is unlikely to be cost effective under current cost and efficacy conditions," said Gellad, of Duke University Medical Center in Durham, N.C.

"Comparative-effectiveness trials should consider protease inhibitor-free strategies as first-line therapy in individuals with the favorable IL28B genotype."

The IL28B polymorphism is the strongest pretreatment predictor of sustained virologic response in patients with HCV genotype 1. Personalized HCV treatment regimens based on pretreatment factors such as IL28B or on-treatment response may improve the efficacy and tolerability of treatment.

By way of background, Gellad noted that a majority of patients with the CC IL28B polymorphism respond to treatment with the combination of pegylated interferon alfa and ribavirin. Direct-acting antivirals, such as telaprevir, have proven effective for patients who do not respond to first-line pegylated interferon alfa-ribavirin therapy or who relapse after the standard treatment.

One potential benefit of tailored therapy is lower cost. Depending on the duration of treatment, dual therapy with pegylated interferon alfa and ribavirin can vary between $18,000 and $36,000. Adding telaprevir or boceprevir (Victrelis) to the other two drugs more than doubles the cost of therapy to a range of $48,000 to $85,000, Gellad continued.

The economic aspects of therapy raise the question of whether clinically effective treatment with a direct-acting antiviral would make sense from a cost-effectiveness perspective if used in treatment-naïve patients with the CC IL28B polymorphism.

To address the question, Gellad and colleagues developed a decision model that evaluated three treatment strategies:

48 weeks of treatment with pegylated interferon-alfa and ribavirin
24 weeks of pegylated interferon alfa-ribavirin in patients with rapid virologic response
12 weeks of telaprevir in combination with 24 or 48 weeks of pegylated interferon alfa-ribavirin

Key assumptions of the analysis were limited societal perspective, no coinfection with other viruses, no factors that accelerated liver-related death or prevented treatment, and retreatment with telaprevir for patients who did not respond to or relapsed with pegylated interferon-ribavirin therapy.

The investigators estimated lifetime treatment costs and quality-adjusted life-years (QALYs) for each strategy and performed multiple sensitivity analyses to evaluate the impact of changes to key assumptions incorporated in the model.

Using data from published clinical trials of pegylated interferon alfa-ribavirin therapy, the investigators assumed a sustained virologic response (SVR) of 66% for 48 weeks of dual therapy, increasing to 90.6% with retreatment. They assumed an SVR of 71% for patients who achieved rapid virologic response with dual therapy, increasing to 87.6% with retreatment.

Using published data for telaprevir therapy, Gellad and colleagues assumed an SVR of 89%.

The three treatment strategies resulted in QALY gains of 19.26 to 19.38 and did not differ significantly. The estimated cost for dual therapy with pegylated interferon alfa and ribavirin was $46,785 when a treatment duration of 24 weeks was assumed for patients achieving rapid virologic response. The cost increased to $54,931 when all patients continued treatment for 48 weeks with the dual-drug regimen.

Adding telaprevir to first-line pegylated interferon alfa-ribavirin therapy increased the cost to $68,788.

"The efficacy of all three strategies is similar," said Gellad. "Telaprevir is dominated by the pegylated interferon alfa-ribavirin strategy, and the preference for interferon-only strategies is driven by cost."

Sensitivity analysis did identify a few specific circumstances under which telaprevir-based treatment became cost-effective versus dual therapy:

When the probability of an extended SVR exceeded 89% with telaprevir (versus a base-case assumption of 78% for dual therapy)
When the probability of achieving SVR with telaprevir exceeded 80% in patients who had not achieved an SVR with dual therapy (versus a 67% base-case assumption)
When the probability of SVR with dual therapy fell below 62% and retreatment with telaprevir was pursued (versus an 88% base-case assumption)

Commenting on the results during an AASLD press briefing, T. Jake Liang, MD, of the National Institute of Diabetes and Digestive and Kidney Diseases, said the study emphasizes the advances that have occurred in using biomarkers to aid treatment decisions related to HCV infection.

"The CC IL28B polymorphism is probably the most important and best genetic marker we have identified to date for predicting response to therapy," said Liang, who also is president of AASLD.

"If you compare the three treatment groups, it is clear that response-directed treatment with pegylated interferon and ribavirin is the most cost-effective way to treat patients with the favorable genotype," he added.

Gellad disclosed relationships with Merck and with PENTAX Medical.


Primary source: American Association for the Study of Liver Diseases
Source reference:
Gellad ZF, et al "The cost-effectiveness of a telaprevir-inclusive regimen as initial therapy for genotype 1 hepaticis C infection in individuals with the CC IL28B polymorphism" AASLD 2011; Abstract 118.

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