High-Dose Steroids, Treatment Escalation, and Healthcare Burden in Myasthenia Gravis: A US Claims-Based Cohort Study

Abstract

Introduction: Myasthenia gravis (MG) is a rare neuromuscular autoimmune disease, characterized by chronic, fluctuating muscle weakness and fatigability. Despite established therapies, many patients have inadequately controlled MG. We describe treatment escalation patterns and outcomes for patients with MG between 2010 and 2018.

Methods: We conducted a retrospective cohort analysis of medical and pharmacy claims data. Patients aged ≥ 18 years at MG diagnosis were included from two US Merative™ MarketScan^® databases. MG treatment escalation was defined as an increase of the administered prednisolone-equivalent corticosteroid dose, use of add-on treatments, or treatment switches.

Results: The cohort included 4925 adults with newly diagnosed MG (1102 aged 18-49 and 3823 aged ≥ 50 at first MG diagnosis) from January 1, 2010 to December 31, 2018. Median follow-up was 30.0 months (18-49 group) and 27.5 months (≥ 50 group). Overall, 71.5% (3521/4925) of patients had ≥ 1 MG treatment escalation; escalation with high-dose corticosteroids was the most common type (64.8% [18-49 group] and 58.5% [≥ 50 group]). In the first year post-diagnosis, median (range) maximal daily prednisolone-equivalent corticosteroid dose was 40.0 (20.0-75.0) mg/day (18-49 group) and 40.0 (20.0-70.0) mg/day (≥ 50 group). Treatment breaks and de-escalation led to rescue treatment or treatment re-escalation in most patients. Exacerbations occurred in 26.3% (n = 290; 18-49 group) and 21.6% (n = 825; ≥ 50 group). Healthcare resource utilization (HCRU) and costs were highest in Year 1, with mean MG-related costs per patient between $24,982 (≥ 50 group) and $33,023 (18-49 group).

Conclusion: The study findings highlight that MG is inadequately controlled in a substantial proportion of patients despite conventional treatment and high reliance on corticosteroids. Earlier treatment with targeted therapies and improved safety profiles may reduce patient burden, HCRU, and costs.

Keywords: Cohort study; Corticosteroids; Healthcare costs; Healthcare resource utilization; Myasthenia gravis; Treatment escalation.

Fig. 1

Percentage of patients with each MG treatment escalation (MG-TE) type by follow-up year after MG diagnosis. a 18–49 years at MG diagnosis; b ≥ 50 years at MG diagnosis. 18–49 years: n = 1102; ≥ 50 years: n = 3823. Data represent patients who had at least one MG-TE of the specified type, but each patient may have had more than one MG-TE (of any type) in any year. HDCS was defined as an oral daily prednisolone-equivalent dose ≥ 15 mg. HDCS high-dose corticosteroid, Ig immunoglobulin, MG myasthenia gravis, MG-TE myasthenia gravis treatment escalation, NSIST non-steroidal immunosuppressive therapy, PLEX plasma exchange, Yr year

Fig. 2

Incidence rate of MG-TEs after MG diagnosis over time, by MG-TE type. a 18–49 years at MG diagnosis; b ≥ 50 years at MG diagnosis. 18–49 years: n = 1102; ≥ 50 years: n = 3823. Each MG-TE type includes all patients who had at least one such treatment escalation at any time during follow-up. Incidence is not shown beyond Year 6 of follow-up due to a low number of events in subsequent years. HDCS was defined as an oral daily prednisolone-equivalent dose ≥ 15 mg. HDCS high-dose corticosteroids, Ig immunoglobulin, MG myasthenia gravis, MG-TE myasthenia gravis treatment escalation, NSIST non-steroidal immunosuppressive therapy, PLEX plasma exchange

Fig. 3

Treatment status following the first MG-TE. Figure depicts the flow of patients through the four possible treatment statuses, following on from the end of their first MG-TE at any point during follow-up. Re-escalation was defined as the start of a new escalation (any type) following the last MG treatment break; treatment break was defined as a gap of ≥ 90 days between consecutive claims of all MG-related treatments (excluding AChEI); rescue treatment was defined as the start of a new escalation (any type) following the last treatment de-escalation; de-escalation was defined as a gap of ≥ 14 days between the end of the first MG-TE (any type) and the start of a new escalation (any type). Appendix: Supplementary Methods provide the definitions for each treatment status and each type of MG-TE. Dashed lines indicate overlap between patients who progressed from either de-escalation to rescue treatment or treatment break to re-escalation. MG myasthenia gravis, MG-TE myasthenia gravis treatment escalation

Fig. 4

Incident comorbidities by follow-up year after MG diagnosis. a 18–49 years at MG diagnosis; b ≥ 50 years at MG diagnosis. 18–49 years: n = 1102; ≥ 50 years: n = 3823. DM diabetes mellitus, MG myasthenia gravis, T2DM type 2 diabetes mellitus, Yr year

Fig. 5

Clinical outcomes by follow-up year after MG diagnosis and by age group. a MG exacerbation without crisis; b MG crisis. 18–49 years: n = 1102; ≥ 50 years: n = 3823. MG myasthenia gravis, Yr year