Incidence of amyotrophic lateral sclerosis in the United States, 2014–2016

Abstract

Objective: To estimate the incidence of amyotrophic lateral sclerosis (ALS) in the United States for calendar years 2014–2016 using data from the National ALS Registry (Registry). The Registry collects data on ALS patients in the United States to better describe the epidemiology of ALS, examine risk factors such as environmental and occupational exposures, and characterize the demographics of those living with the disease. Methods: To identify adult incident cases of ALS, the Registry compiles data from three national administrative databases (maintained by the Centers for Medicare and Medicaid Services, the Veterans Health Administration, and the Veterans Benefits Administration). For cases that are not included in these databases, the Registry includes data collected from patients who voluntarily enroll via a secure web portal. Results: The Registry identified 5695 ALS cases in 2014; 6045 cases in 2015; and 4861 cases in 2016 for age-adjusted incidence rates of 1.8 (2014), 1.6 (2015), and 1.6 (2016) per 100,000 U.S. population, respectively. ALS was more common among whites, males, and persons aged 60–79 years. Conclusions: This is the first time administrative and self-reported databases have been used to describe the incidence of ALS for the United States resulting in a better estimate of disease demographics.

Keywords:

• Amyotrophic lateral sclerosis
• incidence
• United States

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Correction

Introduction

The United States National ALS Registry is a congressionally mandated, multi-faceted research platform. Launched in October 2010, the goals of the Registry are to better describe the incidence and prevalence of ALS in the United States, examine risk factors such as environmental and occupational factors, and characterize the demographics of persons living with ALS (1).

Unlike most communicable diseases and cancer, which are largely notifiable in the United States, ALS is not a notifiable condition to the Centers for Disease Control and Prevention/Agency for Toxic Substances Disease Registry (2,3). The only state where ALS is reportable to state health authorities is Massachusetts (4); however, Massachusetts does not currently notify CDC/ATSDR of their cases. Previously, the Registry has published national prevalence estimates from 2010–2016 as well as incidence from specific state and metropolitan areas in the United States (2,3,5–8). This analysis provides the first national estimates of incidence rates and case counts from 2014–2016 using administrative and self-reported databases. These years were initially selected for analyses since the Registry has previously published national prevalence estimates for 2014–2016 (2,3,8). Future years of incidence findings will be released as the data are received and analyzed.

Methods

All activities involving human subjects were reviewed and approved by CDC’s Institutional Review Board (IRB). To determine the epidemiological characteristics nationally, the Registry employs an innovative use of administrative and self-reported data for case ascertainment. This method has proven successful for the evaluation of prevalence and will be utilized for incidence calculation for patients receiving an ALS diagnosis for the first time through this analysis (9). A description of this method has been previously published and described thoroughly (3,6). Briefly, to identify incident ALS cases, a pilot-tested algorithm was applied to the three administrative databases (Centers for Medicare and Medicaid Services, Veteran Health Administration, and Veteran Benefits Administration) for years 2014−2016. The algorithm evaluates encounter codes (International Classification of Diseases, 9th and 10th revisions) listing ALS during an any office visit or seeing a neurologist, a death certificate containing ALS as a cause of death, or a prescription for Riluzole, one of only two FDA-approved drugs in the United States for ALS (the other drug, Edaravone, came to market in the United States in 2017, which is outside of this study’s timeframe). Once a patient is confirmed as a definite ALS case, the patient is considered a new ALS case in a given year. The second approach for capturing definite ALS cases is through the Registry’s secure online self-enrollment system which can capture cases that may not be found in the administrative databases. This approach allows patients to self-identify and enroll in the National ALS Registry if screening criteria are met to confirm the patient has ALS (10). Both approaches are merged into a single record for each person to obtain the number of new ALS cases for each year. Incidence was then calculated using the de-duplicated total number of persons with ALS newly identified through administrative data and those who self-identified via the online self-enrollment system for the numerator for each year. These patients are then categorized as an incident ALS case for the respective year. The 2014−2016 Census was used for the denominator in incidence calculations (11,12). Definite ALS incidence cases that are identified in the respective calendar year were also cross referenced with data sources of all previous years to verify their exclusivity. Incidence rates per 100,000 persons were standardized to the US 2000 standard population during 2014–2016 using the direct method. Population estimates used where based by age, sex and race determined by the US Census Bureau (12). Weight calculations were derived in five-year interval from 18 years to 85 years and older. Incidence rates were examined by age, sex, race and census region.

Results

The Registry identified 5695 ALS cases, aged 18 years and older, in 2014, 6045 cases in 2015, and 4861 cases in 2016 (Table 1). The age-adjusted standardized incidence rates per 100,000 population and 95% confidence intervals were 1.8 (1.7–1.9) in 2014, 1.6 (1.5–1.6) in 2015, and 1.6 (1.5–1.6) in 2016. Males had a higher incidence rate (2.2, 2.1–2.3) than females (1.2, 1.2–2.3) in 2014 and this pattern continued. Whites had a higher incidence rate than blacks and those classified as other for all years (Table 1). The age groups with the highest incidence rates across all years were between the ages of 60–69 (4.2–4.4 age-adjusted rates per 100,000) and 70–79 (7.0–7.9 age-adjusted rates per 100,000). The age group with the lowest incidence rates was those between the ages of 18–39 (0.1 age-adjusted rates per 100,000), while those between the ages of 60–79 had the highest rates for all years (Table 2). Incidence rates were also calculated for four US Census regions (Northeast, Midwest, South, and West). Rates were highest in the Midwest for all years (range 2.5 to 2.9 per 100,000 population) and lowest in the South (range from 0.9 to 1.0 per 100,000 population, Table 3).

Table 1 Age-adjusted incidence rates, United States, 2014–2016.

Year	2014		2015		2016
Characteristic	No. (%) cases	Age-adjusted standardized incidence rate, (95% CI)^a	No. (%) cases	Age-adjusted standardized incidence rate, (95% CI)^a	No. (%) cases	Age-adjusted standardized incidence rate, (95% CI)^a
Total	5,695	1.75 (1.70, 1.86)	6,045	1.57 (1.53, 1.62)	4,861	1.56 (1.51, 1.61)
Gender
Male	3,088 (54.2)	2.19 (2.11, 2.28)	3,174 (52.5)	2.66 (2.55, 2.77)	3,118 (64.1)	2.61 (2.51, 2.71)
Female	2,178 (38.2)	1.24 (1.19, 1.30)	2,708 (44.8)	1.89 (1.81, 1.97)	1,740 (35.8)	1.01 (0.96, 1.06)
Unknown	429 (7.5)		163 (2.7)		2 (0)
Race
White	4,727 (83.0)	1.80 (1.75, 1.86)	4,962 (82.1)	1.62 (1.57, 1.67)	3,733 (76.8)	1.56 (1.51, 1.61)
Black	333 (5.8)	1.05 (0.93, 1.17)	365 (6.0)	1.02 (0.90, 1.13)	335 (6.9)	1.07 (0.95, 1.18)
Other	254 (4.5)	1.15 (1.00, 1.31)	325 (5.4)	1.48 (1.31, 1.66)	224 (4.6)	1.15 (1.00, 1.31)
Unknown	381 (6.7)		393 (6.5)		569 (11.7)

^aIncidence rate: per 100,000 population.

Table 2 Age-adjusted incidence rates by age group, 2014–2016.

Age Groups (yrs)	2014^a	2015^a	2016^a
18−39	0.1	0.1	0.1
40−49	0.9	0.5	0.6
50−59	2.0	1.4	1.6
60−69	4.4	4.3	4.2
70−79	7.0	7.9	7.1
≥80	5.7	4.0	3.9

^aIncidence rate: per 100,000 population.

Table 3 Age-adjusted incidence rates by Census regions, United States, 2014–2016.

Year/Region+	No. cases (%)	Age-adjusted standardized incidence rate, (95% CI)^a
2014
Region 1 - NE	1,060 (18.6)	1.91 (1.79, 2.03)
Region 2 - MW	1,984 (34.8)	2.85 (2.72, 2.99)
Region 3 - South	1,305 (22.9)	1.00 (0.94, 1.06)
Region 4 - West	1,112 (19.5)	1.59 (1.49, 1.69)
Unknown	234 (4.1)
2015
Region 1 - NE	960 (15.9)	1.52 (1.41, 1.63)
Region 2 - MW	1,925 (31.8)	2.63 (2.50, 2.76)
Region 3 - South	1,297 (21.5)	0.99 (0.93, 1.05)
Region 4 - West	1,202 (19.9)	1.56 (1.46, 1.66)
Unknown	661 (10.9)
2016
Region 1 - NE	891 (18.3)	1.70 (1.59, 1.82)
Region 2 - MW	1,536 (31.6)	2.50 (2.37, 2.62)
Region 3 - South	1,009 (20.8)	0.90 (0.85, 0.96)
Region 4 - West	899 (18.5)	1.39 (1.30, 1.48)
Unknown	526 (10.8)

^aIncidence rate: per 100,000 population.

+ Region: Northeast: Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont; South: Alabama, Arkansas, Delaware, District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, West Virginia; Midwest: Iowa, Illinois, Indiana, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, South Dakota, Wisconsin; West: Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington, Wyoming.

Discussion

These are the first estimated ALS incidence rates for the United States using national administrative databases merged with a self-enrollment system reported by the National ALS Registry. The Registry has previously published incidence rates for 11 specific state and metropolitan areas which represented a higher proportion of minorities and, therefore, does not necessarily reflect the U.S. as a whole (5,13–18). The findings from these previous state and metropolitan areas analyses are largely consistent with other estimates of ALS incidence in the United States (19,20). When compared to European countries, the current US findings show a lower incidence which is most likely attributable to a heterogenous population (21). Additionally, the variation in annual case counts for this analysis is most likely attributable to a delay in diagnosing ALS as well as a delay in data from the National Death Index which can confirm when a patient is a “definite” ALS case (22). Regardless, the overall incidence rates are stable in the United States at this time. Moreover, these results are consistent with previously published findings on ALS incidence as well as past state and metropolitan level ALS surveillance projects (5). While incidence rates are generally higher in European ALS registries (2.6 per 100,000 population), this most likely reflects the homogenous characteristics of these countries (21,23). These demographic patterns also reflect previously published prevalence estimates from the Registry (2,3,6–8).

The demographics of ALS incidence is consistent with previous prevalence estimates as cases are more common in whites, males, and those aged ≥60 years (2,3,6–8). Also consistent with demographics of prevalent cases, patients aged 18–39 at diagnosis have the lowest incidence rates for all years analyzed. This is thought to be due to ALS onset generally occurring later in life and peaking between the ages of 58–63 for sporadic ALS and 47–52 for familial ALS (24).

Males have a higher incidence rate than females for all years. This may be attributable to males having, as a group, higher differential lifetime exposure to environmental toxins than females (25–27). The age-adjusted differences between whites and blacks were also observed and are consistent with the demographics of disease, that is, ALS appears to affect whites more so than any other demographic group (17).

Incidence rates by US Census regions, specifically the Midwest, may reflect demographic patterns that include a higher proportion of whites in this region than other regions (28). This also could reflect a higher proportion of whites living in Mid-Western states than other parts of the country (28). ALS mortality rates are also higher in the Mid-West than other parts of the country (29). The South had the lowest incidence rates for all years and could reflect either a delay in diagnosis, lack of access for minority patients, or the growing population diversity in this area (22,30).

Since this is the first-time incidence has been reported nationally, additional years of data are needed to reliably detect trends. The limited data presented here suggest the incidence of ALS in the United States. may be steady between 1.6 and 1.8 per 100,000 population.

The findings in this report are subject to several limitations. First, because ALS is not a nationally notifiable disease in the United States, it is a difficult to track the disease. While the “gold standard” in public health surveillance is the monitoring of active cases, rare diseases with low prevalence rate like ALS are less conducive to this method (31). As case ascertainment is limited by the non-notifiable disease status and fragmented healthcare system, to overcome this challenge the Registry relies on three national administrative databases (CMS, VHA and VBA) from which the majority of cases are ascertained. Our method closely resembles the passive case ascertainment, given the current limitations. Nevertheless, we recognize the possibility of under ascertainment due to these three databases not necessarily being representative of the US population when ALS patients seek care outside these health systems. Second, although every attempt was made to deduplicate cases, differences in fields collected from the various sources, misspellings of names, and data entry errors could have prevented records from merging correctly. However, it is unlikely that this occurred in numbers sufficient to affect the overall conclusions.

The National ALS Registry is a multi-faceted research platform. The establishment of the Registry fills an important scientific gap by providing estimates of incidence and prevalence of this disease and facilitates further study of risk factors and etiology. Furthermore, the enhancements to the Registry also increase its potential for ALS research and detection of more cases. As more persons with ALS enroll and complete Registry surveys, a better understanding of possible risk factors might emerge. In addition, future years of incident cases will be reported for the United States as new case data are available.

Declaration of interest

Authors have no conflict of interest.

Correction Statement

This article was originally published with errors, which have now been corrected in the online version. Please see Correction (http://dx.doi.org/10.1080/21678421.2023.2178152)

Additional information

Funding

This work was supported by the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry.