Characteristics of Patients in the Refractory Stage of Myasthenia Gravis

Patients with double seronegative myasthenia gravis (DSNMG) who are in the refractory stage of disease exhibited differing trends and may represent a unique subgroup requiring more targeted treatment approaches, according to a retrospective study published in Muscle & Nerve.

Recent advances in disease management have improved the prognosis and quality of life for most patients with myasthenia gravis (MG), however, 10%-15% continue to have frequent relapses. There has been limited study into features of these patients. The objective of the current study was to investigate the autoantibody profile and clinical characteristics of patients with refractory MG, compared to patients with nonrefractory status, based on predefined criteria.

Patient records from University Hospital of Patras in Greece were reviewed through August 2021 for this study. Patients (N=113) with MG were subdivided into refractory and nonrefractory status and assessed for clinical outcomes. Refractory disease was defined as MG Foundation of America (MGFA) ³class III with ³12 months of follow-up, MGFA 2 severe relapses requiring rescue therapy despite adequate treatment for 12 months, or MGFA

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Patients were aged median 57 (interquartile range [IQR]30) years, 52.2% were women, disease had onset at 44 (IQR, 27) years of age, 32.7% had MGFA class I, 25.7% class II, 33.6% class III, 4.4% class IV, 3.5% class V , and 19.5% had DSNMG.

Patients with refractory disease (13.3%) were significantly younger at diagnosis (P = .019), had more DSNMG (P = .031), thymic pathologies (P = .030), and underwent thymectomy (P = .008).

No patients with refractory disease had circulating anti-muscle specific tyrosine kinase (MuSK) antibodies or both circulating MuSK and acetylcholine receptor (AchR) antibodies.

In general, the subset of patients with DSNMG who were in the refractory stage of disease tended to be more resistant to treatment.

This study may have been limited by the small sample size and by the fact that the research institution tended to see more severe cases than other centers, potentially limiting the generalizability.

The study authors concluded, “Approximately 10% of MG patients will experience a refractory period during the course of the disease, in agreement with the literature. However, our findings differ in terms of antibody status; given that DSNMG patients had a higher probability of treatment resistance, whereas none of the MuSK antibody patients had refractory MG.”


Veltsista D, Kefalopoulou Z, Tzartos J, Chroni E. Autoantibody profile in myasthenia gravis patients with a refractory phase. muscle nerves. Published online February 23, 2022. doi:10.1002/mus.27521

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