Drug-refractory myasthenia gravis: Clinical characteristics, treatments, and outcome

Ann Clin Transl Neurol. 2022 Feb;9(2):122-131. doi: 10.1002/acn3.51492. Epub 2022 Jan 26.


Objective: To describe the clinical characteristics and outcomes in patients with refractory myasthenia gravis (MG) and to determine the effectiveness and side effects of the drugs used for their treatment.

Methods: This observational retrospective cross-sectional multicenter study was based on data from the Spanish MG Registry (NMD-ES). Patients were considered refractory when their MG Foundation of America post-interventional status (MGFA-PIS) was unchanged or worse after corticosteroids and two or more other immunosuppressive agents. Clinical and immunologic characteristics of drug-refractory patients, efficiency and toxicity of drugs used, and outcome (MGFA-PIS) at end of follow-up were studied.

Results: We included 990 patients from 15 hospitals. Eighty-four patients (68 of 842 anti-acetylcholine receptor [AChR], 5 of 26 anti-muscle-specific tyrosine kinase [MusK], 10 of 120 seronegative, and 1 of 2 double-seropositive patients) were drug refractory. Drug-refractory patients were more frequently women (p < 0.0001), younger at onset (p < 0.0001), and anti-MuSK positive (p = 0.037). Moreover, they more frequently presented a generalized form of the disease, bulbar symptoms, and life-threatening events (p < 0.0001; p = 0.018; and p = 0.002, respectively) than non-drug-refractory patients. Mean follow-up was 9.8 years (SD 4.5). Twenty-four (50%) refractory patients had side effects to one or more of the drugs. At the end of follow-up, 42.9% of drug-refractory patients (42.6% of anti-AChR, 100% of anti-MuSK, and 10% of seronegative patients) and 79.8% of non-drug-refractory patients (p < 0.0001) achieved remission or had minimal manifestations. Eighty percent of drug-refractory-seronegative patients did not respond to any drug tested.

Interpretation: In this study, 8.5% of MG patients were drug-refractory. New more specific drugs are needed to treat drug-refractory MG patients.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cross-Sectional Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Immunologic Factors / pharmacology*
  • Male
  • Middle Aged
  • Myasthenia Gravis / diagnosis*
  • Myasthenia Gravis / drug therapy*
  • Myasthenia Gravis / immunology*
  • Outcome Assessment, Health Care
  • Registries*
  • Retrospective Studies
  • Spain


  • Immunologic Factors

Grant support

This work was funded by Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER); Health Research and Innovation Strategic Plan (PERIS) grant SLT008/18/00207; Instituto de Salud Carlos III grants JR19/00037 and PI19/01774; Ministry of Health ; European Union .