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Acta Neurologica Belgica Apr 2024International guidelines on the treatment of myasthenia gravis (MG) have been published but are not tailored to the Belgian situation. This publication presents... (Review)
Review
International guidelines on the treatment of myasthenia gravis (MG) have been published but are not tailored to the Belgian situation. This publication presents recommendations from a group of Belgian MG experts for the practical management of MG in Belgium. It includes recommendations for treatment of adult patients with generalized myasthenia gravis (gMG) or ocular myasthenia gravis (oMG). Depending on the MG-related antibody a treatment sequence is suggested with therapies that can be added on if the treatment goal is not achieved. Selection of treatments was based on the level of evidence of efficacy, registration and reimbursement status in Belgium, common daily practice and the personal views and experiences of the authors. The paper reflects the situation in February 2024. In addition to the treatment considerations, other relevant aspects in the management of MG are addressed, including comorbidities, drugs aggravating disease symptoms, pregnancy, and vaccination. As many new treatments might potentially come to market, a realistic future perspective on the impact of these treatments on clinical practice is given. In conclusion, these recommendations intend to be a guide for neurologists treating patients with MG in Belgium.
PubMed: 38649556
DOI: 10.1007/s13760-024-02552-7 -
Neuromuscular Disorders : NMD May 2024Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as...
Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as second-line choices despite widespread consensus on their efficacy. We aimed to gather real-world data comparing the tolerability and reasons for discontinuation for these agents, by performing a national United Kingdom survey of side effects and reasons for discontinuation of immunosuppressants in myasthenia gravis. Of 235 patients, 166 had taken azathioprine, 102 mycophenolate, and 40 methotrexate. The most common side effects for each agent were liver dysfunction for azathioprine (23 %), diarrhoea for mycophenolate (14 %), and fatigue for methotrexate (18 %). Women were generally more likely to experience side effects of immunosuppressants. Azathioprine was significantly more likely to be discontinued than mycophenolate and methotrexate due to side effects. There was no significant difference in treatment cessation due to lack of efficacy. This study highlights the significant side-effect burden of treatment for myasthenia gravis. Mechanisms to reduce azathioprine toxicity should be utilised, however mycophenolate and methotrexate appear to be good treatment choices if teratogenicity is not a concern. Women are disadvantaged due to higher frequency of side effects and considerations around pregnancy and breastfeeding. Treatments with improved tolerability are needed.
Topics: Humans; Myasthenia Gravis; Methotrexate; Female; Mycophenolic Acid; Azathioprine; Immunosuppressive Agents; Male; Middle Aged; Adult; Aged; United Kingdom
PubMed: 38626662
DOI: 10.1016/j.nmd.2024.03.010 -
European Journal of Neurology Dec 2023Existing data regarding the link between COVID-19 vaccine and myasthenia gravis (MG) are scarce. We aimed to assess the association between Pfizer-BioNTech vaccine with...
BACKGROUND
Existing data regarding the link between COVID-19 vaccine and myasthenia gravis (MG) are scarce. We aimed to assess the association between Pfizer-BioNTech vaccine with both new-onset MG and MG exacerbation.
METHODS
For the first aim, we conducted a nested case-control study in a cohort of 3,052,467 adults, without a diagnosis of MG, from the largest healthcare provider in Israel. Subjects were followed from January 1, 2021 until June 30, 2022 for the occurrence of MG. Ten randomly selected controls were matched to each case of new-onset MG on age and sex. For the second aim, a nested case-control study was conducted in a cohort of 1446 MG patients. Four randomly selected MG patients (controls) were matched to each case of MG exacerbation. Exposure to COVID-19 vaccine in the prior 4 weeks was assessed in cases and controls.
RESULTS
Overall, 332 patients had new-onset MG and were matched with 3320 controls. Multivariable conditional logistic regression models showed that the odds ratio (OR) for new-onset MG, associated with COVID-19 vaccine, was 1.14 (95% CI 0.73-1.78). The results were consistent in sensitivity analysis that used more stringent criteria to define MG. Overall, 62 patients with MG exacerbation were matched to 248 MG controls. The multivariable OR for MG exacerbation, associated with COVID-19 vaccine, was 1.35 (95% CI 0.37-4.89). All results were similar when the prior exposure to COVID-19 vaccine was extended to 8 weeks.
CONCLUSION
This study suggests that Pfizer-BioNTech vaccine is not associated with increased risk of new-onset nor exacerbation of MG.
Topics: Adult; Humans; COVID-19 Vaccines; Case-Control Studies; COVID-19; Vaccination; Myasthenia Gravis
PubMed: 37552795
DOI: 10.1111/ene.16025 -
Neurological Sciences : Official... Apr 2024The association between myasthenia gravis (MG) and other autoimmune diseases is well established. In this study, we aimed to investigate the causal effects between MG... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The association between myasthenia gravis (MG) and other autoimmune diseases is well established. In this study, we aimed to investigate the causal effects between MG and five other autoimmune diseases, including autoimmune thyroid disease (AITD), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and type 1 diabetes (T1DM).
METHODS
We conducted a bidirectional Mendelian randomization (MR) study by using seven published genome-wide association studies (GWAS), including MG (1873 patients versus 36,370 controls), AITD (autoimmune hypothyroidism) (22,997 patients versus 175,475 controls), AITD (autoimmune hyperthyroidism) (962 patients versus 172,976 controls), MS (47,429 patients versus 68,374 controls), RA (14,361 patients versus 43,923 controls), SLE (4222 patients versus 8431 controls), and T1DM (9266 patients versus 15,574 controls). We used the inverse-variance-weighted (IVW) method, weighted-median (WM) estimator, MR-Egger regression, and MR PRESSO in our analyses. We also carried out detailed sensitivity analyses for each direction using the aforementioned methods.
RESULTS
When MG was treated as the exposure, MR evidence suggested a causal relationship between MG and T1DM, SLE, AITD (both hypothyroidism and hyperthyroidism), and MS (excluding RA). Using the IVW method, we found that MG was associated with increased risk of T1DM (OR = 1.94; 95% CI, 1.16-3.26; p = 0.012), SLE (OR = 1.47; 95% CI, 1.02-2.13; p = 0.04), AITD (hypothyroidism) (OR = 1.31; 95% CI, 1.02-1.68; p = 0.039), AITD (hyperthyroidism) (OR = 1.55; 95% CI, 1.15-2.09; p = 0.004), and MS (OR = 1.46; 95% CI, 1.01-2.09; p = 0.041). When MG was treated as the outcome, MR evidence suggested that RA, T1DM, and SLE were causal factors in MG. Using the IVW method, we found that the risk of MG increased with exposure to RA (OR = 1.21; 95% CI, 1.08-1.37; p = 0.002), T1DM (OR = 1.09; 95% CI, 1.02-1.16; p = 0.006), and SLE (OR = 1.12; 95% CI, 1.02-1.23; p = 0.018).
CONCLUSIONS
This study demonstrated a causal relationship between MG and several other autoimmune diseases. Our results supported a bidirectional causal association between MG and SLE/T1DM. Our findings also provided reliable evidence that MG is associated with increased risk of AITD. Meanwhile, we also showed that RA is a possible causal driver of MG risk.
Topics: Humans; Diabetes Mellitus, Type 1; Genome-Wide Association Study; Hyperthyroidism; Hypothyroidism; Lupus Erythematosus, Systemic; Mendelian Randomization Analysis; Multiple Sclerosis; Myasthenia Gravis
PubMed: 37910321
DOI: 10.1007/s10072-023-07163-3 -
CNS Neuroscience & Therapeutics Feb 2024This comprehensive review aimed to compile cases of patients with thymoma diagnosed with both autoimmune encephalitis (AE) and myasthenia gravis (MG), and describe their... (Review)
Review
OBJECTIVES
This comprehensive review aimed to compile cases of patients with thymoma diagnosed with both autoimmune encephalitis (AE) and myasthenia gravis (MG), and describe their clinical characteristics.
METHODS
Clinical records of 3 AE patients in the first affiliated hospital of Sun Yat-sen University were reviewed. All of them were diagnosed with AE between 1 November 2021 and 1 March 2022, and clinical evidence about thymoma and MG was found. All published case reports were searched for comprehensive literature from January 1990 to June 2022.
RESULTS
A total of 18 cases diagnosed with thymoma-associated autoimmune encephalitis (TAAE) and thymoma-associated myasthenia gravis (TAMG) were included in this complication, wherein 3 cases were in the first affiliated hospital of Sun Yat-sen University and the other 15 were published case reports. 5/18 patients had alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibody (AMPAR-Ab) in their serum and cerebrospinal fluid (CSF). All of them had positive anti-acetylcholine receptor antibody (AChR-Ab). And 12/18 patients showed a positive response to thymectomy and immunotherapy. Besides, thymoma recurrences were detected because of AE onset. And the shortest interval between operation and AE onset was 2 years in patients with thymoma recurrence.
CONCLUSIONS
There was no significant difference in the clinical manifestations between these patients and others with only TAMG or TAAE. TAAE was commonly associated with AMPAR2-Ab. Significantly, AE more commonly heralded thymoma recurrences than MG onset. And the intervals of thymectomy and MG or AE onset had different meanings for thymoma recurrence and prognoses of patients.
Topics: Humans; Thymoma; Thymus Neoplasms; Myasthenia Gravis; Encephalitis; Hashimoto Disease
PubMed: 38421083
DOI: 10.1111/cns.14568 -
Neurology Oct 2023Ocular myasthenia gravis (OMG) is an autoimmune disorder resulting in ocular symptoms such as diplopia and ptosis. The proportion of patients who convert to secondary... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Ocular myasthenia gravis (OMG) is an autoimmune disorder resulting in ocular symptoms such as diplopia and ptosis. The proportion of patients who convert to secondary generalized myasthenia gravis (SGMG) reported in the literature has been varied. The aim of this systematic review was to determine the clinical characteristics of patients with OMG and the proportion of SGMG conversion.
METHODS
We conducted an electronic database search for randomized controlled trials, prospective nonrandomized studies, observational studies, and retrospective studies in EMBASE, CENTRAL, MEDLINE, and Web of Science. We included studies with patients with OMG who initially presented with ocular symptoms and signs only and were seen in clinical practice, reporting on the characteristics and outcomes of SGMG. We excluded studies with pediatric and congenital myasthenia gravis populations. Eligible studies included articles written in any language and containing data on patients with OMG. The main outcome measured was the proportion of patients with OMG who converted to SGMG and risk factors associated with secondary generalization of OMG. Two independent reviewers screened titles and abstracts and extracted data from full texts, reporting findings according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methodology was evaluated using the Joanna Briggs Institute critical appraisal forms. PROSPERO registration number: CRD2021285257.
RESULTS
Thirty-one studies were included in the quantitative and qualitative analysis. The proportion of generalization ranged from 11% to 84%. The pooled proportion was 39% (95% CI 32%-47%, = 95.86%, < 0.001 unweighted, low certainty). The pooled risk ratio of female sex for conversion to SGMG was 1.06 (95% CI 0.96-1.17, = 0% = 0.614, 21 studies included, very low certainty), and the pooled risk ratio of acetylcholine receptor (AChR) positivity was 1.30 (95% CI 1.05-1.56, = 0% = 0.455, 16 studies included, very low certainty).
DISCUSSION
Risk factors such as female sex and anti-AChR positivity have been identified to have possible associations with SGMG, but there are not enough quality observational studies. There is a need for a prospective global database of patients with OMG, including all countries with different populations.
Topics: Humans; Female; Child; Retrospective Studies; Myasthenia Gravis; Receptors, Cholinergic; Risk Factors; Blepharoptosis
PubMed: 37643888
DOI: 10.1212/WNL.0000000000207642 -
Expert Opinion on Pharmacotherapy Mar 2024Myasthenia gravis (MG) is an autoimmune condition targeting the neuromuscular junction, which manifests with neuromuscular symptoms of varying severity and significant... (Review)
Review
INTRODUCTION
Myasthenia gravis (MG) is an autoimmune condition targeting the neuromuscular junction, which manifests with neuromuscular symptoms of varying severity and significant morbidity. The mainstay of treatment in MG is mitigation of the immune cascade with steroids and non-steroidal immunosuppressive therapies. The therapeutic strategies in MG are transitioning from broad and indiscriminate immunosuppression to novel agents targeting key steps in MG pathogenesis, including T cell activation, B cell proliferation, complement activation, maintenance of pathogenic antibody production, and proinflammatory cytokine production.
AREAS COVERED
In this review, an overview of the pathogenesis of MG and traditional MG therapies is presented, followed by a discussion of the novel MG drugs that have been evaluated in phase 3 clinical trials with an emphasis on those which have received regulatory approval.
EXPERT OPINION
Novel MG therapeutics belonging to the classes of complement inhibitors, neonatal Fc receptor (FcRn) inhibitors and B cell depletors, as well as the other emerging MG drugs in the pipeline constitute promising treatment strategies with potentially better efficacy and safety compared to the conventional MG treatments. However, further long-term research is needed in order to optimize the implementation of these new treatment options for the appropriate patient populations.
Topics: Humans; Myasthenia Gravis; Immunosuppressive Agents; Animals; B-Lymphocytes; Complement Inactivating Agents
PubMed: 38523508
DOI: 10.1080/14656566.2024.2332610 -
Acta Neurologica Belgica Dec 2023Congenital myasthenic syndrome is a disease that occurs due to several types such as mutations in different pre-synaptic, synaptic, post-synaptic proteins and,...
BACKGROUND
Congenital myasthenic syndrome is a disease that occurs due to several types such as mutations in different pre-synaptic, synaptic, post-synaptic proteins and, glycosylation defects associated with congenital myopathy. Juvenile myasthenia gravis is an autoimmune condition usually caused by antibodies targeting the acetylcholine receptor.
AIMS
Our objective is to conduct an analysis on the subgroup traits exhibited by patients who have been diagnosed with congenital myasthenic syndrome and juvenile myasthenia gravis, with a focus on their long-term monitoring and management.
METHODS
This study was conducted on children diagnosed with myasthenia gravis, who were under the care of Dokuz Eylul University's Department of Pediatric Neurology for a period of ten years.
RESULTS
A total of 22 (12 congenital myasthenic syndrome, 10 juvenile myasthenia gravis) patients were identified. Defects in the acetylcholine receptor (6/12) were the most common type in the congenital myasthenic syndrome group. Basal-lamina-related defects (5/12) were the second most prevalent. One patient had a GFPT1 gene mutation (1/12). Patients with ocular myasthenia gravis (n = 6) exhibited milder symptoms. In the generalized myasthenia gravis group (n = 4), specifically in postpubertal girls, a more severe clinical progression was observed, leading to the implementation of more aggressive treatment strategies.
CONCLUSION
This study highlights that clinical recognition of congenital myasthenic syndrome and knowledge of related genes will aid the rapid diagnosis and treatment of these rare neuromuscular disorders. Findings in the juvenile myasthenia gravis group demonstrate the impact of pubertal development and the need for timely and appropriate active therapy, including thymectomy, to improve prognosis.
Topics: Child; Female; Humans; Myasthenic Syndromes, Congenital; Turkey; Myasthenia Gravis; Muscle Weakness; Receptors, Cholinergic
PubMed: 37656362
DOI: 10.1007/s13760-023-02370-3 -
Journal of Neuroimmunology Nov 2023This study measured the serum levels of of 15 cytokines in 15 patients with anti-muscle-specific kinase antibody-positive MG (MuSK-MG) using a multiplex suspension array...
This study measured the serum levels of of 15 cytokines in 15 patients with anti-muscle-specific kinase antibody-positive MG (MuSK-MG) using a multiplex suspension array system. Fifteen patients with non-inflammatory neurological diseases served as controls. Compared with controls, patients with MuSK-MG showed higher levels of Th1- (IFN-γ), Th2- (IL-25, IL-31, and IL-33), Th17- (IL-22), Treg-related cytokines (IL-10), and soluble CD40 ligand (sCD40L). Higher serum Th2-related cytokines (IL-25 and IL-31) levels were correlated with less MG Foundation of America (MGFA) class. These suggest that Th2-related cytokines have protective effects, whereas sCD40L and others may facilitate the disease.
Topics: Humans; Myasthenia Gravis; Cytokines; Th17 Cells
PubMed: 37774555
DOI: 10.1016/j.jneuroim.2023.578205 -
Journal of Neuroimmunology Nov 2023We investigated the humoral response to the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine in patients with myasthenia gravis on or off immunosuppressants and compared this...
We investigated the humoral response to the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine in patients with myasthenia gravis on or off immunosuppressants and compared this to the response in healthy individuals. The SARS-CoV-2 IgG response and neutralizing capacity were measured in 83 patients (57 on immunosuppressants) and 332 healthy controls at baseline, three weeks, and two and six months after the vaccine. We found that the proportion of positive humoral response was lower in patients on immunosuppressants vs. controls at three weeks and two months (p ≤ 0.001), but not at six months post-vaccination (p = 0.379).
Topics: Humans; COVID-19 Vaccines; BNT162 Vaccine; Immunity, Humoral; COVID-19; SARS-CoV-2; Myasthenia Gravis; Antibodies, Viral; Immunosuppressive Agents; Vaccination
PubMed: 37797472
DOI: 10.1016/j.jneuroim.2023.578215