重症筋無力症

AIMS: Generalized myasthenia gravis (gMG) is a rare, chronic autoimmune disorder with substantial healthcare resource utilization (HRU) and high economic burden. This study evaluated HRU, costs, and predictors of high-cost events in adults with gMG, using data from VIVACITY-MG3. METHODS: Post-hoc analyses used the primary efficacy dataset from VIVACITY-MG3, a randomized, double-blind, placebo-controlled study of nipocalimab and standard-of-care (SoC) versus placebo and SoC in seropositive adults with gMG. HRU endpoints included hospital admissions (HA), emergency department visits (EDV), and hospital days. Logistic regression analysis identified clinical and demographic HA/EDV predictors. Hospital costs per patient per year (PPPY) were estimated using United States (US) cost data from published sources and from a claims database, adjusted to 2024 US dollars. RESULTS: Among 153 patients, nipocalimab numerically reduced the proportion experiencing ≥1 all-cause (9.1% vs 15.8%) and gMG-related (3.9% vs 7.9%) HA/EDV events versus placebo. The incidence rate of HA/EDV events was 51% numerically lower with nipocalimab. Mean hospital stay duration was numerically shorter with nipocalimab for all-cause (8.4 vs 14.6 days) and gMG-related admissions (11.2 vs 17.6 days). All-cause and gMG-related hospital days per 100 patient-years were statistically significantly reduced by 60% and 68% with nipocalimab, respectively. Estimated cost offsets for reduced HRU were $10,860-$13,253 PPPY. Multivariate analysis identified worsening in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score and higher baseline Quantitative Myasthenia Gravis (QMG) respiratory total score as independent predictors. Patients switching from placebo to nipocalimab in the VIVACITY-MG3 open-label extension experienced a 64% reduction in hospital days PPPY. LIMITATIONS AND CONCLUSION: Study limitations include the post-hoc nature of the analysis and the relatively short study duration. Nipocalimab added to SoC significantly reduces overall HRU and associated costs in adults with gMG, particularly by lowering rates and severity of HA/EDV events. Clinical deterioration and high baseline disease severity independently predict high-cost events.

BACKGROUND: Telitacicept is approved for acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR-Ab+ gMG) in China. Although clinical trials have demonstrated its efficacy, real-world outcomes and safety require validation. This study compared telitacicept with conventional immunotherapy in a broader AChR-Ab+ GMG population, bridging the gap between RCT data and real-world practice. METHODS: This retrospective real-world study (ChiCTR2500109279) included 215 patients with AChR-Ab+ gMG, with 43 receiving telitacicept and 172 undergoing conventional immunotherapy. Propensity score matching (1:1) yielded 35 patients per group. Treatment response was assessed by changes in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Activities of Daily Living (ADL) scores, time to minimal symptom expression (MSE), and prednisone use. RESULTS: At week 4, the telitacicept group showed greater improvements than the control group in both QMG and ADL scores (QMG: 3.63±1.48 vs 0.37±2.76, p<0.001; ADL: 2.80±1.13 vs 0.46±2.44, p<0.001). These benefits were more pronounced at week 24 and sustained throughout follow-up (QMG: 10.30±4.19 vs 2.86±3.21, p<0.001; ADL: 8.06±3.37 vs 2.63±2.07, p<0.001). The telitacicept group also reached MSE earlier (median 5 months) and had more patients achieving MSE by week 24 (57.1% vs 11.4%, p<0.001), with lower cumulative prednisone doses over 24 weeks (2325 mg vs 6525 mg, p<0.001). A progressive decrease in IgM/IgG ratio was observed during treatment. Telitacicept was well-tolerated with no serious adverse events. CONCLUSION: This real-world study demonstrates that telitacicept effectively improves symptoms and maintains stability in AChR Ab+ gMG patients, with faster onset, reduced corticosteroid dependence, and favorable safety versus conventional immunotherapy.

Myasthenia gravis (MG) is a complex autoimmune neuromuscular disorder, and the role of lipid metabolism dysregulation in MG pathogenesis remains unclear. This study aimed to investigate the molecular mechanisms of lipid metabolism regulation in myasthenia gravis development by integrating single-cell and bulk transcriptomic data. This study analyzed bulk RNA sequencing data from the GSE85452 dataset (13 MG patients and 12 healthy controls) and single-cell RNA sequencing data from the GSE227835 dataset (10 MG patients and 10 healthy controls). Differential expression analysis was performed, and weighted gene co-expression network analysis (WGCNA) was conducted to identify disease-related modules. Key genes were screened through the intersection of differentially expressed genes (DEGs), WGCNA hub genes, and lipid metabolism-related genes. Functional enrichment analysis, protein‒protein interaction (PPI) network construction, immune infiltration analysis, and regulatory network analysis were performed. Single-cell analysis was used to characterize cellular heterogeneity and intercellular communication features. A nomogram prediction model was constructed and internally validated using leave-one-out cross-validation (LOOCV). Potential therapeutic compounds were identified through drug prediction and molecular docking analysis. Furthermore, key genes were validated by RT-qPCR in an independent cohort of 5 MG patients and 5 healthy controls. A total of 823 DEGs and 13 co-expression modules were identified, of which 4 modules were significantly associated with MG. Twenty-one candidate genes were screened, and 2 key genes (IRS2 and ALDH2) were ultimately determined. IRS2 was significantly downregulated while ALDH2 was significantly upregulated in MG patients. The nomogram model based on key genes demonstrated excellent predictive performance (AUC = 0.897). Immune infiltration analysis showed increased regulatory T cells (Tregs) and decreased CD4+ memory activated T cells in MG patients. Single-cell analysis identified 10 major cell types. Cell‒cell communication analysis revealed dense interactions among CD4+ T cells, B cells, and CD14+ monocytes. Drug prediction identified metformin and cyclophosphamide as potential therapeutic candidates, and molecular docking confirmed favorable binding affinities. This integrative study generated the hypothesis that lipid metabolism dysregulation, potentially mediated by IRS2 and ALDH2, may contribute to immune dysfunction in MG pathogenesis. These findings provide preliminary insights into the molecular mechanisms underlying MG development and suggest potential diagnostic biomarkers and therapeutic targets. However, these results are hypothesis-generating, and clinical translation is contingent upon rigorous mechanistic validation through functional experiments, animal models, and larger multicenter clinical cohorts.

BACKGROUND: Thymectomy is a well-established treatment for myasthenia gravis (MG), with minimally invasive approaches increasingly preferred due to reduced morbidity. This study evaluates the safety and clinical outcomes of uni-portal video-assisted thoracoscopic surgery (UVATS) thymectomy in MG patients at a Malaysian tertiary centre. METHODS: We conducted a retrospective cohort study of 30 patients who underwent UVATS thymectomy for MG at Universiti Malaya Medical Centre between August 2016 and July 2025. Of these, 24 patients with complete perioperative and follow-up data were included. Outcomes assessed included postoperative complications, length of stay, disease severity by Modified Osserman classification, medication requirements, and symptomatic improvement. RESULTS: The cohort (58% female, mean age 42.5 ± 18.2 years) had 50% thymoma. Postoperatively, 88% demonstrated clinical improvement. Osserman Class I proportion increased from 8% preoperatively to 75% postoperatively (p < 0.001). Corticosteroid dependency decreased from 75% to 33% (p = 0.003), pyridostigmine from 67% to 29%. Mean hospital stay was 3.4 ± 1.2 days. Complication rate was 8% (all minor), with no perioperative mortality. CONCLUSIONS: "UVATS thymectomy is safe and demonstrates favorable short-term clinical outcomes in appropriately selected MG patients as the result has demonstrated significant clinical improvement, reduced medication requirements, and low morbidity. These findings support UVATS as the preferred minimally invasive approach in suitable candidates.

BACKGROUND: Congenital myasthenic syndromes (CMS) are rare genetic disorders caused by pathogenic variants in proteins expressed at the neuromuscular junction. Current literature surrounding adult CMS patients remains limited, primarily derived from Western cohorts. METHODS: We present a Southeast Asian cohort of adult patients with a clinical diagnosis of CMS who were evaluated at a tertiary neuromuscular referral center. Patients with seronegative myasthenic syndrome who did not respond to immunotherapy were suspected of having CMS and underwent genetic testing. Patients with possible inherited myopathy also underwent comprehensive genetic testing which included genes for myopathies and CMS. Patient demographics and clinical features were recorded and analyzed retrospectively. Electrodiagnostic features, autoantibodies, and molecular testing (where available) were also reported. RESULTS: From a single-center neuromuscular disease cohort of 639 adult patients, we identified seven (1.1%) patients with a clinical diagnosis of CMS. Four (57%) had onset of symptoms in adulthood, of whom two manifested in late adulthood. Six were initially misdiagnosed with seronegative myasthenia gravis or congenital myopathy. A genetic diagnosis was achieved in five (71.4%) patients with a median diagnostic delay of 17.8 years (range 1-38 years). Three patients from two families were identified to have COLQ-CMS, one patient with CHRNE-CMS, and one patient with CHRNA1-CMS. Two patients with COLQ-CMS had a multiphasic clinical course; one had no clear precipitants for her exacerbations. We reclassified two variants, COLQ(NM_005677.4): c.1352G > A p.Cys451Tyr and CHRNA1(NM_000079.4):c.823G > A p.Val275Met as likely pathogenic based on the American College of Medical Genetics criteria. We present an algorithm, based on our institution's experience, which may be helpful to facilitate the diagnosis of CMS in clinical practice. CONCLUSIONS: CMS is rare and challenging to diagnose in the adult neurology setting. We present a Southeast Asian cohort of seven adult patients with CMS and discuss their clinical and genotypic features.