Myotonic dystrophy (DM) is an inherited autosomal dominant disease with progressive myopathy and comorbidities involving multiple organ systems. There is no cure, but a deeper understanding of the patient journey, the use of healthcare resources, and the cost of care before and after diagnosis would assist in managing supportive care. This longitudinal analysis of medical and pharmacy insurance claims between January 2010 and March 2021 included 1,694 patients with two or more DM diagnostic claims compared with 8,470 matched control (MC) patients who were propensity-score matched by index date (i.e., month of diagnosis), age, region, sex, plan, and payer type. Eligible patients had a minimum of 12 months of continuous data. Comorbidities consistent with the clinical profile of DM were more prevalent in patients with DM than in the MC cohort. The aggregate per-member-per-year medical costs were $18,239 for a patient with DM and $5,609 for a MC. The corresponding pharmacy costs were $3,029 and $1,478. Overall, resource utilization – including emergency departments, inpatient facilities, outpatient facilities, office practices, pharmacies, laboratories, procedures (Healthcare Common Procedure Coding System or Current Procedural Terminology codes), prescription medications, and clinician-administered drugs (J-codes) – and their associated costs were higher for patients with DM than MCs. Until a diagnosis of DM is established, the varied presentations of this multisystemic disorder complicates diagnostic testing and medical care. During the pre-diagnosis period, patients, caregivers, and families experience the stress and additional cost burden associated with the uncertainty of an undiagnosed condition. To further elucidate the impact of DM, additional analyses are ongoing to assess changes in comorbidities, use of healthcare resources, and costs.

Healthcare costs; Healthcare resource utilization; Insurance claims database; Rare disease; Myotonic dystrophy; Patient journey

Tai LJ, Day JW, Munoz KA, Chen CY, Brook RA, et al. (2023) Myotonic Dystrophy Patient Journey: Increased Use of Healthcare Resources in the Year Prior to Diagnosis as Evidenced by Insurance Claims. Int J Rare Dis Orph Drugs 6(2): 1017.

AHRQ: Agency for Healthcare Research and Quality; ATC: Anatomical Therapeutic Chemical; DM: Myotonic Dystrophy; CCI: Charlson Comorbidity Index; CPI: Consumer Price Index; CTP: Current Procedural Terminology; DMPK: Dystrophica Myotonica Protein Kinase; ED: Emergency Department; HCPCS: Healthcare Common Procedure Coding System; ICD-9: International Classification of Disease Ninth Revision; ICD-10: International Classification of Disease Tenth Revision; MC: Matched Control; PMPY: Per Member Per Year; SD: Standard Deviation.

Myotonic dystrophy (DM) is the most common form of muscular dystrophy in adults. It is a rare, inherited autosomal dominant disease with progressive myopathy, myotonia, and multiorgan involvement. Comorbidities may involve the respiratory, gastrointestinal, cardiac, and central nervous systems, among others, resulting in a disease burden that has significant impact on patient and family quality of life [1-3]. Two distinct forms of DM have been identified: DM1, or Steinert’s disease, and DM2. They have clinical and pathophysiologic similarities that appear at various ages and times during the disease continuum, but they are different disorders that require genetic diagnostic testing for confirmation. Genetic screening is possible but has not been performed in large populations [4]. The most frequently cited estimate of the prevalence of DM1 is 1 in 8,000 people worldwide [5], while a more recent systematic review estimated the worldwide prevalence of DM as 0.5–18.1 per 100,000 people, without differentiating between types [6]. The prevalence of DM2 appears to be lower than that of DM1, except for populations originating from Northern Europe [7]. The epidemiology of DM has not been systematically studied in the USA, but clinical experience suggests that DM2 is approximately 5-fold less prevalent than DM1 [4]. Rarity, variable presentation, and neuromuscular features that are shared with other diseases complicate diagnosis after the onset of the initial symptoms and result in a long patient journey. There is no cure or diseasemodifying treatment, but establishing a focused, comprehensive approach to clinical care can extend patient lifespan and help maintain mobility and quality of life. Longitudinal data on the use of medical resources by patients with DM prior to diagnosis would add to what is known about the use of available resources, clinical experience, and the cost of medical care. This study analyzed healthcare claims paid during the 12 months before diagnosis (pre-index period). Identifiable claim codes were analyzed to allow in-depth views of the prevalence and costs of comorbid conditions, product use, and procedures prior to patients’ diagnosis of DM and in a matched control (MC) group.

Study design

This study was a longitudinal analysis of medical and pharmacy claims made by insured patients between January 2010 and March 2021 and retrieved from the IQVIA US PharMetrics® Plus database [Figure 1].

Figure 1: Study plan and patient selection. The analysis included medical and pharmacy claims made by insured patients between January 2010 and March 2021. Abbreviations: DM: myotonic dystrophy; ICD-9: International Classification of Disease Ninth Revision; ICD-10: International Classification of Disease Tenth Revision

The claims data were de-identified, and the study did not influence patient care; consequently, the study was exempt from institutional review board approval. The analysis compared a cohort of patients with DM who were identified by claims including International Classification of Disease Ninth Revision (ICD-9) code 359.21 and Tenth Revision (ICD-10) code G71.11 diagnosis codes for myotonic muscular dystrophy without distinguishing type 1 and type 2 DM. Eligible patients had ≥ 2 DM diagnosis claims filed ≥ 30 days apart. The index date was used as a proxy for initial diagnosis of DM, and eligible patients had a minimum of 12 months of continuous data prior to their index date. The patients with DM were compared with a 5% random sample of patients remaining in the PharMetrics® Plus database records after excluding the DM cohort. Patients with ICD-9 359. xx (muscular dystrophies and other myopathies), ICD-10 G71. xxx (primary disorders of muscles), ICD-10 M62.5xx (muscular wasting and disuse atrophy), or ICD-10 M63.8xx (other muscle disorders in disease classified elsewhere) claims were excluded from the MC cohort. Each patient with DM was matched by index month, baseline age, region, sex, plan, and payer type to five MCs using a propensity-score-matching algorithm and nearestneighbor matching (R MatchIt) [8]. Resource utilization was reported in each cohort as the percentage of patients with relevant claims during the pre-index period. For analysis, plan costs plus member-paid costs and days or number of billed services were aggregated for each patient over the 12 months preceding the index date and reported as per-member-per-year (PMPY) values. Costs were inflation-adjusted to December 2020 dollars using the US Bureau of Labor Statistics Consumer Price Index (CPI); medical claims used the medical-cost CPI, and prescription claims used the prescription-cost CPI. The ICD-9 and ICD-10 claims included in the database were assigned and aggregated into 283 specific US Agency for Healthcare Research and Quality (AHRQ) categories (https://hcup-us.ahrq.gov/toolssoftware/ ccsr/DXCCSR-User-Guide-v2019-1.pdf). The categories were used to compare the prevalence of comorbid conditions, reasons for inpatient admissions and emergency department (ED) visits, and related costs and services. As general measures of comorbidity, Charlson Comorbidity Index (CCI) scores [9] were also calculated, along with the number of patients with CCIs >1, the per-patient number of diagnoses (ICD-9s and ICD10s), and the per-patient number of AHRQ condition categories. The utilization, PMPY cost, and number of prescription fills in each cohort were compared using the Anatomical Therapeutic Chemical (ATC) drug hierarchy classification of the World Health Organization (https://www.who.int/tools/atc-ddd-toolkit/atcclassification). Injectable drugs that are not ordinarily selfadministered (i.e., are clinician-administered) were identified by their J-codes in the medical claims. Medical procedures were identified by Healthcare Common Procedure Coding System (HCPCS) and Current Procedural Terminology (CPT) codes.

Statistical analysis

The statistical analysis was descriptive. Results were reported as means ± standard deviation or numbers and percentage. Comparisons of utilization, cost, number of services, and number of days of service in the 12 months prior to the index date were made with two-sample t-tests for continuous variables and chi-square tests for discrete variables. Differences were considered significant at p ≤ 0.01.

Descriptive characteristics of patients with DM

We identified 1,694 patients with DM in the claims database and matched them to 8,470 MCs. The age, region, sex, insurance plan, and payer type of the patients with DM and MCs are shown in Table 1.

Table 1: Age, sex, US region, insurance plan, and payer types of patients with DM and MCs on the index date

There were no significant differences in the descriptive characteristics between cohorts.

Comorbid conditions

Overall, there were observed differences (p < 0.0001) in the CCI mean scores (DM cohort 0.82 ± 1.51 vs MC cohort 0.44 ± 1.19), the percentages of patients with CCI scores ≥ 1 (19.1% vs 9.7%), the number of ICD-9/-10 diagnoses (11.87 ± 10.28 vs 6.26 ± 7.11), and the number of prevalent AHRQ categories (8.66 ± 6.42 vs 4.88 ± 4.90).

The prevalence of pre-index healthcare conditions and associated PMPY costs and services used were higher in patients with DM compared with MCs. The largest differences in prevalence included the AHRQ categories “other nervous system disorders” (54.4% vs 10.2%), “other connective tissue disease” (49.4% vs 20.1%), and “other lower respiratory disease” (29.8% vs 14.6%). The 20 comorbid conditions with the largest cohort differences are shown in [Figure 2A].

Figure 2A: AHRQ categories with the largest between-group differences in (A) utilization, (B) PMPY per member per year costs, and (C) number of billed services

Abbreviations: AHRQ: Agency for Healthcare Research and Quality; DM: myotonic dystrophy; MC: matched control; PMPY: per-member-per-year

Pre-index prevalence was greater in patients with DM than in MCs in 143 of the 283 AHRQ categories. Pre-index PMPY costs differed in 22 AHRQ categories, 18 of which were higher in patients with DM. The 20 categories with the greatest PMPY cost differences are shown in [Figure 2B].

Figure 2b: AHRQ categories with the largest between-group differences in (A) utilization, (B) PMPY per member per year costs, and (C) number of billed services

Abbreviations: AHRQ: Agency for Healthcare Research and Quality; DM: myotonic dystrophy; MC: matched control; PMPY: per-member-per-year

The number of billed pre-index services differed in 50 AHRQ categories, 49 of which were higher in patients with DM. The 20 categories with the greatest differences in number of services are shown in [Figure 2C].

Figure 2C: AHRQ categories with the largest between-group differences in (A) utilization, (B) PMPY per member per year costs, and (C) number of billed services

Abbreviations: AHRQ: Agency for Healthcare Research and Quality; DM: myotonic dystrophy; MC: matched control; PMPY: per-member-per-year

Comparisons between the DM cohort and MCs of the 283 AHRQ categories are shown in [Supplementary Table 1].

Prescription medications

Comparison of claims for 88 ATC category 2 drugs, which are classified by the organ or system on which they act and their therapeutic properties, found 49 that had significantly higher use in the DM cohort. The 20 classes with the greatest differences are shown in [Figure 3A], and are led by systemic antibacterials (46.1% vs 35.5%), ophthalmologicals (36.3% vs 27.4%), and intestinal anti-inflammatory drugs (20.9% vs 13.4%).

Figure 3A: Anatomical Therapeutic Chemical category 2 drugs with the largest between-group differences in (A) utilization, (B) per member per year costs, and (C) number of fills.

Abbreviations: DM: myotonic dystrophy; Rx: prescription

Twenty categories had significant cost differences between cohorts, and the PMPY costs of 18 drug classes were higher in the DM cohort than in the MC cohort. The greatest differences [Figure 3B], were seen in diabetes drugs ($357 vs $227, p = 0.0169), antiepileptics ($122 vs $32, p = 0.0054), and drugs for obstructive-airway diseases ($219 vs $150, p = 0.0441).

Figure 3B: Anatomical Therapeutic Chemical category 2 drugs with the largest between-group differences in (A) utilization, (B) per member per year costs, and (C) number of fills.

Abbreviations: DM: myotonic dystrophy; Rx: prescription

Differences in prescription fills [Figure 3C], were significant in 42 of the 88 drug classes, and patients with DM had significantly more fills than MCs in 40 of the classes. The greatest PMPY differences in number of fills were for ophthalmologicals (1.35 vs 0.82), systemic antibacterials (1.39 vs 0.87), and psychoanaleptics (1.49 vs 1.04).

Figure 3C: Anatomical Therapeutic Chemical category 2 drugs with the largest between-group differences in (A) utilization, (B) per member per year costs, and (C) number of fills.

Abbreviations: DM: myotonic dystrophy; Rx: prescription

Differences in all three metrics in ATC class 2 drugs are in line with those found in class 3 and 4 drugs, which are shown in [Supplementary Tables 2] [Supplementary Table 3].

Supplementary Table 3: Comparisons between the DM cohort and MCs of ATC4 class categories

Clinician-administered medications

The use of 34 of the 290 clinician-administered drugs identified as being used by either cohort and included in the analysis differed significantly between patients with DM and MCs at p < 0.01. For each of the drugs, the percentage of claims was greater in the DM cohort. The PMPY costs of 57 drugs were significantly different, with 17 being higher for DM. The number of administrations was significantly different for 79 drugs, with 38 drugs having more administrations in the DM cohort. Widely used injectable agents with significantly greater prevalence, PMPY costs, and administrations in the DM population are shown in Table 2.

Table 2: Injectable drugs with significantly greater prevalence, PMPY costs, or administrations in patients with DM than in MCs

p < 0.0001 unless noted

*Not significant (p > 0.01)

†p = 0.0065

Abbreviations: DM, myotonic dystrophy; MC, matched control; PMPY, per member per year

The prevalence, PMPY costs, and number of administrations of the 290 administered drugs are shown in [Supplementary Table 4].

Location of care

The percentages of patients with DM who received care at EDs, inpatient facilities, outpatient facilities, office practices, laboratories, pharmacies (i.e., outpatient-dispensed and -filled prescription drugs), and “other” locations were all significantly higher than those of the MCs. The overall use of medical and pharmacy locations of care was 97.7% vs 85.9%. The PMPY number of services were 88.4 ± 115.35 vs 44.1 ± 70.3, and the PMPY days of service were 30.8 ± 33. 4 vs 16. 25 ± 21.5 for patients with DM and MCs, respectively. The aggregate PMPY medical costs associated with locations of care were $18,239 for patients with DM and $5,609 for MCs, a difference of 225.2%. The corresponding pharmacy costs were $3,029 and $1,478, a difference of 105%. The location of care comparisons are shown in [Table 3].

Table 3: Utilization by patients with DM and MCs in the year prior to DM diagnosis by location of care

*Sums may not add to numbers because of rounding

†Relative difference = (DM % – MC %) / MC. DM versus MC utilization differences (chi-square) and PMPY cost, services, and days of service (t-test) by location of care are all p < 0.0001

Abbreviations: DM, myotonic dystrophy; MC, matched control; PMPY, per member per year; SD, standard deviation

Inpatient admissions and ED visits

Inpatient admissions and ED visits were identified by ICD9 and ICD-10 codes corresponding to the 283 AHRQ-specific diagnostic categories. The percentage of inpatient admissions was 17.0% for patients with DM and 7.0% for MCs. The corresponding percentages of ED visits were 22.1% and 13.7%, respectively. Inpatient admissions were significantly higher (p < 0.01) in patients with DM than in MCs in 71 AHRQ categories. ED visits were higher in patients with DM in 28 categories. Patients with DM had higher prevalence for all categories compared with the MCs. Clinically and economically relevant differences in inpatient admissions and ED visits included nervous system disorders, lower respiratory disease, adult respiratory failure and insufficiency, and gastrointestinal disorders. The AHRQ categories with the greatest differences in prevalence are shown in [Figure 4A,Figure 4B], and the results of all categories are shown in [Supplementary Table 5].

Figure 4A: Primary diagnoses with a prevalence 1% more in patients with DM than in MCs on (A) inpatient admission and (B) emergency department visit in the year prior to the index date. Abbreviations: DM: myotonic dystrophy; ED: emergency department; MC: matched control.

Figure 4B: Primary diagnoses with a prevalence 1% more in patients with DM than in MCs on (A) inpatient admission and (B) emergency department visit in the year prior to the index date. Abbreviations: DM: myotonic dystrophy; ED: emergency department; MC: matched control.

HCPCS or CPT procedure codes identified 158 procedure categories, which were then divided into ten groups for analysis [Supplementary Table 6]. The between-cohort differences in utilization were significant in 91 procedure categories with higher utilization for patients with DM. PMPY costs were significantly different in 52 procedures, with the cost of 50 procedures higher in patients with DM. PMPY number of services was different in 64 procedures, with 63 procedures having more services for patients with DM. All three metrics were significantly different in the 31 categories listed in [Table 4].

Table 4: Procedures identified by HCPCS or CPT procedure codes in patients with DM and MCs in the year prior to the DM diagnosis