Quality of life outcomes in APOLLO, the phase 3 trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

• Autor(a) principal: Obici, Laura
• Data de Publicação: 2020
• Outros Autores: Berk, John L, González-Duarte, Alejandra, Coelho, Teresa, Gillmore, Julian, Schmidt, Hartmut H-J, Schilling, Matthias, Yamashita, Taro, Labeyrie, Céline, Brannagan, Thomas H, Ajroud-Driss, Senda, Gorevic, Peter, Kristen, Arnt V, Franklin, Jaclyn, Chen, Jihong, Sweetser, Marianne T, Wang, Jing Jing, Adams, David
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.16/2481
• topic: APOLLO; Norfolk QOL-DN; hereditary transthyretin-mediated amyloidosis; patisiran; quality of life

Introduction: Hereditary transthyretin-mediated (hATTR) amyloidosis is a rare, fatal, multisystem disease leading to deteriorating quality of life (QOL). The impact of patisiran on QOL in patients with hATTR amyloidosis with polyneuropathy from the phase 3 APOLLO study (NCT01960348) is evaluated.Methods: Patients received either patisiran 0.3 mg/kg (n = 148) or placebo (n = 77) intravenously once every three weeks for 18 months. Multiple measures were used to assess varying aspects of QOL.Results: At 18 months, compared with placebo, patisiran improved Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) score; (least squares [LS] mean difference: -21.1; p = 1.10 × 10-10; improved across all domains), EuroQoL 5-dimensions 5-levels (LS mean difference: 0.2; p = 1.4 × 10-12), EuroQoL-visual analog scale (LS mean difference: 9.5; p=.0004), Rasch-built Overall Disability Scale (LS mean difference: 9.0; p = 4.07 × 10-16) and Composite Autonomic Symptom Score-31(COMPASS-31; LS mean difference: -7.5; p=.0008). Placebo-treated patients experienced rapid QOL deterioration; treatment effects for patisiran were observed as early as 9 months. At 18 months, patisiran improved Norfolk QOL-DN total score and three individual domains as well as COMPASS-31 total scores relative to baseline. Consistent benefits were also observed in the cardiac subpopulation.Conclusion: The benefits of patisiran across all QOL measures and the rapid deterioration observed with placebo, highlight the urgency in early treatment for patients with hATTR amyloidosis with polyneuropathy.