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Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update

2022Journal article Open access
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dc.contributor.authorBrannagan, Thomas H.
dc.contributor.authorCoelho, Teresa
dc.contributor.authorWang, Annabel K.
dc.contributor.authorPolydefkis, Michael J.
dc.contributor.authorDyck, Peter J.
dc.contributor.authorBerk, John L.
dc.contributor.authorDrachman, Brian
dc.contributor.authorGorevic, Peter
dc.contributor.authorWhelan, Carol
dc.contributor.authorConceição, isabel
dc.contributor.authorPlante-Bordeneuve, Violaine
dc.contributor.authorMerlini, Giampaolo
dc.contributor.authorObici, Laura
dc.contributor.authorPlana, Josep Maria Campistol
dc.contributor.authorGamez, Josep
dc.contributor.authorKristen, Arnt V.
dc.contributor.authorMazzeo, Anna
dc.contributor.authorGentile, Luca
dc.contributor.authorNarayana, Arvind
dc.contributor.authorOlugemo, Kemi
dc.contributor.authorAquino, Peter
dc.contributor.authorBenson, Merrill D.
dc.contributor.authorGertz, Morie
dc.date.accessioned2022-09-09T13:43:04Z
dc.date.available2022-09-09T13:43:04Z
dc.date.issued2022
dc.description© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attri- bution 4.0 International License, which permits use, sharing, adapta- tion, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/pt_PT
dc.description.abstractBackground: Hereditary transthyretin amyloidosis (hATTR/ATTRv) results from the deposition of misfolded transthyretin (TTR) throughout the body, including peripheral nerves. Inotersen, an antisense oligonucleotide inhibitor of hepatic TTR production, demonstrated a favorable efficacy and safety profile in patients with the polyneuropathy associated with hATTR in the NEURO-TTR (NCT01737398) study. We report longer-term efficacy and safety data for inotersen, with a median treatment exposure of 3 years. Methods: Patients who satisfactorily completed NEURO-TTR were enrolled in its open-label extension (OLE) study. Efficacy assessments included the modified Neuropathy Impairment Score + 7 (mNIS + 7), Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) questionnaire total score, and the Short Form 36 (SF-36v2) Health Survey Physical Component Summary score. Safety and tolerability were also assessed. Efficacy is reported for patients living in Europe and North America (this cohort completed the study approximately 9 months before the remaining group of patients outside these regions); safety is reported for the full safety dataset, comprising patients living in Europe, North America, and Latin America/Australasia. This study is registered with ClinicalTrials.gov, identifier NCT02175004. Results: In the Europe and North America cohort of the NEURO-TTR study, 113/141 patients (80.1%) completed the study, and 109 patients participated in the OLE study. A total of 70 patients continued to receive inotersen (inotersen-inotersen) and 39 switched from placebo to inotersen (placebo-inotersen). The placebo-inotersen group demonstrated sustained improvement in neurological disease progression as measured by mNIS + 7, compared with predicted worsening based on projection of the NEURO-TTR placebo data (estimated natural history). The inotersen-inotersen group demonstrated sustained benefit, as measured by mNIS + 7, Norfolk QoL-DN, and SF-36v2, compared with estimated natural history as well as compared with the placebo-inotersen group. With a maximum exposure of 6.2 years, inotersen was not associated with any additional safety concerns or increased toxicity in the OLE study. Platelet and renal monitoring were effective in reducing the risk of severe adverse events in the OLE study. Conclusion: Inotersen treatment for > 3 years slowed progression of the polyneuropathy associated with hATTR, and no new safety signals were observed.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Neurol. 2022 Jul 31. doi: 10.1007/s00415-022-11276-8pt_PT
dc.identifier.doi10.1007/s00415-022-11276-8pt_PT
dc.identifier.eissn1432-1459
dc.identifier.issn0340-5354
dc.identifier.urihttp://hdl.handle.net/10451/54413
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relation.publisherversionhttps://www.springer.com/journal/415pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectClinical trialpt_PT
dc.subjectFamilial amyloid polyneuropathypt_PT
dc.subjectHereditary transthyretin amyloidosispt_PT
dc.subjectInotersenpt_PT
dc.subjectPeripheral neuropathiespt_PT
dc.subjectPolyneuropathypt_PT
dc.titleLong-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year updatept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleJournal of Neurologypt_PT
person.familyNameCONCEICAO
person.givenNameISABEL
person.identifier.orcid0000-0003-0934-9631
person.identifier.scopus-author-id6701694419
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication52ba30d8-6cbf-424d-b334-4d06a2ecc6e5
relation.isAuthorOfPublication.latestForDiscovery52ba30d8-6cbf-424d-b334-4d06a2ecc6e5

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