Prevalence, Incidence, and Characterization of LIGHT Chain Amyloidosis in the USA: A Real-World Analysis Utilizing Electronic Health Records (EHR)

Background: Light chain (AL) amyloidosis is a rare disease characterized by the deposition of misfolded immunoglobulin light chains, resulting in organ dysfunction and significant morbidity and mortality. However, population-based studies on the epidemiology of AL are limited. This study aimed to provide an up-to-date assessment of the prevalence and incidence of AL, examine temporal changes in prevalence over a 5-year period, and characterize the AL population in the USA.

Methods: A retrospective analysis was conducted using de-identified patient records from Optum's Clinical Electronic Health Record (EHR) database (>140,000 providers and >60 million unique patients). Adults with AL were identified based on ≥2 diagnosis codes (ICD-10-CM code E85.81) or positive mentions about the disease (including clinical features indicative of AL) found in the physician's notes (≥30 days apart). Patients with clinical data at least 12 months pre- index event (defined as the date of the first AL amyloidosis diagnosis or positive mention during the identification period: January 01, 2017 - December 31, 2021) were included in the analysis. Prevalence estimates were calculated for each year between 2017 and 2021, and annual percentage changes were assessed to determine temporal trends. Annual incidence was calculated as the number of newly diagnosed AL cases occurring each year between 2019 and 2021. Additionally, patient demographics, comorbidities, and Mayo 2004 staging with European modification (based on availability of the cardiac biomarkers: NT-proBNP and troponin) were characterized at index date or in the 12-month post index period.

Results: A total of 1471 AL patients were included in the study population. The mean age of the prevalent patients was 67.2 years, with 54.5% being male. Most patients were White (78.5%), followed by Black (14.5%), Hispanic (3.3%), Asian (1.2%), and other/unknown (2.6%).

The diagnosed prevalence of AL substantially increased from 22.7 to 69.1 cases per million between 2017 and 2021, with an annual growth rate of 32.1%. In 2021, the annual incidence of AL was estimated to be 16.7 patients per million in the general population, with an annual growth rate of 7.7% since 2019, at which time incidence was 14.4 patients per million. The distribution of patients by Mayo stage at diagnosis among those with available biomarker information (n=613, 42% of total sample) was: Stage I, 27%; Stage II, 42%; Stage IIIa, 16%; and Stage IIIb, 15%.

The most prevalent comorbidities reported in the year after diagnosis were hypertension (56.6%), dyslipidaemia (51.7%), chronic kidney disease (41.3%), multiple myeloma and malignant plasma cell neoplasms (37.5%), and heart failure (34.5%). Cardiomyopathy was observed in 40.2% of the AL patients.

Conclusions: This study provides an updated report of the prevalence and incidence of AL using a large-scale EHR database. The observed rise in AL prevalence and incidence is likely due to a combination of increased disease awareness and improvements in detection and management. The number of comorbidities, especially those related to cardiac function, suggest a continuing unmet need for more therapeutic options. Furthermore, the Mayo stage distribution of patients highlights the need for enhanced efforts to diagnose AL earlier due to the high mortality associated with advanced Mayo stages. These epidemiological findings reinforce the importance of continuous monitoring of prevalence, incidence trends, and the burden of AL in the US.