To describe neuropathy evolution in patients with minimal neurological findings after treatment with tafamidis. 

HATTR amyloidosis results in rapid progressing polyneuropathy. Tafamidis has demonstrated neurologic function improvement, but is still unclear its role in patients with small fiber symptoms at the time of treatment onset. 

Thirty patients (56% female, mean age 34.4 ± 10.8 years) with rare TTR mutations (73% Ser50Arg, 13% Ser52Pro, and 13% Gly47Arg) were included in an open-label clinical trial of 20 mg of tafamidis per day.

Baseline Polyneuropathy Disability (PND) score was 0 in 21 patients, stage 1 in 8, and stage 2 in one; after two years was unchanged in 53%, improved in 10%, and worsened in 36%. Worsening was seen from PND 0 to I in 7(23%), from I to II in 1(3%), from I to IIIA in 2(6%), and from II to IIIB in 1(3%). 

At entry, NIS ranged from 0 to 38 points. Two years later, 7(23%) of patients had an improvement in NIS score (-4.1, -1 to -8points ), and 11(36%) patients worsened ( +7.6, 2 to 38 points). Small fiber function, assessed with UENS, QST CT, and WT in feet, improved in 30%, 23%, and 26% of patients and worsened in 40%, 26%, and 30%, respectively. Large fiber function assessed with QST VT, NCV sural, and peroneal amplitude improved in 43%, 26%, and 23% and worsened in 33%, 46%, and 30%, respectively. 

Tafamidis improved NIS scores in 7(23%), remained stable in 18(60%), and worsened in 11(36%) patients. Both small and large nerve fiber worsened equally, through clinical evaluations (NIS and UENS) and laboratory studies; however, mean NIS worsening was less than expected when compared to the natural history. Eight patients with PND of 0 converted to stage I, proving that disease progression begins early despite discrete or null neurological signs.