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oai:repisalud.isciii.es:20.500.12105/228602024-11-28T23:54:36Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967
Repisalud author Coelho, Teresa author Adams, David author Conceicao, Isabel author Waddington-Cruz, Marcia author Schmidt, Hartmut H author Bonilla, Alfonso author Campistol, Josep author Berk, John L author Polydefkis, Michael author Wang, Jing Jing author Chen, Jihong author Sweetser, Marianne T author Gollob, Jared author Suhr, Ole B 2024-09-13T09:11:43Z 2024-09-13T09:11:43Z 2020-07-08 Coelho T, Adams D, Conceicao I, Waddington-Cruz M, Schmidt Hartmut H, Buades J, et al. A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis. Orphanet J Rare Dis. 2020 Jul 08;15(1):179. 10.1186/s13023-020-01399-4 1750-1172 Orphanet Journal of Rare Diseases http://hdl.handle.net/20.500.13003/10098 32641071 L632268561 2-s2.0-85087693350 https://hdl.handle.net/20.500.12105/22860 551966000001 Background: Patisiran, an RNA interference therapeutic, has demonstrated robust reduction of wild-type and mutant transthyretin protein and was able to improve polyneuropathy and quality of life following 18 months of treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis.In this 24-month Phase II open-label extension study, we evaluated the effects of patisiran treatment (0.3 mg/kg intravenously every 3 weeks) on safety, serum transthyretin levels, and clinical parameters. Efficacy assessments included modified Neuropathy Impairment Score +7 (mNIS+7) and multiple disease-relevant measures. Cardiac assessments were performed in a pre-specified cardiac subgroup. Results: Twenty-seven patients entered this study, including 12 (44%) with ambulation difficulties due to their neuropathy and 11 (41%) who met criteria for the cardiac subgroup. During treatment, the majority of adverse events were mild/moderate in severity; there were no drug-related adverse events leading to treatment discontinuation. The most common drug-related adverse events were flushing and infusion-related reactions (22% each). Patisiran resulted in rapid, robust (similar to 82%), and sustained reduction of mean transthyretin levels over 24 months. A mean 6.95-point decrease (improvement) in mNIS+7 from baseline was observed at 24 months. Patisiran's impact on mNIS+7 was irrespective of concomitant tafamidis or diflunisal use, sex, or age. Clinical assessments of motor function, autonomic symptoms, disease stage, and quality of life remained stable over 24 months. No significant changes were observed for echocardiographic measures or cardiac biomarkers in the cardiac subgroup. Exploratory analyses demonstrated improvements in nerve-fiber density with corresponding reductions in amyloid burden observed in skin biopsies over 24 months. Conclusions: Long-term treatment with patisiran had an acceptable safety profile and was associated with halting/improvement of polyneuropathy progression in patients with hATTR amyloidosis. eng ATTR amyloidosis Cardiomyopathy Patisiran Polyneuropathy RNA interference A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis research article