J Korean Med Sci.  2021 Oct;36(39):e242. 10.3346/jkms.2021.36.e242.

Survival, Prognosis, and Clinical Feature of Refractory Myasthenia Gravis: a 15-year Nationwide Cohort Study

• Jeong S
• Noh Y
• Oh IS
• Hong YH
• Shin JY

• KMID: 2521181
• DOI: http://doi.org/10.3346/jkms.2021.36.e242

Abstract

Background
Myasthenia gravis (MG) is a rare classic autoimmune disease where immunosuppressant therapies have been successful to reduce MG attributable mortality fairly well. However, patients with refractory MG (rMG) among the actively treated MG (aMG) are nonresponsive to conventional therapy and display high disease severity, which calls for further research. We aimed to determine survival, prognosis, and clinical feature of patients with rMG compared to non-rMG.
Methods
Retrospective nationwide cohort study using Korea's healthcare database between 2002 and 2017 was conducted. Patients with rMG (n = 47) and non-rMG (n = 4,251) who were aged > 18 years, followed-up for ≥ 1 year, and prescribed immunosuppressants within 2 years after incident MG diagnosis were included. Patients with rMG were defined as administered plasma exchange or intravenous immunoglobulin at least 3 times per year after receiving ≥ 2 immunosuppressants. All-cause mortality, myasthenic crisis, hospitalization, pneumonia/ sepsis, and emergency department (ED) visits were measured using Cox proportional hazard models and pharmacotherapy patterns for rMG were assessed.
Results
The rMG cohort included a preponderance of younger patients and women. The adjusted hazard ratio was 2.49 (95% confidence interval, 1.26–4.94) for mortality, 3.14 (2.25–4.38) for myasthenic crisis, 1.54 (1.15–2.06) for hospitalization, 2.69 (1.74–4.15) for pneumonia/sepsis, and 1.81 (1.28–2.56) for ED visits for rMG versus non-rMG. The immunosuppressant prescriptions were more prevalent in patients with rMG, while the difference was more remarkable before rMG onset rather than after rMG onset.
Conclusion
Despite the severe prognosis of rMG, the strategies for pharmacotherapeutic regimens were similar in those two groups, suggesting that intensive monitoring and introduction of timely treatment options in the early phase of MG are required.

Keyword

Refractory Myasthenia Gravis; Population-based Study; Longitudinal Study; Pharmacotherapy; Clinical Outcomes

Figure

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  Fig. 1 Flowchart for the identification and selection of the study cohort.MG = myasthenia gravis, aMG = actively treated myasthenia gravis, rMG = refractory myasthenia gravis.

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  Fig. 2 Kaplan-Meier curves for the time to the clinical outcomes. (A) Mortality, (B) myasthenic crisis, (C) hospital admission, (D) pneumonia or sepsis, (E) emergency department visits.rMG = refractory myasthenia gravis.

• 

  Fig. 3 Comparative pattern of drug prescriptions in the 2-year period BID and AID for the (A) patients with rMG and (B) patients with non-rMG.AChEI = acetylcholine esterase inhibitor, CS = corticosteroid, ISA = non-steroidal immunosuppressive agent, rMG = refractory myasthenia gravis, BID = before the index date, AID = after the index date.aThe index date: the date of rMG incidence defined as the date of first PE or IVIG procedure when the procedures were provided at least three times per year (in rMG) and the date of initial IVIG or PE procedure (in non-rMG).

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