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

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An Erratum to this article was published on 20 April 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.

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Acknowledgments

The authors thank patients and their families.

Author information

Authors and Affiliations

  1. C. Mondino National Neurological Institute, IRCCS, Pavia, Italy

    A. Cortese & A. Lozza

  2. Department of Neurosciences, University of Messina, Messina, Italy

    G. Vita, L. Gentile, C. Stancanelli & A. Mazzeo

  3. NEMO SUD Center for Neuromuscular Disorders, Fondazione Aurora Onlus, Messina, Italy

    G. Vita & M. Russo

  4. Department of Geriatrics, Neurosciences and Orthopedics, Institute of Neurology, Catholic University of Sacred Heart, Rome, Italy

    M. Luigetti, G. Bisogni & M. Sabatelli

  5. Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy

    F. Manganelli & L. Santoro

  6. Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Verona, Italy

    T. Cavallaro & G. M. Fabrizi

  7. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal Health Sciences, University of Genoa, Genoa, Italy

    A. Schenone, M. Grandis & C. Gemelli

  8. Division of Neurology and Neurorehabilitation, Ospedale San Giuseppe, Istituto Auxologico Italiano, IRCCS, Piancavallo, Verbania, Italy

    A. Mauro & L. G. Pradotto

  9. Biomedical Department of Internal and Specialistic Medicine, University of Palermo, Palermo, Italy

    C. Stancanelli

  10. Clinica Medica II, Department of Internal Medicine, Fondazione Policlinico IRCCS San Matteo, University of Pavia, Pavia, Italy

    S. Perlini

  11. Clinic of Central and Peripheral Degenerative Neuropathies Unit, Department of Clinical Neurosciences, IRCCS Foundation, “C. Besta” Neurological Institute, via Celoria 11, 20133, Milan, Italy

    G. Piscosquito, D. Calabrese & D. Pareyson

  12. Amyloidosis Research and Treatment Center, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy

    L. Obici

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  1. A. Cortese
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Corresponding author

Correspondence to D. Pareyson.

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Conflicts of interest

Massimo Russo, Mario Sabatelli, Fiore Manganelli, Lucio Santoro, Tiziana Cavallaro, Gian Maria Fabrizi, Angelo Schenone, Marina Grandis, Chiara Gemelli, Alessandro Mauro, Luca Guglielmo Pradotto, Luca Gentile, Claudia Stancanelli, Alessandro Lozza, Stefano Perlini, Daniela Calabrese, Anna Mazzeo report no disclosures. Andrea Cortese, Giulia Bisogni, Marco Luigetti, Giuseppe Piscosquito, Davide Pareyson received travel grants from Pfizer. Giuseppe Vita and Davide Pareyson received research grants from Pfizer. Laura Obici received financial support from Alnylam to attend scientific meetings and received honoraria from Pfizer for lectures.

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This study was approved by ethics committees of participating centres.

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Written informed consent was obtained from all patients.

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Cortese, A., Vita, G., Luigetti, M. et al. Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area. J Neurol 263, 916–924 (2016). https://doi.org/10.1007/s00415-016-8064-9

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  • DOI: https://doi.org/10.1007/s00415-016-8064-9

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