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Long-Term Efficacy and Safety of Inotersen for Hereditary Transthyretin Amyloidosis: NEURO-TTR Open-Label Extension 2-Year Update (S27.008)

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dc.contributor.author Brannagan, Thomas H.
dc.contributor.author Waddington Cruz, Marcia
dc.contributor.author Wang, Annabel K.
dc.contributor.author Polydefkis, Michael J.
dc.contributor.author Dyck, Peter J.
dc.contributor.author Khella, Sami
dc.contributor.author Plante-Bordeneuve, Violaine
dc.contributor.author Berk, John L.
dc.contributor.author Barroso, Fabio Adrián
dc.contributor.author Merlini, Giampaolo
dc.contributor.author Conceição, Isabel
dc.contributor.author Hughes, Steven G.
dc.contributor.author Kwoh, Jesse
dc.contributor.author Jung, Shiangtung W.
dc.contributor.author Guthrie, Spencer
dc.contributor.author Pollock, Michael
dc.contributor.author Benson, Merrill D.
dc.contributor.author Gertz, Morie
dc.contributor.author Coelho, Teresa
dc.date.accessioned 2020-02-05T16:06:13Z
dc.date.available 2020-02-05T16:06:13Z
dc.date.issued 2019-03-09
dc.identifier.citation Brannagan, T., Cruz, M.W., Wang, A.K., Polydefkis, M.J., Dyck, P.J., Khella, S., Plante-Bordeneuve, V., Berk, J.L., Barroso, F., Merlini, G., Conceição, I., Hughes, S.G., Kwoh, J., Jung, S.W., Guthrie, S., Pollock, M., Benson, M.D., Gertz, M., Coelho, T. Long-Term Efficacy and Safety of Inotersen for Hereditary Transthyretin Amyloidosis: NEURO-TTR Open-Label Extension 2-Year Update (S27.008). Neurology. 2019;92(15 Supplement). S27.008. en_US
dc.identifier.issn 0028-3878
dc.identifier.uri https://repositorio.fleni.org.ar/handle/123456789/177
dc.description.abstract Objective: To provide an update on the long-term efficacy and safety of inotersen, an antisense oligonucleotide inhibitor of transthyretin protein production, in patients with hereditary transthyretin amyloidosis (hATTR) with polyneuropathy. Background: Patients with hATTR, a rare protein misfolding disorder, experience progressive and debilitating polyneuropathy. A randomized, controlled phase 3 trial (NEURO-TTR; NCT01737398) demonstrated efficacy and safety of inotersen treatment in patients with hATTR polyneuropathy (Benson 2018 NEJM). Design/Methods: Patients who completed NEURO-TTR were eligible to enroll in the ongoing open-label extension (OLE) study (NCT02175004). Assessments included modified Neuropathy Impairment Score +7 neurophysiologic tests composite score (mNIS+7), Norfolk Quality of Life–Diabetic Neuropathy questionnaire total score (Norfolk QoL-DN), and adverse events. Results: Of 139 patients who completed NEURO-TTR, 135 (97.1%) enrolled in the OLE. As of 9/15/17, 134 patients had received ≥1 dose of inotersen. Patients were predominantly white (93.3%) and male (69.4%), and 88/134 (65.7%) had both polyneuropathy and cardiac involvement. At OLE baseline, 83/134 (61.9%) patients were ambulatory without assistance, 47/134 (35.1%) required walking aid(s), and 4/134 (3.0%) were unable to walk. Patients who initiated inotersen in the OLE demonstrated slowing of neurologic disease progression by mNIS+7 and Norfolk QoL-DN within 6 months, and patients who had received inotersen for 27 months (15 months in NEURO-TTR + 12 months in the OLE) continued to show benefit. Greater benefit in mNIS+7 and Norfolk QoL-DN was observed in patients treated earlier with inotersen. There was no evidence of increased risk for grade 4 thrombocytopenia or severe renal events with increased duration of exposure, and no new safety concerns have been identified. This presentation will be updated with data from 2 years of follow-up in the OLE. Conclusions: In the OLE, inotersen treatment slowed hATTR polyneuropathy progression, with greater stabilization observed in patients who initiated inotersen earlier. Disclosure: Dr. Brannagan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Grifols, Ionis, Alnylam, and CSL Behring. Dr. Brannagan has received research support from Ionis, Alnyalm, Viromed, Catalyst, Pharnext, Novartis, Grifols. Dr. Waddington Cruz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis Pharmaceuticals, Inc., Genzyme/Sanofi, and Pfizer. Dr. Wang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis Pharmaceuticals, Inc. Dr. Polydefkis has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis, Alnylam, Vertex, Chromocell. Dr. Polydefkis has received compensation for serving on the Board of Directors of Travel-Ionis and Pfizer. Dr. Polydefkis has received research support from Pfizer, Ionis, and Alnylam . Dr. Dyck has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alnylam and Ionis. Dr. Khella has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Akcea Therapeutics and Alnylam Pharmaceuticals. Dr. Khella has received research support from Akcea Therapeutics. Dr. Plante-Bordeneuve has nothing to disclose. Dr. Berk has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Akcea, Alnylam. Dr. Barroso has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer. Dr. Barroso has received research support from Alnylam. Dr. Merlini has nothing to disclose. Dr. Conceicao has nothing to disclose. Dr. Hughes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis Pharmaceuticals Inc. Dr. Kwoh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Akcea Therapeutics. Dr. Jung, PhD has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Akcea Therapeutics. Dr. Guthrie has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Akcea Therapeutics. Dr. Pollock has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Akcea Therapeutics. Dr. Benson has nothing to disclose. Dr. Gertz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis Pharmaceuticals, Inc., Alnylam Pharmaceuticals, and Prothena. Dr. Coelho has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer, Alnylam and Biogen. Dr. Coelho has received research support from Pfizer, Ionis and Alnylam. en_US
dc.language.iso eng en_US
dc.publisher Lippincott Williams & Wilkins en_US
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/2.5/ar/
dc.subject Amyloidosis en_US
dc.subject Amiloidosis en_US
dc.title Long-Term Efficacy and Safety of Inotersen for Hereditary Transthyretin Amyloidosis: NEURO-TTR Open-Label Extension 2-Year Update (S27.008) en_US
dc.type info:eu-repo/semantics/publishedVersion
dc.type info:eu-repo/semantics/other en_US
dc.description.fil Fil: Brannagan, Thomas. Columbia University Medical Center; Estados Unidos.
dc.description.fil Fil: Waddington Cruz, Marcia. Federal University of Rio de Janeiro; Brasil. University Hospital Rio de Janeiro; Brasil.
dc.description.fil Fil: Wang, Annabel K. University of California; Estados Unidos.
dc.description.fil Fil: Polydefkis, Michael J. Johns Hopkins University; Estados Unidos.
dc.description.fil Fil: Dyck, Peter J. Mayo Clinic; Estados Unidos.
dc.description.fil Fil: Khella, Sami. University of Pennsylvania; Estados Unidos.
dc.description.fil Fil: Plante-Bordeneuve, Violaine. CHU Henri Mondor Creteil; Francia.
dc.description.fil Fil: Berk, John L. Boston University Boston; Estados Unidos.
dc.description.fil Fil: Barroso, Fabio Adrián. Fleni. Departamento de Neurología. Sección de Enfermedades Neuromusculares; Argentina.
dc.description.fil Fil: Merlini, Giampaolo. Amyloidosis Center, IRCCS Policlinico San Matteo; Italia. University of Pavia Pavia; Italia.
dc.description.fil Fil: Conceição, Isabel. CHLN Hospital de Santa Maria Lisbon; Portugal.
dc.description.fil Fil: Hughes, Steven G. Ionis Pharmaceuticals Inc; Estados Unidos.
dc.description.fil Fil: Kwoh, Jesse. Akcea Therapeutics; Estados Unidos.
dc.description.fil Fil: Jung, Shiangtung. Indiana University School of Medicine; Estados Unidos.
dc.description.fil Fil: Guthrie, Spencer. Akcea Therapeutics; Estados Unidos.
dc.description.fil Fil: Pollock, Michael. Akcea Therapeutics; Estados Unidos.
dc.description.fil Fil: Benson, Merrill D. Indiana University School of Medicine; Estados Unidos.
dc.description.fil Fil: Gertz, Morie. Mayo Clinic; Estados Unidos.
dc.description.fil Fil: Coelho, Teresa. Centro Hospitalar do Porto Porto; Portugal.
dc.relation.ispartofVOLUME 92
dc.relation.ispartofNUMBER 15 Supplement
dc.relation.ispartofCOUNTRY Estados Unidos
dc.relation.ispartofCITY Hagerstown
dc.relation.ispartofTITLE Neurology
dc.relation.ispartofISSN 1526-632X
dc.type.snrd info:ar-repo/semantics/artículo es_ES


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