Background: Generalized myasthenia gravis (gMG) treatment options include nonspecific immunosuppression with corticosteroids, which are associated with adverse effects, particularly with high-dose, long-term use and in patients with comorbidities.Objective: Quantify the burden associated with high-dose, long-term corticosteroid usage in patients with gMG.Methods: The IQVIA PharMetrics® Plus claims database (1/1/2006-6/30/2022) was retrospectively analyzed. Eligible patients were aged ≥18 years, had ≥2 claims (≥30 days apart) with MG diagnosis ICD9 or ICD10 codes filed via non-ophthalmologic specialist as primary, and continuously enrolled during 6 months before and 24-month follow-up after first MG claim. Outcomes included prednisone daily dose and number of treated days, incidence rates of gMG crisis and exacerbation, and prevalence of comorbidities among propensity score-matched patients.Results: Of 10,816 eligible patients, 49% were male, mean (95% CI) age was 57.8 (57.5-58.1) years, 76% had commercial insurance, 23% Medicare, and 1% Medicaid. Of the 4566 patients with any corticosteroid use, 59% (2684/4566) had long-term (>90 days) treatment courses; the majority (n=4099) with corticosteroid use were treated with prednisone. Among patients who received prednisone, 76% (2033/2677) with long-term use received >10 mg/day and had a mean dose of 21.3 (20.8-21.9) mg/day. Prevalence of cardiovascular disease, gastrointestinal disorder, hypertension, obesity, osteoporosis, and type 2 diabetes was significantly greater among patients treated with long-term corticosteroids than those without corticosteroid use (P≤0.05). Incidence rates of MG inpatient exacerbations were 20.8 and 6.2 per 100 patient-years among patients with long-term use and no corticosteroid use, respectively; incidence of MG crises were 7.0 and 3.0 per 100 patient-years, respectively.Conclusions: This analysis of US claims data illustrates the large burden of high-dose, long-term corticosteroid use in patients with gMG and the high burden of comorbidities. These findings emphasize the importance of considering potentially steroid-sparing, novel treatment options with more tolerable safety profiles, such as complement inhibitors.