Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009–2019) - 20/04/24

Doi : 10.1016/j.neurol.2024.02.393

D. Adams ^a,⁎ , P. Cintas ^b, G. Solé ^c, C. Tard ^d, C. Labeyrie ^a, A. Echaniz-Laguna ^a, C. Cauquil ^a, Y. Pereon ^e, L. Magy ^f, R. Juntas Morales ^g, J.C. Antoine ^h, E. Lagrange ⁱ, P. Petiot ^j, M. Mallaret ⁱ, B. Francou ^k, A. Guiochon-Mantel ^k, A. Coste ^l, O. Demarcq ^l, C. Geffroy ^l, V. Famelart ^l, J Rudant ^l, M Bartoli ^l, E. Donal ^m, O. Lairez ⁿ, J.C. Eicher ^o, M. Kharoubi ^p, S. Oghina ^p, J.N. Trochu ^q, J. Inamo ^r, G. Habib ^s, F. Roubille ^t, A. Hagège ^u, F. Morio ^q, E. Cariou ⁿ, J. Adda ^v, M.S. Slama ^v, P. Charron ^w, V. Algalarrondo ^v, T. Damy ^p, S. Attarian ^x
^a 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
^b Centre de référence neuromusculaire, CHU de Toulouse, Toulouse, France
^c Referral Center for Neuromuscular Diseases, Pellegrin Hospital, Bordeaux, France
^d Centre de référence des maladies neuromusculaires, CHU de Lille, Lille, France
^e Centre de référence maladies neuromusculaire rares, CHU Nantes, Nantes, France
^f Centre de référence neuropathies périphériques rares, CHU de Limoges, Limoges, France
^g Neurology Department, ALS center, University Hospital of Montpellier, Montpellier, France
^h Centre de référence maladies neuromusculaires rares, CHU de Saint-Étienne, Saint-Étienne, France
ⁱ Neurology Department, CHU Michallon, Grenoble, France
^j Medicine, 64, avenue Rockefeller, Lyon, France
^k Molecular Genetics Pharmacogenomics and Hormonology Department, hôpital Bicêtre, Le Kremlin-Bicêtre, France
^l Pfizer, Paris cedex 14, France
^m University of Rennes, CHU de Rennes, Rennes, France
ⁿ Cardiology Department, Rangueil Hospital, Toulouse, France
^o Cardiology Department, University Hospital of Dijon, Dijon, France
^p Referral Center for Cardiac Amyloidosis, CHU Henri-Mondor, Créteil, France
^q Institut du thorax, CHU de Nantes, Nantes, France
^r Cardiology Department, CHU de Martinique, Martinique, France
^s Cardiology Department, La Timone Hospital, AP–HM, Marseille, France
^t Cardiology Department, CHU de Montpellier, Montpellier, France
^u Cardiology Department, hôpital européen Georges-Pompidou, Paris, France
^v Cardiology Department, hôpital Bichat, Paris, France
^w Hôpital Pitié-Salpêtrière, Sorbonne université, Paris, France
^x Neurology Department, La Timone Hospital, AP–HM, Marseille, France

^⁎Corresponding author.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Saturday 20 April 2024
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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.

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Keywords : Amyloidosis, Polyneuropathy, Real-world data, Tafamidis meglumine, Transthyretin