Diaphragmatic ultrasonography as a predictor of respiratory muscle fatigue in myasthenia gravis.

INTRODUCTION/AIMS: Easy fatigability, the clinical hallmark of generalized myasthenia gravis (GMG), cannot be detected in a dynamic way. The aim of this study was to assess respiratory function dynamically through diaphragmatic ultrasonography (DUS) in GMG patients. METHODS: GMG patients and controls were recruited in a 1:1 ratio. DUS was performed during one quiet breath and 15 consecutive deep breaths. The diaphragm thicknesses were measured at different positions. Diaphragm thickening fraction (TFdi) and the maximal change in diaphragm thickness (Tmax) during 15 consecutive deep breaths were calculated and transformed to normality, named N-TFdi and N-Tmax, respectively. The percentages of changes in TFdi and Tmax compared with baseline were named ΔTFdi and ΔTmax, respectively. The diagnostic parameter for respiratory muscle fatigue was chosen from ΔTFdi and ΔTmax at different deep breath times according to their ability to distinguish GMG patients from controls and the interrater reliability of TFdi and Tmax. RESULTS: Thirty-four GMG patients and 30 healthy controls were enrolled. N-TFdi and N-Tmax significantly changed as the number of deep breaths increased (p < .001) in GMG patients, but not in controls. ΔTmax of the 15th deep breath (ΔTmax15) was selected as the diagnostic parameter for respiratory muscle fatigue. There were no significant differences in percentage of predicted values of forced vital capacity and arterial partial pressure of carbon dioxide between patients with normal and abnormal ΔTmax15. DISCUSSION: DUS could identify diaphragm fatiguability in GMG patients, which may be more reliable and sensitive in assessment of diaphragm fatigue than conventional methods.

Efficacy of ravulizumab in patients with generalized myasthenia gravis by time from diagnosis: A post hoc subgroup analysis of the CHAMPION MG study.

INTRODUCTION/AIMS: The CHAMPION MG study demonstrated that ravulizumab significantly improved Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) total scores versus placebo in adults with acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ gMG). This post hoc analysis aimed to assess these outcomes by time from MG diagnosis. METHODS: Changes from baseline to week 26 in MG-ADL and QMG total scores were analyzed by time from MG diagnosis to study entry (≤2 vs. >2 years). Within each subgroup, least-squares (LS) mean changes for ravulizumab and placebo were compared using mixed models for repeated measures. RESULTS: In ravulizumab-treated patients, differences in LS mean (standard error of the mean) changes from baseline to week 26 were not statistically significant in the ≤2-years subgroup versus the >2-years subgroup for MG-ADL (-4.3 [0.70] vs. -2.9 [0.37]; p = .0511) or QMG (-4.3 [0.94] vs. -2.5 [0.50]; p = .0822) scores. No clear trends were observed in the placebo group. LS mean changes from baseline were significantly greater for ravulizumab versus placebo in both the ≤2 and >2 years from diagnosis subgroups for MG-ADL and QMG scores (all p < .05). The difference in treatment effect between the ≤2-years and >2-years subgroups was not statistically significant. No clinically meaningful between-subgroup differences in treatment-emergent adverse events were observed in ravulizumab-treated patients. DISCUSSION: Ravulizumab treatment improved clinical outcomes for patients with AChR+ gMG regardless of time from diagnosis. A numerical trend was observed favoring greater treatment effect with earlier versus later treatment after diagnosis. Further studies are required for confirmation.

Refocusing generalized myasthenia gravis: Patient burden, disease profiles, and the role of evolving therapy.

BACKGROUND AND PURPOSE: Generalized myasthenia gravis (gMG) continues to present significant challenges for clinical management due to an unpredictable disease course, frequent disease fluctuations, and varying response to therapy. The recent availability of new pharmacologic therapies presents a valuable opportunity to reevaluate how this disease is classified, assessed, and managed and identify new ways to improve the clinical care of patients with gMG. METHODS: Narrative review was made of publications identified via searches of PubMed and selected congresses (January 2000-September 2022). RESULTS: New consensus definitions are required to ensure consistency, to better characterize patients, and to identify patients who will benefit from specific drugs and earlier use of these agents. There is a need for more frequent, standardized patient assessment to identify the cause of motor function deficits, provide a clearer picture of the disease burden and its impact on daily living and quality of life (QoL), and better support treatment decision-making. Novel approaches that target different components of the immune system will play a role in more precise treatment of patients with gMG, alongside the development of new algorithms to guide individualized patient management. CONCLUSIONS: gMG has a physical, mental, and social impact, resulting in a considerable burden of disease and substantially decreased QoL, despite standard treatments. The availability of novel, targeted treatments that influence key pathological mediators of gMG, together with new biomarkers, offers the potential to optimize patient management and ultimately enables a greater number of patients to achieve minimal manifestation status and a reduced burden of disease.

Treatment of juvenile myasthenia gravis with tacrolimus: A cohort study.

BACKGROUND: We investigated the proper timing, efficacy and safety of tacrolimus for juvenile myasthenia gravis (JMG). METHODS: We conducted a retrospective cohort study for JMG patients treated with tacrolimus at Xiangya Hospital, Central South University, Changsha, China from 2010 to 2023. The clinical information of patients with a follow-up of more than 1 year was collected. Comparisons of clinical features between groups of patients who achieved therapeutic goal and those who did not achieve therapeutic goal as well as between groups of patients treated with tacrolimus within or after 1 year from JMG onset was carried out. RESULTS: Forty-three patients were enrolled, of whom 28 achieved therapeutic goal. Tacrolimus reduced glucocorticoids (GC) dosages for the 28 cases and 15 cases discontinued GC completely. Generalized myasthenia gravis (GMG) subtype had an association with a group of patients who achieved therapeutic goal (p = 0.001). Median duration from JMG onset to tacrolimus use was 10.50 months for those who achieved therapeutic goal and 36.00 months for those who did not achieve therapeutic goal (p = 0.010). The median Myasthenia Gravis Activities of Daily Living (MG-ADL) score improved significantly (p = 0.003). The initiation of tacrolimus within 1 year of JMG onset showed an association with achievement of therapeutic goal (p = 0.026). GMG subtype showed an association with a group of patients who received tacrolimus within 1 year (p = <0.001). Tacrolimus side effects were tolerable. CONCLUSION: The provision of tacrolimus within 1 year of JMG onset is effective and safe.

Effect of efgartigimod on muscle group subdomains in participants with generalized myasthenia gravis: post hoc analyses of the phase 3 pivotal ADAPT study.

BACKGROUND AND PURPOSE: Generalized myasthenia gravis (gMG) is a rare, chronic, neuromuscular autoimmune disease mediated by pathogenic immunoglobulin G (IgG) autoantibodies. Patients with gMG experience debilitating muscle weakness, resulting in impaired mobility, speech, swallowing, vision and respiratory function. Efgartigimod is a human IgG1 antibody Fc fragment engineered for increased binding affinity to neonatal Fc receptor. The neonatal Fc receptor blockade by efgartigimod competitively inhibits endogenous IgG binding, leading to decreased IgG recycling and increased degradation resulting in lower IgG concentration. METHODS: The safety and efficacy of efgartigimod were evaluated in the ADAPT study. Key efficacy outcome measures included Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. Efgartigimod demonstrated significant improvement in both the MG-ADL and QMG scores. This post hoc analysis aimed to determine whether all subdomains of MG-ADL and QMG improved with efgartigimod treatment. Individual items of MG-ADL and QMG were grouped into four subdomains: bulbar, ocular, limb/gross motor and respiratory. Change from baseline over 10 weeks in each subdomain was calculated for each group. RESULTS: Greater improvements from baseline were seen across MG-ADL subdomains in participants treated with efgartigimod compared with placebo. These improvements were typically observed 1 to 2 weeks after the first infusion and correlated with reductions in IgG. Similar results were observed across most QMG subdomains. CONCLUSIONS: These post hoc analyses of MG-ADL and QMG subdomain data from ADAPT suggest that efgartigimod is beneficial in improving muscle function and strength across all muscle groups, leading to the observed efficacy in participants with gMG.

Rozanolixizumab: A New Therapy in the Treatment of Myasthenia Gravis.

OBJECTIVE: The aims of this article are to review the clinical aspects of rozanolixizumab, to describe clinical trial results that led to the drug's approval, and to examine the impact on patient care to aid clinical decision making. DATA SOURCES: A PubMed search was conducted using the terms Rystiggo™, rozanolixizumab, rozanolixizumab therapy, and myasthenia gravis. The most recent prescribing information was also used for information relating to the drug and for identification of pertinent studies. STUDY SELECTION/DATA EXTRACTION: Phase I, II, and III randomized controlled trials were all eligible for inclusion. Meeting abstracts and articles focusing on the use of rozanolixizumab or any indication other than generalized myasthenia gravis were excluded from this article. DATA SYNTHESIS: Food and Drug Administration approval of rozanolixizumab is based on the phase III MycarinG study in patients with generalized myasthenia gravis. A phase II trial explored initial clinical efficacy and safety pertaining to the dose and frequency of rozanolixizumab across 2 treatment periods in patients with moderate to severe myasthenia gravis. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING AGENTS: Rozanolixizumab is the first therapy approved to treat patients positive for both types of antibodies, anti-acetylcholine receptor or anti-muscle-specific tyrosine kinase, in generalized myasthenia gravis. CONCLUSION/RELEVANCE: The approval of rozanolixizumab represents an advancement in therapy for generalized myasthenia gravis. The provision of individualized, targeted, and well-tolerated treatment is valuable for the patients whose myasthenia gravis is not well controlled and who are seeking a medication with a rapid onset of action to improve their symptoms and overall quality of life.

Therapeutic challenges and unmet needs in the management of myasthenia gravis: an Italian expert opinion.

Myasthenia gravis (MG) is a rare, autoimmune, neurological disorder. Most MG patients have autoantibodies against acetylcholine receptors (AChRs). Some have autoantibodies against muscle-specific tyrosine kinase (MuSK) or lipoprotein-receptor-related protein 4 (LRP4), and some are seronegative. Standard of care, which includes anti-cholinesterase drugs, thymectomy, corticosteroids (CS), and off-label use of non-steroidal immunosuppressive drugs (NSISTs), is bounded by potential side effects and limited efficacy in refractory generalized MG (gMG) patients. This highlights the need for new therapeutic approaches for MG. Eculizumab, a monoclonal antibody that inhibits the complement system, has been recently approved in Italy for refractory gMG. A panel of 11 experts met to discuss unmet therapeutic needs in the acute and chronic phases of the disease, as well as the standard of care for refractory patients. Survival was emphasized as an acute phase outcome. In the chronic phase, persistent remission and early recognition of exacerbations to prevent myasthenic crisis and respiratory failure were considered crucial. Refractory patients require treatments with fast onset of action, improved tolerability, and the ability to slow disease progression and increase life expectancy. The Panel agreed that eculizumab would presumably meet the therapeutic needs of many refractory gMG patients. The panel concluded that the unmet needs of current standard of care treatments for gMG are significant. Evaluating new therapeutic options accurately is essential to find the best balance between efficacy and tolerability for each patient. Collecting real-world data on novel molecules in routine clinical practice is necessary to address unmet needs.

Safety and outcomes with efgartigimod use for acetylcholine receptor-positive generalized myasthenia gravis in clinical practice.

INTRODUCTION/AIMS: Multiple novel therapies have been approved for patients with myasthenia gravis. Our aim is to describe the early experience of efgartigimod use in acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ve gMG). METHODS: This multicenter retrospective study included AChR+ve gMG patients from five major neuromuscular centers who were treated with efgartigimod and had both pre- and post-efgartigimod myasthenia gravis activities of daily living (MG-ADL) scores. Information regarding MG history, concomitant treatment(s), MG-ADL and other MG-specific measures, laboratory data, and adverse events were recorded. RESULTS: A total of 37 patients (M:23, F:14) with a mean age of 65.56 (±14.74) y were included in this cohort. A total of 36/37 patients completed at least one cycle and 28 patients completed at least two cycles of efgartigimod. A total of 72% (26/36) of patients had a clinically meaningful reduction (≥2 point change) in MG-ADL after the completion of the first cycle of efgartigimod (mean pre-efgartigimod 8.02) (±3.09) versus post-efgartigimod 4.33 (±3.62). Twenty-five percent (9/36) achieved minimal symptom expression status after one cycle and 25% (7/28) after the second cycle. Treatment benefit was sustained after cycle 2. Three out of four patients with thymoma in this cohort had clinically significant reductions in MG-ADL scores. Immunoglobulin G (IgG) levels decreased by about 60% (n = 10). One patient had a relapse of Clostridium difficile infection resulting in the discontinuation of therapy. Four patients had mild side effects. DISCUSSION: Efgartigimod led to clinically meaningful improvement in MG-ADL in diverse AChR+ve gMG patients but treatment frequency to achieve optimal symptom control needs to be explored.

Thymectomy in thymomatous generalized myasthenia gravis: An analysis of the prognosis and risk factors.

BACKGROUND AND PURPOSE: This study investigated the postthymectomy outcomes and factors affecting the prognosis of thymomatous generalized myasthenia gravis (TGMG). METHODS: Clinical records of 86 patients with TGMG who underwent thymectomy at our institution between 2012 and 2020 were retrospectively reviewed. Predictors of complete stable remission (CSR) and exacerbation were analyzed using multivariate regression analysis. RESULTS: A total of 16 patients achieved CSR, four achieved pharmacological remission, six exhibited deterioration, and eight died of myasthenia gravis (MG; mean follow-up = 75.1 months). Male sex (p = 0.049) and disease duration < 11.5 weeks before surgery (p = 0.003) were significant positive predictors of CSR. Onset age < 52.8 years and symptoms of ocular and limb muscle weakness had a higher CSR rate than onset age > 52.8 years (p = 0.056) and symptoms of bulbar muscles (p = 0.071). Female patients had a significant higher risk of exacerbation (p = 0.042). CONCLUSIONS: Male sex and disease duration < 11.5 weeks were independent predictors of CSR in TGMG postthymectomy. Onset age < 52.8 years and ocular and limb muscle weakness at onset were associated with a higher probability of achieving CSR than onset age > 52.8 years and bulbar muscle weakness. Female sex was an independent predictor of MG symptom exacerbation in TGMG postthymectomy.

Increased serum IL-2, IL-4, IL-5 and IL-12p70 levels in AChR subtype generalized myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions. Cytokines play important roles in facilitating the immune response and augmenting the pathogenic antibody production. The current study aims to sensitively characterize the serum levels of cytokines with very low concentration in generalized MG (gMG). METHODS: Using ultrasensitive single-molecule arrays (SIMOA), we measured serum IL-2, IL-4, IL-5 and IL-12p70 in 228 participants including 152 immunotherapy-naïve anti-acetylcholine receptor (AChR) subtype gMG from Huashan MG registry and 76 age-matched healthy controls. Subgroup analysis was then performed by stratifying patients according to the onset ages, MGFA classification, disease duration at baseline. RESULTS: Serum IL-2, IL-4, IL-5 and IL-12p70 levels were significantly elevated in gMG compared to controls (0.179 pg/mL versus 0.011 pg/mL, P < 0.0001; 0.029 pg/mL versus 0.018 pg/mL, P = 0.0259; 0.215 pg/mL versus 0.143 pg/mL, P = 0.0007; 0.132 pg/mL versus 0.118 pg/mL, P = 0.0401). Subgroup analysis revealed that IL-2 levels were slightly elevated in gMG with MGFA II compared to MGFA III/IV (0.195 pg/mL versus 0.160 pg/mL, P = 0.022), as well as elevated levels of IL-2 (0.220 pg/mL versus 0.159 pg/mL, P = 0.0002) and IL-5 (0.251 pg/mL versus 0.181 pg/mL, P = 0.004) in late-onset gMG compared with the early-onset gMG. gMG patients with a long duration had a significant increased serum IL-12p70 than those with a short duration (0.163 pg/mL versus 0.120 pg/mL, P = 0.011). CONCLUSION: Serum IL-2, IL-4, IL-5 and IL-12p70 levels were increased in AChR subtype gMG using ultrasensitive measurement. Serum cytokines with very low concentrations may provide as potential biomarkers in stratifying gMG patients in future prospective cohort studies.

Association of immunosuppression treatment with generalization among patients with ocular myasthenia gravis: A propensity score analysis.

BACKGROUND: To analyze disease generalization in patients with ocular myasthenia gravis (OMG) treated with immunosuppression compared with patients without immunosuppression treatment. METHODS: In this retrospective cohort study, we analyzed data from patients with OMG at seven medical centers in China from January 1, 2015 to May 1, 2019 and compared disease generalization in patients (treated with immunosuppression vs. not treated) within 2 years of disease onset using raw and inverse probability of treatment weighting (IPTW) analyses. RESULTS: In the study population of 813 patients with OMG, 425 (52.3%) with immunosuppression had a mean (SD) onset age of 50.0 (15.1) years, and 188 (44.2%) were women. The remaining 388 (47.7%) patients were not immunosuppressed (mean age, 48.4 [15.0] years; 185 [47.7%] women). Disease generalization developed in 122 (31.4%) and 37 (8.7%) patients in the non-immunosuppression and immunosuppression groups, respectively. Relative to non-immunosuppression, immunosuppression was associated with a lower risk of generalization in a multivariable-adjusted Cox model (hazard ratio [HR] 0.27; 95% confidence interval [CI] 0.18-0.40; p < 0.001) and IPTW-weighted Cox model (HR 0.28; 95% CI 0.19-0.42; p < 0.001). In sensitivity analyses, longer duration of immunosuppression was associated with a lower risk of generalization (HR 0.90 for every 1-month increase; 95% CI 0.87-0.92; p < 0.001; IPTW-adjusted). Combination therapy with steroids and non-steroidal immunosuppressants showed superior efficacy in reducing the risk of generalization (HR 0.14; 95% CI 0.07-0.26; p < 0.001). CONCLUSION: Immunosuppression significantly reduced the 2-year risk of generalization in patients with OMG.

Nomogram for short-term outcome assessment in AChR subtype generalized myasthenia gravis.

BACKGROUND: An accurate prediction for prognosis can help in guiding the therapeutic options and optimizing the trial design for generalized myasthenia gravis (gMG). We aimed to develop and validate a predictive nomogram to assess the short-term outcome in patients with the anti-acetylcholine receptor (AChR) subtype gMG. METHODS: We retrospectively reviewed 165 patients with AChR subtype gMG who were immunotherapy naïve at the first visit from five tertiary centers in China. The short-term clinical outcome is defined as the achievement of minimal symptom expression (MSE) at 12 months. Of them, 120 gMG patients from Huashan Hospital were enrolled to form a derivation cohort (n = 96) and a temporal validation cohort (n = 24) for the nomogram. Then, this nomogram was externally validated using 45 immunotherapy naïve AChR subtype gMG from the other four hospitals. Multivariate logistic regression was used to screen independent factors and construct the nomogram. RESULTS: MSE was achieved in 70 (72.9%), 20 (83.3%), and 33 (73.3%) patients in the training, temporal validation, and external validation cohort, respectively. The duration ≤ 12 months (p = 0.021), ocular score ≤ 2 (p = 0.006), QMG score > 13 (p = 0.008), and gross motor score ≤ 9 (p = 0.006) were statistically associated with MSE in AChR subtype gMG. The nomogram has good performance in predicting MSE as the concordance indexes are 0.81 (95% CI, 0.72-0.90) in the development cohort, 0.944 (95% CI, 0.83-1.00) in the temporal validation cohort, and 0.773 (95% CI, 0.63-0.92) in the external validation cohort. CONCLUSION: The nomogram achieved an optimal prediction of MSE in AChR subtype gMG patients using the baseline clinical characters.

Risk Factors for Postoperative Myasthenic Crisis After Thymectomy in Patients With Myasthenia Gravis.

BACKGROUND: The objective of this study is to characterize postoperative myasthenic crisis (POMC), after extended thymectomy and discuss the treatment options for this condition. METHODS: Clinical data from patients with generalized myasthenia gravis (MG) who underwent extended thymectomy at Xuanwu Hospital of the Capital Medical University from 2016 to 2018 were reviewed retrospectively. Patients were divided into two groups-POMC and non-POMC. Variables that could potentially predict POMC were analyzed. In the POMC group, the aforementioned variables were compared between patients with and without pneumonia. RESULTS: Ninety-seven patients were enrolled. Thirty-eight (39.2%) patients developed POMC. The mean duration of mechanical ventilation (MV), length of intensive care unit stay, and duration of hospital stay were significantly longer in the POMC group (P < 0.001). Multivariate logistic regression analysis showed that disease severity, symptom duration longer than 12 mo, and transsternal thymectomy were independent risk factors for POMC. Postoperative pneumonia significantly prolonged the MV period (P = 0.012) and weaning from MV after intravenous immunoglobin (IVIg) treatment (P = 0.005) in POMC patients. Twenty-four (24.7%) POMC patients who received IVIg were successfully weaned from MV and were discharged. CONCLUSIONS: Disease severity, symptom duration longer than 12 mo, and transsternal thymectomy were independent risk factors for POMC. Postoperative pneumonia worsens the prognosis of POMC.

Real-World experience with efgartigimod in patients with myasthenia gravis.

Recommendations for the treatment of myasthenia gravis (MG) have been difficult to develop because of limited evidence from large randomized controlled trials. New drugs and treatment approaches have recently been shown to be effective in phase 3 studies in seropositive generalized (g) MG. One such drug is efgartigimod, a human-Fc-fragment of IgG1, with a high affinity for the endosomal FcRn. We conducted a multicenter study to evaluate the real-world clinical and safety effects of efgartigimod in 22 gMG patients. We evaluated the strategies for the timing of re-treatment with it. The participants received a total of 59 efgartigimod -treatment cycles. The median number of cycles was 2 (range 1-6). Twenty patients (86.3%) improved by at least 2 MG-ADL points after the first treatment cycle. The median MG-ADL score at baseline was 6.5 (range: 3-17) and 2.5 (range: 0-9) post-treatment (p < 0.001). A consistent improvement of at least 2 points in the MG-ADL score after each cycle occurs in 18 patients. The effect duration of the treatment was usually between 4 and 12 weeks. Two major clinical patterns of treatment response were found. Treatment with efgartigimod was also associated with significant reductions of prednisone doses Overall, the treatment was safe and associated with only minor adverse events. The single fatality was apparently due tosevere respiratory failure. We found that efgartigimod is clinically effective, may be used as a steroid sparing agent and is generally safe for gMG patients. We recommend a personalized preventive treatment approach until clinical stabilization, followed by discontinuation and periodic evaluations.

Ravulizumab use for acetylcholine receptor-positive generalized myasthenia gravis in clinical practice.

Purpose: To describe the early experience of ravulizumab use in acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ve gMG). Methods: This multicenter retrospective study included AChR+ve gMG patients who were treated with ravulizumab and had both pre- and post-ravulizumab myasthenia gravis activities of daily living (MG-ADL) scores. Clinical information regarding MG history, concomitant treatment(s), MG-ADL, other MG-specific measures, and adverse events were recorded. Results: A total of 18 patients with mean age of 61.83 (±16.08, n = 18) years were included in this cohort. In 10 complement inhibitor naive patients, a clinically meaningful reduction in mean Mg-ADL (baseline: 6.6 (±3.58) vs. 4.4 (±2.28), post ravulizumab) was seen. 6 out of 10 patients (60%) had clinically meaningful reduction post ravulizumab and two achieved minimum symptom expression (MSE). In 8 patients switched from eculizumab to ravulizumab, further reduction was noted in post ravulizumab mean MG-ADL (Baseline: 3.25 (±3.34) vs. 1.5 (±2.34) post ravulizumab). None of the patients who switched from eculizumab to ravulizumab experienced worsening symptoms. Eleven out of 14 (78.5%) patients on prednisone therapy were able to reduce their prednisone dose post-ravulizumab. None of the patients experienced any major side effects. Conclusion: In our clinical practice, 60% of AChR+ve gMG complement inhibitor naive patients experienced a clinically meaningful improvement in MG-ADL scores with ravulizumab. Patients were safely switched from eculizumab to ravulizumab and had further improvement in their mean MG-ADL scores. Of those on prednisone therapy, the majority were able to reduce their prednisone dosage.

Efficacy and safety of tocilizumab in patients with refractory generalized myasthenia gravis.

BACKGROUND: We aimed to compare the efficacy of tocilizumab with conventional immunotherapy in refractory patients with acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). METHODS: This single-center prospective cohort study was based on patients from an MG registry study in China and conducted from February 10, 2021 to March 31, 2022. Adult refractory patients with AChR-Ab+ gMG were assigned to tocilizumab or conventional immunotherapy groups. The primary efficacy outcome was the mean difference of MG activities of daily living (MG-ADL) change at weeks 4, 8, 12, 16, 20, 24 corresponding to that at the baseline between the two groups. A generalized estimating equation model was used for the primary outcome analysis. Safety was assessed based on adverse events. RESULTS: Of 34 eligible patients, 20 (mean [standard deviation] age, 53.8 [21.9] years; 12 [60.0%] female) received tocilizumab and 14 received conventional immunotherapy (45.8 [18.0] years; 8 [57.1%] female). The tocilizumab group had greater reduction in MG-ADL score at week 4 (adjusted mean difference, -3.4; 95% CI, -4.7 to -2.0; p < 0.001) than the conventional immunotherapy group, with significant differences sustained through week 24 (adjusted mean difference, -4.5; 95% CI, -6.4 to -2.6; p < 0.001). At week 24, the proportion of patients achieving higher levels of MG-ADL (up to 7-point reduction) and QMG (up to 11-point reduction) scores improvement was significantly greater with tocilizumab. Tocilizumab had acceptable safety profiles without severe or unexpected safety issues. CONCLUSION: Tocilizumab is safe and effective in improving the MG-ADL score and reducing prednisone dose in refractory AChR-Ab+ gMG, suggesting tocilizumab has the potential to be a valuable therapeutic option for such patients.

Economic burden of generalized myasthenia gravis (MG) in the United States and the impact of common comorbidities and acute MG-events.

BACKGROUND: This study assessed the incremental healthcare costs and resource utilization (HRU) associated with generalized myasthenia gravis (gMG), as well as variability in these outcomes among patients with gMG and common comorbidities and acute MG-related events. METHODS: Adults with gMG and without MG were identified from a large US database (2017-2021). The index date was the first MG diagnosis (gMG cohort) or random date (non-MG cohort). Cohorts were propensity score matched 1:1. The gMG cohort included subgroups of patients with a 12-month pre-index (baseline) cardiometabolic or psychiatric comorbidity, or a post-index MG exacerbation/crisis. Monthly healthcare costs (2021 USD) and HRU were compared post-index between gMG and non-MG cohorts. RESULTS: The gMG and matched non-MG cohorts each contained 2,739 patients. Mean incremental healthcare costs associated with MG were $4,155 (gMG: $5,567; non-MG: $1,411), with differences driven by incremental inpatient costs of $2,166 (gMG: $2,617; non-MG: $452); all p < 0.001. The gMG versus non-MG cohort had 4.36 times more inpatient admissions and 2.26 times more outpatient visits; all p < 0.001. Among patients with gMG in cardiometabolic (n = 1,859), psychiatric (n = 1,308), and exacerbation/crisis (n = 419) subgroups, mean monthly healthcare costs were $6,660, $7,443, and $17,330, respectively. CONCLUSIONS: gMG is associated with substantial incremental costs and HRU, with inpatient costs driving the total incremental costs. Costs increased by 20% and 34% among patients with cardiometabolic and psychiatric conditions, respectively, and over three times among those with acute MG-related events. gMG is a complex disease requiring management of comorbidities and treatment options that can prevent acute symptomatic events.

Generalized myasthenia gravis (gMG) is a rare long-standing condition that affects the junctions between nerves and muscles, causing them to be weak. In a serious case, the diaphragm ­ a muscle that helps with breathing ­ becomes so weak that a patient will need a machine to breathe for them. This is called MG exacerbation or crisis. In this study, we used a large insurance database in the United States to look at how much money healthcare payers paid for gMG patients on average and what healthcare resources patients with gMG used. We compared these findings with patients without gMG. Also, among patients with gMG, we reported these findings specifically for patients who also had heart, blood, or blood vessel disease; patients who had a mental illness; and patients who had MG exacerbation or crisis later on. We found that patients with gMG used $5,567 per month on average ($4,155 more than patients without gMG), mostly from overnight hospital stays. Patients with gMG also had four times more overnight hospital stays and two times more hospital day visits when we compared them to patients without gMG. Patients with gMG and other health conditions used even more money and resources per month. Patients with MG exacerbation or crisis used $17,330 per month on average. Our results showed that gMG led to higher healthcare cost and resource use. In order to reduce cost and resources, doctors also need to control for other health conditions as they treat patients with gMG, and to prevent patients from having MG exacerbation or crisis later on.

Eculizumab in Adolescent Patients With Refractory Generalized Myasthenia Gravis: A Phase 3, Open-Label, Multicenter Study.

BACKGROUND: This study evaluated the efficacy and safety of eculizumab, a terminal complement C5 inhibitor, in juvenile generalized myasthenia gravis (gMG). METHODS: Adolescents aged 12 to 17 years with refractory anti-acetylcholine receptor (AChR) antibody-positive gMG received eculizumab (weekly induction [one to two doses of 600 mg or four doses of 900 mg] followed by maintenance doses [300 to 1200 mg] every two weeks for up to 26 weeks) in a phase 3, open-label multicenter study (NCT03759366). Change from baseline to week 26 in Quantitative Myasthenia Gravis (QMG) total score (primary end point) and secondary end points including Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score, Myasthenia Gravis Composite score, Myasthenia Gravis Foundation of America postintervention status, EuroQol 5-Dimensions (Youth) and Neurological Quality-of-Life Pediatric Fatigue questionnaire scores, as well as pharmacokinetics, pharmacodynamics, and safety, were recorded. RESULTS: Eleven adolescents (mean ± S.D. age 14.8 ± 1.8 years) were enrolled; 10 completed the primary evaluation period. Least-squares mean changes from baseline at week 26 were -5.8 (standard error [SE] 1.2; P = 0.0004) for QMG total score and -2.3 (SE 0.6; P = 0.0017) for MG-ADL total score. Overall, the primary and all secondary efficacy end point analyses met statistical significance from the first assessment and were sustained throughout. Complete terminal complement inhibition was sustained through 26 weeks in all patients. Treatment-emergent adverse events were all mild/moderate and predominantly unrelated to eculizumab. CONCLUSIONS: Eculizumab was effective in reducing disease burden and was well tolerated in adolescents with refractory AChR antibody-positive gMG.

Prospective cohort study evaluating efficacy and safety of efgartigimod in Chinese generalized myasthenia gravis patients.

Background: Despite the efficacy of efgartigimod demonstrated in ADAPT phase 3 trial, data specifically derived from Chinese participants are not available. Therefore, we aimed to evaluate the efficacy and safety of efgartigimod in Chinese patients with generalized myasthenia gravis (gMG). Methods: This is a prospective cohort study conducted in 8 hospitals across China. gMG patients received weekly intravenous infusions of efgartigimod (10 mg/kg) under a named patient program (NPP). The present study is an 8-week study, consisting of 4 consecutive doses of efgartigimod administered over 3 weeks (one cycle), followed by a 5-week follow-up period to assess the tolerability of efgartigimod's therapeutic effects. The primary outcome was the mean change in MG activities of daily living (MG-ADL) total score from baseline to 4 weeks. MG-ADL responder was defined as a ≥ 2-point improvement that persisted for 4 weeks, starting by week 4. Safety evaluations encompassed the monitoring of adverse events (AE) and serious AE (SAE) throughout the study. Results: Between 5 July 2022 and 25 August 2023, a total of 14 gMG patients were included. The mean age was 57.7 years, with a mean MG-ADL score of 10.86 ± 3.32. At week 4, MG-ADL scores showed a mean reduction of 6 points, reaching a maximum decline of 13 points. Among the patients, 85.7% (12/14) achieved MG-ADL responder status after one cycle of treatment. The most significant reduction in quantitative MG (QMG) scores also occurred at week 4, with a mean decrease of 7 points. Notably, the improvements in MG-ADL and QMG scores persisted until week 8. During treatment and follow-up period, only two mild neck rashes occurred and resolved promptly. No infections or SAE were reported. Discussion: A single cycle of efgartigimod treatment demonstrates effectiveness and the tolerability through week 8, with no new safety signals observed in Chinese gMG patients.

Effectiveness and safety of telitacicept for refractory generalized myasthenia gravis: a retrospective study.

Background: Refractory generalized myasthenia gravis (GMG) remains a substantial therapeutic challenge. Telitacicept, a recombinant human B-lymphocyte stimulator receptor-antibody fusion protein, holds promise for interrupting the immunopathology of this condition. Objectives: This study retrospectively assessed the effectiveness and safety of telitacicept in patients with refractory GMG. Design: A single-center retrospective study. Methods: Patients with refractory GMG receiving telitacicept (160 mg/week or biweekly) from January to September in 2023 were included. We assessed effectiveness using Myasthenia Gravis Foundation of America post-intervention status (MGFA-PIS), myasthenia gravis treatment status and intensity (MGSTI), quantitative myasthenia gravis (QMG), and MG-activity of daily living (ADL) scores, alongside reductions in prednisone dosage at 3- and 6-month intervals. Safety profiles were also evaluated. Results: Sixteen patients with MGFA class II-V refractory GMG were included, with eight females and eight males. All patients were followed up for at least 3 months, and 11 patients reached 6 months follow-up. At the 3-month evaluation, 75% (12/16) demonstrated clinical improvement with MGFA-PIS. One patient achieved pharmacological remission, two attained minimal manifestation status, and nine showed functional improvement; three remained unchanged, and one deteriorated. By the 6-month visit, 90.1% (10/11) sustained significant symptomatic improvement. MGSTI scores and prednisone dosages significantly reduced at both follow-ups (p < 0.05). MG-ADL and QMG scores showed marked improvement at 6 months (p < 0.05). The treatment was well tolerated, with no severe adverse events such as allergy or infection reported. Conclusion: Our exploratory investigation suggests that telitacicept is a feasible and well-tolerated add-on therapy for refractory GMG, offering valuable clinical evidence for this novel treatment option.