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Background and ObjectivesEvidence regarding the safety and efficacy of messenger RNA (mRNA) vaccines in patients with myasthenia gravis (MG) after immunosuppressive therapies is scarce. Our aim is to determine whether the mRNA-1273 vaccine is safe and able to induce humoral and cellular responses in patients with MG.MethodsWe performed an observational, longitudinal, prospective study including 100 patients with MG of a referral center for MG in our country, conducted from April 2021 to November 2021 during the vaccination campaign. The mRNA-1273 vaccine was scheduled for all participants. Blood samples were collected before vaccination and 3 months after a second dose. Clinical changes in MG were measured using the MG activities of daily life score at baseline and 1 week after the first and second doses. A surveillance of all symptoms of coronavirus disease 2019 (COVID-19) was conducted throughout the study. Humoral and cellular immune responses after vaccination were assessed using a spike-antibody ELISA and interferon gamma release assay in plasma. The primary outcomes were clinically significant changes in MG symptoms after vaccination, adverse events (AEs), and seroconversion and T-cell immune response rates.ResultsNinety-nine patients completed the full vaccination schedule, and 98 had 2 blood samples taken. A statistically significant worsening of symptoms was identified after the first and second doses of the mRNA-1273 vaccine, but this was not clinically relevant. Mild AEs occurred in 14 patients after the first dose and in 21 patients after the second dose. Eighty-seven patients developed a humoral response and 72 patients showed a T-cell response after vaccination. A combined therapy with prednisone and other immunosuppressive drugs correlated with a lower seroconversion ratio (OR = 5.97, 95% CI 1.46–24.09, p = 0.015) and a lower T-cell response ratio (OR = 2.83, 95% CI 1.13–7.13, p = 0.024).DiscussionOur findings indicate that the mRNA vaccination against COVID-19 is safe in patients with MG and show no negative impact on the disease course. Patients achieved high humoral and cellular immune response levels.Classification of EvidenceThis study provides Class IV evidence that patients with MG receiving the mRNA-1273 vaccine did not show clinical worsening after vaccination and that most of the patients achieved high cellular or immune response levels.

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.