Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009-2019)

D Adams; P Cintas; G Solé; C Tard; C Labeyrie; A Echaniz-Laguna; C Cauquil; Y Pereon; L Magy; R Juntas Morales; J C Antoine; E Lagrange; P Petiot; M Mallaret; B Francou; A Guiochon-Mantel; A Coste; O Demarcq; C Geffroy; V Famelart; J Rudant; M Bartoli; E Donal; O Lairez; J C Eicher; M Kharoubi; S Oghina; J N Trochu; J Inamo; G Habib; F Roubille; A Hagège; F Morio; E Cariou; J Adda; M S Slama; P Charron; V Algalarrondo; T Damy; S Attarian

doi:10.1016/j.neurol.2024.02.393

Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009-2019)

Rev Neurol (Paris). 2024 Apr 19:S0035-3787(24)00489-2. doi: 10.1016/j.neurol.2024.02.393. Online ahead of print.

Authors

D Adams¹, P Cintas², G Solé³, C Tard⁴, C Labeyrie⁵, A Echaniz-Laguna⁵, C Cauquil⁵, Y Pereon⁶, L Magy⁷, R Juntas Morales⁸, J C Antoine⁹, E Lagrange¹⁰, P Petiot¹¹, M Mallaret¹⁰, B Francou¹², A Guiochon-Mantel¹², A Coste¹³, O Demarcq¹³, C Geffroy¹³, V Famelart¹³, J Rudant¹³, M Bartoli¹³, E Donal¹⁴, O Lairez¹⁵, J C Eicher¹⁶, M Kharoubi¹⁷, S Oghina¹⁷, J N Trochu¹⁸, J Inamo¹⁹, G Habib²⁰, F Roubille²¹, A Hagège²², F Morio¹⁸, E Cariou¹⁵, J Adda²³, M S Slama²³, P Charron²⁴, V Algalarrondo²³, T Damy¹⁷, S Attarian²⁵

Affiliations

¹ Department of Neurology, French Reference Center for Familial Amyloid Polyneuropathy, AP-HP, CHU de Bicêtre, University Paris-Saclay, Inserm U 1195, 78, rue du Général Leclerc, 94270 Le Kremlin-Bicêtre, France. Electronic address: david.adams@aphp.fr.
² Centre de référence neuromusculaire, CHU de Toulouse, Toulouse, France.
³ Referral Center for Neuromuscular Diseases, Pellegrin Hospital, Bordeaux, France.
⁴ Centre de référence des maladies neuromusculaires, CHU de Lille, Lille, France.
⁵ Department of Neurology, French Reference Center for Familial Amyloid Polyneuropathy, AP-HP, CHU de Bicêtre, University Paris-Saclay, Inserm U 1195, 78, rue du Général Leclerc, 94270 Le Kremlin-Bicêtre, France.
⁶ Centre de référence maladies neuromusculaire rares, CHU Nantes, Nantes, France.
⁷ Centre de référence neuropathies périphériques rares, CHU de Limoges, Limoges, France.
⁸ Neurology Department, ALS center, University Hospital of Montpellier, Montpellier, France.
⁹ Centre de référence maladies neuromusculaires rares, CHU de Saint-Étienne, Saint-Étienne, France.
¹⁰ Neurology Department, CHU Michallon, Grenoble, France.
¹¹ Medicine, 64, avenue Rockefeller, Lyon, France.
¹² Molecular Genetics Pharmacogenomics and Hormonology Department, hôpital Bicêtre, Le Kremlin-Bicêtre, France.
¹³ Pfizer, Paris cedex 14, France.
¹⁴ University of Rennes, CHU de Rennes, Rennes, France.
¹⁵ Cardiology Department, Rangueil Hospital, Toulouse, France.
¹⁶ Cardiology Department, University Hospital of Dijon, Dijon, France.
¹⁷ Referral Center for Cardiac Amyloidosis, CHU Henri-Mondor, Créteil, France.
¹⁸ Institut du thorax, CHU de Nantes, Nantes, France.
¹⁹ Cardiology Department, CHU de Martinique, Martinique, France.
²⁰ Cardiology Department, La Timone Hospital, AP-HM, Marseille, France.
²¹ Cardiology Department, CHU de Montpellier, Montpellier, France.
²² Cardiology Department, hôpital européen Georges-Pompidou, Paris, France.
²³ Cardiology Department, hôpital Bichat, Paris, France.
²⁴ Hôpital Pitié-Salpêtrière, Sorbonne université, Paris, France.
²⁵ Neurology Department, La Timone Hospital, AP-HM, Marseille, France.

PMID: 38643028
DOI: 10.1016/j.neurol.2024.02.393

Abstract

Objective: We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg.

Methods: Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance.

Results: Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2±17.2 years. Interval between first symptom(s) and diagnosis was 3.4±4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8-100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients.

Conclusion: In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.

Keywords: Amyloidosis; Polyneuropathy; Real-world data; Tafamidis meglumine; Transthyretin.