Skip to main content

Advertisement

SpringerLink
Log in

Long-term treatment of hereditary transthyretin amyloidosis with patisiran: multicentre, real-world experience in Italy

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Background

Hereditary transthyretin (ATTRv, v for variant) amyloidosis with polyneuropathy is a rare disease caused by mutations in the transthyretin gene. In ATTRv amyloidosis, multisystem extracellular deposits of amyloid cause tissue and organ dysfunction. Patisiran is a small interfering RNA molecule drug that reduces circulating levels of mutant and wild-type TTR proteins. Prior to its regulatory approval, patisiran was available in Italy through a compassionate use programme (CUP). The aim of this study was to analyse the long-term outcomes of patients who entered into the CUP.

Methods

This was a multicentre, observational, retrospective study of patients with ATTRv amyloidosis treated with patisiran. The analysis included change from baseline to 12, 24, 36 and 48 months in familial amyloid polyneuropathy (FAP) stage, polyneuropathy disability (PND) class, neuropathy impairment score (NIS), modified body mass index (mBMI), Compound Autonomic Dysfunction Test (CADT), Karnofsky Performance Status (KPS) scale and Norfolk Quality of Life–Diabetic Neuropathy (QoL-DN) questionnaire. Safety data were also analysed.

Results

Forty patients from 11 Italian centres were enrolled: 23 in FAP 1 (6 in PND 1 and 17 in PND 2) and 17 in FAP 2 (8 in PND 3a and 9 in PND 3b) stage. In this population, the mean NIS at baseline was 71.4 (± 27.8); mBMI, 917.1 (± 207) kg/m2; KPS, 67.1 (± 14.0); Norfolk QoL-DN, 62.2 (± 25.2); and CADT, 13.2 (± 3.3). Statistical analysis showed few significant differences from baseline denoting disease stability. No new safety signals emerged.

Conclusions

Patisiran largely stabilised disease in patients with ATTRv amyloidosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author upon reasonable request.

References

  1. Luigetti M, Romano A, Di Paolantonio A, Bisogni G, Sabatelli M (2020) Diagnosis and treatment of hereditary transthyretin amyloidosis (hATTR) polyneuropathy: current perspectives on improving patient care. Ther Clin Risk Manag 16:109–123. https://doi.org/10.2147/TCRM.S219979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Koike H, Katsuno M (2020) Transthyretin amyloidosis: update on the clinical spectrum, pathogenesis, and disease-modifying therapies. Neurol Ther 9(2):317–333. https://doi.org/10.1007/s40120-020-00210-7

    Article  PubMed  PubMed Central  Google Scholar 

  3. Coelho T, Ines M, Conceicao I, Soares M, de Carvalho M, Costa J (2018) Natural history and survival in stage 1 Val30Met transthyretin familial amyloid polyneuropathy. Neurology 91(21):e1999–e2009. https://doi.org/10.1212/WNL.0000000000006543

    Article  CAS  PubMed  Google Scholar 

  4. Adams D, Coelho T, Obici L, Merlini G, Mincheva Z, Suanprasert N, Bettencourt BR, Gollob JA, Gandhi PJ, Litchy WJ, Dyck PJ (2015) Rapid progression of familial amyloidotic polyneuropathy: a multinational natural history study. Neurology 85(8):675–682. https://doi.org/10.1212/WNL.0000000000001870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Benson MD, Kincaid JC (2007) The molecular biology and clinical features of amyloid neuropathy. Muscle Nerve 36(4):411–423. https://doi.org/10.1002/mus.20821

    Article  CAS  PubMed  Google Scholar 

  6. Manganelli F, Fabrizi GM, Luigetti M, Mandich P, Mazzeo A, Pareyson D (2022) Hereditary transthyretin amyloidosis overview. Neurol Sci 43(Suppl 2):595–604. https://doi.org/10.1007/s10072-020-04889-2

    Article  PubMed  Google Scholar 

  7. Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS (2019) Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol 73(22):2872–2891. https://doi.org/10.1016/j.jacc.2019.04.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sousa MM, Cardoso I, Fernandes R, Guimaraes 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):1993–2000. https://doi.org/10.1016/s0002-9440(10)63050-7

    Article  CAS  PubMed  Google Scholar 

  9. Gonzalez-Duarte A (2019) Autonomic involvement in hereditary transthyretin amyloidosis (hATTR amyloidosis). Clin Auton Res 29(2):245–251. https://doi.org/10.1007/s10286-018-0514-2

    Article  PubMed  Google Scholar 

  10. Ferraro PM, D'Ambrosio V, Di Paolantonio A, Guglielmino V, Calabresi P, Sabatelli M, Luigetti M (2021) Renal involvement in hereditary transthyretin amyloidosis: an Italian single-centre experience. Brain Sci 11(8). https://doi.org/10.3390/brainsci11080980

  11. Luigetti M, Romozzi M, Bisogni G, Cardellini D, Cavallaro T, Di Paolantonio A, Fabrizi GM, Fenu S, Gentile L, Grandis M, Marucci G, Massucco S, Mazzeo A, Pareyson D, Romano A, Russo M, Schenone A, Tagliapietra M, Tozza S, Vita G, Sabatelli M (2020) hATTR pathology: nerve biopsy results from Italian referral centers. Brain Sci 10(11):780. https://doi.org/10.3390/brainsci10110780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Luigetti M, Tortora A, Romano A, Di Paolantonio A, Guglielmino V, Bisogni G, Gasbarrini A, Calabresi P, Sabatelli M (2020) Gastrointestinal manifestations in hereditary transthyretin amyloidosis: a single-centre experience. J Gastrointestin Liver Dis 29(3):339–43. https://doi.org/10.15403/jgld-2474

    Article  PubMed  Google Scholar 

  13. Plante-Bordeneuve V, Said G (2011) Familial amyloid polyneuropathy. Lancet Neurol 10(12):1086–1097. https://doi.org/10.1016/S1474-4422(11)70246-0

    Article  CAS  PubMed  Google Scholar 

  14. Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, Grogan M, Witteles R, Damy T, Drachman BM, Shah SJ, Hanna M, Judge DP, Barsdorf AI, Huber P, Patterson TA, Riley S, Schumacher J, Stewart M, Sultan MB, Rapezzi C, Investigators A-AS (2018) Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med 379(11):1007–16. https://doi.org/10.1056/NEJMoa1805689

    Article  CAS  PubMed  Google Scholar 

  15. Cantone A, Sanguettoli F, Dal Passo B, Serenelli M, Rapezzi C (2022) The treatment of amyloidosis is being refined. Eur Heart J Suppl 24(Suppl I):I131–I138. https://doi.org/10.1093/eurheartjsupp/suac104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Padda IS, Mahtani AU, Parmar M (2023) Small Interfering RNA (siRNA) Based therapy. StatPearls [Internet]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing

  17. Adams D, Gonzalez-Duarte A, O’Riordan WD, Yang CC, Ueda M, Kristen AV, Tournev I, Schmidt HH, Coelho T, Berk JL, Lin KP, Vita G, Attarian S, Plante-Bordeneuve V, Mezei MM, Campistol JM, Buades J, Brannagan TH 3rd, Kim BJ, Oh J, Parman Y, Sekijima Y, Hawkins PN, Solomon SD, Polydefkis M, Dyck PJ, Gandhi PJ, Goyal S, Chen J, Strahs AL, Nochur SV, Sweetser MT, Garg PP, Vaishnaw AK, Gollob JA, Suhr OB (2018) Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med 379(1):11–21. https://doi.org/10.1056/NEJMoa1716153

    Article  CAS  PubMed  Google Scholar 

  18. Adams D, Polydefkis M, Gonzalez-Duarte A, Wixner J, Kristen AV, Schmidt HH, Berk JL, Losada Lopez IA, Dispenzieri A, Quan D, Conceicao IM, Slama MS, Gillmore JD, Kyriakides T, Ajroud-Driss S, Waddington-Cruz M, Mezei MM, Plante-Bordeneuve V, Attarian S, Mauricio E, Brannagan TH 3rd, Ueda M, Aldinc E, Wang JJ, White MT, Vest J, Berber E, Sweetser MT, Coelho T, patisiran Global OLEsg (2021) Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study. Lancet Neurol 20(1):49–59. https://doi.org/10.1016/S1474-4422(20)30368-9

    Article  CAS  PubMed  Google Scholar 

  19. Coelho T, Adams D, Silva A, Lozeron P, Hawkins PN, Mant T, Perez J, Chiesa J, Warrington S, Tranter E, Munisamy M, Falzone R, Harrop J, Cehelsky J, Bettencourt BR, Geissler M, Butler JS, Sehgal A, Meyers RE, Chen Q, Borland T, Hutabarat RM, Clausen VA, Alvarez R, Fitzgerald K, Gamba-Vitalo C, Nochur SV, Vaishnaw AK, Sah DW, Gollob JA, Suhr OB (2013) Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med 369(9):819–829. https://doi.org/10.1056/NEJMoa1208760

    Article  CAS  PubMed  Google Scholar 

  20. Di Stefano V, Fava A, Gentile L, Guaraldi P, Leonardi L, Poli L, Tagliapietra M, Vastola M, Fanara S, Ferrero B, Giorgi M, Perfetto F, Russo M, Russo D (2022) Italian real-life experience of patients with hereditary transthyretin amyloidosis treated with patisiran. Pharmgenomics Pers Med 15:499–514. https://doi.org/10.2147/PGPM.S359851

    Article  PubMed  PubMed Central  Google Scholar 

  21. Suhr OB, Coelho T, Buades J, Pouget J, Conceicao I, Berk J, Schmidt H, Waddington-Cruz M, Campistol JM, Bettencourt BR, Vaishnaw A, Gollob J, Adams D (2015) Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study. Orphanet J Rare Dis 10:109. https://doi.org/10.1186/s13023-015-0326-6

    Article  PubMed  PubMed Central  Google Scholar 

  22. Luigetti M, Wixner J, Ueda M, Marquez W Jr, Dalia S, Arum S, Hale C, Jay P, Capocelli K, Adams D (2023) Patisiran global open-label extension study at 36 months: effect of long-term treatment on mortality and ambulatory function in patients with hATTR amyloidosis with polyneuropathy. J Peripher Nerv Syst 28(Suppl 2):S35. https://doi.org/10.1111/jns.12550

    Article  Google Scholar 

  23. Gentile L, Russo M, Luigetti M, Bisogni G, Di Paolantonio A, Romano A, Guglielmino V, Arimatea I, Sabatelli M, Toscano A, Vita G, Mazzeo A (2021) Patisiran in hATTR amyloidosis: six-month latency period before efficacy. Brain Sci 11(4):515. https://doi.org/10.3390/brainsci11040515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Coutinho PM, Martins da Silva A, Lopes JL, Barbarosa AR (1980) Forty years of experience with type I amyloid neuropathy. Review of 483 cases. In: Glenner GG, Costa PP, de Freitas AF (eds) Amyloid amyloidosis. Excerpta Medica, Amsterdam. https://www.spmi.pt/wp-content/uploads/2019/10/9.-Amyloid-and-Amyloidosis-1979.pdf

  25. Yamamoto S, Wilczek HE, Nowak G, Larsson M, Oksanen A, Iwata T, Gjertsen H, Soderdahl G, Wikstrom L, Ando Y, Suhr OB, Ericzon BG (2007) Liver transplantation for familial amyloidotic polyneuropathy (FAP): a single-center experience over 16 years. Am J Transplant 7(11):2597–2604. https://doi.org/10.1111/j.1600-6143.2007.01969.x

    Article  CAS  PubMed  Google Scholar 

  26. Dyck PJ, Boes CJ, Mulder D, Millikan C, Windebank AJ, Dyck PJ, Espinosa R (2005) History of standard scoring, notation, and summation of neuromuscular signs. A current survey and recommendation. J Peripher Nerv Syst 10(2):158–73. https://doi.org/10.1111/j.1085-9489.2005.0010206.x

    Article  PubMed  Google Scholar 

  27. Denier C, Ducot B, Husson H, Lozeron P, Adams D, Meyer L, Said G, Plante-Bordeneuve V (2007) A brief compound test for assessment of autonomic and sensory-motor dysfunction in familial amyloid polyneuropathy. J Neurol 254(12):1684–1688. https://doi.org/10.1007/s00415-007-0617-5

    Article  CAS  PubMed  Google Scholar 

  28. Karnofsky DA, Burchenal JH (1949) The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod CM (ed) Evaluation of chemotherapeutic agents. Columbia University Press, New York, p 196

  29. Vinik EJ, Hayes RP, Oglesby A, Bastyr E, Barlow P, Ford-Molvik SL, Vinik AI (2005) The development and validation of the Norfolk QOL-DN, a new measure of patients’ perception of the effects of diabetes and diabetic neuropathy. Diabetes Technol Ther 7(3):497–508. https://doi.org/10.1089/dia.2005.7.497

    Article  PubMed  Google Scholar 

  30. ClinTrials.gov. The study of an investigational drug, patisiran (ALN-TTR02), for the treatment of transthyretin (TTR)-mediated amyloidosis in participants who have already been treated with ALN-TTR02 (patisiran) [Internet]. ClinicalTrials.gov. 2023. Available from: https://clinicaltrials.gov/study/NCT02510261?tab=results#outcome-measures. Accessed 26 Feb 2024

  31. de Frutos F, Ochoa JP, Gomez-Gonzalez C, Reyes-Leiva D, Arostegui JI, Casasnovas C, Barriales-Villa R, Sevilla T, Gonzalez-Lopez E, Ramil E, Galan L, Gonzalez-Costello J, Garcia-Alvarez A, Rojas-Garcia R, Espinosa MA, Garcia-Pavia P (2023) Phenotype and clinical outcomes of Glu89Lys hereditary transthyretin amyloidosis: a new endemic variant in Spain. Amyloid 30(2):199–207. https://doi.org/10.1080/13506129.2022.2142110

    Article  PubMed  Google Scholar 

  32. Labeyrie C, Merkel M, Sethi S, Popadic L, Yang H, Lin H, Adams D (2022) Effectiveness of patisiran following switch from tafamidis for the treatment of heredirary transthyretin-mediatied (hATTR) amyloidosis with polyneuropathy. XVIII International Symposium on Amyloidosis, 4th–8th September 2022, Heidelberg, Germany

  33. Quan D, Obici L, Berk JL, Ando Y, Aldinc E, White MT, Adams D (2023) Impact of baseline polyneuropathy severity on patisiran treatment outcomes in the APOLLO trial. Amyloid 30(1):49–58. https://doi.org/10.1080/13506129.2022.2118043

    Article  PubMed  Google Scholar 

  34. De Bleecker JL, Claeys KG, Delstanche S, Van Parys V, Baets J, Tilleux S, Remiche G (2023) A retrospective survey of patients with hereditary transthyretin-mediated (hATTR) amyloidosis treated with patisiran in real-world clinical practice in Belgium. Acta Neurol Belg 123(3):1029–1037. https://doi.org/10.1007/s13760-023-02188-z

    Article  PubMed  PubMed Central  Google Scholar 

  35. Schmidt HH, Wixner J, Plante-Bordeneuve V, Munoz-Beamud F, Llado L, Gillmore JD, Mazzeo A, Li X, Arum S, Jay PY, Adams D, Patisiran Post LTSG (2022) Patisiran treatment in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy after liver transplantation. Am J Transplant 22(6):1646–57. https://doi.org/10.1111/ajt.17009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yarlas A, Gertz MA, Dasgupta NR, Obici L, Pollock M, Ackermann EJ, Lovley A, Kessler AS, Patel PA, White MK, Guthrie SD (2019) Burden of hereditary transthyretin amyloidosis on quality of life. Muscle Nerve 60(2):169–175. https://doi.org/10.1002/mus.26515

    Article  PubMed  PubMed Central  Google Scholar 

  37. Brannagan TH 3rd, Auer-Grumbach M, Berk JL, Briani C, Bril V, Coelho T, Damy T, Dispenzieri A, Drachman BM, Fine N, Gaggin HK, Gertz M, Gillmore JD, Gonzalez E, Hanna M, Hurwitz DR, Khella SL, Maurer MS, Nativi-Nicolau J, Olugemo K, Quintana LF, Rosen AM, Schmidt HH, Shehata J, Waddington-Cruz M, Whelan C, Ruberg FL (2021) ATTR amyloidosis during the COVID-19 pandemic: insights from a global medical roundtable. Orphanet J Rare Dis 16(1):204. https://doi.org/10.1186/s13023-021-01834-0

    Article  PubMed  PubMed Central  Google Scholar 

  38. Gonzalez-Duarte A, Berk JL, Quan D, Mauermann ML, Schmidt HH, Polydefkis M, Waddington-Cruz M, Ueda M, Conceicao IM, Kristen AV, Coelho T, Cauquil CA, Tard C, Merkel M, Aldinc E, Chen J, Sweetser MT, Wang JJ, Adams D (2020) Analysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis. J Neurol 267(3):703–712. https://doi.org/10.1007/s00415-019-09602-8

    Article  CAS  PubMed  Google Scholar 

  39. EMA. ONPATTRO, INN-patisiran. Summary of Product Characteristics (2018) [Available from: https://www.ema.europa.eu/en/documents/product-information/onpattro-epar-product-information_en.pdf.]  Accessed 20 Jun 2023

Download references

Acknowledgements

The paper was written by Alicja M. Gruszka, an independent medical writer on behalf of Springer Healthcare. This writing assistance was sponsored by Alnylam.

Author information

Authors and Affiliations

  1. Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

    Luca Gentile, Anna Mazzeo, Marcella De Luca, Giacomo Iabichella, Giuseppe Occhipinti & Massimo Russo

  2. Department of Neurosciences, Neurology Unit, University of Padova, Padua, Italy

    Chiara Briani & Alessandro Salvalaggio

  3. Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy

    Silvia Casagrande

  4. Department of Neurological Sciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy

    Gian Maria Fabrizi & Matteo Tagliapietra

  5. Cardiology Unit, IRCCS Azienda Ospedaliero-Universitaria of Bologna, Bologna, Italy

    Christian Gagliardi

  6. IRCCS Policlinico San Martino Hospital, Genoa, Italy

    Chiara Gemelli & Marina Grandis

  7. Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, Rome, Italy

    Francesca Forcina & Luca Leonardi

  8. Dipartimento Di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili, Università Di Genova, Genoa, Italy

    Marina Grandis

  9. Dipartimento Di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy

    Valeria Guglielmino & Marco Luigetti

  10. Amyloidosis Research and Treatment Centre, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy

    Alessandro Lozza, Roberta Mussinelli, Giovanni Palladini & Laura Obici

  11. Department of Neuroscience, Reproductive and Odontostomatological Science, University of Naples “Federico II”, Naples, Italy

    Fiore Manganelli & Stefano Tozza

  12. Department of Neurology, “Vito Fazzi” Hospital, Lecce, Italy

    Filomena My

  13. S.C. Malattie Neurologiche Rare, Dipartimento di Neuroscienze Cliniche, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Silvia Fenu

  14. Dipartimento Di Neuroscienze, Organi Di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy

    Angela Romano & Marco Luigetti

  15. Department of Molecular Medicine, University of Pavia, Pavia, Italy

    Giovanni Palladini

Authors
  1. Luca Gentile
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna Mazzeo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chiara Briani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Silvia Casagrande
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marcella De Luca
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gian Maria Fabrizi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christian Gagliardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chiara Gemelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Francesca Forcina
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Marina Grandis
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Valeria Guglielmino
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Giacomo Iabichella
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Luca Leonardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Alessandro Lozza
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Fiore Manganelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Roberta Mussinelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Filomena My
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Giuseppe Occhipinti
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Silvia Fenu
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Massimo Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Angela Romano
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Alessandro Salvalaggio
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Matteo Tagliapietra
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Stefano Tozza
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Giovanni Palladini
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Laura Obici
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Marco Luigetti
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualisation: Luca Gentile, Anna Mazzeo, Fiore Manganelli, Laura Obici, Marco Luigetti. Methodology: Luca Gentile, Anna Mazzeo, Fiore Manganelli, Laura Obici, Marco Luigetti. Formal analysis and investigation: Luca Gentile, Anna Mazzeo, Fiore Manganelli, Laura Obici, Marco Luigetti. Writing—original draft preparation: Luca Gentile, Anna Mazzeo, Fiore Manganelli, Laura Obici, Marco Luigetti. Writing—review and editing: all authors. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Laura Obici.

Ethics declarations

Conflict of interest

Dr Luigetti received financial grants (honoraria and speaking) from Ackea, Alnylam, Sobi, and Pfizer, and travel grants from Ackea, Alnylam, Sobi, Pfizer, Kedrion and Grifols.

Dr. Gentile received financial grants (honoraria and speaking) from Akcea, Alnylam, and Pfizer, and travel grants from Alnylam and CSL Behring.

Dr. Mazzeo received speaker fees and consulting honoraria from Alnylam Pharmaceuticals, Akcea Therapeutics, and Pfizer Inc.

Dr. Manganelli has no conflict of interest to declare.

Dr Obici reports speaker and consulting honoraria from Pfizer, Alnylam, SOBI, Novo Nordisk, Astra Zeneca and BridgeBio.

Dr. Briani received speaker and consulting honoraria from Alnylam, Ionis, and Pfizer, and travel grants from Kedrion, Alnylam and CSL Behring.

Dr. Casagrande has no conflict of interest to declare.

Dr. De Luca received financial grants (speaking) from Pfizer, and travel grants to attend scientific meetings from Pfizer and SOBI.

Dr. Fabrizi received financial grants (honoraria and speaking) from Akcea, Alnylam and travel grants from Akcea, Pfizer and Kedrion.

Dr. Gagliardi received financial grants (consulting and speaking) from Pfizer and Alnylam.

Dr. Gemelli received financial grants (speaking) from Italfarmaco, and travel grants from Biogen for participation in national meetings.

Dr. Forcina has no conflict of interest to declare.

Dr. Grandis acknowledges donations from Sanofi Genzyme to support research activities of her Research Unit. Financial support from Pfizer, Alnylam and Sanofi Genzyme for participation in National and International Meetings. Participation in Advisory Board of Pfizer and Argenx. Speaker honorarium from Sanofi Genzyme and Alexion.

Dr. Guglielmino has no conflict of interest to declare.

Dr. Iabichella received travel grants to attend scientific meetings from Alnylam and SOBI.

Dr. Leonardi received financial grants (honoraria and speaking) from Alnylam, and travel grants to attend scientific meetings from Akcea, SOBI, Alnylam.

Dr. Lozza has no conflict of interest to declare.

Dr. Mussinelli received financial grants (speaking) from Pfizer and SOBI, and travel grants to attend scientific meetings from Alnylam.

Dr. My received financial grants (honoraria and speaking) from Alnylam, and travel grants to attend scientific meetings from Alnylam.

Dr. Occhipinti has no conflict of interest to declare.

Dr. Fenu acknowledges financial support from Alnylam and Pfizer for participation in national and international meetings.

Dr. Russo has no conflict of interest to declare.

Dr. Romano received financial grants (honoraria and speaking) from Akcea, and travel grants to attend scientific meetings from Akcea, Alnylam, Pfizer, and Csl Behring.

Dr. Salvalaggio received travel grant to attend scientific meeting from Alnylam.

Dr. Stefano Tozza received personal fees for scientific events from Alnylam Pharmaceuticals, Amicus Therapeutics and Takeda Pharmaceutical Co, travel grants to attend scientific meetings from Akcea Therapeutics.

Ethical approval

The study protocol was approved by Ethics Committee of Unit of Neurology and Neuromuscular Diseases, AOU G. Martino, Messina, i.e., the coordinating centre (protocol number: 109-21) and subsequently by the Ethics Committees of the participating centres.

Informed consent

Participants provided informed consent.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 7045 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gentile, L., Mazzeo, A., Briani, C. et al. Long-term treatment of hereditary transthyretin amyloidosis with patisiran: multicentre, real-world experience in Italy. Neurol Sci (2024). https://doi.org/10.1007/s10072-024-07494-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10072-024-07494-9

Keywords

Search

Navigation