Quantitative Myasthenia Gravis Research Articles

Long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis: results from the phase 3 CHAMPION MG open-label extension

IntroductionRavulizumab demonstrated efficacy and an acceptable safety profile versus placebo in the randomized controlled period (RCP) of the phase 3 CHAMPION MG trial in patients with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. We report an interim analysis of the ongoing open-label extension (OLE) designed to evaluate long-term treatment effects.MethodsFollowing completion of the 26-week RCP, patients could enter the OLE; patients who received ravulizumab in the RCP continued the drug; patients who previously received placebo switched to ravulizumab. Patients receive body-weight-based maintenance dosing of ravulizumab every 8 weeks. Efficacy endpoints up to 60 weeks included Myasthenia Gravis–Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores, with least-squares (LS) mean change and 95% confidence intervals (95% CI) reported.ResultsLong-term efficacy and safety in the OLE were analyzed in 161 and 169 patients, respectively. Improvements in all scores were maintained through 60 weeks in patients who received ravulizumab during the RCP; LS mean change from RCP baseline in MG-ADL score was − 4.0 (95% CI: − 4.8, − 3.1; p < 0.0001). Rapid (within 2 weeks) and sustained improvements occurred in patients previously receiving placebo; LS mean change in MG-ADL score from OLE baseline to Week 60 was − 1.7 (95% CI: − 2.7, − 0.8; p = 0.0007). Similar trends were seen in QMG scores. Ravulizumab treatment was associated with a decreased rate of clinical deterioration events compared with placebo. Ravulizumab was well tolerated; no meningococcal infections were reported.ConclusionFindings support the sustained efficacy and long-term safety of ravulizumab, administered every 8 weeks, in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis.ClinicalTrials.gov identifier: NCT03920293; EudraCT: 2018-003243-39.

Long-Term Safety, Tolerability, And Efficacy of Efgartigimod in Patients with Generalized Myasthenia Gravis: Concluding Analyses from the ADAPT+ Study (S5.006)

Long-Term Safety, Tolerability, And Efficacy of Efgartigimod in Patients with Generalized Myasthenia Gravis: Concluding Analyses from the ADAPT+ Study (S5.006)

Efgartigimod Demonstrates Consistent Improvements in Generalized Myasthenia Gravis Patients of Shorter Disease Duration (P1-5.015)

Efgartigimod Demonstrates Consistent Improvements in Generalized Myasthenia Gravis Patients of Shorter Disease Duration (P1-5.015)

BioDigit MG: A Pilot Study Examining a Digital Technology for Quantitative Assessment and Remote Monitoring of Myasthenia Gravis (P7-8.005)

<h3>Objective:</h3> To develop a standardized, clinically-validated digital solution for rigorous, longitudinal assessment of ocular weakness and dysarthria in myasthenia gravis (MG), which can be applied remotely. <h3>Background:</h3> MG is a chronic autoimmune neuromuscular disease characterized by fluctuating weakness of skeletal muscle, which frequent affects ocular muscles and speech. Current assessments of myasthenic weakness require neurologic expertise, are time-consuming and can still be subjective. Additionally, measured at one point in time, assessments provide a snapshot of a patient’s MG, which may not adequately reflect the spectrum of fluctuating weakness. Ratings of ocular weakness and dysarthria are particularly subjective. These shortcomings of current outcome measures limit performance of clinical trials and provide a limited view of the patient’s clinical status. <h3>Design/Methods:</h3> We developed a tablet-based digital health solution that captures video data collected by patients and MG-specific patient-reported outcome measures. Ptosis and dysarthria are rated asynchronously. The tablet provides text instruction and audio prompts to the patient and data are uploaded to a cloud. Predetermined measures of success have been defined. <h3>Results:</h3> A pilot study with a target sample size of 20 individuals with MG is ongoing to determine the feasibility of using the proposed solution as a health monitoring platform for MG. Two MG experts will rate speech and video data for dysarthria and ptosis based on the Quantitative Myasthenia Gravis (QMG) scale. Association between the extracted speech and facial characteristics to clinical scores of dysarthria and ptosis will be investigated. <h3>Conclusions:</h3> Despite considerable recent advances in treatments for MG, rigorous, longitudinal tools for monitoring of its characteristic fluctuating weakness remain limited and represent an unmet need. The feasibility, validity and acceptability of the proposed digital solution will be determined for 20 patients with MG. If successful, this technology will be further developed and studied in a larger observational study. <b>Disclosure:</b> An immediate family member of Dr. Guidon has received personal compensation for serving as an employee of GE Healthcare. Dr. Guidon has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Guidon has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Momenta. Dr. Guidon has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. The institution of Dr. Guidon has received research support from MGFA. The institution of Dr. Guidon has received research support from Project Data Sphere. The institution of Dr. Guidon has received research support from MGNet. The institution of Dr. Guidon has received research support from MGNet. Dr. Guidon has received publishing royalties from a publication relating to health care. Dr. Mishra has received personal compensation for serving as an employee of Biosensics. Miss Lindsay has nothing to disclose. Mr. Mulukutla has received personal compensation for serving as an employee of BioSensics LLC. Dr. Vaziri has received personal compensation for serving as an employee of Biosensics.

A Phase 3, Open-Label, Multicenter Study To Evaluate Eculizumab In Adolescents With Refractory Generalized Myasthenia Gravis (S5.009)

A Phase 3, Open-Label, Multicenter Study To Evaluate Eculizumab In Adolescents With Refractory Generalized Myasthenia Gravis (S5.009)

Identifying Digital Biomarkers for the Self-Monitoring of Patients Living with Generalized Myasthenia gravis: a Proof of Concept (P7-8.007)

<h3>Objective:</h3> To identify clinically meaningful digital biomarkers (dBMKs) intended to track symptoms and signs among people living with generalized myasthenia gravis (gMG) and to prepare the development of a software medical device for the patients’ unsupervised digital self-assessment. <h3>Background:</h3> Generalized myasthenia gravis (gMG) is characterized by fluctuating manifestations and heterogeneity in fatigue and muscle group weakness. Literature pinpoints a lack of objective measurement tools for the self-assessment of gMG symptoms outside office visits, resulting in different perceptions between physicians and patients on the impact of the disease. <h3>Design/Methods:</h3> We used a Double Diamond methodology to identify dBMKs of interest for gMG patients and evaluate their relevance for clinicians through qualitative interviews. Unmet needs and dBMKs concepts were prioritized during a technical Proof-of-Concept (PoC) study. The acceptability of the digital device was assessed with prototype-supported interviews. <h3>Results:</h3> Interviews with 27 patients (France, USA) confirmed the feasibility of dBMKs to measure gMG-related neurological functions. All were interested in tracking symptoms. 9 international MG experts were interested in assessing gMG symptomology between office visits with clinically meaningful dBMKs. A PoC study on healthy subjects, performed under different conditions, confirmed the feasibility of analyzing raw data collected by the smartphone’s sensors. 5 digital active measures inspired by clinical gold standards and relying on the smartphone’s sensors were selected with their related dBMKs (ptosis, breathing, dysarthria, upper and lower extremities functions). Patient-reported outcome measures (daily activities, pain, sleep, depression, quality of life) will be incorporated as e-questionnaires. <h3>Conclusions:</h3> We perceived a need for an unsupervised patient self-assessment digital solution to monitor symptomatology outside office visits. In 2023, development of ME&amp;MG, a smartphone solution, will begin. It aims to inform and improve communication between patients and their care teams. International multicenter studies comparing ME&amp;MG to clinical gold standards including the Quantitative Myasthenia Gravis score, will be deployed. <b>Disclosure:</b> Pascal Laforet has nothing to disclose. David Orlikowski has nothing to disclose. Prof. NICOLAS has nothing to disclose. The institution of Prof. Prigent has received research support from VLM - Patients association for lysosomial diseases. The institution of Prof. Prigent has received research support from ADEP Assitance. Dr. Berling has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Adscientiam. Dr. Berling has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Ghislain N’Dah-Sekou has nothing to disclose. Dr. Gorin has received personal compensation for serving as an employee of Ad Scientiam. Dr. Moreira has received personal compensation for serving as an employee of Ad Scientiam. Mrs. Narcy has received personal compensation for serving as an employee of Ad Scientiam. Dr. Plaud has received personal compensation for serving as an employee of Ad Scientiam. Mrs. Touré Cuq has received personal compensation for serving as an employee of Ad Scientiam . Dr. Keller has received personal compensation for serving as an employee of Alexion. Dr. Keller has stock in Alexion, Roche, Novartis, Celgene, Abbvie, Merck, Ionis, Sanofie, Organon, MSD. Mr. Werneburg has received personal compensation for serving as an employee of Alexion. Dr. Aras has received personal compensation for serving as an employee of Alexion Pharmaceuticals Inc. Dr. Benatar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Dr. Benatar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arrowhead. Dr. Benatar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Annexon. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UniQure. Dr. Benatar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Immunovant. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Benatar has received intellectual property interests from a discovery or technology relating to health care. Dr. Benatar has received intellectual property interests from a discovery or technology relating to health care.

The relationship of cognitive impairment and clinical manifestations of myasthenia gravis

BACKGROUND. There are many studies in the literature suggesting that cognitive impairment is more pronounced in patients with myasthenia gravis compared with healthy people, but there is no explanation of the reasons and mechanisms. However, the reverse character the influence of intellectual-mnestic disorders on the course of myasthenia gravis has not been studied enough.&#x0D; AIM. To compare clinical, anamnestiс, laboratory and instrumental data in patients with myasthenia gravis according to the presence or absence of cognitive impairment.&#x0D; MATERIAL AND METHODS. 61 patients with a confirmed diagnosis of myasthenia gravis were divided into 2 groups according to the Montreal cognitive test. Patients scoring 25 or less were assigned to the first group, those scoring 26 points or more to the second group.&#x0D; A comparative assessment was made according to the myasthenia gravis impairment index, age of onset, duration of the disease, duration of hospitalization, severity of myasthenia gravis according to clinical scales, body mass index, electroneuromyography data, levels of antibodies to the acetylcholine receptor and skeletal muscles, and daily doses of the drugs received.&#x0D; RESULTS. In the 1st group, there was a significantly higher score on the Generalised Disorders subscale of the Myasthenia Gravis Impairment Index; the severity of Quantitative myasthenia gravis score was significantly higher in the 1st group than in the 2nd both for the total score and for the Musculoskeletal Lesions subscale. On average, 49 mg more pyridostigmine bromide was required in the first group, while the average body mass index was significantly lower in the first group.&#x0D; CONCLUSION. The presence of a cognitive deficit in patients with myasthenia gravis may worsen the clinical picture of the disease, which should be taken into account by clinicians, especially in elderly patients, who are at increased risk of developing cognitive disorders.

Addressing Outcome Measure Variability in Myasthenia Gravis Clinical Trials.

An increasing number of clinical trials are enrolling patients with myasthenia gravis (MG). A lack of standardization in the performance of outcome measures leads to confusion among site research teams and is a source of variability in clinical trial data. MGNet, the NIH-supported Rare Disease Clinical Research Network for MG, views standardization of MG outcome measures as a critical need. To address this issue, a group of experts summarized key outcome measures used in MG clinical trials and a symposium was convened to address issues contributing to outcome measure variability. Consensus recommendations resulted in changes to outcome measure instructions and, in some cases, modifications to specific instruments. Recommended changes were posted for public commentary before finalization. Changes to the MG-Activities of Daily Living, MG-Quality of Life-15r, and MG-Impairment Index were limited to adding details to the administration instructions. Recommendations for proper positioning of participants and how to score items that could not be performed because of non-MG reasons were provided for the MG Composite. The Quantitative MG (QMG) score required the most attention, and changes were made both to the instructions and the performance of certain items resulting in the QMG-Revised. The Postintervention Status was believed to have a limited role in clinical trials, except for the concept of minimal manifestation status. As a next step, training materials and revised source documents, which will be freely available to study teams, will be created and posted on the MGNet website. Further studies are needed to validate changes made to the QMG-Revised.

Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study

Generalised myasthenia gravis is a chronic, unpredictable, and debilitating rare disease, often accompanied by high treatment burden and with an unmet need for more efficacious and well tolerated treatments. Zilucoplan is a subcutaneous, self-administered macrocyclic peptide complement C5 inhibitor. We aimed to assess safety, efficacy, and tolerability of zilucoplan in patients with acetylcholine receptor autoantibody (AChR)-positive generalised myasthenia gravis. RAISE was a randomised, double-blind, placebo-controlled, phase 3 trial that was done at 75 sites in Europe, Japan, and North America. We enrolled patients (aged 18-74 years) with AChR-positive generalised myasthenia gravis (Myasthenia Gravis Foundation of America disease class II-IV), a myasthenia gravis activities of daily living (MG-ADL) score of least 6, and a quantitative myasthenia gravis score of at least 12. Participants were randomly assigned (1:1) to receive subcutaneous zilucoplan 0·3 mg/kg once daily by self-injection, or matched placebo, for 12 weeks. The primary efficacy endpoint was change from baseline to week 12 in MG-ADL score in the modified intention-to-treat population (all randomly assigned patients who received at least one dose of study drug and had at least one post-dosing MG-ADL score). Safety was mainly assessed by the incidence of treatment-emergent adverse events (TEAEs) in all patients who had received at least one dose of zilucoplan or placebo. This trial is registered at ClinicalTrials.gov, NCT04115293. An open-label extension study is ongoing (NCT04225871). Between Sept 17, 2019, and Sept 10, 2021, 239 patients were screened for the study, of whom 174 (73%) were eligible. 86 (49%) patients were randomly assigned to zilucoplan 0·3 mg/kg and 88 (51%) were assigned to placebo. Patients assigned to zilucoplan showed a greater reduction in MG-ADL score from baseline to week 12, compared with those assigned to placebo (least squares mean change -4·39 [95% CI -5·28 to -3·50] vs -2·30 [-3·17 to -1·43]; least squares mean difference -2·09 [-3·24 to -0·95]; p=0·0004). TEAEs occurred in 66 (77%) patients in the zilucoplan group and in 62 (70%) patients in the placebo group. The most common TEAE was injection-site bruising (n=14 [16%] in the zilucoplan group and n=8 [9%] in the placebo group). Incidences of serious TEAEs and serious infections were similar in both groups. One patient died in each group; neither death (COVID-19 [zilucoplan] and cerebral haemorrhage [placebo]) was considered related to the study drug. Zilucoplan treatment showed rapid and clinically meaningful improvements in myasthenia gravis-specific efficacy outcomes, had a favourable safety profile, and was well tolerated, with no major safety findings. Zilucoplan is a new potential treatment option for a broad population of patients with AChR-positive generalised myasthenia gravis. The long-term safety and efficacy of zilucoplan is being assessed in an ongoing open-label extension study. UCB Pharma.

Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study

Generalised myasthenia gravis is a chronic, unpredictable, and debilitating autoimmune disease. New treatments for this disease are needed because conventional therapies have limitations, such as side-effects (eg, increased infection risk) or inadequate control of symptoms. Rozanolixizumab is a neonatal Fc receptor blocker that might provide a novel therapeutic option for myasthenia gravis. We aimed to assess the safety and efficacy of rozanolixizumab for generalised myasthenia gravis. MycarinG is a randomised, double-blind, placebo-controlled, adaptive phase 3 study done at 81 outpatient centres and hospitals in Asia, Europe, and North America. We enrolled patients (aged ≥18 years) with acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) autoantibody-positive generalised myasthenia gravis (Myasthenia Gravis Foundation of America class II-IVa), a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 3 (non-ocular symptoms), and a quantitative myasthenia gravis score of at least 11. Patients were randomly assigned (1:1:1) to receive subcutaneous infusions once a week for 6 weeks of either rozanolixizumab 7 mg/kg, rozanolixizumab 10 mg/kg, or placebo. Randomisation was stratified by AChR and MuSK autoantibody status. Investigators, patients, and people assessing outcomes were masked to random assignments. The primary efficacy endpoint was change from baseline to day 43 in MG-ADL score, assessed in the intention-to-treat population. Treatment-emergent adverse events (TEAEs) were assessed in all randomly assigned patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT03971422) and EudraCT (2019-000968-18); an open-label extension study has been completed (NCT04124965; EudraCT 2019-000969-21) and another is underway (NCT04650854; EudraCT 2020-003230-20). Between June 3, 2019, and June 30, 2021, 300 patients were assessed for eligibility, of whom 200 were enrolled. 66 (33%) were randomly assigned to rozanolixizumab 7 mg/kg, 67 (34%) to rozanolixizumab 10 mg/kg, and 67 (34%) to placebo. Reductions in MG-ADL score from baseline to day 43 were greater in the rozanolixizumab 7 mg/kg group (least-squares mean change -3·37 [SE 0·49]) and in the rozanolixizumab 10 mg/kg group (-3·40 [0·49]) than with placebo (-0·78 [0·49]; for 7 mg/kg, least-squares mean difference -2·59 [95% CI -4·09 to -1·25], p<0·0001; for 10 mg/kg, -2·62 [-3·99 to -1·16], p<0·0001). TEAEs were experienced by 52 (81%) of 64 patients treated with rozanolixizumab 7 mg/kg, 57 (83%) of 69 treated with rozanolixizumab 10 mg/kg, and 45 (67%) of 67 treated with placebo. The most frequent TEAEs were headache (29 [45%] patients in the rozanolixizumab 7 mg/kg group, 26 [38%] in the rozanolixizumab 10 mg/kg group, and 13 [19%] in the placebo group), diarrhoea (16 [25%], 11 [16%], and nine [13%]), and pyrexia (eight [13%], 14 [20%], and one [1%]). Five (8%) patients in the rozanolixizumab 7 mg/kg group, seven (10%) in the rozanolixizumab 10 mg/kg group, and six (9%) in the placebo group had a serious TEAE. No deaths occurred. Rozanolixizumab showed clinically meaningful improvements in patient-reported and investigator-assessed outcomes in patients with generalised myasthenia gravis, for both 7 mg/kg and 10 mg/kg doses. Both doses were generally well tolerated. These findings support the mechanism of action of neonatal Fc receptor inhibition in generalised myasthenia gravis. Rozanolixizumab represents a potential additional treatment option for patients with generalised myasthenia gravis. UCB Pharma.

Serum neurofilament light chain in myasthenia gravis subgroups: An exploratory cohort and case-Control study.

This study aimed to evaluate the association of neurofilament light chain (Nfl) with neuromuscular destruction and disease severity in the serum of patients with myasthenia gravis (MG). Sera from 134 patients with MG with varying degrees of disease severity and autoantibody (Abs) status were analyzed and compared to controls in a cross-sectional design. Prospectively, we additionally measured serum NfL (sNfl) levels in patients with MG longitudinally for up to 3 years. Based on linear regression, differences between patients and controls were assessed. With correlation coefficients and mixed linear regression, the association among sNfl levels, socio-demographics, disease activity (Quantitative Myasthenia Gravis (QMG) score and Myasthenia Gravis Activities of Daily Living (MG-ADL) scale), Abs-status (acetylcholine receptor antibody (AChR-Abs), muscle-specific receptor tyrosine kinase antibody (MuSK-Abs), lipoprotein-related protein 4 (LRP4), and seronegative), Abs titer, treatment regime (pyridostigmine, steroids, and immunosuppressive therapies), and thymectomy were investigated. sNfl levels were higher in patients with MG compared to controls (median: 11.2 vs. 7.88), where sNfl levels were highest in anti-AChR-Abs positive patients (median 12.6), followed by anti-MuSK-Abs positive, anti-LRP4-Abs positive, and seronegative patients. Adjusting for age and sex, sNfl levels of patients with MG were on average 35% higher compared to controls (35.1, 95% CI: 8.4;68.3) and highest for patients with seronegative MG (44.35; 95% CI 16.47; 78.90). We found no relevant relationship between individual changes in sNfl and changes in QMG and MG-ADL scores. sNfl levels are higher in patients with MG than in controls but were not consistently associated with clinical severity. Thus, sNfl is not a suitable biomarker to monitor individual disease progression in patients with MG.

Myasthenia gravis complicated by the development of COVID-19: an analysis of case series

Myasthenia gravis (MG) is an autoimmune disease characterized by increased dynamic muscleweakness. Patients with myasthenia gravis are united by the phenomenon of deterioration of the clinicalcondition after infection, refusal of treatment or taking certain medications, surgical intervention, exposureto heat and stress. In the context of the COVID‑19 (Coronavirus disease 2019) pandemic, the study ofpatients with myasthenia gravis and a new infectious disease may reveal new pathogenetic patterns andchange the therapeutic strategy.&#x0D; Objective — to identify clinical and paraclinical, therapeutic regularities in patients with MG and COVID‑19.&#x0D; Methods and subjects. From April 2021 to November 2021, the course of MG against the background ofCOVID‑19 in 11 patients was analyzed. The control group consisted of 7 patients with COVID‑19, butwithout MG. General clinical, neurological, instrumental, laboratory and statistical examination methods,scales Myasthenia Gravis Foundation of America (MGFA), The Quantitative Myasthenia Gravis Score (QMGS), Myasthenia Gravis Activities of Daily Living (MG‑ADL), The National Early Warning Score 2 (NEWS2) and questionnaires were used.&#x0D; Results. In the experimental and control groups, the level of SpO2 when breathing atmospheric air wascorrelated with the presence of bronchial asthma (BA) (r = –0.791), diabetes mellitus (DM) (r = –0.553),hypertension (r = –0.301). A positive correlation (r = 0.271) was found between the presence of MG and the level of SpO2 when breathing atmospheric air, which may be associated with the intake of pyridostigmine anda decrease in muscle mass in patients with MG. Presence of a relationship between the NEWS2 indicatorwith DM (r = 0.501), BA (r = 0.483), obesity (r = 0.376), hypertension (r = 0.352), multinodular goiter (r = 0.204), hydrothorax (r = 0.204) and MG (r = 0.120). In the myasthenia group, a relationship was established between the duration of treatment for COVID‑19 and body mass index (BMI) (r = 0.523), age (r = 0.504), pyridostigmine intake (r = –0.243) and weight (r = 0.228). NEWS2 in the experimental group was correlated with pyridostigmine intake (r = –0.386), weight (r = 0.355) and BMI (r = 0.256). Duration of treatment for COVID‑19 was associated with duration of MG (r = 0.570), obesity (r = 0.572), and BMI (r = 0.526). NEWS2 is related to the level of SpO2 when breathing atmospheric air (r = — 0.907), hemoglobin (r = –0.847) and vital capacity of the lungs (VC) (r = –0.699). Obesity (r = 0.787), anemia (r = 0.684) and BA were correlated with NEWS2. The finding of an inverse correlation between NEWS2 and pyridostigmine intake (r = –0.684) was promising. Soft palate paresis (r = –0.614), dysphagia (r = –0.614) and nasality (r = –0.545) were correlated with a decrease in VC. A correlation was found between VC and the NEWS2 (r = –0.699). The duration of COVID‑19 (r = –0.646) and patient age (r = –0.626) were correlated with VC.&#x0D; Conclusions. MG with the addition of COVID‑19 tends to worsen the course, progress of muscle weakness,development of respiratory failure and hypoxia. Aggravating factors are age, duration of MG, duration ofCOVID‑19, BMI, concomitant pathology (DM, hypertension, BA, obesity, anemia). Constitutional features(lower BMI and weight) may contribute to shortening the duration of treatment. Taking pyridostigmineallows to reduce not only the duration of treatment, but also the risk of worsening of the condition, whichmay be associated with the suppression of the inflammatory process when taking an anticholinesteraseagent.&#x0D;

Invigorating spleen, replenishing qi and tonifying kidney method treatment of traditional Chinese medicine for myasthenia gravis: A protocol for systematic review and meta-analysis

Myasthenia gravis (MG) is an autoimmune disease related to the production of autoantibodies. It is mediated by antibodies against acetylcholine receptor (AChR), muscle specific kinase (MuSK) or other AChR related proteins in the postsynaptic muscle membrane, which interfere with the transmission of signals at the neuromuscular junction, resulting in clinical symptoms of skeletal muscle weakness and fatigue, leading to the occurrence and development of MG. At present, the incidence rate of Mg is increasing year by year. At present, the method of invigorating spleen, replenishing qi and tonifying kidney in traditional Chinese medicine has been widely used in the clinical treatment of MG, and the effect is good. The purpose of this study was to systematically evaluate the efficacy and safety of the method of invigorating the spleen, supplementing qi and tonifying the kidney in the treatment of MG. We will search from the following eight databases: PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, Sinomed, Wanfang, and Vip. All randomized controlled trial (RCT) literature has been searched and classified since the establishment of the database to date. In this study, two researchers independently screened and evaluated the quality of the retrieved literature. Cochrane risk bias assessment tool was used to evaluate the risk of bias. The meta-analysis uses RevMan 5.3 software provided by Cochrane Collaboration Network for meta analysis. This study compared the main outcome indicators: clinical response rate, recurrence rate, incidence of adverse reactions, quantitative myasthenia gravis score (QMG). Secondary outcomes were clinical absolute score, quality of life score (QOL), levels of inflammatory factors such as IL-6, IL-10, and serum acetylcholine receptor antibody (AChR-Ab) levels. The purpose of this study was to evaluate the efficacy and safety of the method of invigorating the spleen, supplementing qi and tonifying the kidney in treating MG, and to provide evidence based medicine.

Long-term Safety and Efficacy of Efgartigimod in Patients With Generalized Myasthenia Gravis: Interim Results of the ADAPT+ Study

Objective To evaluate the safety and efficacy of efgartigimod in patients with generalized myasthenia gravis (MG) enrolled in the ADAPT+ long-term extension study. Background Treatment with efgartigimod, a human IgG1 antibody Fc-fragment that blocks neonatal Fc receptor, resulted in clinically meaningful improvement (CMI) in MG-specific outcome measures in the ADAPT phase 3 clinical trial. All patients who completed ADAPT were eligible to enroll in its ongoing open-label, 3-year extension study, ADAPT+. Design/Methods Efgartigimod (10 mg/kg IV) was administered in cycles of once-weekly infusions for 4 weeks, with subsequent cycles initiated based on clinical evaluation. Efficacy was assessed during each cycle utilizing Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scales. Results Ninety-one percent of ADAPT patients (151/167) entered ADAPT+. As of February 2021, 106 AChR-Ab+ and 33 AChR-Ab– patients had received at least 1 dose of open-label efgartigimod (including 66 ADAPT placebo [PBO] patients). The mean (SD) study duration was 363 (114) days, resulting in 138 patient-years of observation. Similar incidence rates per patient year (IR/PY) of serious adverse events were seen in ADAPT (efgartigimod: 0.11; placebo: 0.29) compared to ADAPT+ (0.25). Five deaths (acute myocardial infarction, COVID-19 pneumonia/septic shock, bacterial pneumonia/MG crisis, malignant lung neoplasm, and unknown [multiple cardiovascular risk factors identified on autopsy]) occurred; none were considered related to efgartigimod by the investigator. AEs were predominantly mild or moderate. CMI was observed in AChR-Ab+ patients during each cycle (up to 10 cycles) at magnitudes comparable to improvements observed at week 3 of cycle 1 (mean[SE] improvements: MG-ADL, –5.1[0.34]; QMG, –4.7[0.41]). Clinical improvements mirrored maximal reductions in total IgG and AChR-Abs across all cycles. Conclusions This analysis suggests the efficacy of long-term treatment with efgartigimod was consistent across multiple cycles. No new safety signals were identified, despite being conducted before vaccine availability during the COVID-19 pandemic.

Impact of Thymectomy on Crisis Incidence and Quality of Life amongst Generalised Myasthenia Gravis Patients.

Thymectomy, combined with corticosteroids, immunosuppressive agents, and cholinesterase inhibitors, has been accepted as the standard treatment for myasthenia gravis (MG) patients. Data on the effect of thymectomy on occurrence of myasthenic crisis are few. To assess the long-term impact of thymectomy in patients with generalized Myasthenia gravis (GMG) in terms of occurrence of myasthenia crisis and quality of life. A retrospective analysis of 274 clinical records of patients diagnosed with myasthenia gravis (MG) in Nizam's institute of medical sciences (NIMS), a tertiary level teaching hospital between January 2000 and December 2015 was done. Severity of the disease was assessed using Myasthenia Gravis Foundation of America (MGFA) classification and quantitative myasthenia gravis (QMG) score. Myasthenia crisis was diagnosed in our patients when they required ventilator assistance due to respiratory failure caused by muscle weakness (MGFA class V). Quality of life (QoL) was assessed. Of 230 cases included in the final analysis, 108 (46.9%) underwent thymectomy. Posttreatment crisis occurred in 53.3% of the nonthymectomy subjects, and 25.9% of thymectomy group (P < 0.001). In multivariate logistic regression analysis, after controlling for the effect of gender, age at diagnosis and grade of the disease, the odds ratio of myasthenic crisis in people with thymectomy was 0.186.(95% CI 0.087 to 0.387, P = 0.001). No statistically significant differences were observed in quality of life scores between thymectomy and nonthymectomy groups, either before (P = 0.86) or after surgery (P = 0.939). The odds of myasthenia crisis was lesser in people, who underwent thymectomy even after controlling for MGFA grade and other potential confounders but no significant differences in quality of life were found with thymectomy.

Correlation between neutrophil-to-lymphocyte ratio and severity of myasthenia gravis in adults: A retrospective study

BackgroundThe study aimed to explore the clinical value of neutrophil-to-lymphocyte (NLR) in evaluating myasthenia gravis (MG) severity and the correlation between NLR and the Quantitative Myasthenia Gravis Score (QMGS). MethodsThis study included 128 patients with MG and 116 healthy controls. We completed Myasthenia Gravis Foundation of America (MGFA) classification for patients with MG, and defined MGFA I, II, and III as mild MG and MGFA IV and V as severe MG. The NLR of the patients were calculated, and statistical analysis was performed, with statistical significance set at P < 0.05. When pairwise comparisons between patients with mild MG, severe MG, and the healthy controls were performed, P < 0.017 was considered statistically significant under Bonferroni correction. ResultsNLR was significantly higher in patients with severe MG than in those with mild MG [2.90(2.41–5.83) vs 1.72(1.38–2.51), P = 0.000] and in the healthy controls [2.90(2.41–5.83) vs 1.65(1.34–1.91), P = 0.000]. NLR was independently associated with severe MG. The cut-off value of NLR for differentiating mild MG from severe MG was 2.37, and the sensitivity and specificity were 0.900 and 0.815, respectively. The results of Spearman test showed that NLR was positively correlated with QMGS in mild MG. NLR tended to be correlated QMGS in patients with severe MG, but the difference was not statistically significant. ConclusionNLR may be a helpful marker for identifying patients with severe MG. NLR can also be used to further evaluate disease severity, especially for mild MG.

Application of lymphoplasmapheresis in the treatment of severe myasthenia gravis.

BackgroundLymphoplasmapheresis (LPE) is a treatment that combines traditional plasma exchange and lymphocyte removal technique. It has been applied to treat a variety of autoimmune diseases, but its application value in the treatment of severe myasthenia gravis (MG) is not yet clear. Therefore, the aim of this study was to investigate the efficacy and safety of LPE in severe MG.MethodsClinical data of 123 severe patients with MG (Myasthenia Gravis Foundation of America Clinical Classification, Class IV) who received LPE treatment were included in a retrospective analysis. Efficacy was evaluated by the change of Quantitative Myasthenia Gravis score (QMGS) before and after treatment. Univariate and multivariate logistic regression analysis was used to explore clinical factors affecting efficacy.ResultsA total of 220 replacements were performed in 123 patients, with an average of 1.79 replacements per patient. The overall safety of LPE was good, and no serious adverse reactions occurred. After treatment, the mean QMGS of patients decreased significantly, from 23.40 ± 4.25 points before treatment to 17.93 ± 5.61 points after treatment, a decrease of 5.47 ± 4.16 points. 75.6% of patients experienced remission of clinical symptoms. During a 2-month follow-up of 64 patients, a progressive improvement in QMGS was found. Each muscle group involved in MG responded well to LPE treatment. In addition, LPE significantly reduced the levels of AChR-Ab and inflammatory cytokines in patients. Age ≥ 50 years and co-infection were unfavorable factors affecting the efficacy.ConclusionsIn this study cohort, LPE is safe for the treatment of severe MG and achieves good treatment outcome with fewer replacements. In patients with MG, the avoidance and timely control of infection are necessary. Our study provides a potential new treatment option for severe MG.

FP.20 Serum metabolomics differentiates treatment response of myasthenia gravis clinical outcome measures

The myasthenia gravis (MG) Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) score QMG have been used as primary outcome measures in phase 3 clinical trials of therapeutics of MG. The MG-ADL is a patient-reported outcome measure of performance of common activities over a one to two-week period prior to assessment, while the QMG is a quantitated examination performed at one time by a trained examiner. We were interested if there was a difference in the biological signature of these measures. 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, 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 using the MG-ADL and QMG at 6 months. Principal component analysis, hierarchical clustering and pathway analysis were used to evaluate the profiles. There was limited overlap between the metabolomic and lipidomic profiles related to improvement in MG-ADL and QMG. Increased levels of phospholipids were associated with treatment response as assessed by QMG but not observed in the MG-ADL analysis. Pathway analysis also associated QMG change with alterations of lipid metabolism, while amino acid and glucose metabolism pathways were associated with MG-ADL improvement. The results indicate fundamentally different biological underpinnings of the outcome measures in common use in MG clinical trials and supports the common dissociation of patient and physician observation what is means to be better reflected is serum metabolites.

VP.38 A double-blinded, randomized, placebo-controlled phase II study of FcRn antagonist batoclimab in Chinese generalized myasthenia gravis patients

A randomized, double-blind, placebo-controlled, parallel phase II study was conducted for generalized myasthenia gravis (gMG) in Chinese population to evaluate the efficacy and safety of batoclimab as a novel anti-FcRn therapy. Eligible patients were randomized in a 1:1:1 ratio to placebo, batoclimab 340 mg, 680 mg groups, respectively. In double-blinded period, patients received batoclimab or placebo on days 1, 8, 15, 22, 29, and 36. In the open-label period, all patients received batoclimab 340 mgon days 50, 64, and 78. In follow-up period, patients were examined on days 92, 106, and 120. The primary endpoint was myasthenia gravis activities of daily living (MG-ADL) score change on day 43 from baseline. Secondary endpoints included assessment on Quantitative Myasthenia Gravis (QMG), Myasthenia Gravis Composite (MGC), Myasthenia Gravis Quality of Life (MG-QoL), pharmacokinetics, pharmacodynamics and safety events. Totally 30 subjects were randomized, with 9,10 and 11 in the placebo, batoclimab 340mg and 680mg groups respectively.MG-ADL score changes from baseline to day 43 were -2.2±0.9, -4.7±0.6, and -4.4±1.0 in the placebo, batoclimab 340 mg, and 680 mg groups, respectively. Similar changes were observed in QMG, MGC, and MG-QoL scores. The proportion of patients with clinically significant improvement on day 43 was higher in batoclimab groups. In open-label period, symptom recurrence and IgG levels rise again except the former placebo group. On day 120 the placebo group had more improvement compared to batoclimab groups, with IgG levels reaching a plateau. Treatment-emergent adverse events (TEAEs) were comparable among the three groups. No death or TEAEs leading to study discontinuation was observed. The batoclimab groups experienced mild-to-moderate albumin reductions and total cholesterol elevation, all returned to baseline in follow-up without clinical interference. In conclusion, batoclimab is effective and safe in Chinese patients with gMG.

Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis

Rituximab is a third-line option for refractory generalized myasthenia gravis (MG) based on empirical evidence, but its effect in new-onset disease is unknown. To investigate the efficacy and safety of rituximab compared with placebo as an add-on to standard of care for MG. This randomized, double-blind, placebo-controlled study took place throughout 48 weeks at 7 regional clinics in Sweden. Key inclusion criteria were age older than 18 years, onset of generalized symptoms within 12 months or less, and a Quantitative Myasthenia Gravis (QMG) score of 6 or more. Patients were screened from October 20, 2016, to March 2, 2020. Key exclusion criteria included pure ocular MG, suspected thymoma, previous thymectomy, and prior noncorticosteroid immunosuppressants or high doses of corticosteroids. Participants were randomized 1:1 without stratification to a single intravenous infusion of 500 mg of rituximab or matching placebo. Minimal disease manifestations at 16 weeks defined as a QMG score of 4 or less with prednisolone, 10 mg or less daily, and no rescue treatment. Of 87 potentially eligible patients, 25 were randomized to rituximab (mean [SD] age, 67.4 [13.4] years; 7 [28%] female) and 22 to placebo (mean [SD] age, 58 [18.6] years; 7 [32%] female). Compared with placebo, a greater proportion with rituximab met the primary end point; 71% (17 of 24) in the rituximab group vs 29% (6 of 21) in the placebo group (Fisher exact test P = .007; probability ratio, 2.48 [95% CI, 1.20-5.11]). Secondary end points, comparing changes in Myasthenia Gravis Activities of Daily Living and Myasthenia Gravis Quality of Life at 16 weeks with QMG at 24 weeks did not differ between groups with censoring for rescue treatment (per-protocol analysis) but were in favor of active treatment when rescue treatment was taken into account by worst rank imputation (post hoc analysis). Rescue treatments were also more frequent in the placebo arm (rituximab: 1 [4%]; placebo, 8 [36%]). One patient in the placebo arm had a myocardial infarction with cardiac arrest and 1 patient in the active arm experienced a fatal cardiac event. A single dose of 500 mg of rituximab was associated with greater probability of minimal MG manifestations and reduced need of rescue medications compared with placebo. Further studies are needed to address long-term benefit-risk balance with this treatment. ClinicalTrials.gov Identifier: NCT02950155.