Neuropathy Progression in Variant Transthyretin Amyloidosis: Comparison Between TTR Stabilizers and Gene Silencer Therapies.

Abstract

Introduction/aims: Transthyretin (TTR) stabilizers and gene-silencing therapies are approved for hereditary transthyretin-mediated amyloidosis with polyneuropathy (ATTRv-PN), but data from clinical practice in patients who transition between therapies due to disease progression remains limited. The primary aim of this study is to evaluate the effectiveness of patisiran in ATTRv-PN patients who progressed despite prior treatment with tafamidis 20 mg.

Methods: We conducted a retrospective multicenter observational study including patients with ATTRV30M (p.V50M) with polyneuropathy who were initially treated with tafamidis 20 mg and subsequently switched to patisiran due to documented neuropathy progression. Patients had at least 12 months of follow-up under each treatment. Neuropathy progression was assessed using the Neuropathy Impairment Score (NIS), neurophysiological composite scores, nutritional status, serum biomarkers, and patient-reported outcomes.

Results: Thirty-two patients (mean age 52 ± 14 years; mean disease onset 43 ± 23.5 years) were included. Median disease duration before treatment initiation was 1.8 ± 1.9 years. The mean duration of tafamidis and patisiran treatment was 4.5 ± 2.8 and 2.5 ± 2.3 years, respectively. The annual increase in NIS was significantly lower during patisiran treatment than during tafamidis (0.7 ± 3.9 vs. 3.9 ± 4.7; p = 0.004). Decline in neurophysiological parameters slowed after switching.

Discussion: In this cohort, patisiran attenuated neuropathy progression in patients who had deteriorated despite tafamidis. These findings highlight the importance of ongoing clinical monitoring to guide timely treatment optimization.