-
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 -
Journal For Immunotherapy of Cancer Nov 2019Myasthenia gravis (MG) is a rare but life-threatening adverse event of immune checkpoint inhibitors (ICI). Given the limited evidence, data from a large cohort of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Myasthenia gravis (MG) is a rare but life-threatening adverse event of immune checkpoint inhibitors (ICI). Given the limited evidence, data from a large cohort of patients is needed to aid in recognition and management of this fatal complication.
METHODS
We reviewed our institutional databases to identify patients who had cancer and MG in the setting of ICI. We systematically reviewed the literature through August 2018 to identify all similar reported patients. We collected data on clinical and diagnostic features, management, and outcomes of these cases.
RESULTS
Sixty-five patients were identified. Median age was 73 years; 42 (65%) were males, 31 (48%) had metastatic melanoma, and 13 (20%) had a preexisting MG before ICI initiation. Most patients received anti-PD-1 (82%). Sixty-three patients (97%) developed ICI-related MG (new onset or disease flare) after a median of 4 weeks (1 to 16 weeks) of ICI initiation. Twenty-four patients (37%) experienced concurrent myositis, and respiratory failure occurred in 29 (45%). ICI was discontinued in 61 patients (97%). Death was reported in 24 patients (38%); 15 (23%) due to MG complication. A better outcome was observed in patients who received intravenous immunoglobulin (IVIG) or plasmapheresis (PLEX) as first-line therapy than in those who received steroids alone (95% vs 63% improvement of MG symptoms, p = 0.011).
CONCLUSIONS
MG is a life-threatening adverse event of acute onset and rapid progression after ICI initiation. Early use of IVIG or PLEX, regardless of initial symptoms severity, may lead to better outcomes than steroids alone. Our data suggest the need to reassess the current recommendations for management of ICI-related MG until prospective longitudinal studies are conducted to establish the ideal management approach for these patients.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological; Biomarkers; Disease Progression; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Molecular Targeted Therapy; Myasthenia Gravis; Neoplasms; Symptom Assessment
PubMed: 31753014
DOI: 10.1186/s40425-019-0774-y -
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 -
Journal of Translational Medicine Dec 2021Myasthenia gravis is a neuromuscular autoimmune disorder characterized by weakness and disability in the voluntary muscles. There have been several preliminary studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Myasthenia gravis is a neuromuscular autoimmune disorder characterized by weakness and disability in the voluntary muscles. There have been several preliminary studies on the epidemiology of myasthenia gravis in different parts of the world and the effectiveness of common drugs in its treatment, but there has been no comprehensive study of the efficacy of common drugs in the treatment of myasthenia gravis. Therefore, this study aimed to determine the epidemiology of myasthenia gravis globally and the effectiveness of common drugs in its treatment using systematic review and meta-analysis.
METHODS
Research studies were extracted from IranDoc, MagIran, IranMedex, SID, ScienceDirect, Web of Sciences (WoS), ProQuest, Medline (PubMed), Scopus and Google Scholar based on Cochran's seven-step guidelines using existing keywords extracted in MeSH browser. The I test was used to calculate the heterogeneity of studies, and Begg and Mazumdar rank correlation tests were used to assess publication bias. Data were analyzed using Comprehensive Meta-Analysis software (Version 2).
RESULTS
In the search for descriptive studies based on the research question, 7374 articles were found. After deleting articles unrelated to the research question, finally, 63 articles with a sample size of 1,206,961,907 people were included in the meta-analysis. The prevalence of MG worldwide was estimated to be 12.4 people (95% CI 10.6-14.5) per 100,000 population. For analytical studies on the effectiveness of common myasthenia gravis drugs, 4672 articles were found initially, and after removing articles unrelated to the research question, finally, 20 articles with a sample size of 643 people in the drug group and 619 people in the placebo group were included in the study. As a result of the combination of studies, the difference between the mean QMGS score index after taking Mycophenolate and Immunoglobulin or plasma exchange drugs in the group of patients showed a significant decrease of 1.4 ± 0.77 and 0.62 ± 0.28, respectively (P < 0.01).
CONCLUSION
The results of systematic review of drug evaluation in patients with myasthenia gravis showed that Mycophenolate and Immunoglobulin or plasma exchange drugs have positive effects in the treatment of MG. It also represents the positive effect of immunoglobulin or plasma exchange on reducing SFEMG index and QMGS index and the positive effect of Mycophenolate in reducing MG-ADL index, SFEMG and Anti-AChR antibodies index. In addition, based on a meta-analysis of the random-effect model, the overall prevalence of MG in the world is 12.4 people per 100,000 population, which indicates the urgent need for attention to this disease for prevention and treatment.
Topics: Humans; Immunosuppressive Agents; Myasthenia Gravis; Plasma Exchange; Prevalence
PubMed: 34930325
DOI: 10.1186/s12967-021-03185-7 -
Muscle & Nerve Aug 2017Rituximab is a chimeric mouse/human anti-CD20 monoclonal immunoglobulin. We reviewed the efficacy and safety of rituximab in 169 myasthenia gravis (MG) patients from... (Review)
Review
Rituximab is a chimeric mouse/human anti-CD20 monoclonal immunoglobulin. We reviewed the efficacy and safety of rituximab in 169 myasthenia gravis (MG) patients from case reports and series. Antibodies to the acetylcholine receptor (AChR) were present in 59% and muscle-specific tyrosine kinase (MuSK) in 34%. Modified Myasthenia Gravis Foundation of America postintervention scale of minimal manifestations (MM) or better occurred in 44%, and combined pharmacologic and chronic stable remission in 27% overall; MM or better was achieved in 72% of MuSK MG and 30% of AChR MG (P < 0.001). Posttreatment relapses decreased more in MuSK MG (P = 0.05). Response predictors were MuSK MG, less severe disease, and younger age at treatment. Among a responder subset, 26% of AChR and 82% of MuSK MG patients showed decreased posttreatment antibody titers. Rituximab was generally well tolerated. Detectable serum rituximab and depleted CD20 B-cells were observed up to 20 and 16 weeks, respectively, after 4 weekly infusions. Muscle Nerve 56: 185-196, 2017.
Topics: Humans; Immunologic Factors; Myasthenia Gravis; Rituximab
PubMed: 28164324
DOI: 10.1002/mus.25597 -
Journal of Functional Morphology and... Sep 2020Myasthenia gravis is a rare neuromuscular disorder characterized by muscle weakness and fatigue. This review analyzes the most recent evidence regarding the... (Review)
Review
Myasthenia gravis is a rare neuromuscular disorder characterized by muscle weakness and fatigue. This review analyzes the most recent evidence regarding the effectiveness and safety of different rehabilitative approaches to the disease. The review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 365 articles were found in the main scientific databases. Applying the inclusion/exclusion criteria, 11 studies were admitted to the final phase of the review. Three different rehabilitative approaches were identified: physical training, respiratory training, and balance training. All rehabilitative modalities contributed to enhancing functional outcomes, reducing fatigue, and improving quality of life, but currently none can be recommended over another for the lack of cross-comparative studies. The included studies showed methodological quality from low to fair. Despite the range of rehabilitative interventions available, there is a lack of high-quality evidence. However, this review suggests that a multidisciplinary rehabilitation approach should be recommended to people with myasthenia gravis, and above all, for those with mild to moderate symptomatology.
PubMed: 33467286
DOI: 10.3390/jfmk5040071 -
Obstetric Medicine Jun 2022Myasthenia gravis is an autoimmune disease which can impact pregnancy.
BACKGROUND
Myasthenia gravis is an autoimmune disease which can impact pregnancy.
METHODS
Six databases were systematically searched for studies with at least five subjects reporting pregnancy outcomes for women with myasthenia gravis in pregnancy. Assessment of bias was performed for all included studies. Forty-eight cases from our own centre were also included in the analysis.
RESULTS
In total, 32 publications met inclusion criteria for systematic review, for a total of 33 unique data sets including 48 cases from our institution. Outcome data was available for 824 pregnancies. Spontaneous vaginal delivery occurred in 56.3% of pregnancies. Overall risk of myasthenia gravis exacerbation was 33.8% with a 6.4% risk of myasthenic crisis in pregnancy and 8.2% postpartum. The incidence risk of transient neonatal myasthenia gravis was 13.0%.
CONCLUSIONS
The current systematic review provides the best estimates of risk currently available to aid in counselling women with myasthenia gravis in pregnancy.
PubMed: 35845224
DOI: 10.1177/1753495X211041899 -
The Egyptian Journal of Neurology,... 2022Viral infection such as coronavirus disease 2019 (COVID-19) can exacerbate and aggravate neurological disorders due to autoimmune etiology like myasthenia gravis (MG).... (Review)
Review
INTRODUCTION
Viral infection such as coronavirus disease 2019 (COVID-19) can exacerbate and aggravate neurological disorders due to autoimmune etiology like myasthenia gravis (MG). Experimental therapies used in COVID-19 are also factors that can cause the worsening of MG symptoms. This review aimed to assess and conclude the research-based study systematically to analyze the relationship of MG and COVID-19.
METHOD
This study was conducted in accordance to Cochrane handbook for systematic reviews and the guideline of preferred reporting items for systematic review and meta-analysis (PRISMA) and synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. Inclusion criteria in this review were primary studies of every design, articles published in English around January 2000-October 2021, and the study used human as subject. A systematic literature finding was applied in 15 electronic scientific resources. The authors evaluated the study quality and risk of bias of each retrieved article.
RESULTS
The authors found the study through electronic scientific resources that met inclusion and exclusion criteria. The authors evaluated 362 articles identified in literature searching, 22 articles met the criteria for this review and then underwent the evaluation of study quality and risk of bias.
CONCLUSION
COVID-19 infection can increase the risk of new-onset MG, myasthenic crisis, respiratory failure, and mortality rate due to cytokine storm in MG patients. The management of COVID-19 patients with MG is tailored to each person and based on national guidelines and local expert recommendations.
PubMed: 35818475
DOI: 10.1186/s41983-022-00516-3 -
The Oncologist Dec 2021The development of immune checkpoint inhibitors (ICIs) represents a paradigm shift in the treatment of cancers. Despite showing remarkable efficacy, these agents can be...
BACKGROUND
The development of immune checkpoint inhibitors (ICIs) represents a paradigm shift in the treatment of cancers. Despite showing remarkable efficacy, these agents can be associated with life-threatening immune-related adverse events. In recent years, several cases of myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS) have been reported. However, given the rarity, the clinical features and outcomes of these cases remain poorly understood. We, therefore, attempted to systematically review and summarize all cases of IM3OS reported in the literature.
MATERIALS AND METHODS
Studies reporting IM3OS were identified in Embase and MEDLINE. Only case reports and case series published in journals or presented at conferences were included. We conducted a systematic review according to the PRISMA Harms guidelines.
RESULTS
A total of 60 cases were eligible. The patients' median age was 71 years, and the majority (67%) were males; melanoma was the most common indication for ICIs (38%). The most-reported symptoms were fatigue (80%) and muscle weakness (78%). The median number of doses to the development of IM3OS was one. The average creatine kinase level was 9,645 IU/L. Cardiac arrhythmias occurred in 67% of patients, and 18% had depressed ejection fraction. Initial treatment consisted of immunosuppression with high-dose steroids and supportive therapies. Sixty percent of the patients died in hospital because of acute complications.
CONCLUSION
IM3OS can be associated with significant mortality and morbidity. Prospective studies are needed to understand the optimal approach to diagnose and manage these patients and to develop biomarkers to predict the occurrence and severity of this rare but serious condition.
IMPLICATIONS FOR PRACTICE
Clinicians should suspect coexisting myositis and/or myasthenia gravis in all patients with immune checkpoint inhibitor-induced myocarditis, given their propensity to occur together. Early recognition and prompt treatment with the help of a multidisciplinary team might help improve the outcomes of this life-threatening condition.
Topics: Aged; Humans; Immune Checkpoint Inhibitors; Myasthenia Gravis; Myocarditis; Myositis
PubMed: 34378270
DOI: 10.1002/onco.13931 -
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