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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 -
CNS Drugs Feb 2024The treatment of generalized myasthenia gravis (gMG) has been transformed by the development and approval of new targeted therapies. This analysis aimed to rank and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The treatment of generalized myasthenia gravis (gMG) has been transformed by the development and approval of new targeted therapies. This analysis aimed to rank and compare the new therapies for gMG using efficacy and safety data from randomized controlled trials (RCTs).
METHODS
We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov (up to November 2022) for RCTs of targeted drugs for gMG. We used a Bayesian random-effects network meta-analysis (NMA) model and a Markov chain Monte Carlo (MCMC) model for statistical analysis. The primary outcome was the change in quantitative myasthenia gravis score (QMGS) from baseline, while the secondary outcome was the risk ratio (RR) of adverse events (AEs) during treatment. The surface under the cumulative ranking curve (SUCRA) was used to rank these targeted drugs, with higher SUCRA values indicating better efficacy or lower likelihood of AEs.
RESULTS
In total, 13 studies (872 subjects) were included in this analysis evaluating 10 targeted drugs (batoclimab, belimumab, CFZ533, eculizumab, efgartigimod, nipocalimab, rituximab, ravulizumab, rozanolixizumab, and zilucoplan). With regards to the primary outcome, batoclimab [standardized mean difference (SMD), - 1.61; 95% credible interval (CrI), - 2.78, - 0.43] significantly reduced QMGS in patients with gMG when compared with placebo and was ranked as the most efficacious drug. Ranked second and third were eculizumab (SMD, - 0.67; 95% CrI, 1.43, 0.01) and zilucoplan (SMD, - 0.54; 95% CrI, - 1.56, 0.46), respectively. Nipoclimab (SMD, - 0.02; 95% CrI, - 1.04, 1.00) had the worst efficacy and ranked last among all targeted drugs. In our study, except for batoclimab, there was no statistically significant difference in the reduction of patient QMGS for the remaining targeted agents compared with placebo. With regards to the secondary outcomes, only batoclimab (RR, 0.19; 95% CrI, 0, 0.97) led to a significant reduction in the incidence of AEs when compared with the placebo. Belimumab (RR, 0.85; 95% CrI, 0.57, 1.19), CFZ533 (RR, 0.95; 95% CrI, 0.72, 1.25), eculizumab (RR, 0.99; 95% CrI, 0.85, 1.21), and efgartigimod (RR, 0.93; 95% CrI, 0.76, 1.15) also led to a lower incidence of AEs, although these effects were not significantly different from the placebo.
CONCLUSIONS
Batoclimab had the best efficacy and safety for the treatment of gMG and was ranked first out of the 10 targeted drugs included in this study. Eculizumab was ranked second, and nipocalimab had the worst efficacy. With the exception of batoclimab, the incidence of AEs for the remaining drugs was not statistically significantly different from placebo. We note, however, that wide CrIs reflect the uncertainty in this analysis owing to the small number of available studies and low numbers of study participants; moreover, batoclimab had the widest CrI of all drugs in this analysis. More well-designed studies with long-term follow-up are needed to further evaluate and compare the efficacy and safety of these drugs in the future.
Topics: Humans; Network Meta-Analysis; Drug Delivery Systems; Myasthenia Gravis
PubMed: 38300476
DOI: 10.1007/s40263-024-01062-7 -
Neurology International Sep 2023The aim of this systematic review with meta-analysis was to determine differences in cardiovascular autonomic parameters between patients with myasthenia gravis (MG) and... (Review)
Review
The aim of this systematic review with meta-analysis was to determine differences in cardiovascular autonomic parameters between patients with myasthenia gravis (MG) and healthy controls (HCs). Two reviewers searched four electronic databases, namely PubMed, Web of Science, EMBASE, and SCOPUS, from database inception to 7 July 2023 for studies investigating cardiovascular autonomic parameters in MG vs. HCs. A random-effects meta-analysis was performed to compute Hedges' g ± 95% confidence intervals (CI). Out of a total of 2200 records, 8 observational studies with a sample size of 301 patients with MG and 454 HCs were included in the systematic review. Meta-analysis revealed lower values of expiration/inspiration ratio (g = -0.45, I = 74.7), baroreflex sensitivity (g = -0.56, 95%CI -0.80, -0.33; I = 0.3), percentage of adjacent NN intervals differing by more than 50 ms (g = -1.2, I = 82.8), square root of the mean of squared differences between successive beat intervals (g = -1.94, I = 95.1), mean of the standard deviations of all NN intervals (g = -0.83, 95%CI -1.37, -0.28; I = 55.5), and high frequency of HRV during tilt (g = -0.75, 95%CI -0.11, -0.39; I = 0). MG patients vs. HCs had higher systolic blood pressure (g = 0.39; I = 56.1), sympathovagal balance at rest/during tilt (LF/HF-RRI, g = 0.44; I = 0; LF/HF-RRI, g = 0.86; I = 0; LF/HF, g = 0.40; I = 0). As a group, MG patients have altered cardiac autonomic function, including decreased parasympathetic function, lower baroreflex sensitivity, and higher sympathovagal balance at rest and during orthostatic challenges.
PubMed: 37755362
DOI: 10.3390/neurolint15030071 -
Biomedicines Nov 2023Currently used rescue interventions to prevent rapid myasthenic deterioration are plasma exchange (PLEX) and intravenous immunoglobulin (IVIG). We investigated the... (Review)
Review
Currently used rescue interventions to prevent rapid myasthenic deterioration are plasma exchange (PLEX) and intravenous immunoglobulin (IVIG). We investigated the evidence to determine whether the two methods were interchangeable or whether one was superior to the other. This review was registered on PROSPERO (CRD42021285985). Only randomized controlled trials (RCTs) comparing the efficacy and safety of PLEX and IVIG in patients with moderate-to-severe myasthenia gravis (MG) were included. Five major databases were systematically searched (PubMed, CENTRAL, Embase, Scopus, and Web of Science). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for adverse events and mean differences (MD) for changes in quantitative myasthenia gravis scores (QMG). Three RCTs met the inclusion criteria. Two investigating 114 patients in total were eligible for meta-analysis to analyze efficacy and safety. For the change in QMG score, the MD was -2.8 (95% CI: -5.614-0.113), with PLEX performing better. For adverse events, an OR of 1.04 was found (95% CI: 0.25-4.27). This study demonstrated a low risk of bias in evaluating treatment efficacy but indicated a high risk of bias in assessing procedural safety outcomes. Although the results did not show any significant difference, there was a tendency indicating faster efficacy of PLEX in the first two weeks of treatment. In such a critical clinical condition, this tendency may be clinically meaningful, but further studies should clarify this benefit.
PubMed: 38137401
DOI: 10.3390/biomedicines11123180 -
BMC Neurology Dec 2023Neuromuscular diseases (NMD) emerged as one of the main side effects of the COVID-19 vaccination. We pooled and summarized the evidence on the clinical features and...
BACKGROUND
Neuromuscular diseases (NMD) emerged as one of the main side effects of the COVID-19 vaccination. We pooled and summarized the evidence on the clinical features and outcomes of NMD associated with COVID-19 vaccination.
METHODS
We comprehensively searched three databases, Medline, Embase, and Scopus, using the key terms covering "Neuromuscular disease" AND "COVID-19 vaccine", and pooled the individual patient data extracted from the included studies.
RESULTS
A total of 258 NMD cases following COVID-19 have been reported globally, of which 171 cases were Guillain-Barré syndrome (GBS), 40 Parsonage-Turner syndrome (PTS), 22 Myasthenia Gravis (MG), 19 facial nerve palsy (FNP), 5 single fiber neuropathy, and 1 Tolosa-Hunt syndrome. All (100%) SFN patients and 58% of FNP patients were female; in the remaining NMDs, patients were predominantly male, including MG (82%), GBS (63%), and PTS (62.5%). The median time from vaccine to symptom was less than 2 weeks in all groups. Symptoms mainly appeared following the first dose of vector vaccine, but there was no specific pattern for mRNA-based.
CONCLUSION
COVID-19 vaccines might induce some NMDs, mainly in adults. The age distribution and gender characteristics of affected patients may differ based on the NMD type. About two-thirds of the cases probably occur less than 2 weeks after vaccination.
Topics: Adult; Humans; Female; Male; COVID-19 Vaccines; COVID-19; Neuromuscular Diseases; Myasthenia Gravis; Guillain-Barre Syndrome; Bell Palsy; Facial Paralysis
PubMed: 38082244
DOI: 10.1186/s12883-023-03486-y -
Osteoporosis International : a Journal... May 2024Patients with myasthenia gravis (MG), because of their muscle weakness and exposure to corticosteroids treatment, are generally considered to be at increased risk for... (Review)
Review
Patients with myasthenia gravis (MG), because of their muscle weakness and exposure to corticosteroids treatment, are generally considered to be at increased risk for osteoporosis or fracture. However, clinical evidence of this issue is lacking. In this review, we systematically searched databases, including Cochrane Library, PubMed, Embase, and Airiti library from inception to the end of November 2023 for cohort studies that compared participants with MG and participants without MG for incidence of osteoporosis or fracture. We used the Newcastle-Ottawa Scale for quality assessment. In total, we included 3 studies with 34,865 participants. The pooled meta-analysis using the random effect model demonstrated no significant difference in risk of fracture in the MG group (odds ratio = 1.52; 95% confidence interval = 0.74 to 3.12; I = 93%; between-study variance [τ] = 0.32) compared with that for the non-MG group. Due to limited studies, we could not perform a quantitative analysis for risk of osteoporosis. In conclusion, we found no robust evidence to support the proposition that patients with MG are at higher risk for fracture than general comparators. The explanations and underlying mechanisms of this finding remain unclear, we therefore conclude that additional studies are warranted.
PubMed: 38748216
DOI: 10.1007/s00198-024-07097-2 -
Journal of Clinical Neuroscience :... Mar 2024Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by muscle weakness, posing significant challenges to patients' daily lives. Intravenous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by muscle weakness, posing significant challenges to patients' daily lives. Intravenous immunoglobulin (IVIG) and plasmapheresis are two prominent immunomodulatory therapies used in MG management, but the choice between them remains a clinical dilemma. This systematic review and meta-analysis aim to evaluate the comparative efficacy of IVIG versus plasmapheresis in MG management.
METHODS
We adhered to PRISMA guidelines and prospectively registered the review protocol in PROSPERO. Systematic search across electronic databases identified 14 studies meeting inclusion criteria. Data from these studies were extracted, and assessed risk of bias. Primary outcomes included clinical efficacy, while secondary outcomes encompassed hospitalization, ventilation, antibody titers, and treatment-related complications. Statistical analysis was conducted using R software.
RESULTS
The pooled results indicated that patients receiving plasmapheresis had higher odds of any improvement in MG symptoms compared to IVIG. However, change in severity scores did not significantly differ between the two treatments. Hospitalization durations were similar, but IVIG-treated patients tended to have shorter stays. Antibody titers, particularly anti-MUSK antibodies, favored plasmapheresis treatment. Complication rates were comparable between two groups. However, severe complications were more common in plasmapheresis.
CONCLUSION
This comprehensive analysis suggests that plasmapheresis may offer superior short-term symptom improvement in MG compared to IVIG, while IVIG may lead to shorter hospital stays and lower complication rates. The choice between these treatments should be tailored to individual patient needs and disease characteristics. Further research is needed to explore long-term outcomes and mortality rates in MG management.
Topics: Humans; Immunoglobulins, Intravenous; Plasmapheresis; Myasthenia Gravis; Treatment Outcome; Length of Stay
PubMed: 38306763
DOI: 10.1016/j.jocn.2024.01.025 -
Frontiers in Neurology 2024Immune checkpoint inhibitors (ICI)-induced myasthenia gravis (MG) is an uncommon but potentially fatal neurotoxicity. We aim to help physicians familiarize themselves...
BACKGROUND
Immune checkpoint inhibitors (ICI)-induced myasthenia gravis (MG) is an uncommon but potentially fatal neurotoxicity. We aim to help physicians familiarize themselves with the clinical characteristics of ICI-induced MG, facilitating early diagnosis and prompt intervention.
METHODS
We searched the Chinese People's Liberation Army General Hospital medical record system from January 2017 to August 2023 for patients diagnosed with ICI-induced MG. We systematically reviewed the literature until August 2023 to identify all similar patients. We collected clinical information on these patients.
RESULTS
110 patients were identified, 9 from our institution and 101 from case reports. In our institution, Median age was 66 years (range: 49-79 years). 6 were males. The most common was lung cancer ( = 4). All patients had no previous history of MG and received PD-1 or PD-L1 inhibitors. The median time from ICI initiation to first MG symptoms was 4 weeks (range: 2-15 weeks). ICIs were discontinued in all patients. Most patients initially received high-dose corticosteroids, and their symptoms improved. Some patients are discharged with corticosteroids maintenance therapy. In addition, 55 patients (50%) with concomitant myositis and/or myocarditis and MG-induced mortality were more common in the myositis and/or myocarditis group (10.9% vs. 34.5%, = 0.016). Overlap of myositis with MG (OR = 3.148, = 0.009) and anti-AChR antibody positivity (OR = 3.364, = 0.005) were both significantly associated with poor outcomes.
CONCLUSION
Our study reveals the prognosis of ICI-induced MG and suggests that myositis and/or myocarditis are severe comorbidities of ICI-induced MG, emphasizing the importance of early diagnosis and clinical intervention.
PubMed: 38633537
DOI: 10.3389/fneur.2024.1372861 -
Medicine May 2024Myasthenia gravis (MG) is a common autoimmune disease that often involves the skeletal muscle of the whole body and seriously affects patients' quality of life.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Myasthenia gravis (MG) is a common autoimmune disease that often involves the skeletal muscle of the whole body and seriously affects patients' quality of life. Acupuncture and moxibustion treatment of MG has unique advantages, the aim is to evaluate the clinical effect of acupuncture and moxibustion on MG.
METHODS
The literature on acupuncture and moxibustion treating MG in PubMed, CochraneLibrary, EMBASE, SCI, China Academic Journals full-text database, China Biology Medicine disc, VIP and Wanfang database were searched through computers from the establishment of the database to December 2022.
RESULTS
A total of 11 studies were included, involving 658 patients, where 330 in the treatment group and 328 in the control group. The results of the meta-analysis showed that the treatment group performed better than the control group in improving the total clinical response rate (OR = 3.26, 95%[2.04,5.21], P < .01). Additionally, the treatment group outperformed the control group in raising the absolute clinical score (MD = -3.48, 95%CI[-5.17, -1.78], P < .01). However, there was no significant difference between the treatment group and the control group in improving the level of serum interleukin-6 receptor (MD = -1.45,95%CI[-6.85,3.95], P > .05) and OMG quantitative score (MD = -2.16,95%CI[-4.85,0.52], P > .05). The total clinical effective rate was tested for publication bias, which showed that the 2 sides of the funnel plot were asymmetrical, suggesting the possible existence of publication bias.
CONCLUSION
Acupuncture and moxibustion has a good effect on MG, which is better than conventional Western medicine in improving the total clinical effective rate and absolute clinical score.
Topics: Moxibustion; Humans; Myasthenia Gravis; Acupuncture Therapy; Treatment Outcome; Quality of Life
PubMed: 38701271
DOI: 10.1097/MD.0000000000037961 -
BMC Neurology Feb 2024Myasthenia gravis (MG) is a rare autoimmune disease characterised by muscle weakness, and progression from ocular (oMG) to generalised (gMG) symptoms results in a...
BACKGROUND
Myasthenia gravis (MG) is a rare autoimmune disease characterised by muscle weakness, and progression from ocular (oMG) to generalised (gMG) symptoms results in a substantial negative impact on quality of life (QoL). This systematic review aimed to provide an overview of the patient burden experienced by people living with gMG.
METHODS
Electronic database searches (conducted March 2022), supplemented by interrogation of grey literature, were conducted to identify studies reporting patient burden outcomes in patients with gMG in Europe, the Middle East and Africa. Results were synthesised narratively due to the heterogeneity across trials.
RESULTS
In total, 39 patient burden publications (representing 38 unique studies) were identified as relevant for inclusion in the systematic review, consisting of 37 publications reporting formal patient-reported outcome measures (PROMs), and two publications describing alternative qualitative assessments of patient experience. The studies included a variety of measures including generic and disease-specific PROMs, as well as symptom-specific PROMs focusing on key comorbidities including depression, anxiety, fatigue and sleep disturbance. The findings showed some variation across studies and PROMs; however, in general there was evidence for worse QoL in patients with gMG than in healthy controls or in patients with oMG, and a trend for worsening QoL with increasing MG severity.
CONCLUSIONS
This review highlights the importance of considering patient QoL when developing and assessing treatment and management plans for patients with gMG. However, the heterogeneity identified across studies illustrates the need for further representative and well-powered studies in large cohorts administering consistent, validated questionnaires.
TRIAL REGISTRATION
The protocol for this systematic review was registered in PROSPERO: CRD42022328444.
Topics: Humans; Quality of Life; Myasthenia Gravis; Africa; Middle East; Europe
PubMed: 38336636
DOI: 10.1186/s12883-024-03553-y