Drug, Healthcare and Patient Safety (Feb 2023)
Updated Evaluation of the Safety, Efficacy and Tolerability of Tafamidis in the Treatment of Hereditary Transthyretin Amyloid Polyneuropathy
Abstract
Catarina Falcão de Campos,1,2 Isabel Conceição1,2 1Department of Neurosciences and Mental Health, Centro Hospitalar Universitário de Lisboa-Norte, Lisbon, Portugal; 2Instituto de Fisiologia, Instituto de Medicina Molecular, Centro de Estudos Egas Moniz, Faculdade de Medicina, Universidade de Lisboa, Lisbon, PortugalCorrespondence: Catarina Falcão de Campos, Department of Neurosciences, Hospital de Santa Maria, Av. Professor Egas Moniz, Lisbon, 1648-028, Portugal, Tel/Fax + 351 21 780521, Email [email protected]: Hereditary amyloid transthyretin (ATTRv) amyloidosis is a devastating hereditary multisystemic disease affecting predominantly the peripheral and autonomic nervous systems and the heart. ATTRv is caused by mutations in the transthyretin (TTR) gene, leading to extracellular deposition of amyloid fibrils in multiple organs including the peripheral nervous system. If untreated, it is associated with a fatal outcome 10– 12 years after disease onset. Different treatments are available for patients with ATTRv polyneuropathy. Tafamidis 20 mg is approved in Europe since 2011 for early stages of ATTRv polyneuropathy (stage I – able to walk without support) and it is recommended as first-line therapy in these patients. Tafamidis is a TTR stabilizer that selectively binds to TTR and kinetically stabilizes both wild-type native TTR and mutant TTR. Consequently, it has the potential to prevent the amyloidogenic cascade initiated by TTR tetramer dissociation into its monomers and subsequent misfolding and aggregation. Tafamidis is an oral drug, taken once per day, with proved efficacy, safety and tolerability in ATTRv-PN patients as demonstrated in different clinical trials and open-label extension studies as well in clinical practice setting with around 10 years of experience. Tafamidis treatment started in the earliest stages of the disease is associated with better neurological outcomes. A multidisciplinary approach in referral centres is also fundamental for monitoring patients to assess individual response to treatment.Keywords: hereditary amyloid transthyretin amyloidosis, transthyretin, tafamidis, familial amyloid polyneuropathy, amyloidosis, TTR stabilizer
