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Analysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis.
González-Duarte, Alejandra; Berk, John L; Quan, Dianna; Mauermann, Michelle L; Schmidt, Hartmut H; Polydefkis, Michael; Waddington-Cruz, Márcia; Ueda, Mitsuharu; Conceição, Isabel M; Kristen, Arnt V; Coelho, Teresa; Cauquil, Cécile A; Tard, Céline; Merkel, Madeline; Aldinc, Emre; Chen, Jihong; Sweetser, Marianne T; Wang, Jing Jing; Adams, David.
Afiliação
  • González-Duarte A; Instituto Nacional de Ciencias Médicas Y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Sección XVI, Tlalpan, CdMx, CP 01400, México City, Mexico. gonzalezduarte@aol.com.
  • Berk JL; Boston Medical Center, Boston, MA, USA.
  • Quan D; University of Colorado, Denver, CO, USA.
  • Mauermann ML; Mayo Clinic, Rochester, MN, USA.
  • Schmidt HH; University of Münster, Münster, Germany.
  • Polydefkis M; Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Waddington-Cruz M; Hospital Universitário Clementino Fraga Filho-UFRJ, Rio de Janeiro, Brazil.
  • Ueda M; Kumamoto University Hospital, Kumamoto, Japan.
  • Conceição IM; CHULN, Hospital de Santa Maria and Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
  • Kristen AV; University of Heidelberg, Heidelberg, Germany.
  • Coelho T; Hospital de Santo António, Centro Hospitalar Universitário Do Porto, Porto, Portugal.
  • Cauquil CA; AP-HP Université Paris Saclay, CHU Bicêtre, Le Kremlin Bicêtre, France.
  • Tard C; Université de Lille, Lille, France.
  • Merkel M; Alnylam Pharmaceuticals, Cambridge, MA, USA.
  • Aldinc E; Alnylam Pharmaceuticals, Cambridge, MA, USA.
  • Chen J; Alnylam Pharmaceuticals, Cambridge, MA, USA.
  • Sweetser MT; Alnylam Pharmaceuticals, Cambridge, MA, USA.
  • Wang JJ; Alnylam Pharmaceuticals, Cambridge, MA, USA.
  • Adams D; AP-HP, Université Paris Saclay, CHU Bicêtre, Université Paris-Sud, INSERM 1195, Paris, France.
J Neurol ; 267(3): 703-712, 2020 Mar.
Article em En | MEDLINE | ID: mdl-31728713
Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, - 7.5; 95% CI: - 11.9, - 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, - 1.1; - 1.8, - 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; - 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, - 0.3; - 0.5, - 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, - 5.3; 95% CI: - 7.9, - 2.7) and individual domains, orthostatic intolerance (- 4.6; - 6.3, - 2.9) and gastrointestinal symptoms (- 0.8; - 1.5, - 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças do Sistema Nervoso Autônomo / Neuropatias Amiloides Familiares / RNA Interferente Pequeno Tipo de estudo: Clinical_trials / Etiology_studies Aspecto: Patient_preference Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Neurol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: México País de publicação: Alemanha
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças do Sistema Nervoso Autônomo / Neuropatias Amiloides Familiares / RNA Interferente Pequeno Tipo de estudo: Clinical_trials / Etiology_studies Aspecto: Patient_preference Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Neurol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: México País de publicação: Alemanha