Evaluation of Simeprevir-Based Triple Therapy Using Pegylated-Interferon-α and Ribavirin in Patients With Hepatitis C Virus Genotype-1b Infection

Abstract

Introduction: Pegylated-interferon-alfa(PEG) plus ribavirin(RBV) regimens were the standard of care in patients with hepatitis C virus(HCV) infection, but the sustained virological response(SVR; undetectable HCV-RNA) was not satisfactory in those with HCV-genotype-1b infection. Telaprevir(TLV; HCV NS3/4A protease inhibitor)-based triple therapy improved efficacy in such cases. However, adverse events(AEs) of TLV should be noted as well. In this study, efficacy and safety of simeprevir(SMV; the second generation of HCV NS3/4A protease inhibitor)-based triple-therapy using PEG/RBV were assessed in those with HCV-genotype-1b infection. Methods: Thirty-seven patients with high-load-1b HCV undergoing SMV-based triple-therapy were enrolled (male/female 19/18, age 61.6±11.4, FIB4-index 2.2±1.0). The population consists of treatmentnaïve( 11) and -experienced patients (prior relapsers(13), non-responders(11) or discontinuers(2) to IFN-based therapy). The genotypes of IL28B polymorphism were TT(22), TG(14) and GG(1), respectively. Twelve-week SMV-based triple-combination-therapy was followed by 12-week PEG/RBV therapy. The efficacy(rapid virological response(RVR); undetectable HCV-RNA 4 weeks after initiation of triple therapy, SVR12; undetectable HCV-RNA 12 weeks after the last treatment) as well as safety(including AEs) was assessed. Results: Serum HCV-RNA(LIU/mL) at baseline, weeks1, 2, 3, 4, 12 and 24 was 6.6±0.7, 1.7±0.8, 1.1±0.9, 0.5±0.9, 0.4±1.0, 0.2±1.0 and 0.1±0.3, respectively. HCV-negativity at weeks1, 2, 3, 4, 8 and 12 was 8.1%, 29.7%, 67.6%, 75.7%, 89.2 and 91.9%, respectively. RVR/SVR12 was 75.7% (28/37)/75.7% (28/37), respectively. In the univariate analysis, factors significantly associated with SVR12 were prior relapsers to IFN-based therapy or treatment-naïve, IL28B polymorphism with genotype TT, achievement of RVR, and PEG adherence over 70%, respectively. In the multivariate analysis, the factor significantly associated with SVR12 was prior relapsers to IFN-based therapy or treatment-naïve. Regarding safety, AEs with more than grade-3 such as neutrocytopenia and elevation of bilirubin and ALT observed during treatment were not clinically significant enough to affect therapeutic process. Two patients discontinued therapy because of depression probably due to PEG. At least, addition of SMV to conventional PEG/RBV caused no more additional clinically meaningful AEs. Conclusion: Although SMV-based triple-therapy using PEG/RBV could be feasible in patients with HCV-genotype-1b infection, efficacy could not be expected in prior non-responders to the conventional IFN-based therapy.