Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial

Marcia Waddington-Cruz, Elizabeth J. Ackermann, Michael Polydefkis, Stephen Heitner, Peter J. Dyck, Fabio A. Barroso, Annabel K. Wang, John L. Berk, P. James B. Dyck, Brett P. Monia, Steven G. Hughes, Li Tai, T. Jesse Kwoh, Shiangtung W. Jung, Teresa Coelho, Merrill D. Benson, Morie A. Gertz

    Research output: Contribution to journalArticle

    4 Citations (Scopus)

    Abstract

    Background: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations. Objective: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis. Methods: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial (www.clinicaltrials.gov, NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed. Results: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52%). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70% of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60% of patients had cardiomyopathy, with highest prevalence in the United States (72%) and lowest in South America/Australasia (33%). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity. Conclusions: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems.

    Original languageEnglish (US)
    Pages (from-to)180-188
    Number of pages9
    JournalAmyloid
    Volume25
    Issue number3
    DOIs
    StatePublished - Jul 3 2018

    Fingerprint

    Familial Amyloidosis
    Amyloidosis
    Polyneuropathies
    Quality of Life
    Cardiomyopathies
    Australasia
    Mutation
    Amyloidosis, Hereditary, Transthyretin-Related
    South America
    Biomarkers

    Keywords

    • amyloidosis
    • cardiomyopathy
    • polyneuropathy
    • quality of life
    • Transthyretin

    ASJC Scopus subject areas

    • Internal Medicine

    Cite this

    Waddington-Cruz, M., Ackermann, E. J., Polydefkis, M., Heitner, S., Dyck, P. J., Barroso, F. A., ... Gertz, M. A. (2018). Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial. Amyloid, 25(3), 180-188. https://doi.org/10.1080/13506129.2018.1503593

    Hereditary transthyretin amyloidosis : baseline characteristics of patients in the NEURO-TTR trial. / Waddington-Cruz, Marcia; Ackermann, Elizabeth J.; Polydefkis, Michael; Heitner, Stephen; Dyck, Peter J.; Barroso, Fabio A.; Wang, Annabel K.; Berk, John L.; Dyck, P. James B.; Monia, Brett P.; Hughes, Steven G.; Tai, Li; Jesse Kwoh, T.; Jung, Shiangtung W.; Coelho, Teresa; Benson, Merrill D.; Gertz, Morie A.

    In: Amyloid, Vol. 25, No. 3, 03.07.2018, p. 180-188.

    Research output: Contribution to journalArticle

    Waddington-Cruz, M, Ackermann, EJ, Polydefkis, M, Heitner, S, Dyck, PJ, Barroso, FA, Wang, AK, Berk, JL, Dyck, PJB, Monia, BP, Hughes, SG, Tai, L, Jesse Kwoh, T, Jung, SW, Coelho, T, Benson, MD & Gertz, MA 2018, 'Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial', Amyloid, vol. 25, no. 3, pp. 180-188. https://doi.org/10.1080/13506129.2018.1503593
    Waddington-Cruz, Marcia ; Ackermann, Elizabeth J. ; Polydefkis, Michael ; Heitner, Stephen ; Dyck, Peter J. ; Barroso, Fabio A. ; Wang, Annabel K. ; Berk, John L. ; Dyck, P. James B. ; Monia, Brett P. ; Hughes, Steven G. ; Tai, Li ; Jesse Kwoh, T. ; Jung, Shiangtung W. ; Coelho, Teresa ; Benson, Merrill D. ; Gertz, Morie A. / Hereditary transthyretin amyloidosis : baseline characteristics of patients in the NEURO-TTR trial. In: Amyloid. 2018 ; Vol. 25, No. 3. pp. 180-188.
    @article{047fb544f06842bfa7eff2feea562682,
    title = "Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial",
    abstract = "Background: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations. Objective: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis. Methods: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial (www.clinicaltrials.gov, NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed. Results: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52{\%}). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70{\%} of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60{\%} of patients had cardiomyopathy, with highest prevalence in the United States (72{\%}) and lowest in South America/Australasia (33{\%}). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity. Conclusions: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems.",
    keywords = "amyloidosis, cardiomyopathy, polyneuropathy, quality of life, Transthyretin",
    author = "Marcia Waddington-Cruz and Ackermann, {Elizabeth J.} and Michael Polydefkis and Stephen Heitner and Dyck, {Peter J.} and Barroso, {Fabio A.} and Wang, {Annabel K.} and Berk, {John L.} and Dyck, {P. James B.} and Monia, {Brett P.} and Hughes, {Steven G.} and Li Tai and {Jesse Kwoh}, T. and Jung, {Shiangtung W.} and Teresa Coelho and Benson, {Merrill D.} and Gertz, {Morie A.}",
    year = "2018",
    month = "7",
    day = "3",
    doi = "10.1080/13506129.2018.1503593",
    language = "English (US)",
    volume = "25",
    pages = "180--188",
    journal = "Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis",
    issn = "1350-6129",
    publisher = "Informa Healthcare",
    number = "3",

    }

    TY - JOUR

    T1 - Hereditary transthyretin amyloidosis

    T2 - baseline characteristics of patients in the NEURO-TTR trial

    AU - Waddington-Cruz, Marcia

    AU - Ackermann, Elizabeth J.

    AU - Polydefkis, Michael

    AU - Heitner, Stephen

    AU - Dyck, Peter J.

    AU - Barroso, Fabio A.

    AU - Wang, Annabel K.

    AU - Berk, John L.

    AU - Dyck, P. James B.

    AU - Monia, Brett P.

    AU - Hughes, Steven G.

    AU - Tai, Li

    AU - Jesse Kwoh, T.

    AU - Jung, Shiangtung W.

    AU - Coelho, Teresa

    AU - Benson, Merrill D.

    AU - Gertz, Morie A.

    PY - 2018/7/3

    Y1 - 2018/7/3

    N2 - Background: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations. Objective: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis. Methods: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial (www.clinicaltrials.gov, NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed. Results: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52%). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70% of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60% of patients had cardiomyopathy, with highest prevalence in the United States (72%) and lowest in South America/Australasia (33%). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity. Conclusions: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems.

    AB - Background: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations. Objective: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis. Methods: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial (www.clinicaltrials.gov, NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed. Results: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52%). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70% of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60% of patients had cardiomyopathy, with highest prevalence in the United States (72%) and lowest in South America/Australasia (33%). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity. Conclusions: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems.

    KW - amyloidosis

    KW - cardiomyopathy

    KW - polyneuropathy

    KW - quality of life

    KW - Transthyretin

    UR - http://www.scopus.com/inward/record.url?scp=85053281731&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85053281731&partnerID=8YFLogxK

    U2 - 10.1080/13506129.2018.1503593

    DO - 10.1080/13506129.2018.1503593

    M3 - Article

    C2 - 30169969

    AN - SCOPUS:85053281731

    VL - 25

    SP - 180

    EP - 188

    JO - Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis

    JF - Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis

    SN - 1350-6129

    IS - 3

    ER -