A Consolidated Overview Of 14 Years Of Global Data From The Transthyretin Amyloidosis Outcomes Survey

Abstract

Introduction The Transthyretin Amyloidosis Outcomes Survey (THAOS) is a global, longitudinal, observational study of patients with transthyretin amyloidosis (ATTR amyloidosis), including both inherited (ATTRv amyloidosis) and wild-type (ATTRwt amyloidosis) disease, and asymptomatic patients with transthyretin (TTR) mutations (NCT00628745). Methods This descriptive analysis provides a consolidated overview of 14 years of global demographics and clinical characteristics of patients with ATTR amyloidosis enrolled in THAOS as of January 4, 2021. The data period spans 2007 to 2021. Results There were 3604 symptomatic patients and 1772 asymptomatic carriers enrolled in THAOS. Of the symptomatic patients, 1055 had ATTRwt amyloidosis (93.8% male) and 2549 had ATTRv amyloidosis (61.6% male); the most prevalent TTR mutation was Val30Met (1493/2549; 58.6%). Median age at symptom onset was higher in patients with ATTRwt amyloidosis (73.0 years) vs patients with Val30Met (40.0 years), non-Val30Met (excluding cardiac; 51.5 years), and cardiac (64.5 years) mutations. In North America, the majority of patients had ATTRwt amyloidosis (58.8%), whereas in Europe, South America, and Japan ATTRv amyloidosis was more common. The most common phenotype was cardiac in North America (73.1%) and neurologic in South America (66.1%), Europe (52.1%), and Japan (56.9%). Of the asymptomatic carriers, 41.9% were male and median age at enrollment was 39.8 years. The most prevalent mutation was Val30Met (70.9%), followed by non-Val30Met (excluding cardiac; 18.3%), and cardiac (10.8%) mutations. Conclusions These results revealed regional differences in relative rates of ascertainment of ATTRwt vs ATTRv amyloidosis and predominant phenotypes. However, this registry analysis may be limited by under-ascertainment and underreporting. The Transthyretin Amyloidosis Outcomes Survey (THAOS) is a global, longitudinal, observational study of patients with transthyretin amyloidosis (ATTR amyloidosis), including both inherited (ATTRv amyloidosis) and wild-type (ATTRwt amyloidosis) disease, and asymptomatic patients with transthyretin (TTR) mutations (NCT00628745). This descriptive analysis provides a consolidated overview of 14 years of global demographics and clinical characteristics of patients with ATTR amyloidosis enrolled in THAOS as of January 4, 2021. The data period spans 2007 to 2021. There were 3604 symptomatic patients and 1772 asymptomatic carriers enrolled in THAOS. Of the symptomatic patients, 1055 had ATTRwt amyloidosis (93.8% male) and 2549 had ATTRv amyloidosis (61.6% male); the most prevalent TTR mutation was Val30Met (1493/2549; 58.6%). Median age at symptom onset was higher in patients with ATTRwt amyloidosis (73.0 years) vs patients with Val30Met (40.0 years), non-Val30Met (excluding cardiac; 51.5 years), and cardiac (64.5 years) mutations. In North America, the majority of patients had ATTRwt amyloidosis (58.8%), whereas in Europe, South America, and Japan ATTRv amyloidosis was more common. The most common phenotype was cardiac in North America (73.1%) and neurologic in South America (66.1%), Europe (52.1%), and Japan (56.9%). Of the asymptomatic carriers, 41.9% were male and median age at enrollment was 39.8 years. The most prevalent mutation was Val30Met (70.9%), followed by non-Val30Met (excluding cardiac; 18.3%), and cardiac (10.8%) mutations. These results revealed regional differences in relative rates of ascertainment of ATTRwt vs ATTRv amyloidosis and predominant phenotypes. However, this registry analysis may be limited by under-ascertainment and underreporting.