title: Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial.
abstract: BACKGROUND
  Tafamidis, a non-NSAID highly specific transthyretin stabilizer, delayed neurologic disease progression as measured by Neuropathy Impairment Score-Lower Limbs (NIS-LL) in an 18-month, double-blind, placebo-controlled randomized trial in 128 patients with early-stage transthyretin V30M familial amyloid polyneuropathy (ATTRV30M-FAP). The current post hoc analyses aimed to further evaluate the effects of tafamidis in delaying ATTRV30M-FAP progression in this trial.
  
  
  METHODS
  Pre-specified, repeated-measures analysis of change from baseline in NIS-LL in this trial (ClinicalTrials.gov NCT00409175) was repeated with addition of baseline as covariate and multiple imputation analysis for missing data by treatment group. Change in NIS-LL plus three small-fiber nerve tests (NIS-LL + Σ3) and NIS-LL plus seven nerve tests (NIS-LL + Σ7) were assessed without baseline as covariate. Treatment outcomes over the NIS-LL, Σ3, Σ7, modified body mass index and Norfolk Quality of Life-Diabetic Neuropathy Total Quality of Life Score were also examined using multivariate analysis techniques.
  
  
  RESULTS
  Neuropathy progression based on NIS-LL change from baseline to Month 18 remained significantly reduced for tafamidis versus placebo in the baseline-adjusted and multiple imputation analyses. NIS-LL + Σ3 and NIS-LL + Σ7 captured significant treatment group differences. Multivariate analyses provided strong statistical evidence for a superior tafamidis treatment effect.
  
  
  CONCLUSIONS
  These supportive analyses confirm that tafamidis delays neurologic progression in early-stage ATTRV30M-FAP.
  
  
  BACKGROUND
  NCT00409175.
authors.affiliation: a Pfizer Inc. , New York , NY , USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Keohane
authors.affiliation: a Pfizer Inc. , New York , NY , USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: b inVentiv Health Inc. , Burlington , MA , USA.
authors.forename: Balarama
authors.initials: B
authors.lastname: Gundapaneni
authors.affiliation: a Pfizer Inc. , New York , NY , USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Stewart
authors.affiliation: a Pfizer Inc. , New York , NY , USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Amass
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000188:drug therapy* / Q000378:metabolism; D001583:Benzoxazoles / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011115:Polyneuropathies / Q000188:drug therapy* / Q000378:metabolism; D011228:Prealbumin / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D001583:Benzoxazoles; D011228:Prealbumin; C547076:tafamidis
keywords: Amyloidosis; disease-modifying drug; familial amyloid neuropathy; polyneuropathy; tafamidis; transthyretin