title: Effects of tafamidis treatment on transthyretin (TTR) stabilization, efficacy, and safety in Japanese patients with familial amyloid polyneuropathy (TTR-FAP) with Val30Met and non-Val30Met: A phase III, open-label study.
abstract: BACKGROUND
  The efficacy and safety of tafamidis in transthyretin (TTR) familial amyloid polyneuropathy (TTR-FAP) were evaluated in this open-label study.
  
  
  METHODS
  Japanese TTR-FAP patients (n=10; mean age 60.1 years) received tafamidis meglumine (20mg daily; median treatment duration 713.5 days). The primary endpoint was TTR stabilization at Week 8. Secondary endpoints included Neuropathy Impairment Score-Lower Limb (NIS-LL), Norfolk QOL-DN total quality of life (TQOL), and modified body mass index (mBMI).
  
  
  RESULTS
  TTR stabilization was achieved in all patients at Weeks 8 and 26, 9 out of 10 patients at Week 52, and 8 out of 10 patients at Week 78. The percentage (95% CI) of NIS-LL responders (increase from baseline in NIS-LL<2) was 80.0% (44.4, 97.5), 60.0% (26.2, 87.8), and 40.0% (12.2, 73.8) and mean(SD) NIS-LL change from baseline was 2.1 (5.6), 3.6 (4.4), and 3.3 (4.7), at Weeks 26, 52, and 78, respectively. Mean (SD) changes from baseline in TQOL and mBMI at Weeks 26, 52, and 78 were 11.8 (20.0), 9.1 (12.5), and 10.8 (13.7) for TQOL, and 26.6 (61.9), 64.9 (80.0), and 53.7 (81.4) for mBMI, respectively. Ambulation status was preserved in 4 out of 8 patients at Week 78. Most adverse events (AEs) were mild/moderate, with no discontinuations due to AEs.
  
  
  CONCLUSIONS
  Tafamidis stabilized TTR, was safe and well-tolerated, and was effective over 1.5 years in slowing neurologic progression and maintaining TQOL and nutrition status in TTR-FAP.
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. andoy709@kumamoto-u.ac.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.affiliation: Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan. sekijima@shinshu-u.ac.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sekijima
authors.affiliation: Department of Morphological and Physiological Sciences, Graduate School of Health Sciences, Kumamoto University, Kumamoto, Japan. konen@kumamoto-u.ac.jp.
authors.forename: Konen
authors.initials: K
authors.lastname: Obayashi
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. taro-yamashita@fc.kuh.kumamoto-u.ac.jp.
authors.forename: Taro
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. mitt@rb3.so-net.ne.jp.
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. misumiyohei@hotmail.co.jp.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Misumi
authors.affiliation: Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan. hmorita@shinshu-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morita
authors.affiliation: Pfizer Japan Inc., Tokyo, Japan. kachannachan@aol.com.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Machii
authors.affiliation: Pfizer Japan Inc., Tokyo, Japan. makoto.ohta@pfizer.com.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohta
authors.affiliation: Pfizer Japan Inc., Tokyo, Japan. Ami.Takata@pfizer.com.
authors.forename: Ami
authors.initials: A
authors.lastname: Takata
authors.affiliation: Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan. ikedasi@shinshu-u.ac.jp.
authors.forename: Shû-Ichi
authors.initials: S
authors.lastname: Ikeda
mesh_terms: D000328:Adult; D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000188:drug therapy* / Q000235:genetics*; D001583:Benzoxazoles / Q000627:therapeutic use*; D015992:Body Mass Index; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D010597:Pharmacogenetics; D011228:Prealbumin / Q000235:genetics* / Q000378:metabolism*; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: D001583:Benzoxazoles; D011228:Prealbumin; C547076:tafamidis; D008715:Methionine; D014633:Valine
keywords: Amyloid; TTR Val30Met; TTR non-Val30Met; familial amyloid polyneuropathy; tafamidis; transthyretin amyloidosis