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To the Editor:

We read with interest the evaluation of the efficacy of telaprevir in patients with well-characterized interferon responses. 1 This study adds to the accumulating body of evidence supporting the use of telaprevir for a wide range of patients with hepatitis C virus (HCV) genotype 1 infection. It remains unclear which patients should be prioritized for retreatment with triple therapy and if this decision is likely to have an effect on patient mortality.

We used a number needed to treat (NNT) analysis to determine the benefit of telaprevir-containing triple therapy in preventing liver-related mortality. The NNT approach allows the calculation of a clinically meaningful summary of the effect of a particular treatment 2 and is sensitive to the efficacy of telaprevir and also the underlying risk of mortality by incorporation of the absolute risk reduction (ARR) in its calculation.

A meta-analysis of treatment-experienced patients with HCV estimated the annual liver-related mortality rate at 0.81%. 3 In patients with sustained virological response (SVR), that risk is reduced to 0.19%, an ARR of 0.62%. In the study reported by Muir et al., the overall SVR rate was 59%. 1 Thus, in this selected population, the NNT to prevent 1 death per year is 278. Because the mortality estimate from the meta-analysis included studies with follow-up of approximately 5 years, the NNT can be reasonably extrapolated to a 5-year NNT of 56.

In treatment-experienced patients with advanced fibrosis, the annual liver-related mortality rate is significantly higher at 2.73%. 3 This is reduced in patients with SVR to 0.52%, an ARR of 2.21%. However, the likelihood of SVR is lower in this group and, although few patients with bridging fibrosis or cirrhosis were included, is likely to be in the region of 40%. 1 Taking these data, the 1-year NNT for patients with advanced fibrosis is 113, and the 5-year NNT is 23.

These findings suggest that to have the maximal effect on mortality, the focus should be on treating patients with advanced disease in the first instance. These patients have the most to gain from treatment with triple therapy, and although there are concerns regarding viral resistance, 4 this substantial improvement in outcome should be included in clinical decision making. This analysis cautions against interpretation of SVR rates without consideration of the underlying mortality risks associated with HCV infection and provides clinically useful information for the caring physician when counseling patients regarding retreatment.

References

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  • 1
    Muir AJ, Poordad FF, McHutchison JG, Shiffman ML, Berg T, Ferenci P, et al. Retreatment with telaprevir combination therapy in hepatitis C patients with well-characterized prior treatment response. HEPATOLOGY 2011; 54: 1538-1546.
  • 2
    Smeeth L, Haines A, Ebrahim S. Numbers needed to treat derived from meta-analyses—sometimes informative, usually misleading. BMJ 1999; 318: 1548-1551.
  • 3
    Singal AG, Volk ML, Jensen D, Di Bisceglie AM, Schoenfeld PS. A sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus. Clin Gastroenterol Hepatol 2010; 8: 280-288, 288.e1.
  • 4
    Pawlotsky JM. Treatment failure and resistance with direct-acting antiviral drugs against hepatitis C virus. HEPATOLOGY 2011; 53: 1742-1751.

Ian A. Rowe B.Sc., M.B., Ch.B., M.R.C.P.(UK)* † ‡, Matthew J. Armstrong M.B., Ch.B., M.R.C.P.† ‡, Diarmaid D. Houlihan M.B., Ch.B.† ‡, * Hepatitis C Virus Research Group, University of Birmingham, Birmingham, UK, † Center for Liver Research and NHR Biomedical Research Unit, University of Birmingham, Birmingham, UK, ‡ Liver and Hepatobiliary Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK.