title: Long-term treatment of transthyretin familial amyloid polyneuropathy with tafamidis: a clinical and neurophysiological study.
abstract: Tafamidis is a transthyretin (TTR) stabilizer recently approved to slow the neurologic impairment in TTR familial amyloid polyneuropathy (TTR-FAP). The pivotal studies on Tafamidis reported encouraging results on the short term, in the early onset Val30Met-TTR-FAP patients at an early stage of the neuropathy. However, the effect of the drug in the non-Val30Met patients, at a more advanced stage of the disease and on the long term, is less known. In this study, we report the effect of Tafamidis in 43 TTR-FAP patients with a variety of pathogenic mutations, including 53% of non-Val30Met variants, at different stages of neuropathy followed on the long term. General and neurological assessment was performed in a standardized protocol every 6-12 months along with neurophysiological variables, including testing of small nerve fibres. The mean follow-up under treatment was 2 years with a subset of 26 patients treated for 3 years. Overall, Tafamidis was well tolerated. A significant clinical deterioration of the neuropathy and the patient's general condition was observed across the 3 years follow-up, although neurophysiological parameters remained stable for the first 2 years. In contrast, patients had a significant increase of BMI under treatment. Deterioration of the neuropathy correlated to an older age at disease onset or treatment initiation and to poor clinical status at baseline. A higher BMI at baseline was associated with a lower progression of the neuropathy. About one-third of the patients who received 3 years of tafamidis had still preserved walking capacity or good clinical condition, suggesting that tafamidis slowed the disease progression in some patients. Overall, our work shows that tafamidis is well tolerated in TTR-FAP but does not prevent the steady progression of the neuropathy on the long term. Age, neurologic status, and general condition at baseline appear to be best predictors of tafamidis efficacy on the neurological function.
authors.affiliation: Amyloid Network, Henri Mondor University Hospital, AP-HP, Créteil, France. vplante@free.fr.|Department of Neurology, Henri Mondor University Hospital, AP-HP, 51 avenue du Maréchal de Lattre de Tassigny, 94010, Créteil Cedex, France. vplante@free.fr.|Faculty of Medicine, GRC Amyloid Research Institute, Paris-Est Créteil University, Créteil, France. vplante@free.fr.
authors.forename: Violaine
authors.initials: V
authors.lastname: Planté-Bordeneuve
authors.affiliation: Amyloid Network, Henri Mondor University Hospital, AP-HP, Créteil, France.|Department of Neurology, Henri Mondor University Hospital, AP-HP, 51 avenue du Maréchal de Lattre de Tassigny, 94010, Créteil Cedex, France.|Faculty of Medicine, GRC Amyloid Research Institute, Paris-Est Créteil University, Créteil, France.|Clinical Investigation Center 1430, IMRB, Henri Mondor University Hospital, Inserm, Créteil, France.
authors.forename: Farida
authors.initials: F
authors.lastname: Gorram
authors.affiliation: Amyloid Network, Henri Mondor University Hospital, AP-HP, Créteil, France.|Department of Neurology, Henri Mondor University Hospital, AP-HP, 51 avenue du Maréchal de Lattre de Tassigny, 94010, Créteil Cedex, France.|EA 4391, Faculty of Medicine, Paris-Est Créteil University, Créteil, France.
authors.forename: Hayet
authors.initials: H
authors.lastname: Salhi
authors.affiliation: Amyloid Network, Henri Mondor University Hospital, AP-HP, Créteil, France.|EA 4391, Faculty of Medicine, Paris-Est Créteil University, Créteil, France.|Clinical Neurophysiology Unit, Department of Physiology, Henri Mondor University Hospital, AP-HP, Créteil, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Nordine
authors.affiliation: Amyloid Network, Henri Mondor University Hospital, AP-HP, Créteil, France.|EA 4391, Faculty of Medicine, Paris-Est Créteil University, Créteil, France.|Clinical Neurophysiology Unit, Department of Physiology, Henri Mondor University Hospital, AP-HP, Créteil, France.
authors.forename: Samar S
authors.initials: SS
authors.lastname: Ayache
authors.affiliation: Amyloid Network, Henri Mondor University Hospital, AP-HP, Créteil, France.|Clinical Investigation Center 1430, IMRB, Henri Mondor University Hospital, Inserm, Créteil, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Le Corvoisier
authors.affiliation: Amyloid Network, Henri Mondor University Hospital, AP-HP, Créteil, France.|Liver Transplant Unit, Department of General Surgery, Henri Mondor University Hospital, AP-HP, Créteil, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Azoulay
authors.affiliation: Amyloid Network, Henri Mondor University Hospital, AP-HP, Créteil, France.|Liver Transplant Unit, Department of General Surgery, Henri Mondor University Hospital, AP-HP, Créteil, France.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Feray
authors.affiliation: Amyloid Network, Henri Mondor University Hospital, AP-HP, Créteil, France.|Faculty of Medicine, GRC Amyloid Research Institute, Paris-Est Créteil University, Créteil, France.|Heart Failure Unit, Department of Cardiology, Henri Mondor University Hospital, AP-HP, Créteil, France.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Damy
authors.affiliation: Amyloid Network, Henri Mondor University Hospital, AP-HP, Créteil, France.|EA 4391, Faculty of Medicine, Paris-Est Créteil University, Créteil, France.|Clinical Neurophysiology Unit, Department of Physiology, Henri Mondor University Hospital, AP-HP, Créteil, France.
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Lefaucheur
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D028227:Amyloid Neuropathies, Familial / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D001583:Benzoxazoles / Q000627:therapeutic use*; D015992:Body Mass Index; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006401:Hematologic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001583:Benzoxazoles; D006401:Hematologic Agents; C547076:tafamidis
keywords: Amyloidosis; Genetics; Longitudinal study; Neurophysiology; Peripheral neuropathy; Response; Small nerve fibres; Transthyretin; Treatment