Repositorio Dspace

Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy

Mostrar el registro sencillo del ítem

dc.contributor.author Coelho, Teresa
dc.contributor.author Marques, Wilson
dc.contributor.author Dasgupta, Noel R.
dc.contributor.author Chao, Chi-Chao
dc.contributor.author Parman, Yeşim
dc.contributor.author Cavalcante França Jr, Marcondes
dc.contributor.author Guo, Yuh-Cherng
dc.contributor.author Wixner, Jonas
dc.contributor.author Ro, Long-Sun
dc.contributor.author Calandra, Cristian R.
dc.contributor.author Kowacs, Pedro A.
dc.contributor.author Berk, John L.
dc.contributor.author Obici, Laura
dc.contributor.author Barroso, Fabio Adrián
dc.contributor.author Weiler, Markus
dc.contributor.author Conceição, Isabel
dc.contributor.author Jung, Shiangtung W.
dc.contributor.author Buchele, Gustavo
dc.contributor.author Brambatti, Michela
dc.contributor.author NEURO-TTRansform Investigators
dc.date.accessioned 2024-02-27T17:03:18Z
dc.date.available 2024-02-27T17:03:18Z
dc.date.issued 2023-09-28
dc.identifier.citation Coelho T, Marques W, Dasgupta NR, Chao CC, Parman Y, França MC, et al. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy. JAMA. 17 de octubre de 2023;330(15):1448-58. es_ES
dc.identifier.uri https://doi.org/10.1001/jama.2023.18688
dc.identifier.uri https://repositorio.fleni.org.ar/xmlui/handle/123456789/1024
dc.description.abstract Importance: Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis. Objective: To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy. Design, setting, and participants: NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR (NCT01737398; March 2013-November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo ("placebo") group. Interventions: Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60). Main outcomes and measures: Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, -22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, -4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights. Results: Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was -81.7% with eplontersen and -11.2% with placebo (difference, -70.4% [95% CI, -75.2% to -65.7%]; P < .001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, -24.8 [95% CI, -31.0 to -18.6; P < .001) and for Norfolk QoL-DN (-5.5 vs 14.2; difference, -19.7 [95% CI, -25.6 to -13.8]; P < .001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group. Conclusions and relevance: In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. Trial registration: ClinicalTrials.gov Identifier: NCT04136184; EU Clinical Trials Register: EudraCT 2019-001698-10. es_ES
dc.language.iso eng es_ES
dc.publisher American Medical Association es_ES
dc.subject Amyloid Neuropathies, Familial es_ES
dc.subject Neuropatías Amiloides Familiares es_ES
dc.subject Disease Progression es_ES
dc.subject Progresión de la Enfermedad es_ES
dc.subject Oligonucleotides, Antisense es_ES
dc.subject Oligonucleótidos Antisentido es_ES
dc.subject Polyneuropathies es_ES
dc.subject Polineuropatías es_ES
dc.subject Prealbumin es_ES
dc.subject Prealbúmina es_ES
dc.subject Quality of Life es_ES
dc.subject Calidad de Vida es_ES
dc.title Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.description.fil Fil: Barroso, Fabio Adrián. Fleni. Departamento de Neurología. Sección de Enfermedades Neuromusculares; Argentina.
dc.relation.ispartofVOLUME 330
dc.relation.ispartofNUMBER 15
dc.relation.ispartofPAGINATION 1448-1458
dc.relation.ispartofCOUNTRY Estados Unidos
dc.relation.ispartofCITY Chicago
dc.relation.ispartofTITLE JAMA
dc.relation.ispartofISSN 1538-3598
dc.type.snrd info:ar-repo/semantics/artículo es_ES


Ficheros en el ítem

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem

Buscar en DSpace


Listar

Mi cuenta

Estadísticas