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  • Coelho, TeresaCentro Hospitalar Universitário de Santo António, Porto, Portugal (författare)

Eplontersen for Hereditary Transthyretin Amyloidosis with Polyneuropathy

  • Artikel/kapitelEngelska2023

Förlag, utgivningsår, omfång ...

  • American Medical Association (AMA),2023
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:umu-216127
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-216127URI
  • https://doi.org/10.1001/jama.2023.18688DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Marques, WilsonHospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, Brazil (författare)
  • Dasgupta, Noel R.Indiana University, School of Medicine, Indianapolis, United States (författare)
  • Chao, Chi-ChaoNational Taiwan University Hospital, Taipei, Taiwan (författare)
  • Parman, YeşimIstanbul Universitesi-Istanbul Tip Fakültesi, Istanbul, Turkey (författare)
  • França, Marcondes CavalcanteUniversidade Estadual de Campinas, Campinas, São Paulo, Brazil (författare)
  • Guo, Yuh-CherngChina Medical University Hospital, Taichung, Taiwan (författare)
  • Wixner, JonasUmeå universitet,Institutionen för folkhälsa och klinisk medicin(Swepub:umu)jowi0065 (författare)
  • Ro, Long-SunChang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan (författare)
  • Calandra, Cristian R.Hospital El Cruce, Buenos Aires, Argentina (författare)
  • Kowacs, Pedro A.Instituto de Neurologia de Curitiba, Paraná, Curitiba, Brazil (författare)
  • Berk, John L.Boston University School of Medicine, MA, Boston, United States (författare)
  • Obici, LauraAmyloidosis Research and Treatment Centre, IRCCS, Fondazione Policlinico San Matteo, Pavia, Italy (författare)
  • Barroso, Fabio A.Neurology Department, Fleni, Buenos Aires, Argentina (författare)
  • Weiler, MarkusAmyloidosis Center and Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany (författare)
  • Conceição, IsabelCentro Hospitalar Universitário Lisboa-Norte, Hospital de Santa Maria, Lisbon, Portugal (författare)
  • Jung, Shiangtung W.Ionis Pharmaceuticals Inc, CA, Carlsbad, United States (författare)
  • Buchele, GustavoIonis Pharmaceuticals Inc, CA, Carlsbad, United States (författare)
  • Brambatti, MichelaIonis Pharmaceuticals Inc, CA, Carlsbad, United States (författare)
  • Chen, JerseyLate-Stage Development Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, MD, Gaithersburg, United States (författare)
  • Hughes, Steven G.Ionis Pharmaceuticals Inc, CA, Carlsbad, United States (författare)
  • Schneider, EugeneIonis Pharmaceuticals Inc, CA, Carlsbad, United States (författare)
  • Viney, Nicholas J.Ionis Pharmaceuticals Inc, CA, Carlsbad, United States (författare)
  • Masri, AhmadOHSU, Center for Hypertrophic Cardiomyopathy and Amyloidosis, OR, Portland, United States (författare)
  • Gertz, Morie R.Mayo Clinic, MN, Rochester, United States (författare)
  • Ando, YukioGraduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan (författare)
  • Gillmore, Julian D.National Amyloidosis Centre, University College London, London, United Kingdom (författare)
  • Khella, SamiUniversity of Pennsylvania, School of Medicine, Philadelphia, United States (författare)
  • Dyck, P. James B.Mayo Clinic, MN, Rochester, United States (författare)
  • Waddington Cruz, MárciaHospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (författare)
  • Centro Hospitalar Universitário de Santo António, Porto, PortugalHospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, Brazil (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of the American Medical Association (JAMA): American Medical Association (AMA)330:15, s. 1448-14580098-74841538-3598

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