title: Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy.
abstract: Tafamidis, a transthyretin (TTR) kinetic stabilizer, delayed neuropathic progression in patients with Val30Met TTR familial amyloid polyneuropathy (TTR-FAP) in an 18-month randomized controlled trial (study Fx-005). This 12-month, open-label extension study evaluated the long-term safety, tolerability, and efficacy of tafamidis 20 mg once daily in 86 patients who earlier received blinded treatment with tafamidis or placebo. Efficacy measures included the Neuropathy Impairment Score in the Lower Limbs (NIS-LL), Norfolk Quality of Life-Diabetic Neuropathy total quality of life (TQOL) score, and changes in neurologic function and nutritional status. We quantified the monthly rates of change in efficacy measures, and TTR stabilization, and monitored adverse events (AEs). Patients who continued on tafamidis had stable rates of change in NIS-LL (from 0.08 to 0.11/month; p = 0.60) and TQOL (from -0.03 to 0.25; p = 0.16). In patients switched from placebo, the monthly rate of change in NIS-LL declined (from 0.34 to 0.16/month; p = 0.01), as did TQOL score (from 0.61 to -0.16; p < 0.001). Patients treated with tafamidis for 30 months had 55.9 % greater preservation of neurologic function as measured by the NIS-LL than patients in whom tafamidis was initiated later. Plasma TTR was stabilized in 94.1 % of patients treated with tafamidis for 30 months. AEs were similar between groups; no patients discontinued because of an AE. Long-term tafamidis was well tolerated, with the reduced rate of neurologic deterioration sustained over 30 months. Tafamidis also slowed neurologic impairment in patients previously given placebo, but treatment benefits were greater when tafamidis was begun earlier.
authors: Unidade Clinica de Paramiloidose, Hospital de Santo António, Largo Prof Abel Salazar, 4099-001, Porto, Portugal, tcoelho@netcabo.pt.
authors: Teresa
authors: T
authors: Coelho
authors: Luis F
authors: LF
authors: Maia
authors: Ana Martins
authors: AM
authors: da Silva
authors: Márcia W
authors: MW
authors: Cruz
authors: Violaine
authors: V
authors: Planté-Bordeneuve
authors: Ole B
authors: OB
authors: Suhr
authors: Isabel
authors: I
authors: Conceiçao
authors: Hartmut H-J
authors: HH
authors: Schmidt
authors: Pedro
authors: P
authors: Trigo
authors: Jeffery W
authors: JW
authors: Kelly
authors: Richard
authors: R
authors: Labaudinière
authors: Jason
authors: J
authors: Chan
authors: Jeff
authors: J
authors: Packman
authors: Donna R
authors: DR
authors: Grogan
mesh_terms: D000328:Adult; D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D001583:Benzoxazoles / Q000627:therapeutic use*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007391:International Cooperation; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism*; D011788:Quality of Life; D013997:Time Factors; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: D001583:Benzoxazoles; D011228:Prealbumin; C547076:tafamidis; D008715:Methionine; D014633:Valine
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