Impact of Tafamidis on Life Expectancy and Quality of Life of Transthyretin Amyloid Cardiomyopathy Patients

Background Historically, the prognosis of newly diagnosed patients with transthyretin amyloid cardiomyopathy (ATTR-CM) was poor with a median survival of only 2-6 years. The ATTR-ACT trial showed that tafamidis reduced all-cause mortality by 30.2% resulting in a hazard ratio (HR) of 0.70 [95% CI 0.51 to 0.96] compared to placebo by slowing disease progression. The aim of this study was to estimate the impact of tafamidis on mean survival and quality adjusted life years (QALY) using a disease simulation model. Methods A multi-state cohort Markov model was developed to simulate the disease course of ATTR-CM patients. In the model, patients were followed throughout a lifetime, and survival was stratified by prognostic NYHA I/II and NYHA III patient subgroups using individual patient-level data from both the ATTR-ACT and the long-term extension study to ATTR-ACT. Based on the patients’ distribution in the ATTRACT trial, the total patient cohort entering the model was comprised of 68% in NYHA class I/II and 32% in NYHA class III. Technical best practices were followed to extrapolate survival. Given that the proportional hazard assumption was violated, curves were fitted by treatment arm and by subgroup. The base case parametric distributions selected were Gompertz for NYHA class I/II and Weibull for NYHA class III, based on statistical tests of fit and clinical plausibility of the extrapolations. Utility values for the health states were derived from ATTR-ACT EQ-5D-3L using US tariffs. The outcomes were mean and incremental mean survival and QALYs. Univariate deterministic and multivariate probabilistic sensitivity analyses were conducted. Analyses were conducted for each NYHA class and weighted results presented. Results The overall predicted mean survival for the total population in the simulated patient cohort was 7.01 for tafamidis and 2.82 years for placebo, resulting in an incremental mean survival of 4.19 years [95% CI 1.32 to 5.55]. The corresponding QALYs were 5.64 and 2.09 respectively, resulting in 3.54 incremental QALYs [95% CI 1.20 to 4.72] in favor of tafamidis. The results were sensitive to parametric distributions selected for both placebo and tafamidis. Conclusions Based on the results of the disease simulation model, tafamidis is expected to increase the life expectancy and QALYs of ATTR-CM patients by 4.19 years and 3.54 QALYs, respectively. Longer term follow-up data from the ATTR-ACT extension study will further inform these findings when available.