Abstract
Purpose
Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive genetic disorder characterized by asymmetric muscle weakness and functional decline. Although it is one of the most common muscular dystrophies, its economic burden in the United States (US) is largely unknown. This study aimed to provide an initial, conservative estimate of annual medical claims costs and identify comorbidities disproportionately affecting individuals with FSHD in the US.
Patients and Methods
This retrospective, 1:5 matched case-control study analyzed de-identified claims data from Medicare and commercially insured enrollees from 2018 to 2021. Medical and prescription costs were aggregated and described as means with 95% confidence intervals. T-tests with Bonferroni correction and chi-square tests were used to compare comorbidity prevalence.
Results
The study included 383 individuals with FSHD and 1915 matched controls. The mean annual medical claims cost for the FSHD cohort was $19,370 per person with commercial insurance and $11,704 with Medicare, compared with $5250 among controls. Individuals with FSHD also incurred higher prescription claims costs in commercial and Medicare subgroups without comorbidities. The prevalence of cerebrovascular disease (10.18% vs 4.44%) and ear disorders (8.09% vs. 3.39%) was significantly greater in the FSHD cohort (P<0.05).
Conclusion
This exploratory study provides the first US-based description of the direct medical costs of FSHD, demonstrating a substantially higher healthcare burden than that of matched controls. Because the study design likely underestimates costs, the true economic impact may be even greater. These findings establish a critical foundation for future research into the lifetime medical, nonmedical, and caregiver-related costs of FSHD, and highlight the urgent need for effective therapies and supportive care strategies.
Keywords: FSHD, muscular dystrophy, economic burden, cost of illness, direct cost, HEOR
Plain Language Summary
Facioscapulohumeral muscular dystrophy (FSHD) is a rare muscle disease that causes progressive weakness in the face, shoulders, upper arms, core, and legs. Over time, it can make everyday tasks such as lifting, walking, or speaking more difficult. While FSHD is one of the most common muscular dystrophies, little is known about its financial impact on people living with the condition and the healthcare system in the United States.
To better understand this burden, this study evaluated medical insurance claims for individuals with FSHD and compared them with those of individuals without FSHD. We examined costs from both commercial insurance and Medicare between 2018 and 2021.
Individuals with FSHD had substantially higher medical costs than those without the condition. Average annual medical claims were $19,370 for those with commercial insurance and $11,704 for those on Medicare, compared with $5250 for matched individuals without FSHD. Individuals with FSHD also had more prescriptions and were more likely to have claims for other health problems, such as stroke-related conditions and ear disorders.
These results show that FSHD is associated with a meaningful financial burden on the healthcare system. Because this study was based on claims data and likely underestimates the full cost of care, the real burden may be even higher. Understanding these costs is an important first step toward improving care, planning support services, and encouraging investment in better treatments for people living with FSHD.
Introduction
Facioscapulohumeral muscular dystrophy (FSHD, OMIM #158900) is a rare, progressive, and lifelong autosomal dominant muscular dystrophy that typically affects the facial, shoulder girdle, trunk, and limb muscles.1,2 It is one of the most common hereditary myopathies, with an estimated global prevalence ranging from 1 in 20,000 to 1 in 8000 individuals.3–5 Within the United States (US), Flanigan et al estimated a prevalence of 1 in 15,000 in the Utah/Southern Idaho region.6 FSHD is caused by the epigenetic derepression of Double Homeobox 4 (DUX4), a transcription factor that is normally silenced in most somatic tissues.7–9
Individuals with FSHD generally present in the second or third decade of life, with heterogeneous and asymmetric muscle weakness. The most commonly reported functional motor limitations include difficulty performing activities that require arm elevation above shoulder level, impaired ability to rise from bed, reduced walking capacity, and difficulty climbing stairs. The diagnosis of FSHD is also associated with chronic pain, fatigue, and reduced quality of life.10–12 In more severe cases, individuals with FSHD may experience respiratory insufficiency, cardiac arrhythmias, high-frequency hearing loss, and retinal vascular disease that may progress to Coat’s disease.13,14 Many individuals with FSHD also report persistent symptoms such as sleep disturbances, headaches, and mood alterations. These challenges contribute to poorer physical and emotional health, increased risk of falls and injuries due to muscle weakness, pain, lower educational achievement, and higher unemployment rates.11,13,15–17
Diagnosing FSHD can be challenging for healthcare providers due to clinical heterogeneity and complex genetic mechanisms.18 Furthermore, genetic testing for FSHD is not readily available, and due to the technical complexity of testing, it has not yet benefited from advances in panel-based next-generation sequencing. These factors affect timely patient evaluation, specialty referrals, and treatment planning.19 As a result, the FSHD patient journey often involves initial misdiagnoses, requiring multiple diagnostic modalities (imaging, biopsy, and genetic testing), frequent and costly visits to specialists and allied health providers, and multiple interventions, including medications and surgeries.
Current disease management primarily focuses on pain control, orthotic support, surgical stabilization, and physical therapy.12 Without a disease-modifying therapy, FSHD progression leads to costly management and substantial quality of life impacts for both patients and their families. Individuals with FSHD can require ventilatory support, home care, and facility-based care.20 Caregivers may experience physical strain, significant injuries, mental health challenges, and financial hardship while providing care for a loved one with FSHD.21,22 While the extensive clinical burden justifies economic evaluation, an additional rationale is the accelerating momentum around genetic and molecular therapies for FSHD. As these programs advance, robust baseline estimates of healthcare costs are essential to inform value assessments, coverage decisions, and equitable access strategies.23
Limited research has examined the economic burden of FSHD-specific healthcare management in the US, particularly using healthcare utilization and insurance claims data. Prior studies from other countries suggest that FSHD is associated with a substantial socioeconomic burden. For example, a cross-sectional survey from the Dutch FSHD registry showed that a diagnosis of FSHD incurs substantial direct and indirect socioeconomic costs, especially among individuals with limited mobility.20 Similarly, a German study using patient questionnaires and diaries involving patients with neuromuscular disorders, including FSHD, amyotrophic lateral sclerosis, and myasthenia gravis, demonstrated that disease-related costs are high and increase with severity and clinical progression.24 Beyond FSHD, Larkindale et al used administrative claims data to estimate direct medical costs in other progressive neuromuscular diseases, including amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and myotonic dystrophy.25
Administrative claims offer a valuable method for assessing healthcare utilization and economic impact. In rare diseases, claims-based analyses may be limited by the availability of disease-specific International Classification of Diseases (ICD) codes, resulting in an underestimation of patient numbers and disease burden.26 Claims databases also typically lack information on disease severity and functional status, which may limit characterization of heterogeneous rare-disease populations.27 Prior to 2018, FSHD patients were generally identified under the broad muscular dystrophy code (ICD-10 G71.0). In October 2018, a dedicated ICD-10 code (G71.02) was introduced for FSHD, enabling claims-based studies of medical costs.28
In response to unmet needs within the FSHD community, a coalition of patient advocacy organizations launched Project Mercury, a global initiative to accelerate therapeutic development and improve patient access to future treatments.29 To advance these goals, we aimed to assess the direct medical costs associated with FSHD in the US. The primary objective of this study was to estimate medical claims costs for individuals with FSHD in the US and compare them to those of matched individuals without FSHD. Secondary objectives included identifying comorbidities disproportionately prevalent among individuals with FSHD and subgroups (eg, age, sex, mental health status) with elevated medical claims costs.
Materials and Methods
Study Design
This is a retrospective, matched case-control study utilizing de-identified administrative claims data, encompassing Medicare and commercially insured health plan enrollees in the US. The database contains medical (emergency, inpatient, and outpatient) and pharmacy claims for services submitted for third-party reimbursement, available as ICD-10 Clinical Modification (CM) and National Drug Codes claims, respectively. Depending on the plan type, facility fees may or may not have been captured. The data spanned from October 1, 2018, to August 30, 2021, and included claims during the Coronavirus-19 (COVID-19) pandemic. Baseline patient characteristics included age, sex, urban-suburban-rural (USR) classification, geographic region, income level by zip code, coverage type, and prior comorbid conditions. Comorbid conditions were assessed through paid medical claims based on ICD-10 codes. Cost utilization was stratified by insurance type and categorized into commercial plans with and without prescription medication (Rx) coverage and Medicare plans with and without Rx coverage. The UnitedHealth Group Office of Human Research Affairs determined that the study was exempt from Institutional Review Board review because the data were de-identified and collected for non-research purposes.
Study Cohorts
The FSHD cohort was identified using the ICD-10-CM code G71.02. To preserve sample size, inclusion required at least one FSHD diagnosis within the study period. Each individual with FSHD was matched to five control individuals without FSHD (control cohort) within each insurance type based on age, sex, state, and USR class, with further matching to the nearest neighbor by median income at the zip code level. The index date was defined as the first occurrence of the FSHD ICD-10 code in the medical record during the study period, while controls were assigned a random claim date using a uniform distribution. Inclusion criteria for both cohorts required continuous enrollment for at least six months after the index date. Exclusion criteria included duplicate records, less than six months of continuous enrollment, missing demographic information, and no eligible matches in the control group.
Statistical Analysis
Matched cohort characteristics were compared descriptively, and comorbidity frequencies were compared using t-tests with Bonferroni correction for multiple comparisons for continuous variables and chi-square tests for categorical variables. Statistical significance was defined as p < 0.05. Aggregate cost data provided to the study team included means and sample sizes for (1) procedures, services, and durable medical equipment (DME) costs and (2) Rx costs; both disaggregated by insurance type (commercial or Medicare, with or without Rx coverage). Costs were described as means with 95% confidence intervals (CI) and medians with first and third quartiles.
Subgroup analyses were stratified by age, sex, number of prior comorbidities, and the presence of a mental health diagnosis. Comorbidities were identified using the Charlson Index and a list curated by the study team based on known and suspected FSHD symptomology (Supplementary Table 1).30 From the data provided, descriptive statistics were calculated for procedures, services, and DME costs for a “combined” group across Rx coverage scenarios.
Within the Medicare data, descriptive comparisons focused on two specific subgroups: (1) individuals with no comorbidities and (2) those aged 65 years and older. This approach ensured that the FSHD cohort was compared to control groups representative of the general Medicare population, which typically comprises individuals aged over 65, rather than those under age 65, who qualify for Medicare due to severe disability.31 Comparisons of individuals with FSHD in other age and subgroup categories were made against commercially insured controls to mitigate this confounding factor.
Results
Cohort Characterization
The primary analysis included 383 individuals with FSHD and 1915 matched controls meeting the study selection criteria (Figure 1). Participant demographics and baseline characteristics are listed in Table 1. The FSHD cohort was predominantly aged 40 or older (85.90%), male (53.26%), and resided in rural areas (49.61%). All baseline characteristics were matched in a 1:5 ratio between cohorts.
Figure 1.
FSHD and Control Cohort Selection. Inclusion and exclusion criteria used to select the FSHD (white) and control (gray) cohorts from the de-identified administrative claims database. The number of records assessed at each step is indicated by (n). Cohort stratification by insurance type and prescription (Rx) coverage is shown at the bottom.
Table 1.
Cohort Demographics
| Descriptive Characteristics, N (%) | FSHD Cohort N = 383 |
Control Cohort N = 1915 |
|---|---|---|
| Age Groups (Years) | ||
| <20 | 10 (2.61) | 50 (2.61) |
| 20–39 | 44 (11.49) | 220 (11.49) |
| 40–64 | 162 (42.30) | 810 (42.30) |
| >65 | 167 (43.60) | 835 (43.60) |
| Sex | ||
| Female | 179 (46.74) | 895 (46.74) |
| Male | 204 (53.26) | 1020 (53.26) |
| Region | ||
| Midwest | 85 (22.19) | 425 (22.19) |
| Northeast | 44 (11.49) | 220 (11.49) |
| South | 162 (42.30) | 810 (42.30) |
| West | 92 (24.02) | 460 (24.02) |
| USR Classification | ||
| Urban | 81 (21.15) | 405 (21.15) |
| Suburban | 112 (29.24) | 560 (29.24) |
| Rural | 190 (49.61) | 950 (49.61) |
| Insurance Type | ||
| Commercial without Rx Coverage | 24 (6.27) | 172 (8.98) |
| Commercial with Rx Coverage | 87 (22.72) | 383 (20.00) |
| Medicare without Rx Coverage | 36 (9.40) | 221 (11.54) |
| Medicare with Rx Coverage | 236 (61.62) | 1139 (59.48) |
| Zip Code Level Income ($) | ||
| ≤40,000 | 13 (3.39) | 62 (3.24) |
| 40,001–60,000 | 215 (56.14) | 1,091 (56.97) |
| 60,001–80,000 | 104 (27.15) | 506 (26.42) |
| >80,000 | 51 (13.32) | 256 (13.37) |
| Months Enrolled Prior to Index, Mean (SD) | 9.59 (3.71) | 10.36 (3.24) |
Abbreviations: USR, urban/suburban/rural; Rx, prescription medication; SD, standard deviation.
Comorbid Conditions
Individuals with FSHD had a significantly higher prevalence of cerebrovascular disease and ear disorders compared to controls (Table 2 and Supplementary Table 2). Other comorbidities, such as gastrointestinal disorders and diabetes, did not differ significantly (Supplementary Table 1).
Table 2.
Number of Prior Comorbid Conditions and Significant Comorbidities
| N (%) | FSHD Cohort N = 383 |
Control Cohort N = 1915 |
P-value (Bonferroni) |
|---|---|---|---|
| Total Number of Prior Comorbidities | |||
| 0 | 128 (33.42) | 795 (41.51) | – |
| 1 | 112 (29.24) | 519 (27.10) | – |
| 2 | 80 (20.89) | 312 (16.29) | – |
| 3+ | 63 (16.45) | 289 (15.09) | – |
| Comorbidities with Significant Prevalence Differences in FSHD | |||
| Cerebrovascular disease | 39 (10.18) | 85 (4.44) | 0.002* |
| Ear disorders | 31 (8.09) | 65 (3.39) | 0.0028* |
Note: *indicates p-value <0.05.
Commercial Insurance Coverage
The study cohort included 111 individuals diagnosed with FSHD and 555 matched controls with commercial insurance. Both cohorts had a higher percentage of individuals with Rx coverage than of those without (FSHD: 78.38%; controls: 69.01%). The FSHD cohort with commercial insurance incurred substantially higher medical expenses than matched controls over the 6-month study period, regardless of Rx coverage status ($11,403 vs $3622 with Rx coverage, and $3459 vs $405 without). Patients with Rx coverage had higher mean costs than those without in both cohorts. Among those with Rx coverage, mean Rx claims costs were higher in the FSHD cohort than in controls ($2764 vs $1409). Median costs consistently trailed mean costs across all categories, highlighting the impact of high-cost outliers within the FSHD group (Table 3).
Table 3.
Commercial Insurance Costs Over 6-Month Study Period
| Coverage Type | FSHD Cohort N = 111 |
Control Cohort N = 555 |
|---|---|---|
| Without Rx Coverage (N) | 24 | 172 |
| Mean (95% CI) | 3459 (1290, 5628) | 405 (226, 584) |
| Median (1st and 3rd quartile) | 1080 (419, 3294) | 0 (0, 283) |
| With Rx Coverage (N) | 87 | 383 |
| Mean (95% CI) | 11,403 (5242, 17,563) | 3622 (2141, 5103) |
| Median (1st and 3rd quartile) | 2118 (1005, 8106) | 714 (210, 2085) |
| Mean (95% CI) | 2764 (286, 5242) | 1409 (644, 2174) |
| Median (1st and 3rd quartile) | 112 (45, 787) | 145 (48, 411) |
Abbreviations: Rx, prescription medication; DME, durable medical equipment.
The average cost per patient for procedures, services, and DME over the 6-month study period, regardless of Rx coverage, was 3.7 times higher in the FSHD cohort ($9685) compared to controls ($2625). In the subgroup analysis, individuals with FSHD had higher mean costs for procedures, services, and DME than controls across all groups. Subgroups with the most pronounced cost increases compared to controls in the combined analysis included individuals with no prior comorbidities (6.4x) and males (5.1x) (Table 4).
Table 4.
Commercial Insurance Procedures, Services, and DME Costs by Subgroups Over 6-Month Study Period
| Procedures, Services, DME Claims ($) | Without Rx Coverage | With Rx Coverage | Combined | Fold Change | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| FSHD | Control | FSHD | Control | FSHD | Control | |||||||||
| N | Mean (95% CI) |
N | Mean (95% CI) |
N | Mean (95% CI) |
N | Mean (95% CI) |
N | Mean | N | Mean | |||
| Overall | 24 | 3459 (1290, 5628) |
172 | 405 (226, 584) |
87 | 11,403 (5242, 17,563) |
383 | 3622 (2141, 5103) |
111 | 9685 | 555 | 2625 | 3.7 | |
| Age (Years) | <20 | 5 | 4319 (0, 8956) |
21 | 345 (30, 661) |
5 | 3346 (0, 6907) |
29 | 1549 (340, 2757) |
10 | 3833 | 50 | 1043 | 3.7 |
| 20–39 | 8 | 1337 (140, 2534) |
70 | 388 (0, 778) |
27 | 8560 (0, 19,080) |
105 | 2083 (1173, 2994) |
35 | 6909 | 175 | 1405 | 4.9 | |
| 40–64 | 8 | 6041 (625, 11,457) |
73 | 439 (265, 612) |
52 | 13,851 (5126, 22,576) |
227 | 4667 (2243, 7092) |
60 | 12,809 | 300 | 3638 | 3.5 | |
| 65+ | <5 | N/A | 8 | 406 (0, 817) |
<5 | N/A | 22 | 2920 (0, 6724) |
6 | 4388 | 30 | 2249 | 2.0 | |
| Sex | Female | 13 | 4355 (725, 7985) |
58 | 435 (257, 612) |
43 | 8951 (2109, 15,793) |
222 | 3649 (1693, 5604) |
56 | 7884 | 280 | 2983 | 2.6 |
| Male | 11 | 2400 (368, 4432) |
114 | 390 (135, 645) |
44 | 13,798 (3583, 24,014) |
161 | 3586 (1311, 5861) |
55 | 11,519 | 275 | 2261 | 5.1 | |
| Number of Prior Comorbidities | 0 | 14 | 2651 (0, 5594) |
157 | 370 (181, 558) |
39 | 14,217 (1452, 26,983) |
218 | 2760 (880, 4640) |
53 | 11,162 | 375 | 1759 | 6.4 |
| 1 | 8 | 5462 (1645, 9280) |
11 | 650 (29, 1272) |
26 | 5636 (2339, 8933) |
116 | 4409 (1326, 7492) |
34 | 5595 | 127 | 4084 | 1.4 | |
| 2 | <5 | N/A | <5 | N/A | 17 | 12,861 (2960, 22,761) |
30 | 5468 (855, 10,082) |
19 | 11,623 | 34 | 4957 | 2.3 | |
| 3+ | <5 | N/A | <5 | N/A | 5 | 14,471 (527, 28,416) |
19 | 5798 (1352, 10,244) |
5 | 14,471 | 19 | 5798 | 2.5 | |
| Mental Health Diagnosis | <5 | N/A | 7 | 1426 (477, 2376) |
27 | 9795 (5637, 13,953) |
92 | 4255 (2297, 6214) |
29 | 9370 | 99 | 4055 | 2.3 | |
Notes: Prior comorbidities can include any one or more comorbidities listed in Supplementary Table 1. Mental Health Diagnosis includes anxiety, depression, autism, ADHD, and/or eating disorder (see Supplementary Table 1).
Medicare Insurance Coverage
The Medicare cohort consisted of 272 individuals with FSHD and 1360 matched controls. Like those with commercial insurance, a greater percentage of individuals in both cohorts had Rx coverage (FSHD 86.76% and controls 83.75%). To minimize potential biases, analyses focused on two subgroups: those with no prior comorbidities and those aged 65 years and older. There were 75 individuals with FSHD and 420 matched controls with no prior comorbidities, and 161 individuals with FSHD and 805 matched controls aged 65 years and older. In both subgroups, individuals with FSHD incurred higher medical and Rx claim costs than controls. Within the no-prior-comorbidities subgroup, the FSHD cohort incurred higher costs than controls across all coverage scenarios (Table 5). The average total cost per patient with no prior comorbidities for procedures, services, and DME over the 6-month study period, regardless of Rx coverage, was 2.5 times higher in the FSHD cohort ($5331) compared to controls ($2121). In Table 6, the FSHD cohort with a Medicare insurance plan was compared to the control cohort with commercial insurance to mitigate potential age-matching biases. Overall, the FSHD cohort with a Medicare plan incurred higher costs for procedures, services, and DME than controls with commercial insurance across all subgroups analyzed. The subgroups with the largest cost increases compared to controls in the combined analysis were those with no prior comorbidities (3.0x), followed by males (2.7x), and individuals aged 65+ (2.6x) (Table 6).
Table 5.
Medicare Insurance Costs Over 6-Month Study Period
| No Prior Comorbidities | ||
| Coverage Type |
FSHD Cohort N = 75 |
Control Cohort N = 420 |
| Without Rx Coverage (N) | 12 | 106 |
| Procedures, Services, DME Claims ($) | ||
| Mean (95% CI) | 3900 (0, 9006) | 566 (224, 907) |
| Median (1st and 3rd quartile) | 680 (377, 1975) | 0 (0, 490) |
| With Rx Coverage (N) | 63 | 314 |
| Procedures, Services, DME Claims ($) | ||
| Mean (95% CI) | 5603 (2307, 8900) | 2646 (1701, 3590) |
| Median (1st and 3rd quartile) | 1231 (533, 3270) | 654 (221, 1449) |
| Rx Claims ($) | ||
| Mean (95% CI) | 3733 (0, 7683) | 1486 (692, 2280) |
| Median (1st and 3rd quartile) | 237 (90, 1811) | 259 (81, 806) |
| Age 65+ Years | ||
| Coverage Type |
FSHD Cohort N = 161 |
Control Cohort N = 805 |
| Without Rx Coverage (N) | 22 | 144 |
| Procedures, Services, DME Claims ($) | ||
| Mean (95% CI) | 5863 (2439, 9287) | 3734 (2008, 5462) |
| Median (1st and 3rd quartile) | 3328 (1015, 6335) | 563 (0, 1675) |
| With Rx Coverage (N) | 139 | 661 |
| Procedures, Services, DME Claims ($) | ||
| Mean (95% CI) | 5861 (3947, 7776) | 5194 (3885, 6502) |
| Median (1st and 3rd quartile) | 1991 (736, 4467) | 563 (0, 1675) |
| Rx Claims ($) | ||
| Mean (95% CI) | 2813 (247, 5379) | 2214 (1639, 2788) |
| Median (1st and 3rd quartile) | 399 (184, 993) | 421 (143, 1769) |
Table 6.
Medicare Insurance Procedures, Services, and DME Costs by Subgroups Over 6-Month Study Period
| Procedures, Services, DME Claims ($) | Without Rx Coverage | With Rx Coverage | Combined | Fold Change | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| FSHD (Medicare) | Control (Commercial) | FSHD (Medicare) | Control (Commercial) | FSHD (Medicare) | Control (Commercial) | |||||||||||||
| N | Mean (95% CI) |
N | Mean (95% CI) |
N | Mean (95% CI) |
N | Mean (95% CI) |
N | Mean | N | Mean | |||||||
| Overall | 36 | 4243 (2010, 6476) |
172 | 405 (226, 584) |
236 | 6098 (4608, 7589) |
383 | 3622 (2141, 5103) |
272 | 5853 | 555 | 2625 | 2.2 | |||||
| Age (years) | <20 | <5 | N/A | 21 | 345 (30, 661) |
<5 | N/A | 29 | 1549 (340, 2757) |
<5 | N/A | 50 | 1043 | N/A | ||||
| 20–39 | <5 | N/A | 70 | 388 (0, 778) |
8 | 3887 (722, 7051) |
105 | 2083 (1173, 2994) |
9 | 3474 | 175 | 1405 | 2.5 | |||||
| 40–64 | 13 | 1815 (462, 3167) |
73 | 439 (265, 612) |
89 | 6667 (4090, 9244) |
227 | 4667 (2243, 7092) |
102 | 6049 | 300 | 3638 | 1.7 | |||||
| 65+ | 22 | 5863 (2439, 9287) |
8 | 406 (0, 817) |
139 | 5861 (3947, 7776) |
22 | 2920 (0, 6724) |
161 | 5862 | 30 | 2249 | 2.6 | |||||
| Sex | Female | 18 | 5347 (1907, 8787) |
58 | 435 (257, 612) |
105 | 5686 (3552, 7820) |
222 | 3649 (1693, 5604) |
123 | 5636 | 280 | 2983 | 1.9 | ||||
| Male | 18 | 3139 (286, 5993) |
114 | 390 (135, 645) |
131 | 6429 (4354, 8504) |
161 | 3586 (1311, 5861) |
149 | 6031 | 275 | 2261 | 2.7 | |||||
| Number of Prior Comorbidities | 0 | 12 | 3900 (0, 9006) |
157 | 370 (181, 558) |
63 | 5603 (2307, 8900) |
218 | 2760 (880, 4640) |
75 | 5331 | 375 | 1759 | 3.0 | ||||
| 1 | 12 | 2872 (1567, 4177) |
11 | 650 (29, 1272) |
66 | 5380 (3159, 7601) |
116 | 4409 (1326, 7492) |
78 | 4994 | 127 | 4084 | 1.2 | |||||
| 2 | <5 | N/A | <5 | N/A | 57 | 6728 (3365, 10,091) |
30 | 5468 (855, 10,082) |
61 | 6568 | 34 | 4957 | 1.3 | |||||
| 3+ | 8 | 6791 (601, 12,981) |
<5 | N/A | 50 | 6952 (3884, 10,020) |
19 | 5798 (1352, 10,244) |
58 | 6930 | 19 | 5798 | 1.2 | |||||
| Mental Health Diagnosis | 9 | 5267 (3039, 7495) |
7 | 1426 (477, 2376) |
82 | 6266 (4299, 8234) |
92 | 4255 (2297, 6214) |
91 | 6168 | 99 | 4055 | 1.5 | |||||
Notes: The FSHD cohort with Medicare coverage is compared to the control cohort with commercial insurance. Prior comorbidities can include any one or more comorbidities listed in Supplementary Table 1. Mental Health Diagnosis includes anxiety, depression, autism, ADHD, and/or eating disorder (see Supplementary Table 1).
Notably, fold changes were greater in the cohort without Rx coverage than in those with Rx coverage across both commercial and Medicare insurance types (Table 4 and Table 6). For instance, the overall cost increase in the Medicare group was 10.5x without Rx coverage vs. 1.7x with Rx coverage. This pattern suggests that non-pharmacy services may be key drivers of incremental spending in FSHD.
Discussion
This study is the first to provide a US-based description of direct medical claims costs associated with FSHD, analyzing costs across subgroups by commercial and Medicare insurance. Overall, individuals with FSHD incurred substantially higher healthcare costs for procedures, services, and DME compared to the general population. These findings underscore the significant healthcare burden associated with FSHD and highlight the importance of continued investigation into the cost drivers and utilization patterns in this rare neuromuscular disease.
Several subgroup findings add essential context. A notably high percentage of our FSHD cohort resided in rural areas (49.61%, Table 1), compared to only 19% of the US population.32 Rural residence may exacerbate disparities through longer travel times, limited access to specialists and facilities, and higher indirect costs, suggesting that actual costs may be underrepresented and that access challenges could compound the burden of FSHD.33–35 Further research should assess prevalence, incidence, and care patterns in rural communities.
The age distribution of the cohort reflected known clinical features of FSHD. Ten individuals with FSHD under age 20 were identified in the commercial insurance cohort (Table 4), consistent with reports that approximately 10% of cases are early-onset.13,36 Importantly, 59.20% of the FSHD cohort with Medicare were 65 years and older, compared to 88.40% of controls (Table 6). This indicates that individuals with FSHD are more likely to qualify for Medicare before age 65, pointing to considerable disability and associated societal costs.
Individuals with FSHD had a significantly higher prevalence of cerebrovascular disease, including cerebral infarction and hemorrhagic events (Table 2 and Supplementary Table 2), a finding corroborated by a recent claims study.37 However, we did not adjust for key lifestyle-related and clinical confounders (eg, smoking, hypertension, obesity, physical activity) that influence cardiovascular risk; hence, the observed association should be considered hypothesis-generating rather than causal.38,39 Future studies should incorporate these variables to delineate whether elevated cerebrovascular risk reflects FSHD pathophysiology, secondary effects of disease (eg, immobility, inflammation), or shared risk profiles.
Similarly, ear disorders, including conductive and sensorineural hearing loss, otosclerosis, and inner and middle ear disorders, were more prevalent (Table 2 and Supplementary Table 2), consistent with known FSHD symptoms.13,14 Together, these findings highlight the need to better characterize the full spectrum of comorbidities linked to FSHD to elucidate underlying mechanisms and anticipate healthcare resource needs.
Our study design did not distinguish costs related to diagnostic evaluation from those related to ongoing care. As a result, observed expenditures likely reflect a combination of initial workup, treatment, and chronic management. Additionally, administrative datasets do not include detailed clinical characterization, including disease severity, functional status, and genetic confirmation. These limitations limited our ability to determine how costs may vary with disease severity or other important clinical features. To provide clearer spending detail, we separated Rx costs from medical costs, defined as procedures, services, and DME; however, the data did not consistently permit finer breakdowns (eg, inpatient vs. outpatient, diagnostic vs. ongoing management, rehabilitation vs. specialist care). We therefore recommend a prospective claims analysis with standardized service groupers and longitudinal phase-of-care definitions to map cost trajectories from diagnostic confirmation through chronic management.
Our results align with broader estimates of rare disease burden. Yang et al reported a total US economic burden of $997 billion in 2019 across 379 rare diseases, with $449 billion in direct medical costs.40 Consistent with this, individuals with FSHD in our study incurred substantially higher direct medical costs than controls across both Medicare and commercial insurance. International comparisons reinforce this trend. In the Netherlands, Blokhuis et al reported annual direct medical costs for FSHD of €12,077, approximately five times the national average.20 While absolute estimates differ by setting, the direction and magnitude of burden are similar, underscoring FSHD as a condition with meaningful healthcare and societal impact.
Future work should validate FSHD case-finding algorithms in claims data utilizing two or more diagnostic codes and/or linking to genetic or other confirmation; undertake longer longitudinal studies to capture lifetime utilization and progression (including differentiation of diagnostic vs. ongoing care costs); and clarify comorbidity risks and costs, particularly cerebrovascular and auditory conditions. The evaluation of direct non-medical and indirect costs and the quantification of caregiver burden, including injury risk and financial impacts, should also be prioritized. Such efforts would build on these initial findings and provide a stronger evidence base for healthcare planning and policy.
Limitations
This study had several limitations warranting consideration. The FSHD cohort was identified using a single ICD-10-CM diagnosis code rather than a more stringent case definition. While this may increase the risk of misclassification, the approach was necessary to maintain an adequate sample size in a rare-disease population and reflects real-world diagnostic coding practices. Furthermore, the FSHD-specific ICD-10 code was introduced only in 2018, and cases lacking the updated code were excluded from the analysis, further constraining case ascertainment.
The study period overlapped with the COVID-19 pandemic, during which healthcare utilization declined substantially (eg, from March to May 2020, office visits dropped to 51.25% of pre-pandemic levels).41 As a result, observed costs likely underestimate the actual healthcare burden of FSHD. Similarly, our analysis was limited to a 6-month observation window, and inclusion of facility fees varied by plan type, which may have further lowered overall cost estimates. This conservative capture underscores that our findings are more likely to understate than overstate the true magnitude of economic burden.
As with all claims analyses, the administrative data were not originally collected for research. Our dataset did not include key clinical details such as disease severity, functional status, genetic confirmation, laboratory results, insurance transitions, and access to care. Furthermore, findings apply specifically to commercial and Medicare enrollees and may not generalize to other payor segments. Nonetheless, by leveraging a large, diverse dataset spanning both commercial and Medicare plans, this study captures a meaningful cross-section of individuals with FSHD and provides foundational cost estimates for subsequent evaluative work.
Taken together, these limitations highlight the need for future research that builds on this work with more granular clinical data, longer longitudinal follow-up, and inclusion of indirect and caregiver-related costs. At the same time, they reinforce the value of this analysis: despite conservative assumptions and potential underestimation, the study demonstrates a clear and substantial healthcare burden associated with FSHD. This makes our findings a critical first step toward quantifying the economic impact of the disease and underscores the urgency of developing effective therapies and supportive care strategies.
Conclusions
This study is the first to offer what is likely a conservative description of the economic burden of FSHD in the US, showing that individuals with FSHD covered by commercial insurance or Medicare incur substantially higher medical claims than matched controls. The findings also demonstrate a greater prevalence of comorbidities such as cerebrovascular diseases, underscoring the complexity of disease management and the need for more proactive care strategies.
Further research should include clinical confirmation, disease stage, and phase of care to improve the accuracy and generalizability of these estimates. Expansion beyond claims data will also help capture the full spectrum of economic consequences, including nonmedical expenses, caregiver burden, and lost productivity, while also examining lifelong healthcare utilization patterns. These efforts are essential for informing healthcare policy and optimizing resource allocation, given the anticipated development of disease-modifying therapies. In doing so, they directly support Project Mercury’s mission to expand access to treatment and improve outcomes for the FSHD community. We encourage broad stakeholder collaboration to build on these findings and address the urgent, unmet needs of individuals living with FSHD.
Acknowledgments
We thank Michael Lahm for his guidance on study design and Bakri Elsheikh for his careful reading and advice.
Funding Statement
This study was funded by the FSHD Society.
Abbreviations
CI, Confidence intervals; COVID-19, Coronavirus-19; DUX4, Double Homeobox 4; DME, Durable medical equipment; FSHD, Facioscapulohumeral muscular dystrophy; ICD-10-CM, International Classification of Diseases, Tenth Revision, Clinical Modification; N, Number; Rx, Prescription medication; SD, Standard deviation; US, United States; USR, Urban-suburban-rural.
Data Sharing Statement
The datasets analyzed and generated during this study are not publicly available because they are proprietary and confidential.
Ethics Approval and Informed Consent
This study was determined by the UnitedHealth Group Office of Human Research Affairs to be Exempt from IRB review under exemption category four, secondary use of existing data collected for non-research purposes.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
Dr Jamshid Arjomand reports personal fees from Solve FSHD, personal fees from XPRIZE, outside the submitted work. The authors report no conflicts of interest in this work.
Interim findings from this study were presented as posters at the 2024 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference and the 2024 International Research Congress (IRC) on FSHD.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets analyzed and generated during this study are not publicly available because they are proprietary and confidential.