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Cureus Dec 2023Myasthenia gravis (MG), a rare disease, is the most common neuromuscular junction problem. It's the quintessential autoimmune disease with ocular, bulbar, respiratory,... (Review)
Review
Myasthenia gravis (MG), a rare disease, is the most common neuromuscular junction problem. It's the quintessential autoimmune disease with ocular, bulbar, respiratory, axial, and limb muscles exhibiting a typical fatigable weakening due to the development of antibodies against the acetylcholine receptor (AChR). Infections, stress, surgeries, thymus gland anomalies, and pharmaceutical side effects can also cause it. Ocular symptoms are initially experienced by most of the sufferers. The majority of the sufferers will go through at least one episode of symptom exacerbation during their illness. The immune system in MG interferes with nerve-muscle communication, causing muscles to become weak and tired quickly. The actual cause is not yet known, but a problem in the thymus gland may be the cause. In a person suffering from this disease, the size of the thymus becomes larger than normal, which is also called thymic hyperplasia. It is more common for women to have early-onset MG (EOMG) than for males to have late-onset MG (LOMG). Merely clinical evidence, encompassing the patients' medical history and physical indications of fluctuating muscle weakness in a specific region, is utilized to diagnose MG. Complementary diagnostic procedures and lab techniques aid in confirming the synaptic dysfunction and characterizing its kind and degree. Early diagnosis and the availability of effective treatments have reduced the burden of severe impairment and high mortality previously associated with MG. Current immunomodulation-based therapies come with side effects brought on by persistent immune suppression. Improved knowledge of this relatively uncommon but curable condition is required among primary carers. The objective of this review is to provide information about MG and to help people recognize its symptoms and start treatment without panic so that the progression of this disease can be stopped and complications can be avoided.
PubMed: 38186498
DOI: 10.7759/cureus.50017 -
European Journal of Neurology Dec 2023Therapy for myasthenia gravis (MG) is undergoing a profound change, with new treatments being tested. These include complement inhibitors and neonatal Fc receptor (FcRn)... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Therapy for myasthenia gravis (MG) is undergoing a profound change, with new treatments being tested. These include complement inhibitors and neonatal Fc receptor (FcRn) blockers. The aim of this study was to perform a meta-analysis and network meta-analysis of randomized and placebo-controlled trials of innovative therapies in MG with available efficacy data.
METHODS
We assessed statistical heterogeneity across trials based on the Cochrane Q test and I values, and mean differences were pooled using the random-effects model. Treatment efficacy was assessed after 26 weeks of eculizumab and ravulizumab, 28 days of efgartigimod, 43 days of rozanolixizumab, 12 weeks of zilucoplan, and 16, 24 or 52 weeks of rituximab treatment.
RESULTS
We observed an overall mean Myasthenia Gravis-Activities of Daily Living scale (MG-ADL) score change of -2.17 points (95% confidence interval [CI] -2.67, -1.67; p < 0.001) as compared to placebo. No significant difference emerged between complement inhibitors and anti-FcRn treatment (p = 0.16). The change in Quantitative Myasthenia Gravis scale (QMG) score was -3.46 (95% CI -4.53, -2.39; p < 0.001), with a higher reduction with FcRns (-4.78 vs. -2.60; p < 0.001). Rituximab did not significantly improve the MG-ADL (-0.92 [95% CI -2.24, 0.39]; p = 0.17) or QMG scores (-1.9 [95% CI -3.97, 0.18]; p = 0.07). In the network meta-analysis, efgartigimod had the highest probability of being the best treatment, followed by rozanolixizumab.
CONCLUSION
Anti-complement and FcRn treatments both proved to be effective in MG patients, whereas rituximab did not show a significant benefit for patients. Within the limitations of this meta-analysis, including efficacy time points, FcRn treatments showed a greater effect on QMG score in the short term. Real-life studies with long-term measurements are needed to confirm our results.
Topics: Infant, Newborn; Humans; Rituximab; Network Meta-Analysis; Activities of Daily Living; Myasthenia Gravis; Complement Inactivating Agents; Therapies, Investigational
PubMed: 37204031
DOI: 10.1111/ene.15872 -
Cureus Jul 2023Myasthenia gravis (MG) is an autoimmune disease affecting young women in their second and third decades, coinciding with their reproductive years. We aim to explore the... (Review)
Review
Myasthenia gravis (MG) is an autoimmune disease affecting young women in their second and third decades, coinciding with their reproductive years. We aim to explore the choices and challenges in the treatment of MG in pregnancy. Cochrane, PubMed, Google Scholar, and Embase were the four databases systematically searched for studies with patients reporting pregnancy outcomes for women with MG during pregnancy using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) technique. Quality assessment was done using the Joanna Briggs Institute critical tool (JBI, Adelaide, Australia) for methodological quality. From 2000 to 2023, 40 studies from database search results were considered. There is a substantial risk of complications with MG, especially if it appears during pregnancy. In particular, widespread weakness is a cause of severe, life-threatening disorders, but several treatment options are available.
PubMed: 37663985
DOI: 10.7759/cureus.42772 -
Acta Neurologica Belgica Oct 2023Current myasthenia gravis guidelines recommend the use of azathioprine as first-line steroid sparing agent. However, due to its high cost, compliance to azathioprine is... (Review)
Review
Current myasthenia gravis guidelines recommend the use of azathioprine as first-line steroid sparing agent. However, due to its high cost, compliance to azathioprine is low in developing countries. To determine the efficacy and safety of the cheaper methotrexate as an alternative immunosuppressant, Medline/Pubmed, Embase and Cochrane databases and references were searched for clinical trials and observational studies using the search terms: "Myasthenia OR Myasthenia Gravis OR anti AchR antibody positive Myasthenia Gravis OR anti-MuSK antibody Myasthenia Gravis OR MG" AND "Methotrexate". Of 78 possible articles, only 4 were selected using the following eligibility criteria: population: generalized MG patients; intervention: methotrexate; and outcome: effectiveness, steroid sparing efficacy and adverse effects. Two clinical trials and one observational study noted improvement in different MG outcomes in patients given methotrexate. While one randomized controlled clinical trial concluded that methotrexate has no steroid sparing benefit, a single blinded clinical trial established that methotrexate was a better steroid sparing agent than azathioprine starting at 10th month of use. Adverse effects were rare with non-specific pain and elevated transaminases as the most common complaints. Based on available evidence, MTX may be a safe and effective alternative to AZA as steroid sparing agent in developing countries.
Topics: Humans; Methotrexate; Azathioprine; Immunosuppressive Agents; Myasthenia Gravis; Prednisone; Drug-Related Side Effects and Adverse Reactions; Randomized Controlled Trials as Topic; Observational Studies as Topic
PubMed: 36967437
DOI: 10.1007/s13760-023-02242-w -
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 -
PloS One 2024Randomized controlled trials (RCTs) of acupuncture for myasthenia gravis (MG) were searched and the efficacy of acupuncture in the treatment of MG was evaluated by... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Randomized controlled trials (RCTs) of acupuncture for myasthenia gravis (MG) were searched and the efficacy of acupuncture in the treatment of MG was evaluated by meta-analysis.
METHODS
We searched for RCTs in six main electronic databases, and collected RCTs of acupuncture treatment for MG from database creation to 28 February 2023. The main outcome was the effective rate and the secondary outcome was the Traditional Chinese Medicine (TCM) relative clinical score, absolute clinical score (ACS) of MG, Quantitive myasthenia gravis score (QMG), quality of life, and adverse events. Odds ratios (ORs) and weighted mean differences (WMD) and 95% confidence intervals (CI) were used to assess pooled effect estimates using Review Manager software.
RESULTS
A total of 14 RCTs were included. Meta-analysis showed that the effective rate in the acupuncture group was significantly improved compared with conventional Western medicine alone [OR = 4.28, 95% CI (2.95, 6, 22), P<0.005]. The pooled WMDs revealed that TCM relative clinical score [WMD = -2.22, 95% CI = (-2.53, -1.90), P<0.005], ACS of MG [WMD = -3.14, 95% CI = (-3.67, -2.62), P<0.005], and QMG [WMD = -0.88, 95% CI = (-1.46, -0.29), P<0.005] in the acupuncture group was lower than the control group. Adverse reactions related to acupuncture and quality of life were less mentioned among included RCTs.
CONCLUSION
This meta-analysis demonstrated that acupuncture as an auxiliary may play a positive role in treating MG. It can improve the effective rate of treatment, and reduce TCM relative clinical score, ACS of MG, and QMG. However, the quality of included studies was generally low and caution should be exercised when considering this treatment option. In the future, more rigorous study designs and high-quality RCTs are needed to verify the efficacy of acupuncture in the treatment of MG, because the results of high-quality RCTs are more reliable and accurate.
Topics: Humans; Acupuncture Therapy; Medicine, Chinese Traditional; Myasthenia Gravis; Research Design; Quality of Life
PubMed: 38165870
DOI: 10.1371/journal.pone.0291685 -
European Radiology Jul 2024It is uncertain whether modern iodine-based or gadolinium-based contrast media (CM) administration can lead to increased symptoms in patients with myasthenia gravis. (Review)
Review
OBJECTIVES
It is uncertain whether modern iodine-based or gadolinium-based contrast media (CM) administration can lead to increased symptoms in patients with myasthenia gravis.
METHODS
A systematic search in Medline was conducted for studies describing the symptomatology of myasthenia gravis patients before and after receiving intravenous (IV) CM and having a matched control group of myasthenia gravis patients who did not receive IV CM.
RESULTS
Three retrospective studies were selected with a total of 374 myasthenia gravis patients who received iodine-based CM and a total of 313 myasthenia gravis patients who underwent unenhanced CT and served as controls. Pooling of the data from the three retrospective studies showed that in 23 of 374 patients, increased symptoms after iodine-based CM administration were described (6.1%). Increased symptomatology also occurred in 11 of 313 patients after unenhanced CT (3.5%). When looking more deeply into the data of the three studies, conflicting results were found, as two articles did not find any relationship between CM and myasthenia gravis symptoms. The remaining study only found a significant increase in symptomatology within 1 day after CT scanning: seven patients (6.3%) in the contrast-enhanced CT group and one patient (0.6%) in the unenhanced CT group (p = 0.01).
CONCLUSIONS
There is limited evidence on the relationship between CM and myasthenia gravis symptoms. In the vast majority of myasthenia gravis patients, CM are safe. Probably, in less than 5% of the patients, iodine-based CM administration may lead to increased severity of the symptoms within the first 24 h after administration.
CLINICAL RELEVANCE STATEMENT
Be aware that intravenous administration of iodine-based contrast media can lead to an increase of symptoms in patients with myasthenia gravis within the first 24 h. This can probably happen in less than 5% of the patients.
KEY POINTS
• It is unclear whether modern contrast media can lead to increased symptoms in myasthenia gravis patients after intravenous administration. • There seems to be a small risk of increased myasthenia gravis symptoms within 24 h after intravenous administration of iodine-based contrast media, probably in less than 5% of the administrations. • Gadolinium-based contrast media are safe for patients with myasthenia gravis.
Topics: Myasthenia Gravis; Humans; Contrast Media; Tomography, X-Ray Computed; Gadolinium; Practice Guidelines as Topic; Europe; Iodine
PubMed: 38092951
DOI: 10.1007/s00330-023-10463-z -
Frontiers in Immunology 2023A series of clinical trials support the effectiveness of monoclonal antibodies for generalized myasthenia gravis (MG) compared to the placebo, but the priority among... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A series of clinical trials support the effectiveness of monoclonal antibodies for generalized myasthenia gravis (MG) compared to the placebo, but the priority among drugs remains unclear. Therefore, we conduct a frequentist network meta-analysis (NMA) to compare the relative effects of different drugs for generalized MG.
METHODS
PubMed, Embase, Cochrane Library, and clinicaltrials.gov were systematically searched for eligible studies up to 1 June 2023. The primary outcome was efficacy (Myasthenia Gravis Activities of Daily Living [MG-ADL] score and Quantitative Myasthenia Gravis [QMG] score) and safety (adverse events [AEs]). Mean difference (MD) and risk ratio (RR) with their 95% credible intervals (95%CrIs) were used to show the effect size of continuous and categorical variables, respectively. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Thirteen studies involving 1167 individuals were identified for NMA. For efficacy outcomes, belimumab, efgartigimod, mezagitamab 600mg, and nipocalimab 60mg/kg were inferior to rozanolixzumab 7mg/kg (MD ranged from 2 to 3.69) and rozanolixzumab 10mg/kg (MD ranged from 2.04 to 3.72) in MG-ADL score, and rozanolixzumab had the highest rank probability (83%) according to the subjective surface under the curve ranking area (SUCRA). For QMG score, batoclimab 340mg (MD ranged from 4.32 to 8.52) and batoclimab 680mg (MD ranged from 4.11 to 9.31) were more effective than placebo and other monoclonal antibodies except for rozanolixzumab, with the highest SUCRA value (93% and 97% respectively). For safety outcomes, belimumab achieved the highest SUCRA value (89.8%) with significant statistical difference compared to rozanolixzumab 7mg/kg (RR 0.08, 95%CrI 0.01 to 0.94) and rozanolixzumab 10mg/kg (RR 0.08, 95%CrI 0.01 to 0.86).
CONCLUSION
While all monoclonal antibodies were superior to the placebo, rozanolixzumab and batoclimab might be the most effective for generalized MG. However, rozanolixzumab was associated with higher incidence of AEs. Given the limitations inherent in indirect comparisons, further head-to-head and extensive observational studies are necessary to confirm our findings.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/?s=202370112, identifier 202370112.
Topics: Adult; Humans; Antibodies, Monoclonal; Activities of Daily Living; Bayes Theorem; Myasthenia Gravis
PubMed: 38022544
DOI: 10.3389/fimmu.2023.1280226 -
Journal of Neurology May 2024Myasthenia gravis (MG) is an autoimmune disease that causes local or generalized muscle weakness. Complement inhibitors and targeting of the neonatal Fc receptor (FcRn)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Myasthenia gravis (MG) is an autoimmune disease that causes local or generalized muscle weakness. Complement inhibitors and targeting of the neonatal Fc receptor (FcRn) to block IgG cycling are two novel and successful mechanisms.
METHODS
PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify relevant studies published before May 18, 2023. Review Manager 5.3 software was used to assess the data.
RESULTS
We pooled 532 participants from six randomized controlled trials (RCTs). Compared to the placebo, the FcRn inhibitors were more efficacy in Myasthenia Gravis Activities of Daily Living (MG-ADL) (MD = - 1.69 [- 2.35, - 1.03], P < 0.00001), MG-ADL responder (RR = 2.01 [1.62, 2.48], P < 0.00001), Quantitative Myasthenia Gravis (QMG) (MD = - 2.45 [- 4.35, - 0.55], P = 0.01), Myasthenia Gravis Composite (MGC) (MD = - 2.97 [- 4.27, - 1.67], P < 0.00001), 15-item revised version of the Myasthenia Gravis Quality of Life (MGQoL15r) (MD = - 2.52 [- 3.54, - 1.50], P < 0.00001), without increasing the risk of safety. The subgroup analysis showed that efgartigimod was more effective than placebo in MG-ADL responders. Rozanolixizumab was more effective than the placebo except in QMG, and batoclimab was more effective than the placebo except in MG-ADL responder. Nipocalizumab did not show satisfactory efficacy in all outcomes. With the exception of rozanolixizumab, all drugs showed non-inferior safety profiles to placebo.
CONCLUSION
FcRn inhibitors have good efficacy and safety in patients with MG. Among them, efgartigimod and nipocalimab were effective without causing an increased safety risk. Rozanolixizumab, despite its superior efficacy, caused an increased incidence of adverse events. Current evidence does not suggest that nipocalimab is effective in patients with MG.
Topics: Myasthenia Gravis; Humans; Receptors, Fc; Histocompatibility Antigens Class I; Randomized Controlled Trials as Topic; Antibodies, Monoclonal, Humanized; Outcome Assessment, Health Care
PubMed: 38431900
DOI: 10.1007/s00415-024-12247-x -
Medicine Oct 2023Myasthenia Gravis (MG), a chronic neuromuscular junction disorder, emerged as one of the serious side effects of the Coronavirus Disease 2019 (COVID-19) vaccination. We...
BACKGROUNDS
Myasthenia Gravis (MG), a chronic neuromuscular junction disorder, emerged as one of the serious side effects of the Coronavirus Disease 2019 (COVID-19) vaccination. We aimed to summarize the findings of studies on the clinical features and outcomes of COVID-19 vaccination-associated MG.
METHODS
We performed a systematic search on 3 databases, Medline, Embase, and Scopus, using the query "COVID-19 vaccine" and "Myasthenia Gravis." Patients' data, including clinical data, MG subtype, vaccine type, and vaccine dose number, were extracted from the eligible studies.
RESULTS
A total of 20 COVID-19 vaccination-related MGs have been reported worldwide. The median (interquartile range) age was 64 (51, 75) years; 85% (17/20) of them were male, and 70% (14/20) of patients had received messenger RNA-based vaccines. The most common symptoms, in order of frequency, were binocular diplopia (8/11) and ptosis (4/11); the median (interquartile range) time from vaccine to MG symptoms was 6 (2, 7.5) days. Repetitive nerve stimulation showed abnormal decrement in 85% (11/13) of patients, and all 4 patients getting single-fiber electromyography showed an abnormal finding. Nine out of twelve patients with data on clinical outcomes experienced partial/complete improvement of symptoms within 1 month.
CONCLUSION
MG cases after the COVID-19 vaccine are more likely to occur among males and adults older than 50 years. Our pooled cohort data suggest MG symptoms appear within 2 weeks after receiving the vaccine. The presenting symptoms in MG cases associated with COVID-19 vaccine are possibly similar to non-vaccination related MGs. Most patients are expected to experience partial/complete improvement within 1 month.
Topics: Adult; Humans; Male; Female; COVID-19 Vaccines; COVID-19; Myasthenia Gravis; Diplopia; Vaccines; Vaccination
PubMed: 37800781
DOI: 10.1097/MD.0000000000034890