Contemporary Description of Clinical Characteristics and Outcomes in Patients with Hereditary ATTR Amyloidosis: Results from the Multicountry OverTTuRe Study

Timely diagnosis and treatment are essential for improving outcomes and quality of life in patients with transthyretin (ATTR) amyloidosis. Early multisystem manifestations are often unrecognized, leading to diagnostic delays and misdiagnosis. Large-scale, multicountry, observational studies are needed to better characterize the real-world trajectory of these patients. OverTTuRe, an ANTHOLOGY study, is a retrospective, observational, descriptive, longitudinal, multicountry study using secondary data from claims databases, electronic health records, and healthcare registries. The primary aim of this analysis was to characterize baseline characteristics, early clinical manifestations, and outcomes in patients with hereditary transthyretin (ATTRv) amyloidosis from the United States (US), United Kingdom (UK), Japan, Denmark, and Sweden. Of 1502 patients identified, the predominant phenotype across countries was ATTRv amyloidosis with polyneuropathy (ATTRv-PN 51.3–63.7%); however, many patients had ATTRv with mixed phenotype (ATTRv mixed 36.3–48.8%). Compared to patients with ATTRv mixed, patients with ATTRv-PN were younger, and a higher proportion were female (36.6–64.1% vs. 19.3–56.4%). Median (interquartile range) time from any initial cardiac or noncardiac manifestation to diagnosis varied across countries; time from any noncardiac manifestation to diagnosis was longest for both phenotypes in the US (ATTRv-PN 2.9 1.0–4.0 years; ATTRv mixed 2.4 0.8–3.7 years). Following diagnosis, treatment was not available for most patients. Mortality (ATTRv-PN 14.6–36.2%; ATTRv mixed 21.0–73.0%) and hospitalization (ATTRv-PN 23.5–66.2%; ATTRv mixed 20.8–70.5%) risk varied across countries in the 5 years following diagnosis. Pre- and post-diagnosis healthcare resource utilization was high for both phenotypes. These findings highlight the heterogeneity of clinical manifestations and outcomes of ATTRv amyloidosis across phenotypes and countries. Patients frequently experience diagnostic delays and numerous healthcare interactions. Elevated clinical suspicion to facilitate earlier diagnosis, together with a multidisciplinary care approach and timely access to targeted therapies, is needed to improve outcomes. ClinicalTrials.gov identifier NCT06355934. The goal of this research was to better understand the real-world care of patients with hereditary transthyretin (ATTRv) amyloidosis. Diagnosing this disease can be challenging due to its diverse symptoms, which often lead to delays and misdiagnosis. By studying patients across different countries, researchers aimed to evaluate patterns that could improve early diagnosis and treatment. Researchers identified patients across the US, the UK, Japan, Denmark, and Sweden from 2014 to 2023. Data sources included electronic health records, claims databases, and healthcare registries. Researchers categorized patients into ATTRv with polyneuropathy (ATTRv-PN) and mixed phenotype groups. The study analyzed patient demographics, symptoms, healthcare visits, and treatments. Significant variation in symptoms and outcomes among patients with ATTRv amyloidosis was found. Many patients experienced diagnostic delays of up to 3.5 years, especially those with mixed phenotypes. Healthcare use was high, with frequent outpatient visits and hospital stays. Survival rates varied across countries and phenotypes. Despite available treatment options, many patients did not receive them, especially in the US and UK. These findings highlight the need for increased awareness and better diagnostic practices for ATTRv amyloidosis, including adapting to the diverse disease presentations. Early diagnosis and treatment can improve patient outcomes, reduce healthcare use, and enhance quality of life.