Efficacy and safety of telaprevir- and simeprevir-based triple therapies for older patients with chronic hepatitis C

AIM To evaluate and compare the efficacy and safety of telaprevir(TVR)-and simeprevir(SMV)-based triple therapies in elderly patients, specifically patients aged 66 years or older.METHODS The present study enrolled 112 and 76 Japanese patients with chronic hepatitis C virus genotype 1b infection who were treated with a 12-wk TVR-based or SMV-based triple therapy, respectively, followed by a dual therapy that included pegylated interferon α and ribavirin(RBV) for 12 wk. The patients were categorized into two groups according to age as follows: A younger group of patients aged ≤ 65 years old and an older group of patients aged > 65 years old. Among the patients treated with TVR-based triple therapy, 34 patients were included in the older group. The median ages were 56 years(range: 28-65 years) in the younger group and 69 years(range: 66-81 years) in the older group. Among the patients treated with SMV-based triple therapy, 39 patients were included in the older group. The median ages were 59 years(range: 36-65 years) in the younger group and 71 years(range: 66-86 years) in the older group. The clinical, biochemical and virological data were analyzed before and during treatment.RESULTS Among the patients treated with the TVR-based triple therapy, no significant difference in the sustained virological response(SVR) was found between the younger(80.8%) and older(88.2%) groups. The SVR rates for patients with the interleukin 28B(IL28B)(rs8099917) TG/GGgenotypes(73.9% and 60.0% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype(86.3% and 92.9%, respectively). The cumulative exposure to RBV for the entire 24-wk treatment period(as a percentage of the target dose) was significantly higher in the younger group than in the older group(91.7% vs 66.7%, respectively, P < 0.01), but the cumulative exposure to TVR was not significantly different between the younger and older groups(91.6% vs 81.9%, respectively). A multivariate analysis identified the TT-genotype of IL28B(OR = 8.160; 95%CI: 1.593-41.804, P = 0.012) and the adherence of RBV(> 60%)(OR = 11.052; 95%CI: 1.160-105.273, P = 0.037) as independent factors associated with the SVR. Adverse events resulted in discontinuation of the treatment in 11.3% and 14.7% of the younger and older groups, respectively. Among the patients treated with the SMV-based triple therapy, no significant difference in the SVR rare was found between the younger(81.1%) and older(82.1%) groups. The SVR rates for patients with the IL28B TG/GG-genotypes(77.8% and 64.7% in the younger and older groups, respectively) were significantly lower than for patients with the IL28 B TT-genotype(88.2% and 100%, respectively). A multivariate analysis identified the TT-genotype of IL28B as an independent factor associated with the SVR(OR = 9.677; 95%CI:1.114-84.087, P = 0.040). Adverse events resulted in discontinuation of the treatment in 7.0% and 14.3% of patients in the younger and older groups, respectively.CONCLUSION Both TVR- and SMV-based triple therapies can be successfully used to treat patients aged 66 years or older with genotype 1b chronic hepatitis C. Genotyping of the IL28B indicates a potential to achieve SVR in these difficult-to-treat elderly patients.