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Effect on disability and safety of Tafamidis in late onset of Met30 transthyretin familial amyloid polyneuropathy
Author(s) -
Lozeron P.,
Théaudin M.,
Mincheva Z.,
Ducot B.,
Lacroix C.,
Adams D.
Publication year - 2013
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.12225
Subject(s) - medicine , transthyretin , polyneuropathy , orthostatic vital signs , amyloidosis , adverse effect , prospective cohort study , amyloid polyneuropathy , pediatrics , surgery , age of onset , disease , blood pressure
Background and purpose The aim of this study was to assess the effect of Tafamidis, which slows the progression of early stages of Met30 transthyretin ( TTR ) familial amyloidosis polyneuropathy ( FAP ) in more advanced cases. Methods The study was a prospective, non‐randomized controlled trial carried out at the French national reference centre for FAP with follow‐up at 1 year. Thirty‐seven consecutive Met30‐ TTR ‐ FAP patients were enrolled between December 2009 and July 2011, with NIS ‐ LL (Neuropathy Impairment Score‐lower limbs) > 10 and Karnofsky score > 60. Their mean (SD) age was 56.4 (19) years. Seventy‐seven per cent of patients had a walking disability. Seven patients (19%) were withdrawn for adverse effects. The primary study outcome measurements, planned before data collection began, were NIS ‐ LL and NIS ‐ UL (upper limbs) scores and disability scores. Results Of the 37 patients entered into the study, 29 were evaluated at 6 months and 13 at 12 months. During the first 6 months of treatment, the mean progression of NIS ‐ LL score was 4.8 and was similar to that during the period before treatment. Among the 45% of patients without NIS ‐ LL progression, the NIS ‐ UL score worsened in 55%. During the first year, 55% deteriorated with respect to disability and 38% with respect to NIS only; only two patients (7%) remained stable. Four (out of 20; 20%) patients who were previously stage 1 reached stage 2 (walking with aid) after this period. Two out of nine patients who were initially normotensive developed orthostatic hypotension. There were a total of 19 adverse events, including four febrile urinary tract infections and three severe diarrhoeas, with faecal incontinence in two. Conclusion In most patients with advanced Met30 TTR ‐ FAP , Tafamidis is not able to stop disease progression, in respect of both NIS ‐ LL and disability. Other anti‐amyloid medicines should be assessed in this context.