Telaprevir Improves Outcomes in Some Patients with Hepatitis C

Chicago—An analytic model used to calculate long-term outcomes for hypothetical patients with the hepatitis C virus (HCV) projected that patients treated with a combination of telaprevir and peginterferon/ribavirin (PR) would survive between an average of 2.0 and 3.4 years longer than those using only PR depending on if they were treatment-naïve or treatment-experienced. The researchers who developed the Microsoft Excel-based model presented findings during a poster session at the DDW meeting. The poster was titled Long-Term Clinical Value of Telaprevir for Treatment of Treatment-Naïve and Treatment-Experienced Patients with Hepatitis C Virus (HCV) Infection: Projections Using Decision-Analytic Modeling. The authors reported that, in addition to prolonging survival, telaprevir was associated with fewer major clinical events compared with PR, regardless of whether patients had prior therapy with PR. The authors noted that 3.2 million to 3.9 million Americans have an HCV infection; this study looked at the subpopulation of patients with chronic HCV genotype 1. The study featured 2 cohorts, each involving 1000 theoretical patients with HCV and baseline Metavir scores of F0 to F4. Both cohorts included untreated patients and patients who experienced no response, partial response, or relapse while taking PR. The model assumed 12 weeks of treatment with PR or telaprevir plus PR and generated rates of sustained virologic response (SVR)—the goal of therapy for chronic HCV—based on SVR rates observed in the landmark, phase 3 ADVANCE (A New Direction in HCV Care: A Study of Treatment-Naïve Hepatitis C Patients with Telaprevir) and REALIZE (Re-Treatment of Patients with Telaprevir-Based Regimen to Optimize Outcomes) trials. These randomized controlled trials compared telaprevir plus PR versus PR alone in treatment-naïve and treatment-experienced populations, respectively. Three quarters of telaprevir-treated patients in ADVANCE achieved SVR, which was significantly better than the SVR rate in the PR group. REALIZE demonstrated a 3- to 5-fold improvement in SVR rates with the addition of telaprevir to PR. These findings and those from another randomized, open-label study of treatment-naïve patients prompted the US Food and Drug Administration to approve telaprevir in May 2011 for adults with chronic HCV genotype 1. Stratifying the model’s projected SVR rates according to baseline Metavir scores showed patients treated with telaprevir were more likely to achieve SVR, regardless of fibrosis status or treatment history. In untreated patients with scores of F0 to F2, telaprevir was associated with an SVR rate of 77.9% compared with 46.5% for PR. Among those treatment-naïve patients with the poorest Metavir scores (F3 to F4), the model estimated SVR rates of 61.6% in the telaprevir group and 32.9% in the PR arm. In both cohorts, SVR rates were slightly lower for previously treated patients, at 67.3% in the telaprevir group versus 22.0% in the PR arm for patients with Metavir scores of F0 to F2 and at 61.7% in the telaprevir group versus 10.5% for the PR arm for patients with Metavir scores of F3 to F4. During the model’s posttreatment phase, long-term outcomes were projected using a cyclic Markov process that reassessed each patient’s HCV-related health status annually. Rates of progression (described as transition to another health state) and mortality were culled from the literature and elsewhere and applied according to model patient age, sex, and baseline HCV severity. The model predicted an average accrual of 32.4 life-years for treatment-naïve patients treated with telaprevir compared with 30.4 for their PR-only counterparts. Average life-years accrued for treatment-experienced patients were projected at 26.9 with telaprevir versus 23.5 with placebo. Comparing clinical outcomes between the 2 treatment arms revealed a 50% reduction in the rates of compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplant, and death with telaprevir. These findings suggest that adding telaprevir to a PR regimen could reduce the clinical burden attributable to HCV infection (genotype 1), even for previously treated patients. “Given the high costs of treating advanced liver disease caused by HCV infection, there may be substantial economic value associated with the clinical benefits realized by telaprevir-based therapy, which warrants further study on its own,” concluded the authors. This study was supported by Vertex Pharmaceuticals, Inc.