title: Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy.
abstract: Transthyretin hereditary amyloid polyneuropathy, also traditionally known as transthyretin familial amyloid polyneuropathy (ATTR-FAP), is a rare, relentless, fatal hereditary disorder. Tafamidis, an oral, non-NSAID, highly specific transthyretin stabilizer, demonstrated safety and efficacy in slowing neuropathy progression in early-stage ATTRV30M-FAP in a 1.5-year, randomized, double-blind, placebo-controlled trial, and 1-year open-label extension study, with a second long-term open-label extension study ongoing. Subgroup analysis of the effectiveness of tafamidis in the pivotal study and its open-label extensions revealed a relatively cohesive cohort of patients with mild neuropathy (i.e. Neuropathy Impairment Score for Lower Limbs [NIS-LL] ≤ 10) at the start of active treatment. Early treatment with tafamidis for up to 5.5 years (≥1 dose of tafamidis meglumine 20 mg once daily during the original trial or after switching from placebo in its extension) resulted in sustained delay in neurologic progression and long-term preservation of nutritional status in this cohort. Mean (95% CI) changes from baseline in NIS-LL and mBMI were 5.3 (1.6, 9.1) points and -7.8 (-44.3, 28.8) kg/m2× g/L at 5.5 years, respectively. No new safety issues or side effects were identified. These data represent the longest prospective evaluation of tafamidis to date, confirm a favorable safety profile, and underscore the long-term benefits of early intervention with tafamidis.
  
  
  BACKGROUND
  ClincalTrials.gov Identifier: NCT00409175, NCT00791492, and NCT00925002.
authors: a Hospital Universitário Clementino Fraga Filho (HUCFF), Universidade Federal do Rio de Janeiro (UFRJ) , Rio de Janeiro , Brazil.
authors: Márcia
authors: M
authors: Waddington Cruz
authors: b Pfizer , New York , NY , USA , and.
authors: Leslie
authors: L
authors: Amass
authors: b Pfizer , New York , NY , USA , and.
authors: Denis
authors: D
authors: Keohane
authors: b Pfizer , New York , NY , USA , and.
authors: Jeffrey
authors: J
authors: Schwartz
authors: b Pfizer , New York , NY , USA , and.
authors: Huihua
authors: H
authors: Li
authors: c inVentiv Health Inc. , Burlington , MA , USA.
authors: Balarama
authors: B
authors: Gundapaneni
mesh_terms: D000328:Adult; D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001583:Benzoxazoles / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055502:Secondary Prevention
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001583:Benzoxazoles; C547076:tafamidis
keywords: ATTRV30M; Amyloidosis; TTR Val30Met; disease modification; transthyretin amyloidosis