Toranomon Hospital, Tokyo, Japan.
The efficacy and safety of simeprevir in combination with peginterferon α-2b and ribavirin (PegIFNα-2b/RBV) were investigated in patients infected with hepatitis C virus (HCV) genotype-1 who were treatment-naïve or had previously received interferon (IFN)-based therapy. Combination therapy with peginterferon α-2b and ribavirin (PegIFNα-2b/RBV) has been widely used in treatment-naïve patients with hepatitis C virus (HCV) genotype-1. Options are limited for re-treatment of patients in whom previous interferon-based therapy failed.
CONCERTO-4 (NCT01366638) was an open-label, non-comparative, multicenter study of once-daily simeprevir (TMC435) 100 mg in combination with PegIFNα-2b/RBV in treatment-naïve and -experienced patients (prior relapsers or non-responders to interferon-based therapy) with chronic HCV genotype-1 infection. Twelve-week combination treatment was followed by 24/48-week response-guided PegIFNα-2b/RBV therapy for treatment-naïve patients and prior relapsers, and 48-week PegIFNα-2b/RBV therapy for prior non-responders. Patients were followed for 72 weeks after treatment initiation. The proportions of patients with sustained viral response (SVR; undetectable HCV RNA) at treatment end and 12 weeks after the last treatment (SVR12) were among the major efficacy endpoints. Safety, including adverse events (AEs), was monitored.
Of the 79 patients treated, the proportion achieving SVR12 was highest among treatment-naïve patients (91.7%) and prior relapsers (100%) vs 38.5% of prior non-responders. All treatment-naïve patients and prior non-responders who achieved SVR12 also achieved SVR at treatment end and 24 weeks after last dose; 96.6% of prior relapsers achieved both endpoints. Most AEs were of grade 1 or 2 severity. Grade 3 AEs occurred in 17 patients, most frequently neutropenia (6.3%).
Simeprevir combined with PegIFNα-2b/RBV was effective in patients infected with HCV genotype-1, both for initial treatment of naïve patients and for re-treatment of patients in whom previous interferon-based therapy had failed.