The Safety Profile of Telaprevir-Based Triple Therapy in Clinical Practice: A Retrospective Cohort Study

Abstract

This study was designed to evaluate the safety profile of adding telaprevir to therapy using pegylated interferon-alfa-2b and ribavirin (PR) using real world patient data obtained from a nationwide Japanese interferon database. This retrospective cohort study compared telaprevir-based triple therapy (T/PR) with PR therapy. The study population comprised patients with genotype 1 chronic hepatitis C represented in the database between December 2009 and August 2015. The primary endpoint was dropout from treatment due to adverse events during the relevant standard treatment duration based on guidelines from the Japan Society of Hepatology. The dropout odds ratio (OR) and 95% confidence interval (95% CI) were calculated using univariate logistic regression analysis. Covariates were detected using a stepwise logistic regression analysis, and the adjusted OR and 95% CI were calculated. A total of 25989 patients were registered, and 4619 patients (T/PR: 1334, PR: 3285) were appropriate for primary endpoint analysis. The dropout rate due to adverse events was lower in the T/PR group (13.4%) than in the PR group (22.6%) (OR: 0.530; 95% CI, 0.444-0.633). After adjustment for the covariates detected by stepwise selection, the OR was 0.529 (95% CI, 0.441-0.634). Our study showed that there was a difference in dropout rate between real world T/PR and PR therapy in Japan. Although the addition of telaprevir to PR therapy may improve treatment continuity under the care of hepatologists, this study could not fully determine which therapy was safer or the factors influencing this result. Therefore, additional research will be required to confirm this. Key words telaprevir; real world database; hepatitis C; retrospective cohort study; interferon; ribavirin About 130-150 million people are infected with the hepatitis C virus (HCV) worldwide, and approximately 700000 people die annually of liver diseases related to HCV infection.

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

“…Age, HCV viral load and platelet count were classified according to the guidelines of The Japan Society of Hepatology, 4) these factors having previously been identified as contributing to the differential rate of treatment discontinuation for T/PR versus PR. 14) We also considered treatment experience as a covariate based on previously published guidelines 10) that recommend physicians consider treatment experience when deciding which therapy to provide to a patient. Model performance was assessed using the C-index, with a C-index of '1′ indicative of a perfect discrimination between the T/PR and PR groups, with an index >0.8 recommended to calculate a PS.…”

“…13) As an example, a real-world study reported a lower discontinuation rate for T/PR than for PR therapy. 14) Of clinical relevance is the evaluation of HCV therapy in elderly individuals in whom the risk for HCV is specifically higher than in younger adults 15) and yet, this segment of the population is generally excluded from clinical trials. This issue is of relevance in Japan, where the proportion of elderly in the general population is significantly higher than in Europe and the United States.…”