A sprint to increase response to HCV treatment: Expectancies but caution

Abstract

COMMENTARY ON Boceprevir for untreated chronic HCV genotype 1 infection. Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP; SPRINT-2 Investigators. N Engl J Med 2011 Mar 31;364(13):1195–1206. Copyright (2011) Massachusetts Medical Society. Abstract reprinted with permission from the Massachusetts Medical Society. http://www.ncbi.nlm.nih.gov/pubmed/21449783 Abstract. Background Peginterferon–ribavirin therapy is the current standard of care for chronic infection with hepatitis C virus (HCV). The rate of sustained virologic response has been below 50% in cases of HCV genotype 1 infection. Boceprevir, a potent oral HCV-protease inhibitor, has been evaluated as an additional treatment in phase 1 and phase 2 studies. Methods We conducted a double-blind study in which previouslyuntreated adults with HCV genotype 1 infection were randomly assigned to one of the three groups. In all the three groups, peginterferon alfa-2b and ribavirin were administered for 4weeks (the lead-in period). Subsequently, group 1 (the control group) received placebo plus peginterferon–ribavirin for 44weeks; group 2 received boceprevir plus peginterferon–ribavirin for 24weeks, and those with a detectable HCV RNA level between weeks 8 and 24 received placebo plus peginterferon–ribavirin for an additional 20weeks; and group 3 received boceprevir plus peginterferon–ribavirin for 44weeks. Nonblack patients and black patients were enrolled and analyzed separately. Results A total of 938 nonblack and 159 black patients were treated. In the nonblack cohort, a sustained virologic response was achieved in 125 of the 311 patients (40%) in group 1, in 211 of the 316 patients (67%) in group 2 ( p p p =0.04), and in 29 of the 55 patients (53%) in group 3 ( p =0.004). In group 2, a total of 44% of patients received peginterferon–ribavirin for 28weeks. Anemia led to dose reductions in 13% of controls and 21% of boceprevir recipients, with discontinuations in 1% and 2%, respectively. Conclusions The addition of boceprevir to standard therapy with peginterferon–ribavirin, as compared to standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection. The rates were similar with 24weeks and 44weeks of boceprevir. (Funded by Schering-Plough [now Merck]; SPRINT-2 ClinicalTrials.gov number, NCT00705432) AND Boceprevir for previously treated chronic HCV genotype 1 infection. Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S, Poordad F, Goodman ZD, Sings HL, Boparai N, Burroughs M, Brass CA, Albrecht JK, Esteban R; HCV RESPOND-2 Investigators. N Engl J Med 2011 Mar 31;364(13):1207–1217. Copyright (2011) Massachusetts Medical Society. Abstract reprinted with permission from the Massachusetts Medical Society. http://www.ncbi.nlm.nih.gov/pubmed/21449784 Abstract. Background In patients with chronic infection with hepatitis C virus (HCV) genotype 1 who do not have a sustained response to therapy with peginterferon–ribavirin, outcomes after retreatment are suboptimal. Boceprevir, a protease inhibitor that binds to the HCV nonstructural 3 (NS3) active site, has been suggested as an additional treatment. Methods To assess the effect of the combination of boceprevir and peginterferon–ribavirin for retreatment of patients with chronic HCV genotype 1 infection, we randomly assigned patients (in a 1:2:2 ratio) to one of the three groups. In all the three groups, peginterferon alfa-2b and ribavirin were administered for 4weeks (the lead-in period). Subsequently, group 1 (control group) received placebo plus peginterferon–ribavirin for 44weeks; group 2 received boceprevir plus peginterferon–ribavirin for 32weeks, and patients with a detectable HCV RNA level at week 8 received placebo plus peginterferon–ribavirin for an additional 12weeks; and group 3 received boceprevir plus peginterferon–ribavirin for 44weeks. Results A total of 403 patients were treated. The rate of sustained virologic response was significantly higher in the two boceprevir groups (group 2, 59%; group 3, 66%) than in the control group (21%, p Conclusions The addition of boceprevir to peginterferon–ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared to peginterferon–ribavirin alone. (Funded by Schering-Plough [now Merck]; HCV RESPOND-2 ClinicalTrials.gov number, NCT00708500).