Impact of RNAi therapeutics on cardiac parameters in patients with hereditary transthyretin amyloidosis initially treated with stabilizers: A French real-world study.

BACKGROUND

Cardiomyopathy in hereditary transthyretin amyloidosis (ATTRv) is increasingly reported due to improved diagnostic techniques and increased clinician awareness. Optimal therapeutic strategies for mixed phenotypes remain challenging.

AIMS: To describe the changes in cardiac parameters among patients with ATTRv and cardiac involvement who had switched from stabilizer monotherapy to ribonucleic acid interference (RNAi) therapeutics or added RNAi to stabilizer monotherapy (switching/adding RNAi).

METHODS

Data from patients with ATTRv and confirmed cardiomyopathy who had started tafamidis monotherapy between 2010 and 2022 and switched to/added RNAi therapeutics (patisiran or vutrisiran) between 2018 and 2023 were retrospectively collected from October 2023 to May 2024. Functional, laboratory and imaging parameters were collected, and progression assessed according to the 2021 expert consensus on transthyretin amyloidosis with cardiomyopathy monitoring.

RESULTS

Fifty patients (median [interquartile range] age 63 [58-70] years; 66% male) from 10 French centres were included. Mean±standard deviation follow-up durations on treatment were 3.8±2.7 years for tafamidis monotherapy and 2.5±1.9 years for RNAi (±tafamidis). Switching/adding RNAi was mainly for neurological progression (n=40; 80%). Under tafamidis monotherapy, 24% of patients worsened with simultaneous declines in clinical, laboratory and imaging parameters, while 76% were stable. After switching/adding RNAi, 90% of patients were stable, none worsened and 10% improved.

CONCLUSION

This real-world French study is the first switch/add-on study in mixed phenotypes of ATTRv. It highlights the potential benefits of early switching/adding of RNAi in patients with insufficient cardiac response under tafamidis.