A real-world study of health care resource utilization (HCRU) in patients with myasthenia gravis on second-line therapy identified the factors that led to increased financial burdens.
A recent study examined health care costs in myasthenia gravis (MG) for patients receiving second-line therapy.
The authors, writing in Journal of the Neurological Sciences, said they wanted to describe health care resource utilization (HCRU) and associated costs faced by these patients when they start advanced therapy, and to pinpoint the factors linked with high-cost disease burden in the second year after second-line therapy begins.
In MG, antibodies inhibit the receptors for acetylcholine at the neuromuscular junction, which prevents the muscle from contracting. This may be caused by antibodies to the acetylcholine receptor or by antibodies to other proteins, such as the MuSK (Muscle-Specific Kinase) protein. In a myasthenic crisis, the muscles weaken to the point of respiratory failure and a ventilator is required.
First-line therapies include acetylcholinesterase inhibitors (AChEI), followed by steroidal or nonsteroidal immunosuppressive therapies (NSISTs) for those who do not respond to an AChEI, including patients with MuSK autoantibody-positive MG.
If refractory MG is diagnosed, the next level of therapy includes chronic intravenous immunoglobulin (IVIg) or plasma exchange, cyclophosphamide, and targeted biologic therapy (eg, rituximab).
To understand the burden of this disease, the researchers used retrospective claims data from the IBM MarketScan Commercial, Medicare, and Medicaid Supplemental of patients with MG from January 2008 through September 2019.
The observation period included 1 year prior to the index date, defined as the date second-line therapy began, and 2 years after the index date.
Assessments were made at baseline (1 year preceding the index date), year 1 (the year following the index date) and year 2 (the year following year 1), as well as overall for the 2-year follow-up period.
Second-line therapy was defined as starting NSIST; any claim for azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, cyclophosphamide, leflunomide, or tacrolimus; biologics (rituximab and eculizumab); chronic IVIg, defined as 6 or more IVIg cycles during year 1; or chronic steroids, defined as any dose of oral steroid use for at least 90 days.
High dose and low dose steroids were defined as at least 40 mg/day prednisone or equivalent and less than 40 mg/day prednisone or equivalent.
Patients were included in the study regardless of autoantibody status. The researchers included characteristics such as age, treatment history, and comorbidities. Overall and MG-related HCRU costs were assessed during the baseline period, year 1, and year 2, both overall and by inpatient, outpatient, and pharmacy settings.
The study also included the total cost per site of care, total medical costs, and total health care costs; all costs were inflation adjusted to 2019. All outcomes were also stratified by second-line treatment at index date.
Between 2008 and 2019, 1498 adults (≥18 years) starting second-line MG therapy were followed for 2 years; of those, 49% had chronic steroids and 31% received NSISTs as their second-line therapy.
The mean (SD) age at second-line treatment initiation was 58.5 (16.11) years, with nearly three-quarters of patients were older than 50 years. The most common comorbidities in these patients were hypertension (52.9%), infection (51.7%), dyslipidemia (34.0%), and type 2 diabetes (28.0%).
During the 12 months prior to the index date, AChEI, alone or in combination with short-term steroids, was the most common first-line therapy (44.5%). Most patients initiated second-line treatment with chronic steroids (n = 737), followed by NSIST (n = 469), chronic IVIg (n = 114), and biologics (n = 25). Some patients started a nonsteroidal second-line therapies in combination with low-dose steroids (n = 85) or high-dose steroids (n = 66).
During follow-up, 49% of the patients had 1 or more MG exacerbations.
The top 2 most frequently used therapies—steroids and NSISTs—are linked with increased risks of adverse events, said the authors. For steroids, they cited infection, venous thromboembolism, osteoporosis, dyslipidemia, diabetes, and obesity. For NSISTs, they cited nausea, vomiting, hyperglycemia, malignancy, hepatotoxicity, nephrotoxicity and pancreatitis.
Among all patients, the mean all-cause total health care cost was $106,821 per patient during follow-up, with $88,040 and $18,780 attributed to medical and pharmacy costs, respectively.
In a univariable analysis, any number of exacerbations was linked with high cost.
In a multivariable analysis, factors significantly linked with high cost included use of high-dose steroids, 6 or more cycles of IVIg, and 1 and at least 4 (but not 2–3) MG exacerbations in the first year after beginning second-line therapy.
In a stratified cost analysis, 3 factors in the first year were associated with more total health care costs for patients:
These data suggest that patients receiving chronic IVIg or NSISTs for MG experience significant economic burden, said the researchers, who said their findings help to clarify the costs linked with second-line MG therapies.
Using high-dose steroids in year 1 was one of the factors linked with high health care costs in year 2, as well as chronic IVIg therapy or 4 or more exacerbations in year 1.
“These variables can be indications of severe disease or suboptimal disease management,” the researchers noted. Having this real-world knowledge could “help identify and proactively manage specific subpopulations that may be susceptible to high costs.”
The results “help to build a broader overall picture of the burden of MG experienced by patients and on the health care system,” said the authors, some of whom are from UCB Pharma, which is developing 2 MG therapies: rozanolixizumab, a neonatal Fc receptor inhibitor, and zilucoplan, a macrocyclic peptide inhibitor of complement component 5. UCB also funded the study.
The limitations in the study were “mostly inherent to analyses of claims databases such as patient and treatment data, and health care resource use and cost information being limited to the measures available in the database."
Ting A, Story T, Lecomte C, Estrim A, Syed S, Lee E. A real-world analysis of factors associated with high healthcare resource utilization and costs in patients with myasthenia gravis receiving second-line treatment. J Neurol Sci. Published online December 22, 2022. doi:10.1016/j.jns.2022.120531