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Eplontersen for Her...
Eplontersen for Hereditary Transthyretin Amyloidosis with Polyneuropathy
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- Coelho, Teresa (författare)
- Centro Hospitalar Universitário de Santo António, Porto, Portugal
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- Marques, Wilson (författare)
- Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, Brazil
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- Dasgupta, Noel R. (författare)
- Indiana University, School of Medicine, Indianapolis, United States
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- Chao, Chi-Chao (författare)
- National Taiwan University Hospital, Taipei, Taiwan
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- Parman, Yeşim (författare)
- Istanbul Universitesi-Istanbul Tip Fakültesi, Istanbul, Turkey
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- França, Marcondes Cavalcante (författare)
- Universidade Estadual de Campinas, Campinas, São Paulo, Brazil
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- Guo, Yuh-Cherng (författare)
- China Medical University Hospital, Taichung, Taiwan
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- Wixner, Jonas (författare)
- Umeå universitet,Institutionen för folkhälsa och klinisk medicin
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- Ro, Long-Sun (författare)
- Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
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- Calandra, Cristian R. (författare)
- Hospital El Cruce, Buenos Aires, Argentina
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- Kowacs, Pedro A. (författare)
- Instituto de Neurologia de Curitiba, Paraná, Curitiba, Brazil
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- Berk, John L. (författare)
- Boston University School of Medicine, MA, Boston, United States
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- Obici, Laura (författare)
- Amyloidosis Research and Treatment Centre, IRCCS, Fondazione Policlinico San Matteo, Pavia, Italy
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- Barroso, Fabio A. (författare)
- Neurology Department, Fleni, Buenos Aires, Argentina
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- Weiler, Markus (författare)
- Amyloidosis Center and Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany
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- Conceição, Isabel (författare)
- Centro Hospitalar Universitário Lisboa-Norte, Hospital de Santa Maria, Lisbon, Portugal
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- Jung, Shiangtung W. (författare)
- Ionis Pharmaceuticals Inc, CA, Carlsbad, United States
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- Buchele, Gustavo (författare)
- Ionis Pharmaceuticals Inc, CA, Carlsbad, United States
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- Brambatti, Michela (författare)
- Ionis Pharmaceuticals Inc, CA, Carlsbad, United States
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- Chen, Jersey (författare)
- Late-Stage Development Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, MD, Gaithersburg, United States
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- Hughes, Steven G. (författare)
- Ionis Pharmaceuticals Inc, CA, Carlsbad, United States
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- Schneider, Eugene (författare)
- Ionis Pharmaceuticals Inc, CA, Carlsbad, United States
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- Viney, Nicholas J. (författare)
- Ionis Pharmaceuticals Inc, CA, Carlsbad, United States
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- Masri, Ahmad (författare)
- OHSU, Center for Hypertrophic Cardiomyopathy and Amyloidosis, OR, Portland, United States
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- Gertz, Morie R. (författare)
- Mayo Clinic, MN, Rochester, United States
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- Ando, Yukio (författare)
- Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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- Gillmore, Julian D. (författare)
- National Amyloidosis Centre, University College London, London, United Kingdom
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- Khella, Sami (författare)
- University of Pennsylvania, School of Medicine, Philadelphia, United States
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- Dyck, P. James B. (författare)
- Mayo Clinic, MN, Rochester, United States
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- Waddington Cruz, Márcia (författare)
- Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
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(creator_code:org_t)
- American Medical Association (AMA), 2023
- 2023
- Engelska.
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 330:15, s. 1448-1458
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
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Coelho, Teresa
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Marques, Wilson
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Dasgupta, Noel R ...
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Chao, Chi-Chao
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Parman, Yeşim
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França, Marconde ...
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Guo, Yuh-Cherng
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Wixner, Jonas
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Ro, Long-Sun
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Calandra, Cristi ...
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Kowacs, Pedro A.
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Berk, John L.
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Obici, Laura
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Barroso, Fabio A ...
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Weiler, Markus
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Conceição, Isabe ...
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Jung, Shiangtung ...
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Buchele, Gustavo
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Brambatti, Miche ...
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Chen, Jersey
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Hughes, Steven G ...
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Schneider, Eugen ...
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Viney, Nicholas ...
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Masri, Ahmad
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Gertz, Morie R.
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Ando, Yukio
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Gillmore, Julian ...
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Khella, Sami
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Dyck, P. James B ...
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Waddington Cruz, ...
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och Klinisk medicin
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