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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 -
Frontiers in Neuroscience 2023COVID-19 infection has had a profound impact on society. During the initial phase of the pandemic, there were several suggestions that COVID-19 may lead to acute and... (Review)
Review
COVID-19 infection has had a profound impact on society. During the initial phase of the pandemic, there were several suggestions that COVID-19 may lead to acute and protracted neurologic sequelae. For example, peripheral neuropathies exhibited distinctive features as compared to those observed in critical care illness. The peripheral nervous system, lacking the protection afforded by the blood-brain barrier, has been a particular site of sequelae and complications subsequent to COVID-19 infection, including Guillain-Barre syndrome, myasthenia gravis, and small fiber neuropathy. We will discuss these disorders in terms of their clinical manifestations, diagnosis, and treatment as well as the pathophysiology in relation to COVID-19.
PubMed: 37712090
DOI: 10.3389/fnins.2023.1198327 -
Neurological Research Jan 2024Although observational studies have suggested a link between hypothyroidism and myasthenia gravis (MG), a causal relationship has not been established. We aimed to...
OBJECTIVES
Although observational studies have suggested a link between hypothyroidism and myasthenia gravis (MG), a causal relationship has not been established. We aimed to investigate the causal association using a two-sample Mendelian randomization (MR) study.
METHODS
Using summary statistics from genome-wide association studies involving 494,577 and 38,243 individuals, single-nucleotide polymorphisms exhibiting no linkage disequilibrium (r2 ≤ 0.001) and displaying significant differences ( ≤ 5 × 10) were selected for hypothyroidism and MG. To assess the potential causality relationship between hypothyroidism and MG, MR analysis was conducted using inverse variance weighted (IVW), weighted median method, and MR-Egger. The MR-Egger regression, heterogeneity test, pleiotropy test, and leave-one-out sensitivity test were employed to examine sensitivity analyses. In addition, validation datasets were used to validate the relevant results.
RESULTS
Genetic liability to hypothyroidism was positively associated with MG (IVW, OR: 1.36, 95% CI: 1.17-1.58, = 7.53 × 10-05; weighted median, OR: 1.19, 95% CI: 0.70-2.02, = 0.522; MR-Egger, OR: 1.19, 95% CI: 0.98-1.45, = 0.080). Among the three MR methods, the correlation between hypothyroidism and MG genetic prediction was consistent. The independent validation set (IVW, OR: 466.47, 95% CI: 4.70 -46,285.95, = 0.01) further supported this. Additionally, bidirectional studies showed that using IVW, there was no reverse causality (OR: 1.104, 95%CI: 0.96-1.27, = 0.170).
DISCUSSION
This MR study showed that hypothyroidism can increase the risk of MG. Further investigation into the underlying mechanisms of this potential causality is warranted to offer novel therapeutic options for MG in the future.
Topics: Humans; Genome-Wide Association Study; Hypothyroidism; Linkage Disequilibrium; Mendelian Randomization Analysis; Myasthenia Gravis
PubMed: 37695759
DOI: 10.1080/01616412.2023.2257458 -
Neurological Sciences : Official... Mar 2024
Topics: Humans; Myasthenia Gravis; Receptors, Cholinergic; Autoantibodies
PubMed: 37875596
DOI: 10.1007/s10072-023-07122-y -
Der Nervenarzt Apr 2024There is evidence that gender-specific differences can influence the diagnostics, treatment and long-term disease course of myasthenia gravis (MG). In women the... (Review)
Review
BACKGROUND
There is evidence that gender-specific differences can influence the diagnostics, treatment and long-term disease course of myasthenia gravis (MG). In women the diagnosis is often made during childbearing age.
OBJECTIVE
Gender-specific differences in MG and relevant aspects in routine clinical practice are presented. In addition, current studies on family planning, pregnancy and childbirth in MG are highlighted and treatment recommendations are derived.
MATERIAL AND METHODS
Narrative literature review.
RESULTS
In addition to sociodemographic data, gender-specific differences encompass clinical as well as paraclinical factors, such as disease severity and antibody status. With few exceptions pregnancy is possible with good maternal and neonatal outcome. During pregnancy and peripartum, children of MG patients should be closely monitored for early detection and treatment of potential syndromes caused by diaplacental transfer of maternal antibodies.
CONCLUSION
Gender-specific factors can influence the course of MG. Adequate medical counselling and multidisciplinary collaboration are essential for MG patients who wish to have children.
Topics: Pregnancy; Child; Infant, Newborn; Humans; Female; Family Planning Services; Myasthenia Gravis; Autoantibodies; Family; Pregnancy Complications
PubMed: 38499774
DOI: 10.1007/s00115-024-01640-6 -
Journal of Translational Medicine Feb 2024Myasthenia gravis (MG) and the experimental autoimmune MG (EAMG) animal model are characterized by T-cell-induced and B-cell-dominated autoimmune diseases that affect... (Review)
Review
BACKGROUND
Myasthenia gravis (MG) and the experimental autoimmune MG (EAMG) animal model are characterized by T-cell-induced and B-cell-dominated autoimmune diseases that affect the neuromuscular junction. Several subtypes of CD4 T cells, including T helper (Th) 17 cells, follicular Th cells, and regulatory T cells (Tregs), contribute to the pathogenesis of MG. However, increasing evidence suggests that CD8 T cells also play a critical role in the pathogenesis and treatment of MG.
MAIN BODY
Herein, we review the literature on CD8 T cells in MG, focusing on their potential effector and regulatory roles, as well as on relevant evidence (peripheral, in situ, cerebrospinal fluid, and under different treatments), T-cell receptor usage, cytokine and chemokine expression, cell marker expression, and Treg, Tc17, CD3CD8CD20 T, and CXCR5 CD8 T cells.
CONCLUSIONS
Further studies on CD8 T cells in MG are necessary to determine, among others, the real pattern of the Vβ gene usage of autoantigen-specific CD8 cells in patients with MG, real images of the physiology and function of autoantigen-specific CD8 cells from MG/EAMG, and the subset of autoantigen-specific CD8 cells (Tc1, Tc17, and IL-17IFN-γCD8 T cells). There are many reports of CD20-expressing T (or CD20 + T) and CXCR5 CD8 T cells on autoimmune diseases, especially on multiple sclerosis and rheumatoid arthritis. Unfortunately, up to now, there has been no report on these T cells on MG, which might be a good direction for future studies.
Topics: Animals; Humans; CD8-Positive T-Lymphocytes; T-Lymphocytes, Helper-Inducer; Myasthenia Gravis, Autoimmune, Experimental; T-Lymphocytes, Regulatory; Autoantigens
PubMed: 38378668
DOI: 10.1186/s12967-024-04965-7 -
PloS One 2023High-dose prednisone use, lasting several months or longer, is the primary initial therapy for myasthenia gravis (MG). Upwards of a third of patients do not respond to... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
High-dose prednisone use, lasting several months or longer, is the primary initial therapy for myasthenia gravis (MG). Upwards of a third of patients do not respond to treatment. Currently no biomarkers can predict clinical responsiveness to corticosteroid treatment. We conducted a discovery-based study to identify treatment responsive biomarkers in MG using sera obtained at study entry to the thymectomy clinical trial (MGTX), an NIH-sponsored randomized, controlled study of thymectomy plus prednisone versus prednisone alone.
METHODS
We applied ultra-performance liquid chromatography coupled with electro-spray quadrupole time of flight mass spectrometry to obtain comparative serum metabolomic and lipidomic profiles at study entry to correlate with treatment response at 6 months. Treatment response was assessed using validated outcome measures of minimal manifestation status (MMS), MG-Activities of Daily Living (MG-ADL), Quantitative MG (QMG) score, or a strictly defined composite measure of response.
RESULTS
Increased serum levels of phospholipids were associated with treatment response as assessed by QMG, MMS, and the Responders classification, but all measures showed limited overlap in metabolomic profiles, in particular the MG-ADL. A panel including histidine, free fatty acid (13:0), γ-cholestenol and guanosine was highly predictive of the strictly defined treatment response measure. The AUC in Responders' prediction for these markers was 0.90 irrespective of gender, age, thymectomy or baseline prednisone use. Pathway analysis suggests that xenobiotic metabolism could play a major role in treatment resistance. There was no association with outcome and gender, age, thymectomy or baseline prednisone use.
INTERPRETATION
We have defined a metabolomic and lipidomic profile that can now undergo validation as a treatment predictive marker for MG patients undergoing corticosteroid therapy. Metabolomic profiles of outcome measures had limited overlap consistent with their assessing distinct aspects of treatment response and supporting unique biological underpinning for each outcome measure. Interindividual variation in prednisone metabolism may be a determinate of how well patients respond to treatment.
Topics: Humans; Prednisone; Activities of Daily Living; Glucocorticoids; Myasthenia Gravis; Combined Modality Therapy; Thymectomy; Treatment Outcome
PubMed: 37816000
DOI: 10.1371/journal.pone.0287654 -
Frontiers in Neurology 2023
PubMed: 38073651
DOI: 10.3389/fneur.2023.1335308 -
Frontiers in Endocrinology 2024Previous studies have suggested a potential association between AITD and MG, but the evidence is limited and controversial, and the exact causal relationship remains...
BACKGROUND
Previous studies have suggested a potential association between AITD and MG, but the evidence is limited and controversial, and the exact causal relationship remains uncertain.
OBJECTIVE
Therefore, we employed a Mendelian randomization (MR) analysis to investigate the causal relationship between AITD and MG.
METHODS
To explore the interplay between AITD and MG, We conducted MR studies utilizing GWAS-based summary statistics in the European ancestry. Several techniques were used to ensure the stability of the causal effect, such as random-effect inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO. Heterogeneity was evaluated by calculating Cochran's Q value. Moreover, the presence of horizontal pleiotropy was investigated through MR-Egger regression and MR-PRESSO.
RESULTS
The IVW method indicates a causal relationship between both GD(OR 1.31,95%CI 1.08 to 1.60,P=0.005) and autoimmune hypothyroidism (OR: 1.26, 95% CI: 1.08 to 1.47, P =0.002) with MG. However, there is no association found between FT4(OR 0.88,95%CI 0.65 to 1.18,P=0.406), TPOAb(OR: 1.34, 95% CI: 0.86 to 2.07, P =0.186), TSH(OR: 0.97, 95% CI: 0.77 to 1.23, P =0.846), and MG. The reverse MR analysis reveals a causal relationship between MG and GD(OR: 1.50, 95% CI: 1.14 to 1.98, P =3.57e-3), with stable results. On the other hand, there is a significant association with autoimmune hypothyroidism(OR: 1.29, 95% CI: 1.04 to 1.59, P =0.019), but it is considered unstable due to the influence of horizontal pleiotropy (MR PRESSO Distortion Test P < 0.001). MG has a higher prevalence of TPOAb(OR: 1.84, 95% CI: 1.39 to 2.42, P =1.47e-5) positivity and may be linked to elevated TSH levels(Beta:0.08,95% CI:0.01 to 0.14,P =0.011), while there is no correlation between MG and FT4(Beta:-9.03e-3,95% CI:-0.07 to 0.05,P =0.796).
CONCLUSION
AITD patients are more susceptible to developing MG, and MG patients also have a higher incidence of GD.
Topics: Humans; Mendelian Randomization Analysis; Hashimoto Disease; Myasthenia Gravis; Hypothyroidism; Thyrotropin; Thyroiditis, Autoimmune
PubMed: 38405140
DOI: 10.3389/fendo.2024.1310083 -
Arquivos de Neuro-psiquiatria Jan 2024(MG) is an autoimmune disease usually caused by antibodies against the acetylcholine receptor (AChR-Abs), muscle-specific tyrosine kinase (MuSK-Abs), or low-density...
BACKGROUND
(MG) is an autoimmune disease usually caused by antibodies against the acetylcholine receptor (AChR-Abs), muscle-specific tyrosine kinase (MuSK-Abs), or low-density lipoprotein receptor-related protein 4 (LRP4-Abs). However, there are MG patients who do not have these antibodies and are thus said to have triple-seronegative (triple-SN) MG.
OBJECTIVE
This study aims to describe the frequency and clinical and epidemiological characteristics of patients with triple-SN MG.
METHODS
This was a retrospective cross-sectional study carried out through the analysis of medical records. Descriptive and analytical statistical analysis was performed comparing subgroups of myasthenic patients, classified according to serological profile.
RESULTS
The sample population consisted of 93 MG patients: 85 were positive for antibodies, 80 (86%) with AChR-Abs, 5 (5.4%) with MuSK-Abs, and no MG patients with LRP4-Abs. Eight patients (8.6%) had triple-SN MG; they had a median age at disease onset of 30 years (21-45). Their most common initial symptoms were ptosis, diplopia, and generalized weakness. Most patients presented with mild symptoms at their last visit, reflecting a median MG composite scale score of 4 (0-6), and 75% of patients had an adequate response to treatment.
CONCLUSION
Our study showed a low frequency of triple-SN MG in Brazilian MG patients. Triple-SN MG was predominant in females, who presented with ptosis, diplopia, and generalized weakness, and most patients had an adequate response to immunosuppressive treatment. There was no significant difference between triple-SN MG and the other subgroups.
Topics: Female; Humans; Young Adult; Adult; Middle Aged; Retrospective Studies; Diplopia; Cross-Sectional Studies; Autoantibodies; Receptor Protein-Tyrosine Kinases; LDL-Receptor Related Proteins; Myasthenia Gravis
PubMed: 38316426
DOI: 10.1055/s-0044-1779052