A New Era of Hepatitis C Therapy Begins — NEJM

Editorial


A New Era of Hepatitis C Therapy Begins
Donald M. Jensen, M.D.

N Engl J Med 2011; 364:1272-1274March 31, 2011
ArticleReferencesA new era of therapy for hepatitis C virus (HCV) infection is dawning with the development of two effective HCV protease inhibitors, boceprevir and telaprevir. In this issue of the Journal, the results of two phase 3 trials involving boceprevir, in combination with peginterferon and ribavirin, are presented: the SPRINT-2 (Serine Protease Inhibitor Therapy 2) trial (ClinicalTrials.gov number, NCT00705432), by Poordad and colleagues,1 and HCV RESPOND-2 (Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2; NCT00708500), by Bacon and colleagues.2 Both studies focused on patients infected with HCV genotype 1; the SPRINT-2 trial involved those who had not previously received treatment, whereas HCV RESPOND-2 involved those who had previously received treatment.

What are the key background concepts to keep in mind when reading these two important studies? First, boceprevir, a competitive inhibitor of the nonstructural 3 (NS3) protease complex of HCV genotype 1, does not have clinically significant activity against other HCV genotypes.3,4 Second, HCV has been shown to rapidly develop resistance when exposed to protease-inhibitor monotherapy, but the addition of interferon reduces the rate of emergence of these resistant variants.5 Third, black patients respond less well to antiviral therapy with peginterferon plus ribavirin than do nonblacks, in part because of the decreased prevalence among blacks of an interleukin-28B gene (IL28B) polymorphism associated with interferon responsiveness.6 Finally, the presence of cirrhosis has a negative impact on response to therapy,7 yet it affects a considerable percentage of patients awaiting treatment.

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A New Era of Hepatitis C Therapy Begins — NEJM