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

Andrea Cortese, G. Vita, Marco Luigetti, M. Russo, Giulia Bisogni, M. Sabatelli, Fiore Manganelli, L. Santoro, Tiziana Cavallaro, G. M. Fabrizi, Angelo Schenone, M. Grandis, Chiara Gemelli, Alessandro Mauro, Luca Pradotto, Luca Gentile, Claudia Stancanelli, Alessandro Lozza, Stefano Perlini, Giuseppe PiscosquitoDaniela Calabrese, A. Mazzeo, Laura Piera Obici, Davide Pareyson

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalJournal of Neurology
DOIs
Publication statusAccepted/In press - Mar 16 2016

Keywords

  • Amyloid polyneuropathy
  • Tafamidis
  • Transthyretin

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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    Cortese, A., Vita, G., Luigetti, M., Russo, M., Bisogni, G., Sabatelli, M., Manganelli, F., Santoro, L., Cavallaro, T., Fabrizi, G. M., Schenone, A., Grandis, M., Gemelli, C., Mauro, A., Pradotto, L., Gentile, L., Stancanelli, C., Lozza, A., Perlini, S., ... Pareyson, D. (Accepted/In press). Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area. Journal of Neurology, 1-9. https://doi.org/10.1007/s00415-016-8064-9