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

Detalhes bibliográficos
Autor(a) principal: Brannagan, Thomas H.
Data de Publicação: 2022
Outros Autores: Coelho, Teresa, Wang, Annabel K., Polydefkis, Michael J., Dyck, Peter J., Berk, John L., Drachman, Brian, Gorevic, Peter, Whelan, Carol, Conceição, isabel, Plante-Bordeneuve, Violaine, Merlini, Giampaolo, Obici, Laura, Plana, Josep Maria Campistol, Gamez, Josep, Kristen, Arnt V., Mazzeo, Anna, Gentile, Luca, Narayana, Arvind, Olugemo, Kemi, Aquino, Peter, Benson, Merrill D., Gertz, Morie
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/54413
Resumo: © 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/
id RCAP_df0cb0254d17c137637d8c5700a7820a
oai_identifier_str oai:repositorio.ul.pt:10451/54413
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year updateClinical trialFamilial amyloid polyneuropathyHereditary transthyretin amyloidosisInotersenPeripheral neuropathiesPolyneuropathy© 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/Background: 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.Springer NatureRepositório da Universidade de LisboaBrannagan, Thomas H.Coelho, TeresaWang, Annabel K.Polydefkis, Michael J.Dyck, Peter J.Berk, John L.Drachman, BrianGorevic, PeterWhelan, CarolConceição, isabelPlante-Bordeneuve, ViolaineMerlini, GiampaoloObici, LauraPlana, Josep Maria CampistolGamez, JosepKristen, Arnt V.Mazzeo, AnnaGentile, LucaNarayana, ArvindOlugemo, KemiAquino, PeterBenson, Merrill D.Gertz, Morie2022-09-09T13:43:04Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/54413engJ Neurol. 2022 Jul 31. doi: 10.1007/s00415-022-11276-80340-535410.1007/s00415-022-11276-81432-1459info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:00:44Zoai:repositorio.ul.pt:10451/54413Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:05:13.365130Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update
title Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update
spellingShingle Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update
Brannagan, Thomas H.
Clinical trial
Familial amyloid polyneuropathy
Hereditary transthyretin amyloidosis
Inotersen
Peripheral neuropathies
Polyneuropathy
title_short Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update
title_full Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update
title_fullStr Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update
title_full_unstemmed Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update
title_sort Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update
author Brannagan, Thomas H.
author_facet Brannagan, Thomas H.
Coelho, Teresa
Wang, Annabel K.
Polydefkis, Michael J.
Dyck, Peter J.
Berk, John L.
Drachman, Brian
Gorevic, Peter
Whelan, Carol
Conceição, isabel
Plante-Bordeneuve, Violaine
Merlini, Giampaolo
Obici, Laura
Plana, Josep Maria Campistol
Gamez, Josep
Kristen, Arnt V.
Mazzeo, Anna
Gentile, Luca
Narayana, Arvind
Olugemo, Kemi
Aquino, Peter
Benson, Merrill D.
Gertz, Morie
author_role author
author2 Coelho, Teresa
Wang, Annabel K.
Polydefkis, Michael J.
Dyck, Peter J.
Berk, John L.
Drachman, Brian
Gorevic, Peter
Whelan, Carol
Conceição, isabel
Plante-Bordeneuve, Violaine
Merlini, Giampaolo
Obici, Laura
Plana, Josep Maria Campistol
Gamez, Josep
Kristen, Arnt V.
Mazzeo, Anna
Gentile, Luca
Narayana, Arvind
Olugemo, Kemi
Aquino, Peter
Benson, Merrill D.
Gertz, Morie
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Brannagan, Thomas H.
Coelho, Teresa
Wang, Annabel K.
Polydefkis, Michael J.
Dyck, Peter J.
Berk, John L.
Drachman, Brian
Gorevic, Peter
Whelan, Carol
Conceição, isabel
Plante-Bordeneuve, Violaine
Merlini, Giampaolo
Obici, Laura
Plana, Josep Maria Campistol
Gamez, Josep
Kristen, Arnt V.
Mazzeo, Anna
Gentile, Luca
Narayana, Arvind
Olugemo, Kemi
Aquino, Peter
Benson, Merrill D.
Gertz, Morie
dc.subject.por.fl_str_mv Clinical trial
Familial amyloid polyneuropathy
Hereditary transthyretin amyloidosis
Inotersen
Peripheral neuropathies
Polyneuropathy
topic Clinical trial
Familial amyloid polyneuropathy
Hereditary transthyretin amyloidosis
Inotersen
Peripheral neuropathies
Polyneuropathy
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/
publishDate 2022
dc.date.none.fl_str_mv 2022-09-09T13:43:04Z
2022
2022-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/54413
url http://hdl.handle.net/10451/54413
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv J Neurol. 2022 Jul 31. doi: 10.1007/s00415-022-11276-8
0340-5354
10.1007/s00415-022-11276-8
1432-1459
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
_version_ 1799134603459428352