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

Marcia Waddington-Cruz, Elizabeth J. Ackermann, Michael Polydefkis, Stephen B. 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 Benson, Morie A. Gertz

Research output: Contribution to journalArticle

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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)
JournalAmyloid
DOIs
StateAccepted/In press - Jan 1 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. B., Dyck, P. J., Barroso, F. A., ... Gertz, M. A. (Accepted/In press). Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial. Amyloid. 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 B.; 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; Gertz, Morie A.

In: Amyloid, 01.01.2018.

Research output: Contribution to journalArticle

Waddington-Cruz, M, Ackermann, EJ, Polydefkis, M, Heitner, SB, Dyck, PJ, Barroso, FA, Wang, AK, Berk, JL, Dyck, PJB, Monia, BP, Hughes, SG, Tai, L, Jesse Kwoh, T, Jung, SW, Coelho, T, Benson, M & Gertz, MA 2018, 'Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial', Amyloid. https://doi.org/10.1080/13506129.2018.1503593
Waddington-Cruz M, Ackermann EJ, Polydefkis M, Heitner SB, Dyck PJ, Barroso FA et al. Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial. Amyloid. 2018 Jan 1. https://doi.org/10.1080/13506129.2018.1503593
Waddington-Cruz, Marcia ; Ackermann, Elizabeth J. ; Polydefkis, Michael ; Heitner, Stephen B. ; 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 ; Gertz, Morie A. / Hereditary transthyretin amyloidosis : baseline characteristics of patients in the NEURO-TTR trial. In: Amyloid. 2018.
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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.",
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AU - Heitner, Stephen B.

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.

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