Age- and Sex-Related Differences in Patients With Wild-Type Transthyretin Amyloidosis: Insights From THAOS.

Background

Wild-type transthyretin amyloidosis (ATTRwt amyloidosis) is primarily diagnosed in elderly men but diagnoses in younger patients and women have recently increased.

Objectives

The purpose of this study was to examine age- and sex-related differences in patients with ATTRwt amyloidosis enrolled in the THAOS (Transthyretin Amyloidosis Outcomes Survey).

Methods

THAOS was a global, longitudinal, observational survey of patients with transthyretin amyloidosis, including both hereditary and wild-type disease, and asymptomatic carriers of pathogenic transthyretin gene variants. Patient characteristics at enrollment were analyzed by age at enrollment and sex (data cutoff date: August 1, 2022).

Results

Of 1,251 patients with ATTRwt amyloidosis, 13.7%, 49.1%, 34.5%, and 2.8% were aged <70 years, 70 to 79 years, 80 to 89 years, and ≥90 years, respectively. The proportion of women increased with age, from 4.1% in patients aged <70 years to 14.3% in patients aged ≥90 years. In the respective age groups, median time from symptom onset to diagnosis overall (male, female) was 1.7 (1.3, 5.2), 2.0 (2.0, 2.2), 1.8 (1.9, 0.8), and 0.7 (0.6, 2.5) years. A Karnofsky Performance Status score ≤70 was observed in 17.1%, 30.1%, 46.1%, and 44.4% of patients aged <70 years, 70 to 79 years, 80 to 89 years, and ≥90 years, respectively.

Conclusions

In this THAOS analysis of patients with ATTRwt amyloidosis, patients were diagnosed an average of 2 years after symptom onset, with the greatest diagnostic delay in women aged <70 years at 5 years. Patients were predominantly men, but the proportion of women increased with age. A substantial proportion of patients had significant functional impairment regardless of age. (Transthyretin Amyloidosis Outcome Survey [THAOS]; NCT00628745).

Informations de copyright

© 2024 The Authors.

Déclaration de conflit d'intérêts

The THAOS registry and this analysis were sponsored by 10.13039/100004319Pfizer. Dr Dispenzieri has received research grants from 10.13039/100006436Celgene, Millennium, 10.13039/100004319Pfizer, Janssen, and Alnylam; funding from 10.13039/100004319Pfizer for meeting expenses (travel); and attending advisory boards for Akcea and Intellia. Dr Kristen has received research support from and advisory board attendance for Pfizer, Neurimmune, Alnylam, Intellia, Ionis, Akcea, Novo Nordisk, AstraZeneca, and Alexion. Dr Maurer has received grant support from 10.13039/100000002NIH R01HL139671 and grants from 10.13039/100004319Pfizer during the conduct of the study; grants and personal fees from Alnylam, Pfizer, BridgeBio, Prothena, and Ionis; and personal fees from AstraZeneca, Ionis, Intellia, and Novo Nordisk. Dr Diemberger has received research funding and speaker fees from Daiichi Sankyo and Pfizer outside the scope of the present research. Dr Drachman has received consultancy fees from Alnylam and Eidos. Dr Grogan has received grants, advisory board, and consultancy fees paid to her institution from Alnylam, Eidos, Prothena, and Pfizer. Drs Gupta, Glass, and Amass are full-time employees of Pfizer and hold stock and/or stock options in Pfizer. Dr Garcia-Pavia has received speaking fees from AstraZeneca, Pfizer, Bridgebio, Novo Nordisk, Ionis, Intellia, and Alnylam; consulting fees from Pfizer, Ionis, Intellia, Bridgebio, Neurimmune, Attralus, Novo Nordisk, Alnylam, and AstraZeneca; and research/educational support to his institution from 10.13039/100004319Pfizer, Bridgebio, and Alnylam. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.