Despite poor interferon response in advanced hepatitis C virus infection, models of protease inhibitor treatment predict maximum treatment benefit

Abstract

Protease inhibitors have improved sustained virological response (SVR) rates for subjects with genotype 1 hepatitis C virus infection (HCV). There is however uncertainty regarding how, and in whom, these agents should be used. In previously treated subjects, prior response to interferon has a major effect on SVR rates with protease inhibitor therapy. To assess the benefits of treatment and to understand the utility of a stopping rule for subjects with a poor interferon response following a 4-week lead-in with pegylated interferon and ribavirin. Treatment responses and long-term outcomes were modelled using hypothetical 1000 subject cohorts with 5 years of follow-up. Treatment strategies were compared with number needed to treat (NNT) and comparative effectiveness approaches. Over 5 years of follow-up the NNT to prevent liver-related mortality for subjects with advanced fibrosis was substantially lower than that for subjects with all fibrosis stages (18 vs. 60) indicating particular benefit in this high-risk population. The use of a stopping rule for subjects with advanced fibrosis and a poor interferon response after a 4-week lead-in reduces the number of subjects exposed to a protease inhibitor by 55%. However, 33% fewer liver-related deaths are prevented using this strategy, indicating that there is unacceptable harm associated with this approach over a 5-year follow-up period. Subjects with advanced fibrosis should be prioritised for triple therapy on the basis of need. Treatment should be continued regardless of initial interferon response to maximise the early prevention of hepatitis C virus-related mortality.