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Analysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

2020Journal article Open access
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dc.contributor.authorGonzález-Duarte, Alejandra
dc.contributor.authorBerk, John L.
dc.contributor.authorQuan, Dianna
dc.contributor.authorMauermann, Michelle L.
dc.contributor.authorSchmidt, Hartmut H.
dc.contributor.authorPolydefkis, Michael
dc.contributor.authorWaddington-Cruz, Márcia
dc.contributor.authorUeda, Mitsuharu
dc.contributor.authorConceição, Isabel M.
dc.contributor.authorKristen, Arnt V.
dc.contributor.authorCoelho, Teresa
dc.contributor.authorCauquil, Cécile A.
dc.contributor.authorTard, Céline
dc.contributor.authorMerkel, Madeline
dc.contributor.authorAldinc, Emre
dc.contributor.authorChen, Jihong
dc.contributor.authorSweetser, Marianne T.
dc.contributor.authorWang, Jing Jing
dc.contributor.authorAdams, David
dc.date.accessioned2022-03-21T12:11:01Z
dc.date.available2022-03-21T12:11:01Z
dc.date.issued2020
dc.description.abstractHereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, - 7.5; 95% CI: - 11.9, - 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, - 1.1; - 1.8, - 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; - 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, - 0.3; - 0.5, - 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, - 5.3; 95% CI: - 7.9, - 2.7) and individual domains, orthostatic intolerance (- 4.6; - 6.3, - 2.9) and gastrointestinal symptoms (- 0.8; - 1.5, - 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.pt_PT
dc.description.sponsorshipThe study was funded by Alnylam Pharmaceuticals, Inc. Medical writing services provided by Kristen Brown (PhD) of Adelphi Communications Ltd, Macclesfeld, UK were funded by Alnylam Pharmaceuticals, Inc. in accordance with Good Publication Practice (GPP3) guidelines. We would like to thank Anastasia McManus (Alnylam Pharmaceuticals, Inc.) for her assistance during preparation of this manuscript.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGonzález-Duarte A, Berk JL, Quan D, et al. Analysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis. J Neurol. 2020;267(3):703-712. doi:10.1007/s00415-019-09602-8pt_PT
dc.identifier.doi10.1007/s00415-019-09602-8pt_PT
dc.identifier.issn0340-5354
dc.identifier.issn1432-1459
dc.identifier.urihttp://hdl.handle.net/10400.16/2666
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer-Verlagpt_PT
dc.relation.publisherversionhttps://link.springer.com/article/10.1007/s00415-019-09602-8pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAutonomic nervous system diseasespt_PT
dc.subjectHereditary transthyretin-mediated amyloidosispt_PT
dc.subjectPatisiranpt_PT
dc.subjectPolyneuropathypt_PT
dc.subjectSmall interfering ribonucleic acid (siRNA)pt_PT
dc.subjectTransthyretin.pt_PT
dc.titleAnalysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceGermanypt_PT
oaire.citation.endPage712pt_PT
oaire.citation.issue3pt_PT
oaire.citation.startPage703pt_PT
oaire.citation.titleJournal of Neurologypt_PT
oaire.citation.volume267pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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