Up to 3 in 100,000 people in US affected by cold agglutinin disease
Researchers analyzed 2016-2023 data from national claim databases
Up to about 1 person in 100,000 in the U.S. is estimated to be diagnosed with primary cold agglutinin disease (CAD) each year and up to 3 in 10,000 people are living with the disease, a study that analyzed 2016-2023 data from national claim databases suggests.
Primary CAD refers to a form of the disease where its cause is unknown, while secondary CAD refers to an association with other underlying conditions. In addition, primary autoimmune hemolytic anemia (AIHA), a group of conditions that include CAD, was estimated to affect up to 20 people per 100,000.
“This research offers a comprehensive view of the current burden of AIHA and CAD, which is essential for improving clinical care and informing public health planning,” the researchers wrote. The study, “Prevalence and incidence of primary autoimmune hemolytic anemia and cold agglutinin disease in the United States, 2016–2023,” was published in PLOS One. All its authors are employees of or consultants for Sanofi, which manufactures Enjaymo (sutimlimab-jome), the only CAD-approved therapy.
AIHA refers to conditions wherein the immune system mistakenly targets red blood cells. In CAD, which accounts for up to 20% of AIHA cases, this immune response is triggered by cold temperatures, with resulting lower red blood cell counts leading to a shortage of oxygen in the bloodstream, causing symptoms such as fatigue and pain.
“Although AIHA is recognized as a serious health condition, the available estimates of its incidence and prevalence remain limited and often outdated,” the researchers wrote. “This is particularly true for CAD, which, despite its impact on older adults, is underrepresented in contemporary epidemiological studies [which look at occurrence, distribution, and patterns of health and disease].” Incidence refers to the number of new cases within a given time, while prevalence is the total number of cases. Previous estimates across North American and Nordic countries put the incidence of CAD at 0.3 per 100,000 people and the prevalence at 1.6 per 100,000 people.
Updating CAD data
“The lack of comprehensive, updated epidemiological data has hindered the development of targeted interventions and accurate healthcare resource allocation,” wrote the researchers, who performed what they called a first-of-its-kind comprehensive epidemiological analysis of primary AIHA and CAD in the U.S.
Their sources were three databases of health insurance claims, two of which included information from several insurance providers. The third included people covered only by Medicare, a federal health insurance program primarily for older people.
Standardized insurance claim codes allowed the researchers to identify cases of adults with primary AIHA or CAD. To increase the reliability of this method, they only included people with at least 180 days (about six months) of continuous health plan enrollment and at least two claims with appropriate codes. The team then standardized these estimates using census data from different age and sex groups.
This methodology yielded the estimated annual incidence of 0.6 to 1.2 new CAD cases per 100,000 people. Over a calendar year, there were about 1.4 to 3.1 total cases per 100,000 people (one-year prevalence). These estimates include the years 2021 through 2022, as insurance claims began using CAD-specific codes in 2020.
Estimates for AIHA spanned 2016 to 2022. The annual incidence was about 1.4 to 6.6 per 100,000 people and the one-year prevalence was about 4.2 to 20.6 per 100,000 people.
“Prevalence and incidence of AIHA and CAD varied across the three databases,” with the Medicare database showing “the highest estimates, primarily capturing individuals aged [65 years or older],” the researchers wrote.
Prevalence, incidence affected by age, sex
Consistent with these findings, prevalence and incidence also increased with age with people over age 65 at the highest risk, possibly due to natural changes in the immune system. Therefore, the Medicare database was likely the most representative of these patient populations.
Also, both AIHA and CAD had higher incidence and prevalence in females than males, which “may be attributed to hormonal influences, particularly estrogen, which can modulate immune system responses and increase susceptibility to autoimmune diseases,” the researchers wrote.
No clear geographical patterns emerged in CAD prevalence across the 50 states. Previous studies have found higher rates of CAD in colder climates, but these results didn’t mirror that finding.
Several limitations may apply to the study because of the nature of insurance claims data. The databases only include diagnosed cases and don’t cover people without health insurance. Also, the case counts may have excluded some AIHA and CAD claims coded as “unspecified” or “other.”
Still, the updated incidence and prevalence estimates can help direct resources to those who need them most, the researchers said. “Public health policy should focus on improving early detection, particularly in high-risk populations, and support research into the mechanisms that drive the higher incidence among females and older individuals,” they wrote.
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