Efficacy of diflunisal for hereditary transthyretin amyloidosis: the Swedish real-world experience

BACKGROUND: Diflunisal has been shown to slow the progression of hereditary transthyretin (ATTRv) amyloidosis. We examined the efficacy of diflunisal using data from SveATTR, a longitudinal Swedish registry open for patients with ATTR amyloidosis. METHODS: Data from diflunisal treated patients registered in SveATTR through Dec 2022 were included. Available data on Kumamoto score, PND score/FAP stage, mBMI, NYHA classification and Karnofsky performance status were analyzed using random coefficients mixed effects modeling, and the results were combined with those of the pivotal diflunisal trial. RESULTS: In total, 118 registry subjects were included. Estimated mean time of diflunisal therapy was 3.4 (range 0.1 to 10.2) years. Random coefficients mixed effects modeling demonstrated gradual progression of disease over time by upward trend of Kumamoto score, PND score and FAP stage, and downward trend in Karnofsky score and mBMI while NYHA class score remained unchanged. A Bayesian augmentation analysis was undertaken using registry data and pivotal trial data. After 24 months, the probability of superiority for diflunisal over placebo was 99.6% and 97.2% for Kumamoto score and mBMI, respectively. CONCLUSIONS: SveATTR registry data align with the results of the pivotal trial, providing long-term real-world evidence that confirm the efficacy of diflunisal for ATTRv amyloidosis.