Top

Published in:

01-05-2016 | Original Communication

Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area

Authors: A. Cortese, G. Vita, M. Luigetti, M. Russo, G. Bisogni, M. Sabatelli, F. Manganelli, L. Santoro, T. Cavallaro, G. M. Fabrizi, A. Schenone, M. Grandis, C. Gemelli, A. Mauro, L. G. Pradotto, L. Gentile, C. Stancanelli, A. Lozza, S. Perlini, G. Piscosquito, D. Calabrese, A. Mazzeo, L. Obici, D. Pareyson

Published in: Journal of Neurology | Issue 5/2016

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.

Available only for authorised users

Planté-Bordeneuve V, Said G (2011) Familial amyloid polyneuropathy. Lancet Neurol 10(12):1086–1097CrossRefPubMed

Koike H, Tanaka F, Hashimoto R, Tomita M, Kawagashira Y, Iijima M et al (2012) Natural history of transthyretin Val30Met familial amyloid polyneuropathy: analysis of late-onset cases from non-endemic areas. J Neurol Neurosurg Psychiatry 83(2):152–158CrossRefPubMed

Herlenius G, Wilczek HE, Larsson M, Ericzon B-G, Familial Amyloidotic Polyneuropathy World Transplant Registry (2004) Ten years of international experience with liver transplantation for familial amyloidotic polyneuropathy: results from the Familial Amyloidotic Polyneuropathy World Transplant Registry. Transplantation 77(1):64–71CrossRefPubMed

Okamoto S, Wixner J, Obayashi K, Ando Y, Ericzon B-G, Friman S et al (2009) Liver transplantation for familial amyloidotic polyneuropathy: impact on Swedish patients’ survival. Liver Transplant 15(10):1229–1235CrossRef

Suhr OB, Friman S, Ericzon B-G (2005) Early liver transplantation improves familial amyloidotic polyneuropathy patients’ survival. Amyloid 12(4):233–238CrossRefPubMed

Yamashita T, Ando Y, Okamoto S, Misumi Y, Hirahara T, Ueda M et al (2012) Long-term survival after liver transplantation in patients with familial amyloid polyneuropathy. Neurology 78(9):637–643CrossRefPubMed

Adams D, Samuel D, Goulon-Goeau C, Nakazato M, Costa PM, Feray C et al (2000) The course and prognostic factors of familial amyloid polyneuropathy after liver transplantation. Brain 123(Pt 7):1495–1504CrossRefPubMed

Coelho T, Maia LF, Martins da Silva A, Waddington Cruz M, Planté-Bordeneuve V, Lozeron P et al (2012) Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. Neurology 79(8):785–792CrossRefPubMedPubMedCentral

Coelho T, Maia LF, da Silva AM, Cruz MW, Planté-Bordeneuve V, Suhr OB et al (2013) Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy. J Neurol 260(11):2802–2814CrossRefPubMedPubMedCentral

10.

Lozeron P, Théaudin M, Mincheva Z, Ducot B, Lacroix C, Adams D, et al. (2013) Effect on disability and safety of Tafamidis in late onset of Met30 transthyretin familial amyloid polyneuropathy 20(12):1539–45

11.

Merlini G, Planté-Bordeneuve V, Judge DP, Schmidt H, Obici L, Perlini S et al (2013) Effects of tafamidis on transthyretin stabilization and clinical outcomes in patients with non-Val30Met transthyretin amyloidosis. J Cardiovasc Transl Res 6(6):1011–1020CrossRefPubMedPubMedCentral

12.

Mariani LL, Lozeron P, Théaudin M, Mincheva Z, Signate A, Ducot B et al (2015) Genotype-phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France. Ann Neurol 78(6):901–916CrossRefPubMedPubMedCentral

13.

Dyck PJ, Davies JL, Litchy WJ, O’Brien PC (1997) Longitudinal assessment of diabetic polyneuropathy using a composite score in the Rochester Diabetic Neuropathy Study cohort. Neurology 49(1):229–239CrossRefPubMed

14.

Tashima K, Ando Y, Ando E, Tanaka Y, Ando M, Uncino M (1997) Amyloid. Heterogenous clininical symptoms in patients with familial amyloidotic polyneuropathy FAP-TTR Met30 4:108–11

15.

Murphy SM, Herrmann DN, McDermott MP, Scherer SS, Shy ME, Reilly MM et al (2011) Reliability of the CMT neuropathy score (second version) in Charcot-Marie-Tooth disease. J Peripher Nerv Syst 16(3):191–198CrossRefPubMedPubMedCentral

16.

Coutinho P, Martins da Silva A, Lopes Lima J, Resende Barbosa A (1980) Forty years of experience with type I amyloid neuropathy. Review of 483 cases. In: Glenner GG, Pinho e Costa P, de Falcao Freitas A (eds) Amyloid and amyloidosis. Excerpta Medica, Amsterdam, pp 88–98

17.

Ando Y, Coelho T, Berk JL, Cruz MW, Ericzon BG, Ikeda S et al (2013) Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis 8:31CrossRefPubMedPubMedCentral

18.

Suhr OB, Conceição IM, Karayal ON, Mandel FS, Huertas PE, Ericzon B-G (2014) Post hoc analysis of nutritional status in patients with transthyretin familial amyloid polyneuropathy: impact of tafamidis. Neurol Ther 3(2):101–112CrossRefPubMedPubMedCentral

19.

Lehrke S, Steen H, Kristen AV, Merten C, Lossnitzer D, Dengler TJ et al (2009) Serum levels of NT-proBNP as surrogate for cardiac amyloid burden: new evidence from gadolinium-enhanced cardiac magnetic resonance imaging in patients with amyloidosis. Amyloid 16(4):187–195CrossRefPubMed

20.

Cohen J (1997) Statistical power analysis for the behavioral sciences. Academic Press Inc., New York

21.

(1995) Diabetic polyneuropathy in controlled clinical trials: consensus report of the peripheral nerve society. Ann Neurol 38(3):478–82

22.

Adams D, Coelho T, Obici L, Merlini G, Mincheva Z, Suanprasert N et al (2015) Rapid progression of familial amyloidotic polyneuropathy: a multinational natural history study. Neurology 85(8):675–682CrossRefPubMed

23.

Mazzeo A, Russo M, Di Bella G. Transthyretin-related familial amyloid polyneuropathy (TTR-FAP): a single-center experience in Sicily, an Italian endemic area. J Neuromuscul Dis. doi: 10.3233/JND-150091 (in press)

24.

Russo M, Mazzeo A, Stancanelli C, Di Leo R, Gentile L, Di Bella G et al (2012) Transthyretin-related familial amyloidotic polyneuropathy: description of a cohort of patients with Leu64 mutation and late onset. J Peripher Nerv Syst 17(4):385–390CrossRefPubMed

25.

Cappellari M, Cavallaro T, Ferrarini M, Cabrini I, Taioli F, Ferrari S et al (2011) Variable presentations of TTR-related familial amyloid polyneuropathy in seventeen patients. J Peripher Nerv Syst 16(2):119–129CrossRefPubMed

26.

Luigetti M, Conte A, Del Grande A, Bisogni G, Madia F, Lo Monaco M et al (2013) TTR-related amyloid neuropathy: clinical, electrophysiological and pathological findings in 15 unrelated patients. Neurol Sci 34(7):1057–1063CrossRefPubMed

27.

Rapezzi C, Quarta CC, Obici L, Perfetto F, Longhi S, Salvi F et al (2013) Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: an Italian perspective. Eur Heart J 34(7):520–528CrossRefPubMed

28.

Misu KI, Hattori N, Nagamatsu M, Ikeda SI, Ando Y, Nakazato M et al (1999) Late-onset familial amyloid polyneuropathy type I (transthyretin Met30-associated familial amyloid polyneuropathy) unrelated to endemic focus in Japan. Clinicopathological and genetic features. Brain 122(Pt 10):1951–1962CrossRefPubMed

29.

Koike H, Misu K, Sugiura M, Iijima M, Mori K, Yamamoto M et al (2004) Pathology of early- vs late-onset TTR Met30 familial amyloid polyneuropathy. Neurology 63(1):129–138CrossRefPubMed

30.

Sousa MM, Cardoso I, Fernandes R, Guimarães A, Saraiva MJ (2001) Deposition of transthyretin in early stages of familial amyloidotic polyneuropathy: evidence for toxicity of nonfibrillar aggregates. Am J Pathol 159(6):1993–2000CrossRefPubMed

31.

Rajkumar SV, Gertz MA, Kyle RA (1998) Prognosis of patients with primary systemic amyloidosis who present with dominant neuropathy. Am J Med 104(3):232–237CrossRefPubMed

32.

Ericzon B-G, Wilczek HE, Larsson M, Wijayatunga P, Stangou A, Pena JR et al (2015) Liver transplantation for hereditary transthyretin amyloidosis: after 20 years still the best therapeutic alternative? Transplantation 99(9):1847–1854CrossRefPubMed

33.

Palorini R, Cammarata FP, Cammarata F, Balestrieri C, Monestiroli A, Vasso M et al (2013) Glucose starvation induces cell death in K-ras-transformed cells by interfering with the hexosamine biosynthesis pathway and activating the unfolded protein response. Cell Death Dis 4:e732CrossRefPubMedPubMedCentral

Title: Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area
Authors: A. Cortese
G. Vita
M. Luigetti
M. Russo
G. Bisogni
M. Sabatelli
F. Manganelli
L. Santoro
T. Cavallaro
G. M. Fabrizi
A. Schenone
M. Grandis
C. Gemelli
A. Mauro
L. G. Pradotto
L. Gentile
C. Stancanelli
A. Lozza
S. Perlini
G. Piscosquito
D. Calabrese
A. Mazzeo
L. Obici
D. Pareyson
Publication date: 01-05-2016
Publisher: Springer Berlin Heidelberg
Published in: Journal of Neurology / Issue 5/2016
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-016-8064-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2016

Coprophagia in neurologic disorders

Vestibular hypofunction after monosodium glutamate ingestion: broadening the spectrum of ‘Chinese restaurant syndrome’

Expanded phenotypic spectrum of the m.8344A>G “MERRF” mutation: data from the German mitoNET registry

Clinical phenotype and risk of levodopa-induced dyskinesia in Parkinson’s disease

Detection of intrathecal immunoglobulin G synthesis by capillary isoelectric focusing immunoassay in oligoclonal band negative multiple sclerosis

Early infantile neuronal ceroid lipofuscinosis (CLN10 disease) associated with a novel mutation in CTSD