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Patients were considered refractory when their MG Foundation of America post\u2010interventional status (MGFA\u2010PIS) was unchanged or worse after corticosteroids and two or more other immunosuppressive agents. Clinical and immunologic characteristics of drug\u2010refractory patients, efficiency and toxicity of drugs used, and outcome (MGFA\u2010PIS) at end of follow\u2010up were studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 990 patients from 15 hospitals. Eighty\u2010four patients (68 of 842 anti\u2010acetylcholine receptor [AChR], 5 of 26 anti\u2010muscle\u2010specific tyrosine kinase [MusK], 10 of 120 seronegative, and 1 of 2 double\u2010seropositive patients) were drug refractory. Drug\u2010refractory patients were more frequently women (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), younger at onset (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), and anti\u2010MuSK positive (<jats:italic>p<\/jats:italic>\u2009=\u20090.037). Moreover, they more frequently presented a generalized form of the disease, bulbar symptoms, and life\u2010threatening events (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001; <jats:italic>p<\/jats:italic>\u2009=\u20090.018; and <jats:italic>p<\/jats:italic>\u2009=\u20090.002, respectively) than non\u2010drug\u2010refractory patients. Mean follow\u2010up was 9.8\u2009years (SD 4.5). Twenty\u2010four (50%) refractory patients had side effects to one or more of the drugs. At the end of follow\u2010up, 42.9% of drug\u2010refractory patients (42.6% of anti\u2010AChR, 100% of anti\u2010MuSK, and 10% of seronegative patients) and 79.8% of non\u2010drug\u2010refractory patients (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) achieved remission or had minimal manifestations. Eighty percent of drug\u2010refractory\u2010seronegative patients did not respond to any drug tested.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>In this study, 8.5% of MG patients were drug\u2010refractory. New more specific drugs are needed to treat drug\u2010refractory MG patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51492","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T09:44:09Z","timestamp":1643190249000},"page":"122-131","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Drug\u2010refractory myasthenia gravis: Clinical characteristics, treatments, and outcome"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1428-1072","authenticated-orcid":false,"given":"Elena","family":"Cort\u00e9s\u2010Vicente","sequence":"first","affiliation":[{"name":"Neuromuscular Diseases Unit, Department of Neurology Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Department of Medicine Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Biomedical Research Institute Sant Pau (IIB Sant Pau)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"\u00c1lvarez\u2010Velasco","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Unit, Department of Neurology Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Department of Medicine Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Biomedical Research Institute Sant Pau (IIB Sant Pau)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"Pla\u2010Junca","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricard","family":"Rojas\u2010Garcia","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Unit, Department of Neurology Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Department of Medicine Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Biomedical Research Institute Sant Pau (IIB Sant Pau)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Paradas","sequence":"additional","affiliation":[{"name":"Neurology Department, Neuromuscular Disorders Unit, Instituto de Biomedicina de Sevilla, Hospital U. 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