title: Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area.
abstract: Tafamidis is a transthyretin (TTR) stabilizer able to prevent TTR tetramer dissociation. There have been a few encouraging studies on Tafamidis efficacy in early-onset inherited transthyretin amyloidosis (ATTR) due to Val30Met mutation. However, less is known about its efficacy in later disease stages and in non-Val30Met mutations. We performed a multi-center observational study on symptomatic ATTR patients prescribed to receive Tafamidis. We followed up patients according to a standardized protocol including general medical, cardiological and neurological assessments at baseline and every 6 months up to 3 years. Sixty-one (42 males) patients were recruited. Only 28 % of enrolled subjects had the common Val30Met mutation, mean age of onset was remarkably late (59 years) and 18 % was in advanced disease stage at study entry. Tafamidis proved safe and well-tolerated. One-third of patients did not show significant progression along 36 months, independently from mutation type and disease stage. Neurological function worsened particularly in the first 6 months but progression slowed significantly thereafter. Autonomic function remained stable in 33 %, worsened in 56 % and improved in 10 %. Fifteen percent of patients showed cardiac disease progression and 30 % new onset of cardiomyopathy. Overall, Tafamidis was not able to prevent functional progression of the disease in 23 (43 %) subjects, including 16 patients who worsened in their walking ability and 12 patients who reached a higher NYHA score during the follow-up period. A higher mBMI at baseline was associated with better preservation of neurological function. In conclusion, neuropathy and cardiomyopathy progressed in a significant proportion of patients despite treatment. However, worsening of neurological function slowed after the first 6 months and also subjects with more advanced neuropathy, as well as patients with non-Val30Met mutation, benefited from treatment. Body weight preservation is an important favorable prognostic factor.
authors.affiliation: C. Mondino National Neurological Institute, IRCCS, Pavia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cortese
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.|NEMO SUD Center for Neuromuscular Disorders, Fondazione Aurora Onlus, Messina, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Vita
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Institute of Neurology, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Luigetti
authors.affiliation: NEMO SUD Center for Neuromuscular Disorders, Fondazione Aurora Onlus, Messina, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Russo
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Institute of Neurology, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bisogni
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Institute of Neurology, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Sabatelli
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Manganelli
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Santoro
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Verona, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Cavallaro
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Verona, Italy.
authors.forename: G M
authors.initials: GM
authors.lastname: Fabrizi
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Schenone
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Grandis
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Gemelli
authors.affiliation: Division of Neurology and Neurorehabilitation, Ospedale San Giuseppe, Istituto Auxologico Italiano, IRCCS, Piancavallo, Verbania, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mauro
authors.affiliation: Division of Neurology and Neurorehabilitation, Ospedale San Giuseppe, Istituto Auxologico Italiano, IRCCS, Piancavallo, Verbania, Italy.
authors.forename: L G
authors.initials: LG
authors.lastname: Pradotto
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Gentile
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.|Biomedical Department of Internal and Specialistic Medicine, University of Palermo, Palermo, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Stancanelli
authors.affiliation: C. Mondino National Neurological Institute, IRCCS, Pavia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lozza
authors.affiliation: Clinica Medica II, Department of Internal Medicine, Fondazione Policlinico IRCCS San Matteo, University of Pavia, Pavia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Perlini
authors.affiliation: Clinic of Central and Peripheral Degenerative Neuropathies Unit, Department of Clinical Neurosciences, IRCCS Foundation, "C. Besta" Neurological Institute, via Celoria 11, 20133, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Piscosquito
authors.affiliation: Clinic of Central and Peripheral Degenerative Neuropathies Unit, Department of Clinical Neurosciences, IRCCS Foundation, "C. Besta" Neurological Institute, via Celoria 11, 20133, Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Calabrese
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mazzeo
authors.affiliation: Amyloidosis Research and Treatment Center, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Obici
authors.affiliation: Clinic of Central and Peripheral Degenerative Neuropathies Unit, Department of Clinical Neurosciences, IRCCS Foundation, "C. Besta" Neurological Institute, via Celoria 11, 20133, Milan, Italy. davide.pareyson@istituto-besta.it.
authors.forename: D
authors.initials: D
authors.lastname: Pareyson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D001583:Benzoxazoles / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011228:Prealbumin / Q000235:genetics; D011379:Prognosis; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D001583:Benzoxazoles; D011228:Prealbumin; C547076:tafamidis
keywords: Amyloid polyneuropathy; Tafamidis; Transthyretin