Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update
Autor(a) principal: | |
---|---|
Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , |
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 |