Patisiran treatment in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy after liver transplantation
Publication Details
American Journal of Transplantation
June 2022
Author(s)
Hartmut H Schmidt1, Jonas Wixner2, Violaine Planté-Bordeneuve3 4, Francisco Muñoz-Beamud5, Laura Lladó6 7, Julian D Gillmore8, Anna Mazzeo9, Xingyu Li10, Seth Arum10, Patrick Y Jay10, David Adams 11 12; Patisiran Post-LT Study Group
Affiliations
1Department of Gastroenterology, Hepatology and Transplant Medicine, University Hospital Essen, University of Duisburg-Essen (formerly of University Hospital Munster, Munster, Germany), Essen, Germany; 2Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden; 3Department of Neurology, East Paris University, Hospital Henri Mondor - Public Assistance Hospital of Paris, Créteil, France; 4Mondor Biomedical Research Institute - IMRB, INSERM, U955 Team 10 "Biology of the Neuro-Muscular System", Créteil, France; 5Hereditary Amyloidosis Unit, Department of Internal Medicine, Juan Ramón Jiménez Hospital, Huelva, Spain; 6Liver Transplantation Unit, Department of Surgery, and the Multidisciplinary Familial Amyloidosis Unit, Hospital Universitari de Bellvitge, Barcelona, Spain; 7Biomedical Research Institute, IDIBELL, University of Barcelona, Barcelona, Spain; 8National Amyloidosis Centre, Division of Medicine, University College London Medical School, London, UK; 9Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; 10Alnylam Pharmaceuticals, Inc, Cambridge, Massachusetts, USA; 11Neurology Department, Université Paris-Saclay, U1195, INSERM, Le Kremlin Bicêtre, France; 12Neurology Department, AP-HP, CHU Bicêtre, Le Kremlin Bicêtre, France
Abstract
Hereditary transthyretin-mediated (hATTR) amyloidosis, or ATTRv amyloidosis, is a progressive disease, for which liver transplantation (LT) has been a long-standing treatment. However, disease progression continues post-LT. This Phase 3b, open-label trial evaluated efficacy and safety of patisiran in patients with ATTRv amyloidosis with polyneuropathy progression post-LT. Primary endpoint was median transthyretin (TTR) reduction from baseline. Twenty-three patients received patisiran for 12 months alongside immunosuppression regimens. Patisiran elicited a rapid, sustained TTR reduction (median reduction [Months 6 and 12 average], 91.0%; 95% CI: 86.1%–92.3%); improved neuropathy, quality of life, and autonomic symptoms from baseline to Month 12 (mean change [SEM], Neuropathy Impairment Score, −3.7 [2.7]; Norfolk Quality of Life-Diabetic Neuropathy questionnaire, −6.5 [4.9]; least-squares mean [SEM], Composite Autonomic Symptom Score-31, −5.0 [2.6]); and stabilized disability (Rasch-built Overall Disability Scale) and nutritional status (modified body mass index). Adverse events were mild or moderate; five patients experienced ≥1 serious adverse event. Most patients had normal liver function tests. One patient experienced transplant rejection consistent with inadequate immunosuppression, remained on patisiran, and completed the study. In conclusion, patisiran reduced serum TTR, was well tolerated, and improved or stabilized key disease impairment measures in patients with ATTRv amyloidosis with polyneuropathy progression post-LT (www.clinicaltrials.gov NCT03862807).
PMID
35213769
DOI
10.1111/ajt.17009
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