Clinical Features Identified in Subgroup of Drug-Resistant Myasthenia Gravis

About 8.5% of patients with myasthenia gravis (MG) are drug-refractory, and these patients are more likely to be women, have an early onset age, and have anti–muscle-specific tyrosine kinase (MuSK) antibodies, according to a study in the Annals of Clinical and Translational Neurology.

Patients with MG are considered to be drug-refractory when their MG Foundation of America post-intervention status (MGFA-PIS) is either unchanged or worsens following treatment with corticosteroids and a minimum of 2 other autoimmune suppressive agents. These drugs are used in adequate doses for an adequate duration, but if patients present disabling symptoms or side effects, they may be classified as a patient with drug-refractory MG after an international expert consensus. Researchers believe identifying the characteristics of this patient population could potentially lead to new treatments and decrease mortality and morbidity.

The objective of the current study was to determine the clinical, immunologic, and therapeutic characteristics in patients with drug-refractory MG by reviewing data from the MG Registry in Spain, which is part of the Spanish Neuromuscular Diseases Registry.

The cross-sectional, multicenter study included patients with MG onset from January 1, 2000, to December 31, 2017. Follow-up ended at death or at the end of the study on December 31, 2019.

A total of 990 patients with MG from 15 hospitals were included; their mean age at onset was 57.2 years (SD 19.1), and 52.2% were men.

Of the cohort, 84 patients (8.5%) were drug-refractory. This group had a mean onset age of 44.4 years (SD 18.0), 75% were women, 81% had anti–acetylcholine receptor (AChR) antibodies, 6% had anti-MuSK antibodies, 1.2% had anti-AChR and anti-MuSK antibodies, and 11.9% were seronegative.

Participants with drug-refractory MG were more frequently women (P < .0001), younger at onset (P < .0001), and anti-MuSK positive (P =.0001), compared with nondrug-refractory participants. Drug-refractory patients also had generalized MG (P =.001 at onset and P <.0001 at maximal worsening), bulbar symptoms (P =.018), and life-threatening events (P =.002) at maximal worsening more frequently than did nondrug-refractory patients.

After a mean follow-up of 9.8 years (SD 4.5), fewer drug-refractory patients achieved remission or had minimal manifestations vs nondrug-refractory patients (42.9% vs 79.8%, P <.0001). Also, 42.6% of anti-AChR–positive MG patients achieved remission or had minimal manifestations at the end of follow-up. This MGFA-PIS status was attained by 10% of seronegative patients and 100% of those who were anti-MuSK positive.

A total of 42 patients (50%) had side effects that led to drug withdrawal.

The main study limitation is that the population may be biased regarding disease severity and nonresponse to commonly used drugs, as data were primarily collected at tertiary university hospitals. Also, the findings may be not transferable to smaller hospitals or other settings in different countries where not all treatments are available.

“Seronegative drug-refractory patients specifically need more effective drugs, as most patients do not respond favorably to any treatment,” stated the researchers. “The clinical and immunological characteristics associated with drug-refractory MG may indicate that distinctive immunopathologic pathways or biological mechanisms are involved in the development of drug-refractory MG.”

Reference

Cortés-Vicente E, Álvarez-Velasco R, Pla-Junca F, et al. Drug-refractory myasthenia gravis: clinical characteristics, treatments, and outcome. Ann Clin Transl Neurol. Published online January 26, 2022. doi:10.1002/acn3.51492