Triple Therapy for Chronic Hepatitis C Virus Infection

Triple therapy with peginterferon, ribavirin, and a direct antiviral agent is considered the next therapeutic regimen for patients with chronic hepatitis C virus (HCV) infection. To evaluate the potential benefit of adding boceprevir — a protease inhibitor that binds to the nonstructural 3 active site of the virus — to standard peginterferon and ribavirin, investigators conducted two industry-sponsored, phase III, randomized, controlled studies involving treatment-naive or treatment-experienced patients with HCV genotype 1 infection. The primary endpoint in both studies was sustained virologic response (SVR; undetectable viral count 24 weeks after completion of therapy).

In the first study, 1097 treatment-naive patients (159 black and 938 nonblack patients) received a 4-week lead-in regimen of standard-of-care (SOC) peginterferon alfa-2b (1.5µg/kg/weekly) and ribavirin (600–1400 mg daily by body weight). Patients were then randomized to receive SOC plus placebo for 44 weeks (SOC group); triple therapy with peginterferon, ribavirin, and boceprevir (800 mg three times daily) for 24 weeks, plus an additional 20 weeks in patients with detectable viral count between weeks 8 and 24 (group 2); or triple therapy for 44 weeks (group 3).

SVR was higher in groups 2 and 3 than in the SOC group in the nonblack cohort (67% and 68%, respectively, vs. 40%; P<0.001 for both comparisons) as well as in the black cohort (42% and 53% vs. 23%; P=0.004 for both). Among nonblack patients in group 2, 47% received shorter-duration triple therapy (28 weeks). Dose reduction because of anemia was required by more triple-therapy recipients than SOC recipients (21% vs. 13%), as was the use of erythropoietin (43% vs. 24%). Rates of dysgeusia were twofold higher in triple-therapy recipients than SOC recipients. Boceprevir resistance-associated variants were found in 17% and 15% of patients in groups 2 and 3, respectively.

In the second study, 403 treatment-experienced patients received SOC during a 4-week lead-in period. Patients were then randomized to receive SOC plus placebo for 44 weeks (SOC group); triple therapy with peginterferon, ribavirin, and boceprevir for 32 weeks, plus an additional 12 weeks in patients with detectable viral count at week 8 (group 2); or triple therapy for 44 weeks (group 3).

SVR was higher in groups 2 and 3 than in the SOC group overall (59% and 66% vs. 21%; P<0.001 for both) as well as in patients with prior relapse (69% and 75% vs. 29%; P<0.001 for both), in patients with prior nonresponse (40% and 52% vs. 7%), and in those with poor response to SOC at week 4 (33% and 34% vs. 0%). Among patients in group 2, 46% were able to receive shorter-duration therapy (36 weeks). Boceprevir resistance-associated variants were noted in 44% of patients without SVR in the triple-therapy groups. Safety data were similar to that in the first study.