Laura Obici1, John L Berk2, Alejandra González-Duarte3, Teresa Coelho4, Julian Gillmore5, Hartmut H-J Schmidt6, Matthias Schilling7, Taro Yamashita8, Céline Labeyrie9, Thomas H Brannagan10, Senda Ajroud-Driss11, Peter Gorevic12, Arnt V Kristen13, Jaclyn Franklin14, Jihong Chen14, Marianne T Sweetser14, Jing Jing Wang14, David Adams9. 1. Amyloidosis Research and Treatment Centre, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 2. Amyloidosis Center, Boston Medical Center, Boston, MA, USA. 3. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. 4. Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal. 5. Division of Medicine, National Amyloidosis Centre, University College London, London, UK. 6. Medical Clinic for Gastroenterology and Hepatology, University of Münster, Münster, Germany. 7. Department of Neurology, Institute of Translational Neurology, University Hospital Münster, Münster, Germany. 8. Department of Neurology, Kumamoto University, Kumamoto, Japan. 9. Assistance Publique-Hôpitaux de Paris (APHP), French National Reference Center for Familial Amyloidotic Polyneuropathy, Centre Hospitalier Universitaire Bicêtre, Universite Paris-Sud, INSERM Unite, Paris, France. 10. Department of Neurology, Columbia University Medical Center, New York, NY, USA. 11. Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. 12. Department of Medicine, Mount Sinai Medical Center, New York, NY, USA. 13. Department of Cardiology, University of Heidelberg, Heidelberg, Germany. 14. Alnylam Pharmaceuticals, Cambridge, MA, USA.
Abstract
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.
RCT Entities:
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 hATTRamyloidosis 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 hATTRamyloidosis with polyneuropathy.
Entities:
Keywords:
APOLLO; Norfolk QOL-DN; hereditary transthyretin-mediated amyloidosis; patisiran; quality of life
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