Real-life experience with disease-modifying drugs in hereditary transthyretin amyloid polyneuropathy: A clinical and electrophysiological appraisal.

Introduction: New treatments have dramatically improved the prognosis for Hereditary Transthyretin Amyloid Polyneuropathy (ATTRv-PN). However, there is a lack of routine follow-up studies outside of therapeutic trials. Our aim was to report the long-term clinical and electrophysiological evolution of a cohort of ATTRv-PN patients and to determine which biomarkers are most sensitive to change.

Methods: We retrospectively collected neuropathy impairment scale (NIS), polyneuropathy disability scale (PND), overall neuropathy limitation scale (ONLS), rash built overall disability scale (RODS), electrodiagnostic data, motor unit number index (MUNIX), troponin and N-terminal pro-brain natriuretic peptide levels. Electrophysiological worsening was defined as a 20% decrease in previous values.

Results: Thirty-five patients, with a median age of 58 (interquartile ranges 42-71) years, were followed for a median of 36 (24-48) months. All patients received a transthyretin stabiliser, gene silencer or liver transplant. Overall assessment of the cohort showed clinical, biological and electrophysiological stability. However, on an individual basis, NIS worsened in 45% of patients (14/31), ONLS in 46% (13/28), PND in 28% (9/32) and RODS in 39% (11/28) at the last follow-up. Motor amplitude sum score decreased in 33% (11/33), amplitude recorded on tibialis anterior muscle in 44% (12/27), sensory amplitude sum score in 39% (11/28) and MUNIX sum score in 27% (7/26).

Conclusions: Overall effectiveness of ATTRv-PN treatments in routine care is good. However, individual assessments show up to 40% deterioration over time. Electrophysiological measures are valuable monitoring tools but are not more sensitive to change than clinical scores. Results must be confirmed in larger cohorts.