Safety Profile of Telaprevir-Based Triple Therapy in Elderly Patients: A Real-World Retrospective Cohort Study

Abstract

To compare the rate of treatment discontinuation due to adverse events for telaprevir-based triple (T/PR) and pegylated interferon-alfa-2b and ribavirin (PR) therapy for the treatment of hepatitis C virus (HCV) infection in patients over the age of 65 years, in Japan. Retrospective analysis of the health data of patients over the age of 65 years treated for a HCV infection genotype 1 using T/PR or PR therapy, from 38 prefectures in Japan. The primary outcome was the rate of treatment discontinuation due to adverse events for T/PR and PR. The secondary outcome was to evaluate the prevalence and type of adverse events during the treatment period that resulted in treatment discontinuation for both therapies. For comparison, the T/PR and PR populations were matched using the propensity score method, and adjusted odds ratios (ORs) for treatment discontinuation calculated by multivariate logistic regression analysis. The study group included 1330 patients, 328 in the T/PR group and 1002 in the PR group. The rate of treatment discontinuation due to adverse events in the matched population was lower for T/PR (19.82%) than PR (35.98%) therapy, (adjusted OR, 0.418; 95% confidence interval, 0.292-0.599; p<0.01). Malaise was the principal cause of treatment discontinuation in both groups (T/PR, 30.77%, and PR, 42.37%). Using real-world health data of elderly individuals in Japan, we identified a lower rate of treatment discontinuation for T/PR than PR. Our outcomes provide information for a segment of the population that is generally excluded for clinical trials.Key words elder patient; hepatitis C; safety profile; telaprevir; real-world data Hepatitis C virus (HCV) infection is one of the most serious diseases worldwide, with 70% of individuals infected with HCV developing a chronic infection status 1) and 22% developing liver cirrhosis within 20 years of HCV infection, 2) with progression to liver cancer in some cases. Considering that liver cancer is the second highest cause of mortality in the world, 3) providing anti-viral treatment to individuals infected with HCV would be important to prevent the development of these secondary HCV-related comorbidities. 4)The effectiveness of anti-viral treatment for HCV infection has improved recently with the approval of direct-acting anti-viral agents (DAAs), used as an alternative to or in combination with pegylated interferon-alfa-2b and ribavirin (PR) therapy. Telaprevir is one such DAA that has been used in combination with PR therapy for the treatment of HCV genotype 1 infection. Telaprevir-based triple therapy (T/PR) has been shown to be effective in achieving a sustained virologic response (SVR) in 60-70% of HCV cases, compared to a 40-50% SVR with PR therapy.5,6) Moreover, a 90% SVR has been reported in clinical trials using DAA interferon-free therapy. [7][8][9] In practice, HCV treatment is selected based on a patient's individual clinical background. 10)T/PR therapy, however, is associated with a high risk of adverse events, with a discontinuation rate of >10% for T/PR ...