Neuropathy symptom and change: Inotersen treatment of hereditary transthyretin amyloidosis

P. James B. Dyck; Teresa Coelho; Marcia Waddington Cruz; Thomas H. Brannagan; Sami Khella; Chafic Karam; John L. Berk; Michael J. Polydefkis; John C. Kincaid; Janice F. Wiesman; William J. Litchy; Michelle L. Mauermann; Elizabeth J. Ackermann; Brenda F. Baker; Shiangtung W. Jung; Spencer Guthrie; Michael Pollock; Peter J. Dyck

doi:10.1002/mus.27023

Neuropathy symptom and change: Inotersen treatment of hereditary transthyretin amyloidosis

P. James B. Dyck, Teresa Coelho, Marcia Waddington Cruz, Thomas H. Brannagan, Sami Khella, Chafic Karam, John L. Berk, Michael J. Polydefkis, John C. Kincaid, Janice F. Wiesman, William J. Litchy, Michelle L. Mauermann, Elizabeth J. Ackermann, Brenda F. Baker, Shiangtung W. Jung, Spencer Guthrie, Michael Pollock, Peter J. Dyck

Neurology

Research output: Contribution to journal › Article › peer-review

Abstract

Introduction: Hereditary transthyretin-mediated amyloidosis (hATTR) manifests as multisystem dysfunction, including progressive polyneuropathy. Inotersen, an antisense oligonucleotide, improved the course of neuropathic impairment in patients with hATTR in the pivotal NEURO-TTR study (NCT01737398). To determine inotersen's impact on symptoms and patients’ neuropathy experience, we performed a post hoc analysis of the Neuropathy Symptoms and Change (NSC) score. Methods: Stage 1 or 2 hATTR patients were randomized to receive weekly subcutaneous inotersen or placebo for 65 weeks. NSC score was assessed at baseline and 35 and 66 weeks. Results: At 66 weeks, inotersen-treated patients had symptom stabilization as compared with worsening in patients receiving placebo, based on total NSC score. There were also improvements in the subdomains of muscle weakness, sensory, pain, and autonomic symptoms, and for various individual items. Discussion: Inotersen treatment stabilized neuropathy symptoms, including autonomic symptoms, in patients with hATTR according to NSC score. Thus, the NSC may be an effective measure to assess neuropathy progression and patients’ neuropathy experience in clinical practice.

Original language	English (US)
Pages (from-to)	509-515
Number of pages	7
Journal	Muscle and Nerve
Volume	62
Issue number	4
DOIs	https://doi.org/10.1002/mus.27023
State	Published - Oct 1 2020

Keywords

Neuropathy Symptoms and Change
amyloidosis
hATTR
inotersen
transthyretin

ASJC Scopus subject areas

Physiology
Clinical Neurology
Cellular and Molecular Neuroscience
Physiology (medical)

Access to Document

10.1002/mus.27023

Cite this

Dyck, P. J. B., Coelho, T., Waddington Cruz, M., Brannagan, T. H., Khella, S., Karam, C., Berk, J. L., Polydefkis, M. J., Kincaid, J. C., Wiesman, J. F., Litchy, W. J., Mauermann, M. L., Ackermann, E. J., Baker, B. F., Jung, S. W., Guthrie, S., Pollock, M., & Dyck, P. J. (2020). Neuropathy symptom and change: Inotersen treatment of hereditary transthyretin amyloidosis. Muscle and Nerve, 62(4), 509-515. https://doi.org/10.1002/mus.27023

Dyck, PJB, Coelho, T, Waddington Cruz, M, Brannagan, TH, Khella, S, Karam, C, Berk, JL, Polydefkis, MJ, Kincaid, JC, Wiesman, JF, Litchy, WJ , Mauermann, ML, Ackermann, EJ, Baker, BF, Jung, SW, Guthrie, S, Pollock, M & Dyck, PJ 2020, 'Neuropathy symptom and change: Inotersen treatment of hereditary transthyretin amyloidosis', Muscle and Nerve, vol. 62, no. 4, pp. 509-515. https://doi.org/10.1002/mus.27023

@article{59007149adc041b3845d3973a2d6f1ab,

title = "Neuropathy symptom and change: Inotersen treatment of hereditary transthyretin amyloidosis",

abstract = "Introduction: Hereditary transthyretin-mediated amyloidosis (hATTR) manifests as multisystem dysfunction, including progressive polyneuropathy. Inotersen, an antisense oligonucleotide, improved the course of neuropathic impairment in patients with hATTR in the pivotal NEURO-TTR study (NCT01737398). To determine inotersen's impact on symptoms and patients{\textquoteright} neuropathy experience, we performed a post hoc analysis of the Neuropathy Symptoms and Change (NSC) score. Methods: Stage 1 or 2 hATTR patients were randomized to receive weekly subcutaneous inotersen or placebo for 65 weeks. NSC score was assessed at baseline and 35 and 66 weeks. Results: At 66 weeks, inotersen-treated patients had symptom stabilization as compared with worsening in patients receiving placebo, based on total NSC score. There were also improvements in the subdomains of muscle weakness, sensory, pain, and autonomic symptoms, and for various individual items. Discussion: Inotersen treatment stabilized neuropathy symptoms, including autonomic symptoms, in patients with hATTR according to NSC score. Thus, the NSC may be an effective measure to assess neuropathy progression and patients{\textquoteright} neuropathy experience in clinical practice.",

keywords = "Neuropathy Symptoms and Change, amyloidosis, hATTR, inotersen, transthyretin",

author = "Dyck, {P. James B.} and Teresa Coelho and {Waddington Cruz}, Marcia and Brannagan, {Thomas H.} and Sami Khella and Chafic Karam and Berk, {John L.} and Polydefkis, {Michael J.} and Kincaid, {John C.} and Wiesman, {Janice F.} and Litchy, {William J.} and Mauermann, {Michelle L.} and Ackermann, {Elizabeth J.} and Baker, {Brenda F.} and Jung, {Shiangtung W.} and Spencer Guthrie and Michael Pollock and Dyck, {Peter J.}",

note = "Publisher Copyright: {\textcopyright} 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.",

year = "2020",

month = oct,

day = "1",

doi = "10.1002/mus.27023",

language = "English (US)",

volume = "62",

pages = "509--515",

journal = "Muscle and Nerve",

issn = "0148-639X",

publisher = "John Wiley and Sons Inc.",

number = "4",

}

TY - JOUR

T1 - Neuropathy symptom and change

T2 - Inotersen treatment of hereditary transthyretin amyloidosis

AU - Dyck, P. James B.

AU - Coelho, Teresa

AU - Waddington Cruz, Marcia

AU - Brannagan, Thomas H.

AU - Khella, Sami

AU - Karam, Chafic

AU - Berk, John L.

AU - Polydefkis, Michael J.

AU - Kincaid, John C.

AU - Wiesman, Janice F.

AU - Litchy, William J.

AU - Mauermann, Michelle L.

AU - Ackermann, Elizabeth J.

AU - Baker, Brenda F.

AU - Jung, Shiangtung W.

AU - Guthrie, Spencer

AU - Pollock, Michael

AU - Dyck, Peter J.

PY - 2020/10/1

Y1 - 2020/10/1

N2 - Introduction: Hereditary transthyretin-mediated amyloidosis (hATTR) manifests as multisystem dysfunction, including progressive polyneuropathy. Inotersen, an antisense oligonucleotide, improved the course of neuropathic impairment in patients with hATTR in the pivotal NEURO-TTR study (NCT01737398). To determine inotersen's impact on symptoms and patients’ neuropathy experience, we performed a post hoc analysis of the Neuropathy Symptoms and Change (NSC) score. Methods: Stage 1 or 2 hATTR patients were randomized to receive weekly subcutaneous inotersen or placebo for 65 weeks. NSC score was assessed at baseline and 35 and 66 weeks. Results: At 66 weeks, inotersen-treated patients had symptom stabilization as compared with worsening in patients receiving placebo, based on total NSC score. There were also improvements in the subdomains of muscle weakness, sensory, pain, and autonomic symptoms, and for various individual items. Discussion: Inotersen treatment stabilized neuropathy symptoms, including autonomic symptoms, in patients with hATTR according to NSC score. Thus, the NSC may be an effective measure to assess neuropathy progression and patients’ neuropathy experience in clinical practice.

AB - Introduction: Hereditary transthyretin-mediated amyloidosis (hATTR) manifests as multisystem dysfunction, including progressive polyneuropathy. Inotersen, an antisense oligonucleotide, improved the course of neuropathic impairment in patients with hATTR in the pivotal NEURO-TTR study (NCT01737398). To determine inotersen's impact on symptoms and patients’ neuropathy experience, we performed a post hoc analysis of the Neuropathy Symptoms and Change (NSC) score. Methods: Stage 1 or 2 hATTR patients were randomized to receive weekly subcutaneous inotersen or placebo for 65 weeks. NSC score was assessed at baseline and 35 and 66 weeks. Results: At 66 weeks, inotersen-treated patients had symptom stabilization as compared with worsening in patients receiving placebo, based on total NSC score. There were also improvements in the subdomains of muscle weakness, sensory, pain, and autonomic symptoms, and for various individual items. Discussion: Inotersen treatment stabilized neuropathy symptoms, including autonomic symptoms, in patients with hATTR according to NSC score. Thus, the NSC may be an effective measure to assess neuropathy progression and patients’ neuropathy experience in clinical practice.

KW - Neuropathy Symptoms and Change

KW - amyloidosis

KW - hATTR

KW - inotersen

KW - transthyretin

UR - http://www.scopus.com/inward/record.url?scp=85089074041&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85089074041&partnerID=8YFLogxK

U2 - 10.1002/mus.27023

DO - 10.1002/mus.27023

M3 - Article

C2 - 32654156

AN - SCOPUS:85089074041

SN - 0148-639X

VL - 62

SP - 509

EP - 515

JO - Muscle and Nerve

JF - Muscle and Nerve

IS - 4

ER -

Neuropathy symptom and change: Inotersen treatment of hereditary transthyretin amyloidosis

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this