Dataset Information

Safety and tolerability of SARS-Cov-2 vaccination in patients with myasthenia gravis: A multicenter experience.

ABSTRACT:

Background and purpose

During the COVID-19 pandemic, myasthenia gravis (MG) patients have been identified as subjects at high risk of developing severe COVID-19, and thus were offered vaccination with priority. The lack of direct data on the safety and tolerability of SARS-CoV-2 vaccines in MG have contributed to vaccine hesitancy. To address this issue, the safety and tolerability of SARS-CoV-2 vaccines were assessed in a large cohort of MG patients from two referral centers.

Methods

Patients with confirmed MG diagnosis, consecutively seen between October and December 2021 at two MG centers, were enrolled. Demographics, clinical characteristics, and information regarding SARS-CoV-2 infection/vaccination were extracted from medical reports and/or collected throughout telephonic or in-person interviews.

Results

Ninety-eight (94.2%) of 104 patients included were administered at least two vaccine doses 4 weeks before the interview or earlier, and among them, 63 of 98 (64.2%) have already received the "booster" dose. The most frequently used vaccines were BNT162b2-Pfizer-BioNTech and mRNA-1273-Moderna. Overall, only minor side effects were reported, most commonly local pain and fever. MG worsening after vaccination was observed in eight of 104 (7.7%) cases. The frequency of worsening among muscle-specific tyrosine kinase MG cases (3/9, 33.3%) was significantly higher compared to other serological subgroups. Spontaneous symptom regression was observed in six of eight cases. Twelve of 104 (11.5%) patients had SARS-CoV-2 infection, and none of the SARS-CoV-2-infected MG patients worsened after vaccination.

Conclusions

Our data support the safety and tolerability of mRNA COVID-19 vaccines, which should be strongly recommended in MG patients, who could be at higher risk of complications if exposed to SARS-CoV-2 infection.

SUBMITTER: Farina A

PROVIDER: S-EPMC9111609 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Safety and tolerability of SARS-Cov-2 vaccination in patients with myasthenia gravis: A multicenter experience.

Farina Antonio A Falso Silvia S Cornacchini Sara S Spagni Gregorio G Monte Gabriele G Mariottini Alice A Massacesi Luca L Barilaro Alessandro A Evoli Amelia A Damato Valentina V

European journal of neurology 20220417 8

<h4>Background and purpose</h4>During the COVID-19 pandemic, myasthenia gravis (MG) patients have been identified as subjects at high risk of developing severe COVID-19, and thus were offered vaccination with priority. The lack of direct data on the safety and tolerability of SARS-CoV-2 vaccines in MG have contributed to vaccine hesitancy. To address this issue, the safety and tolerability of SARS-CoV-2 vaccines were assessed in a large cohort of MG patients from two referral centers.<h4>Methods ...[more]

PMID: 35390184

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Project description:Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction, whose clinical hallmark is muscle weakness and early fatigability. Azathioprine (AZA) is commonly used in Myasthenia Gravis therapy. AZA is a purine antagonist, which inhibits the cell cycle in the resting and DNA synthesis phases. It is usually used as an immunosuppressant to block T- and B-cell proliferation. AZA, bioconverted to 6-mercaptopurine by glutathione S-transferase (GST), can be metabolized either through the hypoxanthine phosphoribosyl transferase pathway to active 6-thioguanine nucleotides (6-TGN) or through the thiopurine S-methyltransferase (TPMT) pathway to inactive methyl-thiopurine metabolites. The incorporation of active 6-TGNs into DNA, causing breaks in DNA strands resulting in interference with RNA production and thereby protein synthesis, is responsible for the drug effect. The response to AZA is determined by which metabolic pathway is being favored. While balanced use of both HPRT and TPMT pathways results in responsiveness to AZA, hyperactivity of TPMT skews the balance towards the TPMT pathway and results in unresponsiveness to AZA with no pharmacological effect. In contrast, low TPMT activity skews the balance towards the HPRT pathway, resulting in increasing side-effects due to the accumulation of 6-TGNs. Current treatments for MG therapy are often inadequate because less than 40% of patients achieve complete remission with available drugs. This reflects the lack of drugs acting on target sites for which there is strong evidence of pathogenicity and the inability to identify responder patients. No criteria for responsiveness are available, exposing patients to unpredictable failures and unpredictable side effects. These individuals are at particular risk for adverse drug reaction (ADRs) or therapeutic failure. Genetic profiling with the Affymetrix drug metabolizing enzymes and transports genotyping array offers the ability to determine 1,931 variants and 225 genes involved in drug metabolism and disposition. Accordingly, the study of well-known drug-metabolizing genes can be involved in the specific metabolic pathway of a drug, which is more likely to define genotype-phenotype association and thereby genotype profiles relevant to drug response that can be applied as predictive biomarkers for pharmacological treatment.

Project description:IntroductionEculizumab, a complement active antibody, and efgartigimod, an Fc fragment that blocks neonatal Fc receptor, are both approved to treat generalized myasthenia gravis (gMG) patients. The objective of this study is to describe the clinical response to both treatments in a real-life setting.MethodsWe collected baseline and follow-up clinical data using the Myasthenia Gravis-Activities of Daily Living (MG-ADL), and Quantitative Myasthenia Gravis (QMG). We included 63 patients, 32 treated with eculizumab and 31 with efgartigimod. Of the efgartigimod-treated patients, 22 were anti-acetylcholine receptor antibody-positive (AChR-Ab +) and 9 were AChR-Ab- (3 MuSK-Ab + and 6 seronegative).ResultsBoth treatments showed similar efficacy relative to the MG-ADL scale reduction (p = 0.237). Efgartigimod had a similar effect on both AChR-Ab + and AChR-Ab- (p = 0.280). Eculizumab was superior to efgartigimod relative to the QMG score reduction for the entire dataset (p = 0.003) and was more likely to achieve a clinical response at the QMG compared to efgartigimod (OR 1.373; p = 0.016). Steroid-sparing effect was higher for eculizumab than efgartigimod ( - 16.7 vs - 5.2 mg of the baseline daily dose at follow-up; p = 0.001). Mean speed of prednisone reduction was - 13.1 mg of the daily dose for each month of follow-up for eculizumab-treated patients and - 3.2 for efgartigimod (p = 0.001). We found three serious events, all not related to treatment in the investigator's opinion. One eculizumab-treated patient experienced a severe pneumonia and died despite treatment.ConclusionsOur study provides evidence that eculizumab and efgartigimod can be used in clinical practice to reduce disability in gMG patients. Eculizumab-treated patients had a higher QMG response and steroid sparing effect. Efgartigimod may offer a more flexible schedule due to its cyclical use, no need for vaccination, and efficacy in AChR-Ab- patients.

Dataset Information

Safety and tolerability of SARS-Cov-2 vaccination in patients with myasthenia gravis: A multicenter experience.

Background and purpose

Methods

Results

Conclusions

Publications

Safety and tolerability of SARS-Cov-2 vaccination in patients with myasthenia gravis: A multicenter experience.

Similar Datasets

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