• Jonas Wixner, John L Berk, David Adams, Michael Polydefkis, Isabel Conceição, Shahram Attarian, Julian D Gillmore, DyckP James BPJBDepartment of Neurology, Mayo Clinic, Rochester, MN, USA., Folke Folkvaljon, Wunan Zhou, Jersey Chen, Nicholas J Viney, T Jesse Kwoh, Teresa Coelho, and Márcia Waddington-Cruz.
• Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
• Amyloid. 2024 Nov 17: 1101-10.

BackgroundThe NEURO-TTRansform trial showed that after 66 weeks of treatment, eplontersen significantly reduced neuropathic impairment and improved quality of life (QoL) in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy (ATTRv-PN). In this secondary analysis from NEURO-TTRansform, autonomic impairment, and the impact of eplontersen on autonomic impairment progression was evaluated through 85 weeks in patients randomised to eplontersen (n = 144) versus external placebo (n = 60; through Week 66 from the NEURO-TTR trial).MethodsChange from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) composite score, Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) total score, and the Neuropathy Symptoms and Change (NSC) total score was evaluated. Exploratory assessments were change in autonomic components of these instruments, Composite Autonomic Symptom Score-31 (COMPASS-31) total score, and nutritional status (modified body mass index [mBMI]).ResultsPatients reported profound autonomic dysfunction at baseline. Improvements with eplontersen versus placebo were observed up to Week 66 in autonomic components of mNIS+7, Norfolk QoL-DN, NSC, and mBMI; eplontersen results were sustained up to Week 85, including improvements in COMPASS-31 (Week 81).ConclusionsEplontersen demonstrated benefit across multiple measures of autonomic impairment known to progress rapidly and negatively impact QoL without treatment, without deterioration in nutritional status.

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