Abstract
Introduction
Post-stroke spasticity (PSS) occurs in ~25–43% of patients between 2 weeks and 3 months following a stroke. This retrospective claims study examined the occurrence of spasticity, treatment patterns, healthcare resource utilization, and healthcare costs among patients who experienced a stroke over a 2-year period.
Methods
Analyses were conducted using healthcare claims from the IQVIA PharMetrics Plus database of commercially/self-insured members from 2015 to 2021. Patients were selected based on two International Classification of Diseases, 10th revision diagnosis codes for stroke requiring an inpatient stay (index date) with continuous enrollment with medical/pharmacy benefits 12 months before (pre-index) and 24 months starting on the index date (post-index). PSS was defined by a diagnosis code for spastic hemiplegia or muscle contracture starting ≥ 7 days post-index, or claims indicating PSS treatment [botulinum toxin A (BoNT-A) or muscle relaxants] any time in the post-index period. A generalized linear model was developed to estimate cost ratios between patients with and without PSS.
Results
Overall, 7851 patients fulfilled study criteria; 47.7% were treated with physical or occupational therapy, 11.3% with muscle relaxants, and 0.8% with BoNT-A; 12.4% met the post-index definition of PSS; 84.2% were identified using muscle relaxant or BoNT-A codes, 6.6% using diagnosis codes, and 9.2% using both. Median time to codes identifying PSS was 213 days. Patients treated with BoNT-A received an average of three treatments, starting 253 days (median) post-stroke. Mean all-cause healthcare costs were US$62,875 among patients with PSS versus $44,472 among patients without (P < 0.001), representing 39.6% higher adjusted all-cause healthcare costs among patients with PSS versus patients without PSS.
Conclusion
Patients with PSS utilized numerous treatment modalities and experienced higher mean all-cause healthcare costs than did those without PSS. Earlier identification to optimize treatment of PSS may represent an opportunity for cost savings within managed healthcare systems.
Keywords: Botulinum toxin type A, Post-stroke spasticity, Healthcare costs, Healthcare resource utilization, Real-world evidence
Plain Language Summary
Each year, about 795,000 people in the US experience a stroke, of whom an estimated 25% or more go on to develop spasticity, an abnormal, involuntary muscle tightness due to extended muscle contraction. Treatment guidelines, which help healthcare providers decide the best way to treat people with a specific condition, recommend botulinum toxin type A for individuals with post-stroke spasticity. This study assessed treatment patterns, healthcare use, and healthcare costs in US patients with post-stroke spasticity over a 2-year period. Results showed that spasticity was first identified in patients’ medical records using relevant diagnosis codes or prescribed drug therapies about 8 months after a stroke. Only 6.6% of patients who were treated with drug therapy for spasticity were given botulinum toxin type A. Patients with stroke and spasticity needed more healthcare visits than those with stroke but without spasticity. Patients with spasticity also had significantly higher healthcare costs than those without spasticity (average per patient: $62,875, compared with $44,472). Hospital stays accounted for most of the costs (average per patient: $40,243 for those with spasticity, compared with $27,426 for those without spasticity). The results of this real-world study suggest that healthcare costs could potentially be reduced if spasticity after stroke were identified sooner and treated effectively. While our study found an association between healthcare costs and post-stroke spasticity, it’s important to note that the patients in this study had managed care plans, so the results might not apply to patients with other types of health insurance.
Key Summary Points
| Why carry out this study? |
| There is limited real-world evidence on treatment patterns, healthcare resource utilization (HCRU), and healthcare costs in patients with post-stroke spasticity. |
| What was learned from the study? |
| Patients with post-stroke spasticity had a higher utilization of rehabilitation services, higher readmission rates, and more physician office and hospital visits than patients with stroke but without spasticity. |
| Although botulinum toxin type A (BoNT-A) is first-line treatment for post-stroke spasticity, a limited number of patients treated with drug therapy for spasticity received it. |
| The results suggest that healthcare costs could potentially be reduced if spasticity after stroke is identified sooner and treated effectively. |
Introduction
Stroke, a major cause of disability for adults, affects approximately 795,000 patients in the US annually and is the fifth-leading cause of death [1]. Nearly one of every four incidences of stroke occurs in patients with a prior history of stroke; most (87%) are ischemic strokes and about 13% are hemorrhagic strokes [2, 3]. Accounting for nearly 2% of the current national health expenditures, by 2030 3.9% of the US adult population is projected to have had a stroke, with total direct annual stroke-related medical costs increasing to US$184 billion [4]. One of the most common sequelae of stroke is spasticity, a motor disorder that occurs in 25–43% of patients, with the majority of cases occurring within the first 6 weeks after stroke [5–14]. Hemorrhagic stroke, stroke lesions in the brain stem, and younger age are factors associated with the onset of spasticity after stroke [15].
Spasticity is a component of upper motor neuron syndrome defined as an involuntary, velocity-dependent increase in muscle tone resulting from an upper motor neuron lesion, which leads to resistance to movement [16–19]. Spasticity contributes to functional motor disability or impairment, pain, and discomfort with varying degrees of severity [20–22]. Patients with post-stroke spasticity show statistically and clinically meaningful decreases in validated health-related quality of life measures compared with patients with stroke but without spasticity [23]. When asked about the impact of their symptoms, individuals with spasticity have reported reductions in their ability to move around independently and to perform daily activities, as well as negative effects on self-confidence, mood, and sleep [24].
Non-surgical management of post-stroke spasticity involves rehabilitative and pharmacologic interventions [15]. The efficacy, safety, and therapeutic impact of botulinum toxins type A (BoNT-As), such as abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A), as first-line treatment for adult spasticity are well established (Level A evidence) across numerous therapeutic guidelines [25–27]. The economic impact of stroke is high and increases when spasticity is also present; a previous retrospective study showed that median healthcare resource utilization (HCRU) and direct healthcare costs were higher among adult patients with history of stroke and spasticity than among matched controls with stroke but without spasticity [28]. Effective treatment of post-stroke spasticity thus may represent an opportunity for potential direct healthcare cost savings. However, evidence on real-world treatment patterns, HCRU, and direct healthcare costs among patients with post-stroke spasticity remains limited.
This study evaluated patients after an initial stroke requiring an inpatient stay in a hospital setting over a 2-year follow-up period, to better understand the development of spasticity, treatment patterns, HCRU, and associated direct healthcare costs.
Methods
Study Design and Data Source
This was an observational, retrospective, real-world study conducted among adult patients with stroke using healthcare claims data derived from the IQVIA PharMetrics® Plus database of commercially or self-insured members. Representative of geography, payers, and providers, PharMetrics Plus consists of detailed information on inpatient and outpatient diagnoses and procedures, pharmacy, medical benefits, and inpatient stay. Other data elements include dates of service, demographic variables, product type, and payer type.
The study period was from October 1, 2015 to January 31, 2021; patients were identified during the selection window, from October 1, 2016 through January 31, 2019 (Fig. 1). All data were de-identified according to the Health Insurance and Accountability Act to guard patients’ privacy and are thus exempt from institutional review board oversight. Ethics approval and consent to participate were not required.
Fig. 1.
Study overview
Eligibility Criteria
Patients were identified based upon two non-same-day International Classification of Diseases, 10th revision (ICD-10) diagnosis codes for stroke requiring an inpatient stay that overlapped by at least 1 day with the index date in order to reduce the probability of false positives for stroke (Table 1). Other selection criteria included continuous health plan enrollment with pharmacy benefits for 12 months preceding the index date (pre-index) and for 24 months starting at the index date (post-index). Index date was defined as the date of the first evidence of stroke requiring hospitalization, whether hemorrhagic, ischemic, or unspecified. Post-index, post-stroke spasticity was defined with a diagnosis code for spastic hemiplegia (G81.1x) or muscle contracture (M62.4x) starting 7 days post-index, or claims indicating post-stroke spasticity treatment (BoNT-A or skeletal muscle relaxants) any time in the post-index period.
Table 1.
Inclusion and exclusion criteria
| Inclusion criteria | Exclusion criteria |
|---|---|
| Two non-same-day ICD-10 diagnosis codes in any position for hemorrhagic, ischemic or unspecified strokea | Diagnosis code for stroke in any position during the pre-index perioda |
| Evidence of an inpatient stay, with place of service in a hospital only, overlapping by at least 1 day with the index date | Diagnosis code for spasticity in any position during the pre-index periodb |
| Continuous enrollment with medical and pharmacy benefits for 12 months prior to the index date | Pharmacy or HCPCS code for a BoNT-A, BoNT-B, treatment for migraine, or skeletal muscle relaxant during the pre-index period |
| Continuous enrollment with medical and pharmacy benefits for 2 years starting on and following the index date | Diagnosis code for migraine, blepharospasm, sialorrhea, traumatic brain injury, spinal cord injury, cervical dystonia, multiple sclerosis, cerebral palsy, or neuromuscular bladder during the study period |
| Age ≥ 18 years during the year of the index date | Patients with data quality issues (i.e., missing valid age or gender) |
BoNT-A botulinum toxin type A, BoNT-B botulinum toxin type B, HCPCS Healthcare Common Procedure Coding System, ICD-10 International Classification of Diseases, 10th revision
aAll diagnosis codes for stroke were used to identify patients in these steps
bIn the inclusion criteria, spasticity was defined using any diagnosis codes for spasticity
Patients were at least 18 years of age during the year of the index date. Patients were excluded if there was evidence of stroke, spasticity, or use of BoNT-A or a muscle relaxant during the pre-index period. Patients were also excluded if there was evidence of other conditions associated with the onset of spasticity or use of BoNT-A for indications not related to spasticity during the study period to minimize any potential confounding; these were: migraine, blepharospasm, sialorrhea, traumatic brain injury, spinal cord injury, cervical dystonia, multiple sclerosis, cerebral palsy, or neuromuscular bladder.
Study Measures
Baseline measures such as demographics included age, gender, geographic region, payer type, and index year. Clinical characteristics included Charlson Comorbidity Index (CCI; as continuous and categorical measures), selected comorbidities of interest, and selected medications of interest. Spasticity treatment modalities were assessed over the post-index period. The therapy types assessed as lines of therapy were BoNT-As, skeletal muscle relaxants, and combination therapies (i.e., BoNT-A + skeletal muscle therapies). Pre- and post-index all-cause HCRU and healthcare costs were evaluated and included total pharmacy costs, total outpatient medical costs (emergency room [ER] visits, physician office visits, laboratory/pathology, radiology, surgical services, ancillary/other services, physical therapy, occupational therapy), and total inpatient medical costs. The CCI is a public domain, so no permissions for use were required.
Statistical Analyses
Descriptive analyses were used to examine the study measures. Categorical variables were reported in frequency (n) and percentage (%), whereas continuous variables were reported with mean, standard deviation (SD), and median. A logistic regression model was built to estimate the predictors of post-stroke initiation of a BoNT-A. A generalized linear model with a log link and gamma distribution was built to estimate the adjusted all-cause healthcare costs between patients with and without post-stroke spasticity. HCRU and costs were expressed as both the proportion of patients with such utilization and as per-patient mean, SD, and median. Utilization and costs were calculated on a per-patient basis, averaged across the cohort. All costs were converted to 2021 US dollars using the medical component of the Consumer Price Index. The analyses were based on observed, not projected, data. Analyses were conducted using SAS Release 9.4 (SAS Institute, Cary, NC, USA).
Results
Study Sample and Baseline Patient Characteristics
The overall sample consisted of 7851 patients who fulfilled study criteria. Most patients (n = 6680; 85.1%) had ischemic stroke, 957 (12.2%) had hemorrhagic stroke, and 214 (2.7%) had unspecified stroke. The mean ± SD age for the overall sample was 60.1 ± 12.0 years, with 43.4% (n = 3404) of the patients being in the 55–64-years age group, and fewer than half (33.7%) of the patients were female. Hypertension (n = 4141; 52.7%), diabetes (n = 1917; 24.4%), coronary artery disease (n = 1141; 14.5%), and arrhythmia (n = 895; 11.4%) were the most frequent comorbidities (Table 2). Prior to the index date, use of antihypertensives (n = 4097; 52.2%), statins (n = 2426; 30.9%), and anti-diabetes medications (n = 1559; 19.9%) was prevalent. The use of opioids (n = 1715; 21.8%), antidepressants (n = 998; 12.7%), anti-epileptics (n = 542; 6.9%), and benzodiazepines (n = 462; 5.9%) was also observed (Table 2). Mean pre-index all-cause healthcare costs were $16,261 ± $58,782 in the overall study sample and were largely driven by inpatient costs ($7543 ± $42,798), although outpatient ($5220 ± $23,308) and pharmacy ($3497 ± $17,950) costs were also high.
Table 2.
Demographic characteristics and concomitant medications in the baseline period
| Characteristics | Total population n = 7851 |
Hemorrhagic stroke n = 957 |
Ischemic stroke n = 6680 |
Unspecified stroke n = 214 |
|---|---|---|---|---|
| Age, years | ||||
| Mean (SD) | 60.1 (12.0) | 57.4 (13.5) | 60.5 (11.7) | 59.4 (13.4) |
| Median | 60 | 58 | 60 | 59 |
| Age group, years, n (%) | ||||
| 18‒34 | 188 (2.4) | 57 (6.0) | 126 (1.9) | 5 (2.3) |
| 35‒44 | 474 (6.0) | 86 (9.0) | 365 (5.5) | 23 (10.7) |
| 45‒54 | 1582 (20.2) | 223 (23.3) | 1305 (19.5) | 54 (25.2) |
| 55‒64 | 3404 (43.4) | 363 (37.9) | 2971 (44.5) | 70 (32.7) |
| 65‒74 | 1161 (14.8) | 114 (11.9) | 1016 (15.2) | 31 (14.5) |
| ≥ 75 | 1042 (13.3) | 114 (11.9) | 897 (13.4) | 31 (14.5) |
| Female, n (%) | 2647 (33.7) | 373 (39.0) | 2198 (32.9) | 76 (35.5) |
| Spasticitya, n (%) | 975 (12.4) | 121 (12.6) | 826 (12.4) | 28 (13.1) |
| Geographic region, n (%) | ||||
| Northeast | 1542 (19.6) | 193 (20.2) | 1311 (19.6) | 38 (17.8) |
| Midwest | 2208 (28.1) | 270 (28.2) | 1898 (28.4) | 40 (18.7) |
| South | 3097 (39.4) | 338 (35.3) | 2658 (39.8) | 101 (47.2) |
| West | 1004 (12.8) | 156 (16.3) | 813 (12.2) | 35 (16.4) |
| Index year, n (%) | ||||
| 2016 | 879 (11.2) | 87 (9.1) | 759 (11.4) | 33 (15.4) |
| 2017 | 3339 (42.5) | 412 (43.1) | 2831 (42.4) | 96 (44.9) |
| 2018 | 3371 (42.9) | 426 (44.5) | 2868 (42.9) | 77 (36.0) |
| 2019 | 262 (3.3) | 32 (3.3) | 222 (3.3) | 8 (3.7) |
| Time to diagnosis or indicator of spasticity, days | ||||
| Mean (SD) | 264.6 (215.3) | 217.4 (218.2) | 273.8 (213.9) | 198.0 (212.5) |
| Median | 213.0 (377.0) | 117.0 (324.0) | 230.5 (385.0) | 79.0 (305.0) |
| Treatment modalities, n (%) | ||||
| BoNT-A injections | 60 (0.8) | 14 (1.5) | 44 (0.7) | 2 (0.9) |
| Skeletal muscle relaxants | 887 (11.3) | 107 (11.2) | 754 (11.3) | 26 (12.1) |
| PT or OT | 3746 (47.7) | 483 (50.5) | 3174 (47.5) | 89 (41.6) |
| CCI, n (%) | ||||
| 0 | 4140 (52.7) | 611 (63.8) | 3423 (51.2) | 106 (49.5) |
| 1–2 | 2355 (30.0) | 219 (22.9) | 2076 (31.1) | 60 (28.0) |
| 3–4 | 852 (10.9) | 75 (7.8) | 755 (11.3) | 22 (10.3) |
| 5–6 | 351 (4.5) | 30 (3.1) | 303 (4.5) | 18 (8.4) |
| 7 + | 153 (1.9) | 22 (2.3) | 123 (1.8) | 8 (3.7) |
| Comorbidities of interest, n (%) | ||||
| Hypertension | 4141 (52.7) | 412 (43.1) | 3608 (54.0) | 121 (56.5) |
| Diabetes | 1917 (24.4) | 152 (15.9) | 1709 (25.6) | 56 (26.2) |
| Coronary artery disease | 1141 (14.5) | 70 (7.3) | 1040 (15.6) | 31 (14.5) |
| Peripheral artery disease | 657 (8.4) | 45 (4.7) | 595 (8.9) | 17 (7.9) |
| Atrial fibrillation | 639 (8.1) | 61 (6.4) | 550 (8.2) | 28 (13.1) |
| Anxiety | 583 (7.4) | 66 (6.9) | 492 (7.4) | 25 (11.7) |
| Heart failure | 542 (6.9) | 41 (4.3) | 479 (7.2) | 22 (10.3) |
| Depression | 466 (5.9) | 46 (4.8) | 409 (6.1) | 11 (5.1) |
| Transient ischemic attack | 198 (2.5) | 7 (0.7) | 187 (2.8) | 4 (1.9) |
| Seizure | 123 (1.6) | 19 (2.0) | 96 (1.4) | 8 (3.7) |
| Medications of interest, n (%) | ||||
| NSAIDs | 943 (12.0) | 105 (11.0) | 811 (12.1) | 27 (12.6) |
| Opioid analgesics | 1715 (21.8) | 183 (19.1) | 1474 (22.1) | 58 (27.1) |
| NSAID/opioid analgesic combinations | 12 (0.2) | 1 (0.1) | 11 (0.2) | 0 (0.0) |
| Antihypertensives | 4097 (52.5) | 418 (43.7) | 3565 (53.4) | 114 (53.3) |
| ACE/ARBs | 2996 (38.2) | 294 (30.7) | 2618 (39.2) | 84 (39.3) |
| Beta blockers | 2062 (26.3) | 191 (20.0) | 1806 (27.0) | 65 (30.4) |
| Calcium channel blockers | 1266 (16.1) | 142 (14.8) | 1084 (16.2) | 40 (18.7) |
| Antiarrhythmics | 359 (4.6) | 33 (3.4) | 313 (4.7) | 13 (6.1) |
| Antiepileptics | 542 (6.9) | 49 (5.1) | 471 (7.1) | 22 (10.3) |
| Benzodiazepines | 462 (5.9) | 50 (5.2) | 395 (5.9) | 17 (7.9) |
|
Anticholinergics (i.e., trihexyphenidyl) |
3 (0.0) | 2 (0.2) | 1 (0.0) | 0 (0.0) |
| Tetrabenazine | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Statins | 2426 (30.9) | 226 (23.6) | 2127 (31.8) | 73 (34.1) |
|
Other lipid-lowering medications (nitrates, fibrates, PCSK9 inhibitors) |
229 (2.9) | 21 (2.2) | 207 (3.1) | 1 (0.5) |
| Anticoagulants | ||||
| Vitamin K antagonists | 213 (2.7) | 39 (4.1) | 165 (2.5) | 9 (4.2) |
| Non–vitamin K antagonists | 254 (3.2) | 20 (2.1) | 225 (3.4) | 9 (4.2) |
|
Tissue plasminogen activator (administered in the hospital) |
12 (0.2) | 3 (0.3) | 8 (0.1) | 1 (0.5) |
| Antidepressants | 998 (12.7) | 115 (12.0) | 857 (12.8) | 26 (12.1) |
| Anti-diabetes medications | 1559 (19.9) | 116 (12.1) | 1400 (21.0) | 43 (20.1) |
ACE angiotensin-converting enzyme, ARBs angiotensin receptor blockers, BoNT-A botulinum toxin type A, CCI Charlson Comorbidity Index, NSAID non-steroidal anti-inflammatory drug, OT occupational therapy, PT physical therapy, SD standard deviation
aPatients with ≥ 1 diagnosis code for spasticity or with spasticity indicator
Post-index, more than 71.9% (n = 5641) of patients were discharged to home or self-care, and 13.0% (n = 1023) of patients were discharged to home through a home health organization.
Post-Stroke Spasticity
Of the overall study sample, 975 (12.4%) patients met the definition of post-stroke spasticity, which required patients to either have a diagnosis code for spastic hemiplegia or muscle contracture recorded at least 7 days post-stroke, or a post-index claim for BoNT-A or muscle relaxant (Table 2). Of these patients, 84.2% were identified using medication codes, 6.6% using diagnosis codes, and 9.2% using both. For patients with post-stroke spasticity, the mean ± SD time to spasticity diagnosis code or indicator was 264.6 ± 215.3 days overall, and was 217.4 ± 218.2, 273.8 ± 213.9, and 198.0 ± 212.5 days for hemorrhagic, ischemic, and unspecified stroke, respectively. The corresponding median times for hemorrhagic, ischemic, and unspecified stroke were 117, 231, and 79 days, respectively.
Treatment Modalities
During the 2-year, post-index period, 47.7% (n = 3746) of the overall study population was treated with physical or occupational therapy beginning an average of 100.3 ± 166.2 (median 24) days or 77.0 ± 143.0 (median 22) days from discharge, respectively. Meanwhile, 11.6% (n = 911) of patients required post-stroke spasticity pharmacotherapy with muscle relaxants and/or BoNT-A; none of these patients had a healthcare claim for BoNT type B (Table 3). Skeletal muscle relaxants were the most common of the pharmacologic treatments, used in 11.3% (n = 887) of patients overall and in 11.2% (n = 881) as first-line treatment. BoNT-A was used in 0.8% (n = 60) of patients overall [i.e., 6.6% (n = 60/911) of patients receiving pharmacologic treatments], including in 0.7% (n = 44) of patients with ischemic stroke and 1.5% (n = 14) of those with hemorrhagic stroke. Almost half (43.3%; n = 26) of BoNT-A–treated patients received it as the first line of pharmacologic treatment. The mean time to initiating first-line pharmacologic therapy was 269.8 ± 214.4 days (median 226 days). Those treated with BoNT-A received an average of 3.3 ± 1.8 treatments, beginning 319.8 ± 184.9 days post-stroke (median: 253 days) (Table 4). In patients treated with physical or occupational therapy, findings from the logistic regression model revealed that previous use of muscle relaxants, antidepressants, or physical therapy were associated with increased odds of BoNT-A initiation, while increase in age was associated with decreased odds of BoNT-A initiation (Table 5).
Table 3.
Lines of therapy (LOT) among patients with post-stroke spasticity
| Total population n = 7851 |
Hemorrhagic stroke n = 957 |
Ischemic stroke n = 6680 |
Unspecified stroke n = 214 |
|
|---|---|---|---|---|
| Spasticity treatment modalities, n (%) | ||||
| BoNT-A injections | 60 (0.8) | 14 (1.5) | 44 (0.7) | 2 (0.9) |
| Skeletal muscle relaxants | 887 (11.3) | 107 (11.2) | 754 (11.3) | 26 (12.1) |
| PT/OT | 3,746 (47.7) | 483 (50.5) | 3,174 (47.5) | 89 (41.6) |
| Patients with ≥ 1 LOT, n (%) | 911 (11.6) | 112 (11.7) | 772 (11.6) | 27 (12.6) |
| BoNT-A | 26 (0.3) | 6 (0.6) | 19 (0.3) | 1 (0.5) |
| Skeletal muscle relaxant | 881 (11.2) | 105 (11.0) | 750 (11.2) | 26 (12.1) |
| BoNT-A + skeletal muscle relaxant | 4 (0.1) | 1 (0.1) | 3 (0.0) | 0 (0.0) |
| Time to start of 1st LOT, days | ||||
| Mean (SD) | 269.8 (214.4) | 223.3 (218.5) | 278.8 (213.0) | 207.4 (212.6) |
| Median | 226 | 134 | 239 | 145 |
| Length of 1st LOT, months | ||||
| Mean (SD) | 3.3 (5.5) | 3.4 (5.4) | 3.3 (5.5) | 2.3 (5.1) |
| Median | 1 | 1 | 1 | 0.8 |
| Patients with 2nd LOT, n (%) | 118 (1.5) | 16 (1.7) | 100 (1.5) | 2 (0.9) |
| BoNT-A | 11 (0.1) | 3 (0.3) | 7 (0.1) | 1 (0.5) |
| Skeletal muscle relaxant | 81 (1.0) | 7 (0.7) | 74 (1.1) | 0 (0.0) |
| BoNT-A + skeletal muscle relaxant | 26 (0.3) | 6 (0.6) | 19 (0.3) | 1 (0.5) |
| Length of 2nd LOT, months | ||||
| Mean (SD) | 4.4 (5.7) | 6.3 (6.3) | 4.1 (5.6) | 6.4 (0.0) |
| Median | 1 | 3 | 1 | 6.4 |
| Patients with 3rd LOT, n (%) | 9 (0.1) | 5 (0.5) | 3 (0.0) | 1 (0.5) |
| BoNT-A | 3 (0.0) | 3 (0.3) | 0 (0.0) | 0 (0.0) |
| Skeletal muscle relaxant | 5 (0.1) | 2 (0.2) | 3 (0.0) | 0 (0.0) |
| BoNT-A + skeletal muscle relaxant | 1 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.5) |
| Length of 3rd LOT, months | ||||
| Mean (SD) | 3.0 (3.3) | 2.2 (1.9) | 3.6 (5.7) | 5.4 |
| Median | 2 | 2 | 1 | 5 |
| Patients with 4th LOT, n (%) | 1 (0.0) | 1 (0.0) | 0 (0.0) | 0 (0.0) |
| BoNT-A | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Skeletal muscle relaxant | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| BoNT-A + skeletal muscle relaxant | 1 (0.0) | 1 (0.0) | 0 (0.0) | 0 (0.0) |
| Length of 4th LOT, months | ||||
| Mean (SD) | 5.4 | 5.4 | – | – |
| Median | 5 | 5 | – | – |
BoNT-A botulinum toxin type A, OT occupational therapy, PT physical therapy, SD standard deviation
Table 4.
Post-stroke spasticity BoNT treatment patterns
| Total population n = 7851 |
Hemorrhagic stroke n = 957 |
Ischemic stroke n = 6680 |
Unspecified stroke n = 214 |
|
|---|---|---|---|---|
| Patients with ≥ 1 BoNT-A injection, n (%) | 60 (0.8) | 14 (1.5) | 44 (0.7) | 2 (0.9) |
| Time to 1st BoNT injection, days | ||||
| Mean (SD) | 319.8 (184.9) | 301.2 (167.9) | 330.5 (194.0) | 212.5 (4.9) |
| Median | 253 | 253 | 274 | 213 |
| No. of BoNT-A injections, n (%) | ||||
| Mean (SD) | 3.3 (1.8) | 3.4 (1.7) | 3.2 (1.9) | 4.0 (0.0) |
| Median | 3 | 4 | 3 | 4 |
| Patients with ≥ 2 BoNT-A injections, n (%) | 47 (0.6) | 11 (1.1) | 34 (0.5) | 2 (0.9) |
| Time between 1st and 2nd injection, days | ||||
| Mean (SD) | 114.7 (49.2) | 97.8 (19.8) | 116.8 (51.3) | 173.0 (103.2) |
| Median | 98 | 98 | 98 | 173 |
| Patients with ≥ 3 BoNT-A injections, n (%) | 34 (0.4) | 9 (0.9) | 23 (0.3) | 2 (0.9) |
| Time between 2nd and 3rd injection, days | ||||
| Mean (SD) | 116.0 (55.5) | 137.0 (74.9) | 102.8 (34.8) | 173.0 (124.5) |
| Median | 98 | 99 | 96 | 173 |
BoNT-A botulinum toxin type A, SD standard deviation
Table 5 .
Logistic regression model: post-stroke initiation of BoNT-A
| Odds ratio | Lower limit | Upper limit | Chi-square | P value | |
|---|---|---|---|---|---|
| Age (continuous) | 0.953 | 0.929 | 0.977 | 14.242 | 0.0002 |
| Gender (ref: female) | |||||
| Male | 0.683 | 0.389 | 1.197 | 1.777 | 0.1826 |
| Payer type (ref: self-insured/other/unknown) | |||||
| Commercial | 0.991 | 0.548 | 1.794 | 0.001 | 0.9762 |
| Medicaid/Medicare risk | 1.389 | 0.441 | 4.371 | 0.316 | 0.5742 |
|
Stroke type (ref: unspecified type) | |||||
| Hemorrhagic | 1.232 | 0.252 | 6.025 | 0.066 | 0.7970 |
| Ischemic | 0.926 | 0.203 | 4.220 | 0.010 | 0.9211 |
| Charlson score (continuous) | 0.882 | 0.722 | 1.077 | 1.521 | 0.2175 |
| Muscle relaxanta (ref: no) | 5.859 | 3.371 | 10.183 | 39.295 | < 0.0001 |
| Benzodiazepineb (ref: no) | 0.361 | 0.125 | 1.042 | 3.548 | 0.0596 |
| Antidepressantb (ref: no) | 3.460 | 1.988 | 6.024 | 19.265 | < 0.0001 |
| Anti-epilepticb (ref: no) | 1.223 | 0.683 | 2.187 | 0.459 | 0.4983 |
| PT visitc (ref: no) | 6.952 | 2.907 | 16.627 | 18.996 | < 0.0001 |
| Discharge location | |||||
| Home/self-care | 0.250 | 0.101 | 0.617 | 9.047 | 0.0026 |
| Home under care of HHSO | 0.195 | 0.057 | 0.664 | 6.824 | 0.0090 |
|
Short-term, in-patient care (e.g., SNF, IRF) |
0.678 | 0.261 | 1.764 | 0.634 | 0.4261 |
HHSO home health service organization, IRF inpatient rehabilitation facility, PT physical therapy, SNF skilled nursing facility
aPrior to BoNT-A
bIn post-index period prior to BoNT-A initiation and with no usage in the pre-index period
cIn post-index period prior to BoNT-A initiation
All-Cause HCRU and Healthcare Costs Over the 2-Year Post-index Period
Post-index HCRU included high percentages of ER visits (42.5%) and inpatient readmissions (42.4%) in the overall study sample. In the overall population, stroke-related readmissions occurred in 32.7% (n = 2564) of patients, with 79.4% (n = 2037) of those occurring within 90 days of the index date. Stroke-related readmissions were significantly more common in patients with post-stroke spasticity (44.4%; n = 433/975) compared to those without post-stroke spasticity (31.0%; n = 2131/6876) (P < 0.0001). Patients with post-stroke spasticity had more mean prescription fills and higher pharmacy costs (Fig. 2); more physician office, physical, and occupational therapy visits (Fig. 3); more laboratory, radiology, and surgical service visits; and longer total inpatient stays than did those with stroke but without spasticity (all P < 0.0001).
Fig. 2.
Mean pharmacy utilization and costs (post-index period). OT occupational therapy, PT physical therapy, USD US dollars
Fig. 3.
Utilization of rehabilitation services (post-index period). OT occupational therapy, PT physical therapy
Patients with post-stroke spasticity incurred significantly higher mean all-cause healthcare costs compared with patients without spasticity ($62,875 ± $79,583 vs. $44,472 ± $70,522; P < 0.001), representing 39.6% higher adjusted all-cause healthcare costs (Fig. 4 and Table 6). Median post-index all-cause healthcare costs were $36,795 [interquartile range (IQR) $51,937] in patients with post-stroke spasticity versus $25,284 (IQR $34,902) in patients without spasticity. Patients with hemorrhagic stroke experienced particularly high mean post-index all-cause healthcare costs (with vs. without spasticity: $109,649 ± $136,062 vs. $68,908 ± $101,816; P < 0.001), with median post-index all-cause healthcare costs of $64,916 versus $35,504 for patients with versus without spasticity. Inpatient costs accounted for the majority of mean healthcare costs among patients with post-stroke spasticity ($40,243 ± $61,611 vs. $27,426 ± $46,689 for those without spasticity; P < 0.0001). Mean costs of rehabilitation services were also significantly higher in patients with post-stroke spasticity than in those with stroke without spasticity, although, overall, rehabilitation services costs were relatively low (Fig. 5).
Fig. 4.
Mean all-cause healthcare costs (post-index period). USD US dollars
Table 6.
Generalized estimating equation: post-stroke all-cause healthcare costs
| Cost ratio | Lower limit | Upper limit | Chi-square | P value | |
|---|---|---|---|---|---|
| Post-index spasticity (ref: no) | |||||
| Yes | 1.396 | 1.318 | 1.479 | 128.960 | < 0.0001 |
| Age (continuous) | 0.991 | 0.989 | 0.993 | 75.860 | < 0.0001 |
| Gender (ref: female) | |||||
| Male | 0.977 | 0.938 | 1.018 | 1.230 | 0.268 |
| Payer type (ref: self-insured/other/unknown) | |||||
| Commercial | 0.931 | 0.891 | 0.973 | 10.290 | 0.001 |
| Medicaid/Medicare risk | 0.616 | 0.575 | 0.659 | 194.250 | < 0.0001 |
|
Stroke type (ref: unspecified type) | |||||
| Hemorrhagic | 1.334 | 1.176 | 1.515 | 19.910 | < 0.0001 |
| Ischemic | 0.785 | 0.699 | 0.882 | 16.590 | < 0.0001 |
| Charlson score (continuous) | 1.132 | 1.118 | 1.145 | 394.060 | < 0.0001 |
|
Geographic region (ref: northeast) | |||||
| Midwest | 0.879 | 0.831 | 0.929 | 20.730 | < 0.0001 |
| South | 0.847 | 0.803 | 0.893 | 37.770 | < 0.0001 |
| West | 1.277 | 1.193 | 1.367 | 49.090 | < 0.0001 |
| Pre-index all-cause healthcare costs (log form) | 1.026 | 1.020 | 1.033 | 67.740 | < 0.0001 |
Fig. 5.
Mean cost of rehabilitation services (post-index period). OT occupational therapy, PT physical therapy, USD US dollars
Discussion
In this large, retrospective claims analysis of real-world data from 7851 patients with stroke, 12.4% of patients met the criteria for post-stroke spasticity. First identification of spasticity occurred after an average of 8.1 months (246.6 days). During the 2 years post-stroke, approximately half of all study patients were treated with physical or occupational therapy; meanwhile, 11.3% were treated with skeletal muscle relaxants and just under 1% of patients were treated with BoNT-A. Patients with post-stroke spasticity had mean all-cause healthcare costs of $62,875 over the 2-year post-index period, which represented an adjusted cost ratio of 39.6% higher than for patients with stroke but without spasticity.
Previous studies have reported a prevalence of 25–43% for post-stroke spasticity, with the incidence being highest within the first 6 weeks after stroke [5–14]. In our study, we found that fewer patients with stroke met the criteria for post-stroke spasticity—and at a later spasticity onset time—than were reported in previous epidemiological studies [5–14]. The low rate and late onset of post-stroke spasticity observed in our study may be due to underreporting, diagnostic misclassification, and/or delayed reporting in clinical practice [5, 9, 29]. Although BoNT-A is the recommended first-line treatment for spasticity affecting the upper limbs in patients with stroke and is considered safe and effective in reducing post-stroke spasticity, only 6.6% of patients receiving pharmacologic treatments received BoNT-A treatment post-stroke in this study [26, 30]. A median of 4 BoNT-A treatments for patients with hemorrhagic stroke and 3 for ischemic stroke were noted. The low utilization of BoNT-A for the management of post-stroke spasticity seen in our study could have been due to the length of the follow-up period, as patients could have initiated therapy beyond the 2-year time frame [31]. However, other factors such as an overall lack of an established clinical pathway for rehabilitation, physicians’ limited awareness of clinical practice guidelines and the fact that BoNT-A is the recommended first-line treatment of spasticity, lack of access to treating physicians or specialists performing BoNT-A injections, and poor insurance or financial support should not be overlooked [31–35]. The exact reasons for apparent low utilization of BoNT-A therapy in these patients is a key topic for future research.
Patients with post-stroke spasticity incurred higher healthcare costs and greater HCRU compared with patients post-stroke without spasticity, and percentages of patients with all-cause and stroke-related hospital readmissions were higher among patients with spasticity than among those without. There are few previous studies that have compared healthcare costs in patients with stroke with and without spasticity. Results from a Swedish registry study conducted in 2003–2004 that included 140 patients indicated that patients post-stroke with spasticity have about 4-times higher healthcare costs than patients post-stroke without spasticity in the first year, with significantly higher costs for hospital care and municipality services such as home help and residential care [6, 36]. Healthcare costs in the year after stroke were about twice as high for patients with post-stroke spasticity than for matched controls in a UK database study conducted in 2007–2011 [37]. In the current study, conducted in the US in 2015–2021, the management of patients with post-stroke spasticity was associated with about 40% higher adjusted healthcare costs than that of patients without spasticity.
Limitations
Although claims data are valuable for the efficient and effective examination of healthcare outcomes, treatment patterns, HCRU, and costs, all claims databases have inherent limitations affecting generalizability because the claims are collected for the purpose of payment within the commercially insured population and not for research. The presence of a diagnosis code on a medical encounter or outside claim may not have been conclusive of the positive presence of disease or accounted for potential confounders such as disease severity, as the diagnosis code may have been incorrectly coded or included as rule-out criteria rather than reflecting the actual disease. However, this risk was mitigated by the requirement that patients had at least two diagnosis codes for stroke, the first of which overlapped with an inpatient stay with place of service only in a hospital setting.
Given the observational nature of the retrospective study design, all study findings are associative and no causal inferences can be made. Results and conclusions are limited to the patient population, which consisted of patients enrolled in managed care plans, and may not be generalizable to other commercially insured populations in the US. Only patients with continuous eligibility were included; thus, patients who did not maintain membership during the outcome period for 1 year prior to the index date and 2 years starting on the index date were excluded from the sample.
Other study variables may also have been affected by these claims-based limitations. Although the algorithm to identify patients with post-stroke spasticity was rigorous in its concept and application, the algorithm is subject to the assumptions of objective and consistent coding practices as no specific identifier of spasticity in patients post-stroke exists.
Conclusion
Among patients with stroke, 12.4% were identified as having had post-stroke spasticity. These patients incurred higher healthcare costs and HCRU compared with patients post-stroke without spasticity. Although treatment guidelines recommend BoNT-A as first-line treatment for post-stroke spasticity based on the most robust evidence (Level A), BoNT-As were utilized in only 6.6% of patients with claims indicating post-stroke spasticity.
These findings demonstrate significantly higher healthcare costs, further confirming the economic burden associated with post-stroke spasticity. Further research into the limited use of BoNT-A among patients with post-stroke spasticity is warranted. As successful rehabilitation requires prompt diagnosis and treatment, earlier identification of post-stroke spasticity with subsequent treatment optimization may therefore represent an opportunity for cost savings within managed healthcare systems.
Acknowledgments
Medical Writing and Editorial Assistance. The authors thank Kate Katsaval, CMPP, of The Medicine Group (New Hope, PA, USA) for providing medical writing support / editorial support, which were sponsored by Ipsen (Cambridge, MA, USA) in accordance with Good Publication Practice guidelines.
Author Contributions
Michael Hull, Vamshi Ruthwik Anupindi, Jing He, Mitchell DeKoven, Jumaah Goldberg, and Jonathan Bouchard contributed to the study design, analysis, and interpretation of the data, as well as the drafting and revision of the manuscript. All authors have read and approved the final manuscript and agree to be accountable for all aspects of the work.
Funding
This study was sponsored by Ipsen (Cambridge, MA, USA), and funded the journal’s Rapid Service Fee.
Data Availability
The data that support the findings of this study are available from IQVIA PharMetrics Plus database, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are, however, available from the authors upon reasonable request and with permission of IQVIA.
Declarations
Conflict of Interest
This study was sponsored by Ipsen, Cambridge, MA, USA. Vamshi Ruthwik Anupindi and Mitchell DeKoven are employees of IQVIA, contracted by Ipsen to conduct this study. Michael Hull and Jing He are a former employees of IQVIA, contracted by Ipsen to conduct this study. Jumaah Goldberg is a former employee of Ipsen. Jonathan Bouchard is an employee of Ipsen.
Ethical Approval
All data are compliant with the Health Insurance Portability and Accountability Act to guard patients’ privacy. This was a retrospective claims study in which all data were de-identified according to regulations. Ethics approval and consent to participate were not required.
Footnotes
Prior Presentation: Results reported here were presented as posters at the Academy of Managed Care Pharmacy Nexus (October 11–14, 2022, National Harbor, MD), the American Physical Therapy Association (February 23–25, 2022, San Diego, CA), the American Society of Neurorehabilitation (March 14–16, 2023, Charleston, SC), the American Occupational Therapy Association Inspire (April 20–23, 2023, Kansas City, MO), the International Society for Pharmacoeconomics and Outcomes Research (May 7–10, 2023, Boston, MA), the Academy of Neurologic Physical Therapy (September 28–30, 2023, Minneapolis, MN), the Acadamy of Managed Care Pharmacy (October 16–19, 2023, Orlando, FL), the American Congress of Rehabilitation Medicine (October 30–November 2, 2023, Atlanta, GA), and the American Academy of Physical Medicine and Rehabilitation (November 15–19, 2023, New Orleans, LA).
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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 data that support the findings of this study are available from IQVIA PharMetrics Plus database, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are, however, available from the authors upon reasonable request and with permission of IQVIA.