America Foundation Research Articles

Clinical characteristics and impairment of activities of daily living among patients with myasthenia gravis with differing degrees of muscle weakness: a real-world study of patients in the US and five European countries

BackgroundReal-world data were employed to determine clinical characteristics of patients with myasthenia gravis (MG) with differing degrees of muscle weakness, as defined using the Myasthenia Gravis Foundation of America (MGFA) classification system.MethodsData were drawn from the Adelphi MG Disease Specific Programme (DSP)™, a multinational (United States, France, Germany, Italy, Spain, United Kingdom) survey completed by physicians and their patients with MG in 2020. The association between MGFA class and impairment in activities of daily living (ADL) was tested using linear regression adjusting for sex and Charlson Comorbidity Index. Bivariate comparisons were performed for each individual item. A range of other clinical characteristics were also explored according to MGFA class.ResultsAmong 1232 patients, those in MGFA class I had significantly lower ADL impairment versus class II or III/IV (adjusted for sex and Charlson Comorbidity Index) (p < 0.01). However, heterogeneity occurred within each MGFA class. Bulbar symptoms (impaired speech, difficulty swallowing, and/or difficulty chewing/choking on food) were reported in some class I patients (mild in 1.1–1.9% and moderate in 0.3–1.1% of patients) and class II patients (mild in 8.5–16.4%, moderate in 4.7–7.4%, and severe in 0.3–0.9% of patients), and shortness of breath was reported in some class I (mild in 0.5% of patients) and class II patients (mild in 9.8%, moderate in 4.8%, and severe in 0.3% of patients). Conversely, in 11.2–19.2% of class III/IV patients, bulbar symptoms and shortness of breath reported were only mild in severity. In line with this finding, despite significant correlations between MGFA class and several clinical characteristics, patients across every class were at risk of experiencing myasthenic crisis or hospitalization, experiencing comorbidities including anxiety and depression, and not being in remission.ConclusionsAlthough MGFA class correlates with greater ADL impairment and presence of other clinical characteristics, there is variability between patients in each class in terms of symptoms experienced, overall disease burden, and the precise nature of ADL impairment.

Interpretable machine learning models for predicting short-term prognosis in AChR-Ab+ generalized myasthenia gravis using clinical features and systemic inflammation index.

Myasthenia Gravis (MG) is an autoimmune disease that causes muscle weakness in 80% of patients, most of whom test positive for anti-acetylcholine receptor (AChR) antibodies (AChR-Abs). Predicting and improving treatment outcomes are necessary due to varying responses, ranging from complete relief to minimal improvement. Our study aims to develop and validate an interpretable machine learning (ML) model that integrates systemic inflammation indices with traditional clinical indicators. The goal is to predict the short-term prognosis (after 6 months of treatment) of AChR-Ab+ generalized myasthenia gravis (GMG) patients to guide personalized treatment strategies. We performed a retrospective analysis on 202 AChR-Ab+ GMG patients, dividing them into training and external validation cohorts. The primary outcome of this study was the Myasthenia Gravis Foundation of America (MGFA) post-intervention status assessed after 6 months of treatment initiation. Prognoses were classified as "unchanged or worse" for a poor outcome and "improved or better" for a good outcome. Accordingly, patients were categorized into "good outcome" or "poor outcome" groups. In the training cohort, we developed and internally validated various ML models using systemic inflammation indices, clinical indicators, or a combination of both. We then carried out external validation with the designated cohort. Additionally, we assessed the feature importance of our most effective model using the Shapley Additive Explanations (SHAP) method. In our study of 202 patients, 28.7% (58 individuals) experienced poor outcomes after 6 months of standard therapy. We identified 11 significant predictors, encompassing both systemic inflammation indexes and clinical metrics. The extreme gradient boosting (XGBoost) model demonstrated the best performance, achieving an area under the receiver operating characteristic (ROC) curve (AUC) of 0.944. This was higher than that achieved by logistic regression (Logit) (AUC: 0.882), random forest (RF) (AUC: 0.917), support vector machines (SVM) (AUC: 0.872). Further refinement through SHAP analysis highlighted five critical determinants-two clinical indicators and three inflammation indexes-as crucial for assessing short-term prognosis in AChR-Ab+ GMG patients. Our analysis confirms that the XGBoost model, integrating clinical indicators with systemic inflammation indexes, effectively predicts short-term prognosis in AChR-Ab+ GMG patients. This approach enhances clinical decision-making and improves patient outcomes.

Toyota USA Foundation commits $8.6 million for STEM education

Toyota USA Foundation commits $8.6 million for STEM education

Low-intensity aerobic cycle ergometer effects on lung function of myasthenia gravis patients: A randomized controlled trial

Patients with generalized myasthenia gravis (MG) often show restrictive spirometry results. Although regular exercise and physical fitness are linked to better respiratory function, there is limited research assessing the effects of aerobic exercise on lung function in MG patients. The aim of this study was to analyze the effect of low-intensity aerobic exercise using a cycle ergometer on lung function parameters in MG patients. A randomized controlled trial with pre- and post-test was conducted at the Medical Rehabilitation Outpatient Clinic of Dr. Soetomo General Academic Hospital in Surabaya, Indonesia, in 2023. MG patients classified as I−IIb based on the Myasthenia Gravis Foundation of America (MGFA) classification were recruited and randomly divided into treatment and control groups. The treatment group was given low-intensity aerobic exercise using a cycle ergometer, education on lifestyle changes, and breathing exercises (deep and pursed lip breathing). Lung function parameters, including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and forced expiratory volume ratio (FEVR), were then measured. Measurements were conducted before and after eight weeks of low-intensity aerobic cycle ergometer exercise and compared with those of a control group. A total of 17 MG patients were included in this study. The results showed a significant increase in FVC in the treatment group (p=0.003), whereas no significant change in the control group (p=0.068). A significant increase in FEV1 was observed both in the treatment (p=0.029) and the control group (p=0.016). There was no improvement in FEVR in either group. After the intervention, significant differences were observed in FVC (p=0.009) and FEV1 (p=0.029) between the treatment and control groups. There was no significant difference in FEVR values after the intervention between both groups (p=0.491). In conclusion, eight weeks of low-intensity aerobic cycle ergometer exercise led to significant improvements in FVC and FEV1 among MG patients.

Effect of Follicular T Helper and T Helper 17 Cells-Related Molecules on Disease Severity in Patients with Myasthenia Gravis.

Contribution of T helper 1 and 2 cells-related cytokines to pathogenesis of myasthenia gravis (MG) is well known. Recently, the contribution of follicular T helper (Tfh) and T helper 17 cells-related molecules to the pathogenesis has gained importance. In this study, we aimed to evaluate the changes in Tfh- and Th17-related molecules before and after rescue therapy in patients with myasthenic crisis (cMG) and to reveal the molecular differences between stable MG and cMG patients. Patients with stable generalized MG (gMG) and cMG were classified according to Myasthenia Gravis Foundation of America (MGFA) classification. Serum samples were collected from cMG patients both before and after rescue therapy (plasmapheresis or intravenous immunoglobulin [IVIg]). Serum levels of Tfh- and selected Th17-related molecules (IL-22, IL-17A, CXCL13, sPD-L1, sICOSLG, and sCD40L) were analyzed by commercial ELISA kits. Twelve cMG (6 for IVIg, 6 for plasmapheresis) and 10 gMG patients were included in the study. A decrease in serum sPD-L1 and CXCL13 levels was observed in cMG patients after treatment, regardless of the treatment modality (p &lt; 0.05). In contrast, serum sICOSLG levels decreased only in patients treated with IVIg (p &lt; 0.05) and serum IL-22 levels increased in patients receiving plasmapheresis (p &lt; 0.05). cMG patients had higher serum IL-17A levels compared to stable patients (p &lt; 0.001) and its level was positively correlated with disease severity (r = 0.678, p = 0.001). Our results confirm the contribution of Tfh- and Th17-related cell pathways to MG pathogenesis. Both IVIg and plasmapheresis appear to be effective in reducing Tfh- and Th17-related cytokine/molecule levels in cMG patients. Increased serum IL-17A levels may contribute to disease severity.

Efgartigimod as a fast-acting add-on therapy in manifest and impending myasthenic crisis: A single-center case series

Efgartigimod was the first-in-class neonatal Fc receptor antagonist approved for the treatment of acetylcholine receptor antibody positive (AChR+), Myasthenia Gravis Foundation of America (MGFA) Class II-IV generalized myasthenia gravis (gMG) patients. As a novel therapy, the clinical experiences are still lacking, especially for the use of efgartigimod in manifest and impending myasthenic crisis (IMC). We reported three AChR+, gMG patients, two with myasthenic crisis (MC) and one with IMC, treated with efgartigimod. MGFA class, MG-Activity of Daily Living score (MG-ADL), Quantitative MG score (QMG), and Muscle Research Council sum score (MRC), concentration of anti-AChR antibody, IgG, globulin, and albumin, subsets of T and B lymphocyte were evaluated or measured before, during and after efgartigimod treatment. All patients showed fast and robust response to efgartigimod with marked improvement in MGFA, MG-ADL, QMG, and MRC scores. Patient 1 did not respond effectively to IVIg but was successfully rescued by add-on efgartigimod. She extubated at 7 days after the first infusion and got rid of NIV after 14-days treatment. Patient 2 and patient 3 directly used efgartigimod when symptoms were not ameliorated by adjusting of oral drugs. Patient 2 wean from BiPAP at seven days after the first infusion. Patient 3 in IMC status, overcame the severe dysphagia at three days after the first infusion. Clinical symptoms continued to improve 1–2 weeks after discharge. Concentration of anti-AChR antibody, IgG and globulin were remarkably reduced by efgartigimod treatment. Our study supported that efgartigimod could act as a fast-acting rescue therapy for patients with MC or IMC. Larger studies from multicenter are required to provide further evidence.

2024 Public Health Actions to Reduce the Burden of Asthma: Influenza and COVID-19 Vaccination Uptake Among People with Asthma.

This study sought to identify COVID-19 and influenza vaccination rates and barriers among people with asthma. The Asthma and Allergy Foundation of America (AAFA) conducted an online survey from April to May in 2022 among a convenience sample of 350 individuals with asthma. Most survey respondents reported that they had received an influenza vaccine for the 2021-2022 flu season (77%) and at least 1 dose of a COVID-19 vaccine (87%). Age, gender, race and ethnicity, and household income were significantly associated with influenza vaccination. Age and urban-rural classification were associated with COVID-19 vaccination. Access issues were not commonly reported as vaccination barriers, highlighting educational opportunities.

Clinical and laboratory remission with rituximab in anti-MuSK-positive myasthenia gravis.

Increasing data are available on the use and efficacy of rituximab (RTX) in patients with anti-muscle-specific tyrosine kinase (MuSK)-positive myasthenia gravis (MG), especially those steroid-dependent or unresponsive to traditional immunotherapies. We aimed to evaluate the clinical characteristics and treatment responses of adult patients with generalized anti-MuSK-positive MG treated with RTX. We retrospectively recruited 16 patients who were on RTX, between January 2010 and September 2023. RTX was given 1000mg/day intravenously twice, two weeks apart. Maintenance treatment was administered at intervals of 3-6months based on clinical evaluation. The outcome was assessed by Myasthenia Gravis Foundation of America (MGFA) and Myasthenia Gravis Status and Treatment Intensity (MGSTI) scores. Additionally, anti-MuSK antibody levels were retested after treatment in all patients except one. Twelve patients were female. The mean age at disease onset was 35.3± 17.3 years. The median duration between disease onset and RTX administration was 2.4 years (min-max: 0.5-36.5 years). The worst MGFA class before RTX was between IIIb-V. After RTX treatment, 81.3% of patients achieved MGFA minimal manifestations or better and MGSTI level 1 or better. Anti-MuSK antibodies became negative in 12 patients, while they remained positive in three. The changes in antibody levels seemed associated with clinical outcomes. RTX is an effective treatment in anti-MuSK-positive MG. Furthermore, our results support the inhibition of antibody production by RTX and we recommend monitoring anti-MuSK antibody titers to follow disease progression and treatment response.

Effectiveness and Safety of Mycophenolate Mophetil in Myasthenia Gravis: A Real-Life Multicenter Experience.

Myasthenia gravis (MG) is an autoimmune disease characterized by fluctuating muscle weakness due to autoantibodies targeting neuromuscular junction proteins. Mycophenolate mofetil (MMF), an immunosuppressive therapy, has shown potential for managing MG with fewer side effects compared to other treatments. This study aims to evaluate the effectiveness and safety of MMF in MG patients in a real-life multicenter setting. A retrospective cohort study was conducted on generalized MG patients, refractory to azathioprine (AZA) and treated with MMF alone or with steroids, at three Italian centers from January 2011 to February 2024. Patients were assessed using the Myasthenia Gravis Foundation of America (MGFA) classification, MG composite score (MGCS), and MG activity of daily living (MGADL) scores at baseline, 6, 12, 18, and 24 months. Statistical analyses included the Spearman correlation, the Friedman test, and ANOVA. Thirty-two patients were enrolled (13 males, mean age 66.5 ± 11.5 years). Significant improvements in MGADL and MGCS scores were observed at 6 and 12 months (p < 0.001), with continued improvement over 24 months. Side effects were reported in 12% of patients. MMF showed a faster onset of symptom control compared to azathioprine, with a significant improvement noted within 6 months. A recent study found that MMF and AZA were equally effective in improving patients' quality of life, but because AZA had more serious adverse events than MMF, lower doses of AZA were therefore recommended to reduce the adverse events while maintaining efficacy. Conversely, results showed that MMF is effective and well-tolerated in the long-term management of MG, providing faster symptom control and a favorable safety profile. Future prospective studies with larger cohorts are needed to confirm these findings and explore sex differences in response to MMF treatment.

Psychometric properties of MG-ADL items and MG-ADL score: An assessment of distributional characteristics, validity and factor structure in two large datasets

BackgroundThe Myasthenia Gravis–Activities of Daily Living scale (MG-ADL) is an 8-item outcome measure to assess symptoms and functional limitations in myasthenia gravis (MG) patients. The MG-ADL score is an equally weighted level sum score that is used as primary outcome measures in clinical trials, in clinical practice, and as an end-point in health economic evaluation. This data analysis aims to obtain detailed knowledge of measurement properties of MG-ADL items and the MG-ADL score. MethodsCross-sectional data from a real-world prospective study (MRW) were combined with longitudinal data from the ADAPT trial. Outcome measures included were MG-ADL, Quantitative Myasthenia Gravis score (QMG), MG 15-item Quality of Life (MG-QOL15r) and EQ-5D-5L. Patients were categorized by their Myasthenia Gravis Foundation of America (MGFA) clinical classification. The following measurement properties were assessed: distributional characteristics, inter-item correlation, convergent, known groups and construct validity and internal factor structure. ResultsCorrelations of items within MG-ADL dimensions were moderate, while MG-ADL correlations between comparable MG-QOL15r and QMG items were mixed. Known groups validity for the MG-ADL score was demonstrated for MGFA class. Mean MG-ADL item level scores by MGFA class demonstrated construct validity. PCA, including all four outcome measures, resulted in a nine factor solution. DiscussionPsychometric properties of individual MG-ADL items were moderate to good. This study showed that the MG-ADL adequately captures the multidimensional heterogeneous nature of MG. This is, however, accompanied by mixed psychometric performance of the MG-ADL score, which may complicate health economic modelling.Registration: MyRealWorld-MG was registered on November 25, 2019, with registration numberNCT04176211. The ADAPT randomized clinical trial is registered atClinicalTrials.gov(NCT03669588).

A new pragmatic classification system for thymoma associated myasthenia gravis: a retrospective cohort study.

The management and outcomes of patients with thymoma associated with myasthenia gravis (TAMG) are heterogeneous. Here, we propose a novel classification system based on Masaoka stage and Myasthenia Gravis Foundation of America (MGFA) classification, aiming to guide surgical decisions and perioperative management for these patients. Considering both oncological and neurological factors, this novel TAMG classification provides valuable information on outcome stratification and clinical decision-making for TAMG.

Glucagon-Like Peptide-1 Receptor Agonists and Risk for Suicidal Ideation and Behaviors in U.S. Older Adults With Type 2 Diabetes : A Target Trial Emulation Study.

A major concern has recently emerged about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and increased risk for suicidal ideation and behaviors based on International Classification of Diseases codes. To investigate the association between GLP-1 RAs, compared with sodium-glucose cotransporter-2 inhibitors (SGLT2is) or dipeptidyl peptidase-4 inhibitors (DPP4is), and risk for suicidal ideation and behaviors in older adults with type 2 diabetes (T2D). Two target trial emulation studies comparing propensity score (PS)-matched cohorts for GLP-1 RAs versus SGLT2is and GLP-1 RAs versus DPP4is. U.S. national Medicare administrative data from January 2017 to December 2020. Older adults (≥66 years) with T2D; no record of suicidal ideation or behaviors; and a first prescription for a GLP-1 RA, SGLT2i, or DPP4i. The primary end point was a composite of suicidal ideation and behaviors. New GLP-1 RA users were matched 1:1 on PS to new users of an SGLT2i or DPP4i in each pairwise comparison. A Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% CIs within matched groups. This study included 21 807 pairs of patients treated with a GLP-1 RA versus an SGLT2i and 21 402 pairs of patients treated with a GLP-1 RA versus a DPP4i. The HR of suicidal ideation and behaviors associated with GLP-1 RAs relative to SGLT2is was 1.07 (95% CI, 0.80 to 1.45; rate difference, 0.16 [CI, -0.53 to 0.86] per 1000 person-years); the HR relative to DPP4is was 0.94 (CI, 0.71 to 1.24; rate difference, -0.18 [CI, -0.92 to 0.57] per 1000 person-years). Low event rate; imprecise estimates; unmeasured confounders, such as body mass index; and potential misclassification of outcomes. Among Medicare beneficiaries with T2D, this study found no clear increased risk for suicidal ideation and behaviors with GLP-1 RAs, although estimates were imprecise and a modest adverse risk could not be ruled out. American Foundation for Pharmaceutical Education, Pharmaceutical Research and Manufacturers of America Foundation, National Institute on Aging, and National Institute of Diabetes and Digestive and Kidney Diseases.

Sleep in Myasthenia Gravis: A Questionnaire-Based Study.

Disturbed sleep and its impact on quality of life (QoL) are underrecognized in myasthenia gravis (MG). To evaluate the quality of sleep in MG using standard sleep questionnaires and assess factors that determine sleep. Prospective, cross-sectional, hospital-based study. Fifty patients on stable drug therapy for at least 1 month and age- and gender-matched controls were assessed using standard sleep questionnaires [Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and NIMHANS Comprehensive Sleep Disorders Questionnaire (NCSDQ)]. Myasthenia Gravis Foundation of America (MGFA) grade was I, IIA, IIB, IIIA, IIIB, and IVA in 11, 19, 3, 10, 6, and 1 respectively. The mean PSQI and ESS scores were similar in patients and controls. Patients with abnormal ESS (>10) were older and had greater neck circumference (P = 0.018 and <0.001). Body mass index was greater in patients with PSQI > 5 (P < 0.05). Age, gender, and clinical severity did not affect PSQI. Compared with ESS and PSQI, NCSDQ showed higher frequency of disturbed sleep, snoring, early morning headache, difficulty in initiation, and maintenance of sleep in MG, although the differences between patients and controls were not significant. No correlation was found between QoL and ESS or PSQI. Patients of MG with stable clinical course with adequate treatment have sleep quality comparable with healthy controls. Longitudinal assessment of sleep quality at multiple time points throughout the disease course and correlating with cross-sectional disease severity may further delineate the impact of disease on sleep and QoL.

Dynamic changes of peripheral inflammatory markers link with disease severity and predict short-term poor outcome of myasthenia gravis.

The relationship between peripheral inflammatory markers, their dynamic changes, and the disease severity of myasthenia gravis (MG) is still not fully understood. Besides, the possibility of using it to predict the short-term poor outcome of MG patients have not been demonstrated. This study aims to investigate the relationship between peripheral inflammatory markers and their dynamic changes with Myasthenia Gravis Foundation of America (MGFA) classification (primary outcome) and predict the short-term poor outcome (secondary outcome) in MG patients. The study retrospectively enrolled 154 MG patients from June 2016 to December 2021. The logistic regression was used to investigate the relationship of inflammatory markers with MGFA classification and determine the factors for model construction presented in a nomogram. Finally, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were utilized to evaluate the incremental capacity. Logistic regression revealed significant associations between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), aggregate index of systemic inflammation (AISI) and MGFA classification (p = 0.013, p = 0.032, p = 0.017, respectively). Incorporating dynamic changes of inflammatory markers into multivariable models improved their discriminatory capacity of disease severity, with significant improvements observed for NLR, systemic immune-inflammation index (SII) and AISI in NRI and IDI. Additionally, AISI was statistically associated with short-term poor outcome and a prediction model incorporating dynamic changes of inflammatory markers was constructed with the area under curve (AUC) of 0.953, presented in a nomograph. The inflammatory markers demonstrate significant associations with disease severity and AISI could be regarded as a possible and easily available predictive biomarker for short-term poor outcome in MG patients.

Systemic Inflammatory Response Index, a Potential Inflammatory Biomarker in Disease Severity of Myasthenia Gravis: A Pilot Retrospective Study.

Myasthenia gravis (MG) is a chronic autoimmune disease caused by neuromuscular junction (NMJ) dysfunction. Our current understanding of MG's inflammatory component remains poor. The systemic inflammatory response index (SIRI) presents a promising yet unexplored biomarker for assessing MG severity. This study aimed to investigate the potential relationship between SIRI and MG disease severity. We conducted a retrospective analysis of clinical data from 171 MG patients admitted between January 2016 and June 2021. Patients with incomplete data, other autoimmune diseases, or comorbidities were excluded. Disease severity was evaluated using the Myasthenia Gravis Foundation of America (MGFA) classification and Myasthenia Gravis Activities of Daily Living (MG-ADL) on admission. The association between SIRI and disease severity was assessed through logistic regression analysis, along with receiver operating characteristic (ROC) curve and decision curve analysis (DCA) comparisons with established inflammation indicators. After exclusion, 143 patients were analyzed in our study. SIRI levels significantly differed between patients with higher and lower disease severity (p < 0.001). Univariate logistic regression showed that SIRI had a significant effect on high disease severity (OR = 1.376, 95% CI 1.138-1.664, p = 0.001). This association remained significant even after adjusting for age, sex, disease duration, history of MG medication and thymoma (OR = 1.308, 95% CI 1.072-1.597, p = 0.008). Additionally, a positive correlation between SIRI and MG-ADL was observed (r = 0.232, p = 0.008). Significant interactions were observed between SIRI and immunosuppressor (p interaction = 0.001) and intravenous immunoglobulin (p interaction = 0.005). DCA demonstrated the superior net clinical benefit of SIRI compared to other markers when the threshold probability was around 0.2. Our findings indicate a strong independent association between SIRI and disease severity in MG, suggesting SIRI's potential as a valuable biomarker for MG with superior clinical benefit to currently utilized markers.

Intravenous methylprednisolone therapy for ocular myasthenia gravis: A retrospective study

AbstractBackgroundAlthough intravenous methylprednisolone pulse (IVMP) therapy has been recommended for ocular myasthenia gravis (OMG), the evidence is limited.AimWe aimed to investigate the efficacy and safety of IVMP for OMG.MethodsThe patients with OMG were chosen retrospectively from May 2010 to December 2022. The therapeutic effects between IVMP‐treated and non‐IVMP‐treated groups were determined by ∆ocular quantitative MG (QMG) score and the ∆ocular MG activities of daily living profile (MG‐ADL) score, which is the disparities of the scores between before and after 1 month of drug administration; and Myasthenia Gravis Foundation of America post‐intervention status at 1, 3, 6, and 12 months.ResultsThere were 26 patients with OMG included, with the mean age of 67.2 ± 13.1 years. 13 of the 26 people with OMG received IVMP and subsequent low‐dose immunotherapies. The ∆ocular QMG and ∆ocular MG‐ADL scores were significantly higher in the IVMP group of 3 (1.5, 4) and 3 (2, 4.5) than in the non‐IVMP group of 1.5 (0, 3) and 1 (0, 2), p = 0.038 and p = 0.0027, respectively. The rates of minimal manifestation or better status in post‐intervention status at 1 and 12 months were also considerably higher in the IVMP group of 77% and 92% compared with the non‐IVMP group of 0% and 23%, p = 0.0001 and 0.001. There were no serious side effects discovered.ConclusionIVMP induction therapy can quickly and safely improve symptoms of OMG, and subsequent low‐dose immunotherapy can keep symptoms at bay for 12 months.

Juvenile Myasthenia Gravis in North Texas: Clinical Features, Treatment Response, and Outcomes

BackgroundJuvenile myasthenia gravis (JMG) is a rare autoimmune disease that causes fatigable muscle weakness in children aged <18 years. There is currently no curative treatment or internationally accepted standard of care for JMG. The objective is to investigate relationships between clinical presentation, antibody status, severity of disease onset, electrodiagnostic evaluation, and response to therapy in JMG. MethodsThis study was a retrospective chart review. Congenital myasthenic syndromes were excluded. Data on demographics, treatments, and outcomes were collected. Disease severity was evaluated using Myasthenia Gravis Foundation of America (MGFA) clinical classifications. ResultsWe identified 84 patients with JMG at Children's Medical Center Dallas between January 2014 and February 2022. It was found that 52% of patients presented with ocular JMG (median onset age 4.5 years) and 48% with generalized JMG (median onset age 11.5 years); 81% tested positive for acetylcholine receptor antibodies. Patients were 17% non-Hispanic white, 29% Hispanic, 39% black, and 12% Asian. There was a significant difference in average MGFA scores between ethnicities (P = 0.047) and age groups (P = 0.004), with postpubertal patients having higher average MGFA scores than prepubertal patients. Seventy-one percent of patients who underwent thymectomy experienced a decrease in MGFA scores postprocedure. ConclusionsOur study showed that there were significant differences in disease severity between ethnicities and age groups and that most patients who underwent thymectomy showed clinical improvement. These outcomes highlight the need for additional therapies in the treatment of JMG and the importance of extending clinical trials to the pediatric population.

Constructing and Validating a Nomogram Model for Short-Term Prognosis of Patients with AChR-Ab+ GMG.

This study aimed to establish and validate a nomogram prognostic model for predicting short-term efficacy of acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (GMG). A retrospective observational study was conducted at the First Hospital of Shanxi Medical University, enrolling patients diagnosed with AChR-Ab+ GMG from May 2020 to September 2022. The primary outcome was the change in the Myasthenia Gravis Foundation of America (MGFA) post-intervention status after 6months of standard treatment. Predictive factors were identified through univariate and multivariate logistic regression analyses, with significant factors incorporated into the nomogram. The bootstrap test was used for internal validation of the nomogram model. Model performance was assessed using calibration curves, receiver-operating characteristic curve analysis, and decision curve analysis (DCA). A total of 90 patients were enrolled, of whom 30 achieved unchanged or worse status after 6months of standard therapy. Univariate logistic regression analysis showed that quantitative myasthenia gravis score, gender, body mass index, course of disease, hemoglobin levels, and white blood cell counts were six potential predictors. These factors were used for multivariate logistic regression analysis, and a nomogram was constructed. The calibration curve showed that the predicted value was in good agreement with the actual value (p = 0.707), and the area under the curve value (0.792, 95% CI 0.686-0.899) indicated good discrimination ability. DCA suggests that this model has potential clinical application value. The constructed nomogram, based on key patient indicators, shows promise as a clinically useful tool for predicting the short-term efficacy of treatment of AChR-Ab+ GMG. Validation in larger, multicenter cohorts is needed to further substantiate its applicability.

Comparative effectiveness of azathioprine and mycophenolate mofetil for myasthenia gravis (PROMISE-MG): a prospective cohort study

Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. Treatment typically includes symptomatic oral cholinesterase inhibitors, immunosuppression, and immunomodulation. In addition to corticosteroids, azathioprine and mycophenolate mofetil are the most frequently used immunosuppressants in North America. We aimed to evaluate the comparative effectiveness of these two drugs, and to assess the effect of the dose and duration of treatment. We did a prospective cohort study at 19 academic centres in Canada and the USA. We included patients (aged ≥18 years) with autoimmune myasthenia gravis, who were never treated with immunosuppressants. Treating clinicians determined the choice of medication, dose, follow-up intervals, and drug monitoring. Outcome measures and adverse events were recorded at each visit. We assessed two co-primary outcomes. The first was the patient-reported Myasthenia Gravis-Quality of Life 15-revised (MGQOL-15r) score, measured as the mean change from treatment initiation to the follow-up visit with the lowest score. A clinically meaningful reduction (CMR) in MGQOL-15r was defined as a 5-point decrease. The second was a composite clinical outcome of disease improvement (Myasthenia Gravis Foundation of America Post-Intervention Status Minimal Manifestations or better) and low adverse event burden (defined as grade ≤1 Common Terminology Criteria for Adverse Events). We also compared these outcomes in patients receiving an adequate dose and duration of azathioprine (≥2 mg/kg per day for at least 12 months) or mycophenolate mofetil (≥2 g per day for at least 8 months) and a lower dose or shorter duration of these agents. We used propensity score weighting with generalised linear regression models. This study is registered with ClinicalTrials.gov (NCT03490539). Between May 1, 2018, and Aug 31, 2020, 167 patients were enrolled; 85 did not receive azathioprine or mycophenolate mofetil and were excluded. Four were excluded from outcome analyses because they had scores of 0 on an outcome measure at treatment initiation. Of the 78 patients included in analyses, 47 received mycophenolate mofetil (median follow-up 25 months [IQR 13·5-31·5]) and 31 received azathioprine (median follow-up 20 months [IQR 13-30]). The mean change in MG-QOL15r was -10·4 (95% CI -18·9 to -1·3) with mycophenolate mofetil and -6·8 (-17·2 to 3·6) with azathioprine (mean difference -3·3, 95% CI -7·7 to 1·2; p=0·15). 38 (81%) of 47 patients receiving mycophenolate mofetil and 18 (57%) of 31 receiving azathioprine had a CMR in MG-QOL15r (risk difference 24·0%; 95% CI -0·2 to 48·0; p=0·052). The clinical composite outcome was achieved in 22 (47·7%) of 47 patients who received mycophenolate mofetil and nine (28·1%) of 31 who received azathioprine (risk difference 19·6%, 95% CI -4·9 to 44·2; p=0·12). Descriptive analysis did not find a difference in the proportion of patients reaching a CMR in MG-QOL15r between the adequate dose and duration group and the lower dose or shorter duration group. Adverse events occurred in 11 (32%) of 34 patients who received azathioprine and nine (19%) of 48 who received mycophenolate mofetil. The most frequent adverse events were hepatotoxicity with azathioprine (five [15%] of 34) and gastrointestinal disturbances (seven [15%] of 48) with mycophenolate mofetil. There were no study-related deaths. More than half of patients treated with azathioprine and mycophenolate mofetil felt their quality of life improved; no difference in clinical outcomes was noted between the two drugs. Adverse events associated with azathioprine were potentially more serious than those with mycophenolate mofetil, although mycophenolate mofetil is teratogenic. Lower than recommended doses of azathioprine might be effective, with reduced dose-dependent adverse events. More comparative effectiveness studies are required to inform treatment choices in myasthenia gravis. Patient-Centered Outcomes Research Institute, Myasthenia Gravis Foundation of America.

A263 IRONING OUT THE DETAILS: CROHN’S DISEASE PATIENT DERIVED MACROPHAGES ARE MORE SUSCEPTIBLE TO FERROPTOSIS

Abstract Background Death of intestinal epithelial cells is ubiquitous in Crohn’s disease (CD) but the death of immune cells such as macrophages is less explored. We have found that monocyte derived macrophages from patients with active CD are more susceptible to H2O2-induced cytotoxicity but the form of regulated cell death these cells undergo remains to be elucidated. Selenium (Se)—a common micronutrient deficiency in patients with CD—is used in the synthesis of selenoproteins that have antioxidant properties (e.g., glutathione peroxidases (GPx)) and are highly expressed in macrophages. Whether Se deficiency plays a role in the increased cytotoxicity also remains to be elucidated. Aims To determine the form of cell death of macrophages in response to H2O2-induced cytotoxicity and whether selenium deficiency plays a role in the increased susceptibility to H2O2-induced cytotoxicity. Methods Blood collected from healthy volunteers and patients with active CD was analyzed for serum GPx activity. Monocytes isolated by plastic adherence were treated with M-CSF (10ng/ml, 7d) to derive macrophages. Macrophages were treated with H2O2 (500μm, 2h) and lactate dehydrogenase release was measured. GPX1, SLC7A11 and PTGS2 mRNA expression were determined by qPCR. The presence of cleaved caspase 3 was determined by immunoblotting and IL-1β by ELISA. Lipid peroxidation a marker of ferroptosis was assessed by staining macrophages with Bodipy C-11 (± liproxstatin-1, an inhibitor of ferroptosis). Results CD macrophages were two times more susceptible to H2O2-evoked cell death. In response to H2O2 macrophages did not express cleaved caspase 3 or IL-1β, but there was an induction of ferroptosis markers (SLC7A11 and PTGS2). Moreover, lipid peroxidation was induced and could be blocked with liproxstatin-1. Dietary Se intake did not differ between groups but serum GPx activity was greater in patients with CD compared to control. In contrast, GPX1 mRNA expression and GPx1 protein expression were decreased in CD macrophages compared to healthy controls. Conclusions Macrophages derived from patients with CD are inherently more sensitive to ferroptosis potentially through reduced GPx1 expression. Future studies warrant testing if GPx1 prevents ferroptotic macrophage cell death and if it holds therapeutic relevance in CD pathophysiology. Funding Agencies Helmsley Charitable Trust, Crohn's and Colitis Foundation of America