Boceprevir for Untreated Chronic HCV Genotype 1 Infection

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 previously untreated adults with HCV genotype 1 infection were randomly assigned to one of three groups. In all three groups, peginterferon alfa-2b and ribavirin were administered for 4 weeks (the leadin period). Subsequently, group 1 (the control group) received placebo plus peginterferon–ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon–ribavirin for 24 weeks, and those with a detectable HCV RNA level between weeks 8 and 24 received placebo plus peginterferon–ribavirin for an additional 20 weeks; and group 3 received boceprevir plus peginterferon–ribavirin for 44 weeks. 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<0.001), and in 213 of the 311 patients (68%) in group 3 (P<0.001). In the black cohort, a sustained virologic response was achieved in 12 of the 52 patients (23%) in group 1, in 22 of the 52 patients (42%) in group 2 (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 28 weeks. 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 with 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 24 weeks and 44 weeks of boceprevir. (Funded by Schering-Plough [now Merck]; SPRINT-2 ClinicalTrials.gov number, NCT00705432.)

STARTVerso1: A randomized trial of faldaprevir plus pegylated interferon/ribavirin for chronic HCV genotype-1 infection

“…While differences in patient populations and trial designs preclude direct comparison of these data with other studies, the 27% increase in SVR12 with faldaprevir plus PegIFN and RBV compared with PegIFN and RBV alone was similar to that reported in phase 3 trials of telaprevir (31% vs. placebo), boceprevir (28% vs. placebo), and simeprevir (30% vs. placebo) plus PegIFN and RBV in treatment-naïve patients with HCV genotype-1 [2,3,25,27]. More patients were able to stop treatment at week 24 with faldaprevir compared with telaprevir and boceprevir (88% vs. 58% and 47%, respectively), although that may be due in part to different HCV RNA criteria used for shortening treatment duration in the different trials [2,3].…”

“…Compared with simeprevir-treated patients, a similar proportion of faldaprevirtreated patients were able to stop at week 24 (88%) [25,27]. In all trials, patients who qualified for shortened treatment achieved a high SVR (>83%) [2,3,25,27].…”

“…More patients were able to stop treatment at week 24 with faldaprevir compared with telaprevir and boceprevir (88% vs. 58% and 47%, respectively), although that may be due in part to different HCV RNA criteria used for shortening treatment duration in the different trials [2,3]. Compared with simeprevir-treated patients, a similar proportion of faldaprevirtreated patients were able to stop at week 24 (88%) [25,27].…”

“…Telaprevir or boceprevir with peginterferon (PegIFN) and ribavirin (RBV) resulted in a sustained virologic response (SVR) in 63%-75% of treatment-naïve patients, compared with 38%-44% with PegIFN and RBV alone [1][2][3][4]. However, these drugs have limitations, including serious skin reactions with telaprevir [5], and an increased incidence of anemia, compared with PegIFN and RBV alone, with both telaprevir and boceprevir [1][2][3][4].…”

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

“…[173][174][175] Obesity does not have a similar negative impact on the response to newer protease-inhibitor based anti-viral regimens, [176][177][178][179][180] but the impact of insulin resistance and hepatic steatosis has not yet been investigated sufficiently. It is not known if the treatment of steatosis and steatohepatitis alters the natural history of other chronic liver diseases such as HCV and PBC.…”