Myasthenia Gravis Activities Of Daily Living Research Articles

Association Between Myasthenia Gravis-Activities of Daily Living (MG-ADL) and EQ-5D-5L Utility Values: The Additional Effect of Efgartigimod on Utilities.

For patients with generalized myasthenia gravis (gMG), the association between symptom severity, often measured with the Myasthenia Gravis Activities of Daily Living (MG-ADL) instrument, and utility values is unknown. Data was analyzed from the phase3 ADAPT trial, which included adult patients with gMG randomly assigned to treatment with efgartigimod + conventional therapy (EFG + CT) or placebo + CT (PBO + CT). MG-ADL total symptom scores and the EQ-5D-5L, a measure of health-related quality of life (HRQoL), were collected biweekly up to 26weeks. Utility values were derived from the EQ-5D-5L data with the United Kingdom value set. Descriptive statistics were reported for MG-ADL and EQ-5D-5L at baseline and follow-up. A normal identity-link regression model estimated the association between utility and the eight MG-ADL items. A generalized estimating equations (GEE) model was estimated to predict utility based on the patient's MG-ADL score and treatment received. A total of 167 patients (84 EFG + CT, 83 PBO + CT) contributed 167 baseline and 2867 follow-up measurements of MG-ADL and EQ-5D-5L. EFG + CT-treated patients experienced more improvements than PBO + CT-treated patients in most MG-ADL items and EQ-5D-5L dimensions, with the largest improvements observed in chewing, brushing teeth/combing hair, eyelid droop (MG-ADL); self-care, usual activities, mobility (EQ-5D-5L). The regression model indicated that individual MG-ADL items contributed differently to utility values, with the largest impact from brushing teeth/combing hair, rising from a chair, chewing, and breathing. The GEE model showed that each unit improvement in MG-ADL led to a statistically significant utility increase of 0.0233 (p < 0.001). In addition, a statistically significant improvement of 0.0598 (p = 0.0079) in utility was found for patients in the EFG + CT group compared to the PBO + CT group. Among patients with gMG, improvements in MG-ADL were significantly associated with higher utility values. MG-ADL scores alone were not sufficient to capture the utility gained from efgartigimod therapy.

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.

Iron metabolism in non-anemic myasthenia gravis patients: A cohort study

BackgroundThe association of iron metabolism parameters with disease severity and outcome in myasthenia gravis (MG) patients has not been reported. This study was conducted to determined clinical factors including iron metabolism parameters correlated with disease severity and future outcome in non-anemic immunotherapy-naïve MG patients first receiving immunotherapy. Material and methodsOne hundred and ten patients were included at baseline to explore predictor variables associated with disease severity represented by variables derived from MG activities of daily living (MG-ADL) score using multivariate logistic regression, after which 103 and 98 patients were included respectively in multivariate survival analyses at 6-month and 12-month follow-up to identify predictors for minimal manifestation status (MMS) after starting immunotherapy. ResultsHigher ferritin level was independently associated with higher risk of severe generalized disease in non-anemic immunotherapy-naïve MG patients. Total iron binding capacity <250 μg/dL and the interval between onset and immunotherapy <1 year were independent predictors for MMS at 6-month and 12-month follow-up after initiating immunotherapy. Transferrin <2.00 g/L was an independent predictor for MMS at 12-month follow-up. ConclusionIron metabolism parameters might be promising biomarkers for evaluating disease severity and guiding therapeutic decision in MG patients.

Patient-reported burden of myasthenia gravis: baseline results of the international prospective, observational, longitudinal real-world digital study MyRealWorld-MG

ObjectivesMyasthenia gravis (MG) is a rare, chronic, autoimmune neuromuscular disease which can affect functional and mental aspects of health and health-related quality of life (HRQoL). This study aims to obtain...

Autologous hematopoietic stem cell transplant for the treatment of refractory myasthenia gravis with anti-muscle specific kinase antibodies.

Up to 25% of patients with myasthenia gravis (MG) have refractory disease despite trials of multiple immunosuppressants. Several case series describe acetylcholine receptor antibody-positive (AChR) MG patients treated with autologous hematopoietic stem cell transplant (HSCT). In this report, we describe three patients with anti-muscle-specific kinase (MuSK) MG treated with HSCT. We included all patients who had undergone HSCT with anti-MuSK myasthenia gravis identified through the records of the Alberta Blood and Marrow Transplant Program. We collected demographic and clinical data including validated MG scales as well as questionnaire data. All 3 patients had severe disease (Myasthenia Gravis Foundation of America score IVb-V) and were refractory to multiple treatments, including rituximab. All patients improved with no clinical manifestations or mild symptoms and remained as such for 2, 3.5, and 5.5y. Adverse events ranged from treatable infections and transient dyspnea to persistent fatigue and premature menopause. The average worst Myasthenia Gravis Activities of Daily Living (MG-ADL) scores improved from 14.7 before to 0.3 after HSCT. The mean worst Myasthenia Gravis Quality of Life Questionnaire (MG-QoL15) scores improved from 26.7 to 0. All patients reported they would undergo transplant again for their MG. We describe three patients with anti-MuSK MG treated with HSCT, all of whom became symptom free from MG with a tolerable side effect profile. In patients with severe refractory anti-MuSK MG, it may be reasonable to consider HSCT.

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;

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.

Serum Autoantibody Lowering by the Anti-FcRn Monoclonal Antibody, Nipocalimab, Correlates With Clinical Improvement in Generalized Myasthenia Gravis Patients

Objective To evaluate the relationship between clinical improvement in Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores and the pharmacodynamic effects of IgG autoantibody lowering induced by nipocalimab in the Vivacity MG Phase 2 study. Background Nipocalimab is a fully human, aglycosylated, effectorless IgG1 anti-FcRn monoclonal antibody that targets the neonatal Fc receptor (FcRn) with high affinity, thereby lowering IgG pathogenic antibodies in autoimmune disease. Design/Methods The relationship between the reduction in acetylcholine-receptor (AChR)- and Muscle-Specific-Tyrosine-Kinase (MuSK)- autoantibodies with improvement in MG-ADL scores were explored across the four nipocalimab dose arms in the Vivacity MG Phase 2 Study in generalized myasthenia gravis (gMG) patients. Results Of the 68 patients enrolled, 54 were randomized to one of the four nipocalimab dosing arms. 51 (94%) were seropositive for anti-AChR, 3 (6%) for anti-MuSK. Nipocalimab was well-tolerated and achieved substantial, dose-dependent and rapid reductions in serum total IgG, including all IgG subtypes and anti-AChR autoantibodies. These reductions were associated with dose-dependent, durable and rapid MG-ADL responses in all nipocalimab-treated groups. A similar trend in IgG4 reduction was noted, though the sample size of MuSK positive patients was small. Conclusions The results support the rapid, dose-dependent and predictable effect of nipocalimab in lowering pathogenic autoantibodies and inducing clinical improvement in patients with gMG. In addition, the close correlation between serum IgG, anti-AChR and clinical response suggest the potential of using serial serum IgG levels as a biomarker in management of gMG patients treated with nipocalimab; this will be tested in the ongoing Phase 3 gMG trial.

Vivacity MG Phase 3 Study: Clinical Trial of Nipocalimab Administered to Adults With Generalized Myasthenia Gravis

Objective We describe Vivacity-MG3. our pivotal Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Nipocalimab Administered to Adults With gMG (NCT04951622). Background Nipocalimab is a high affinity, fully human, aglycosylated, effectorless IgG1 anti FcRn monoclonal antibody that targets the neonatal Fc receptor (FcRn) with high affinity, thereby lowering IgG pathogenic antibodies in autoimmune disease. Data from Vivacity-MG, a Phase 2 randomized placebo-controlled study of nipocalimab in adult generalized myasthenia gravis (gMG), demonstrated safety, tolerability, and efficacy of nipocalimab (clinicaltrials.gov NCT03772587). Design/Methods This global study will enroll approximately 180 participants with gMG, aged 18 and older, with an insufficient clinical response to ongoing, stable standard-of-care therapy, as reflected by a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of &gt;/= to 6 at screening and baseline, and a Myasthenia Gravis Foundation of America (MGFA) Class of IIa/b–IVa/b at screening. The study will consist of a screening period of up to 4 weeks, a 24-week double-blind placebo-controlled phase where participants will be randomly assigned in a 1:1 ratio to receive either placebo or nipocalimab intravenously every two weeks, and an open label extension phase of variable duration. The primary outcome is the average change in MG-ADL score from baseline to weeks 22, 23 and 24 of the double-blind placebo-controlled phase. Results Study enrollment began in July 2021 and is ongoing. Conclusions The ongoing Vivacity MG Phase 3 study will assess the efficacy, safety, and PK/PD of Nipocalimab in adult gMG.

Clinical Experience With Efgartigimod in Generalized Myasthenia Gravis: Results From a Case Series of US-Based Patients Participating in an Expanded Access Program

Objective To describe the efgartigimod treatment regimens and response among 6 US-based patients with generalized myasthenia gravis (gMG) enrolled in an Expanded Access Program (EAP). Background For some patients with gMG, available therapies do not provide sufficient symptom relief and can cause serious side effects. Efgartigimod, a human IgG1 antibody Fc-fragment (natural ligand of the neonatal crystalline fragment receptor [FcRn]), has increased affinity to FcRn vs endogenous IgG. Efgartigimod reduces IgG recycling and increases IgG degradation. Efgartigimod received FDA approval in 2021 for the treatment of gMG in adults who are anti-acetylcholine receptor (AChR) antibody positive. Design/Methods In the efgartigimod EAP (NCT04777734), gMG patients had access to open-label efgartigimod. Eligible patients (=18 y) met clinical criteria of the Myasthenia Gravis Foundation of America classifications II–IV and had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score =5 points (&gt;50% attributed to non-ocular symptoms). During the first two, fixed-treatment cycles, patients received 4 weekly infusions of efgartigimod 10 mg/kg. During the 4-week inter-treatment period, patients received their ongoing treatments and no efgartigimod infusions. Baseline demographic characteristics and safety data were collected. Treating physicians had the option to assess and track clinical function and burden of disease among treated patients. Results As of the cutoff date (Dec 17, 2021), 8 patients have been enrolled in the US; follow-up data are available for 6 (3 males and 3 females; median age 59 y). 83% (5/6) of patients received at least 2 treatment cycles and 4–5 infusions per cycle. Symptom improvements were noted. Four patients reported 6 AEs: fatigue (resolved), tachycardia and headache (both resolved), dyspnea and diplopia (both not resolved), and back spasms (status unknown). Conclusions We report on 6 patients with gMG who received efgartigimod as part of an EAP. Detailed patient narratives will be presented.

PCR82 Association between Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Eq-5D-5L Utility Values: The Additional Effect of Efgartigimod on Utilities

MG-ADL is a widely-used outcome in generalized Myasthenia Gravis (gMG), measuring impairments in talking, chewing, swallowing, breathing, brushing teeth/combing hair, rising from a chair, double vision and eyelid droop. No relationship has been established between MG-ADL and Health-Related Quality-of-Life. This analysis aimed to estimate the relationship between gMG symptoms and utility values (UK value set) using the Phase-3 ADAPT data, and to verify what the effect was of efgartigimod on this association.

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.

A retrospective study of the safety and efficacy of rituximab in Iranian patients with myasthenia gravis: A single-center experience.

Background: This retrospective cohort study was conducted to evaluate the efficacy and tolerance of rituximab (RTX) for the management of myasthenia gravis (MG). Methods: This retrospective cross-sectional study was conducted on 61 patients with refractory and non-refractory MG who received RTX. The Myasthenia Gravis Activities of Daily Living (MG-ADL) profile was used to assess MG symptoms and their effects on daily activities at the start of RTX and in the last follow-up. The Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS) scale has been used as an outcome measure after treatment with RTX in the 12th month and the last follow-up. Results: The mean age of the patients was 40.31 ± 13.53 years (range: 15-78 years). Of 61 patients, eight (13.1%) were double seronegative, 29 (47.5%) had anti-acetylcholine receptor (AChR+) antibody, and 24 (39.3%) had anti-muscle-specific tyrosine kinase antibody (MuSK+). According to the mean rank table, the results of this study showed that the drug was more effective in improving the symptoms of MuSK+ patients compared to the other two groups (P = 0.006). The mean MG-ADL was 4.86 ± 1.83 before treatment and 1.51 ± 2.02 in the last follow-up visit. Paired t-test showed a significant association between MG-ADL before and after treatment in the last visit [t(55): 11.30, 95% confidence interval (CI): 2.79-3.99, P = 0.001)]. Conclusion: This retrospective study showed a considerable effect of RTX as induction therapy in patients with MG, especially those with MuSk+ MG.

Safety and effectiveness of eculizumab in Japanese patients with generalized myasthenia gravis: Analysis of 1‐year postmarketing surveillance

AbstractIntroductionEculizumab, a terminal complement protein C5 inhibitor, is approved in Japan for the treatment of patients with anti‐acetylcholine receptor antibody‐positive (AChR Ab+) generalized myasthenia gravis (gMG) that is difficult to control with plasmapheresis or high‐dose intravenous immunoglobulin therapy.MethodsThis analysis of mandatory postmarketing surveillance in Japan assessed the safety and effectiveness of eculizumab in patients with AChR Ab+ gMG who had completed case‐report forms at 26 wk after eculizumab initiation up to the cutoff date of April 2021. Changes from baseline were assessed for Myasthenia Gravis‐Activities of Daily Living (MG‐ADL) and Quantitative Myasthenia Gravis (QMG) total scores overall, and MG‐ADL scores in patient subgroups according to sex, age at diagnosis and baseline, and baseline disease severity. The change in concomitant corticosteroid use was also evaluated.ResultsData were available for 134 adults (67.2% female; mean age 51.9 y); the effectiveness‐analysis set comprised 126 patients. After 26 wk, 78% of patients were continuing eculizumab treatment. Adverse drug reactions were reported by 49 patients (37%) (most frequently headache [n = 10]). Improvements in MG‐ADL scores were seen regardless of sex; age at diagnosis (&lt;50/≥50 y); baseline age (18 to &lt;40/≥40 to &lt;65/≥65 y); Myasthenia Gravis Foundation of America disease classification (IIa/IIb/IIIa/IIIb/IVa/IVb/V); or baseline MG‐ADL score (&lt;6/≥6). Of patients receiving corticosteroids, the proportion receiving low doses (average ≤5 mg/d) increased from 7.0% before eculizumab initiation to 26.4% by Week 52.ConclusionEculizumab was well tolerated and effective in treating AChR Ab+ gMG across a broad spectrum of adult Japanese patients with difficult‐to‐control gMG.

Quality of Life in Myasthenia Gravis and Correlation of MG-QOL15 with Other Functional Scales.

Health-related quality of life (HRQOL) in myasthenia gravis (MG) is frequently decreased. Further, there are many validated clinical scales and questionnaires to evaluate the clinical status in MG. We aimed to determine if there was an improvement in HRQOL following an intensive treatment for MG, identify which demographic and clinical features influenced patients’ HRQOL, and investigate if the questionnaire MG-QOL15 correlated with other evaluation scales. We recruited 45 patients with generalised MG who were starting immunomodulatory treatment with intravenous immunoglobulins and prednisone for the first time. At each visit, we administered several validated scales for MG. The mean MG-QOL15 score improved significantly at 4 and 6 weeks of the study. Additionally, the MG-QOL15 score correlated strong with the Myasthenia Gravis-Activities of Daily Living (MG-ADL) and the Neuro-QOL Fatigue and weakest with the Quantitative Myasthenia Gravis Scoring System (QMG). The QMG score prior to study enrolment was associated with HRQOL. We observed that HRQOL in MG improved after receiving an intensive immunomodulatory treatment and achieving better control of the symptoms. The questionnaire MG-QOL15 correlated positively with other clinical measures. As MG is a fluctuating condition, and some symptoms are difficult to examine, we direct physicians toward the use of scales and questionnaires composed of items perceived by the patient.

Therapeutic Effects of Batoclimab in Chinese Patients with Generalized Myasthenia Gravis: A Double-Blinded, Randomized, Placebo-Controlled Phase II Study.

IntroductionWe investigated the safety and explore potential efficacy of batoclimab administered subcutaneously in Chinese patients with generalized myasthenia gravis (gMG).MethodsA randomized, double-blinded, placebo-controlled, parallel phase II study was conducted. First, in the double-blinded treatment period, eligible patients received batoclimab (680 mg), batoclimab (340 mg), or placebo on days 1, 8, 15, 22, 29, and 36. In the open-label treatment period, patients received batoclimab (340 mg) on days 50, 64, and 78. In the 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.ResultsIn total, 30 eligible patients were enrolled, with 11, 10, and 9 patients in the batoclimab 680 mg, batoclimab 340 mg, and placebo 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 Quantitative Myasthenia Gravis, Myasthenia Gravis Composite, and 15-item Myasthenia Gravis Quality of Life scores in the placebo, batoclimab 340 mg, and 680 mg groups, respectively. The proportion of patients with clinically significant improvement on day 43 was higher in the batoclimab groups. On day 120, all four scales in the placebo group had more significant improvement compared with the batoclimab groups, with total serum IgG levels reaching a plateau. No death or treatment-emergent adverse events (TEAEs) led to study discontinuation.ConclusionBatoclimab is effective and safe in Chinese patients with gMG.Trial RegistrationThis study was registered at ClinicalTrials.gov (NCT04346888) on 15 April 2020, with the first patient enrolled on 23 July 2020.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-022-00345-9.

Efficacy and Safety of Tacrolimus Therapy for a Single Chinese Cohort With Very-Late-Onset Myasthenia Gravis.

Background and PurposePrevious studies have found tacrolimus to be a favorable drug for treating different types of myasthenia gravis (MG), but few have focused on very-late-onset MG (VLOMG). This study evaluated the efficacy and safety of tacrolimus for VLOMG therapy.MethodsThis was a retrospective single-center cohort study of 70 patients with VLOMG (onset ≥65 years) who visited Peking University First Hospital in 2019. Participants were divided into the tacrolimus (Tac) group and the control group based on tacrolimus usage. We further divided the Tac group into patients treated without corticosteroids and with corticosteroids. Sociodemographic features, clinical profiles, and outcomes were compared between different therapies and further analyzed by multivariate regression. Details of tacrolimus treatment, comorbidities, and adverse drug reactions (ADRs) were described.ResultsAmong 70 patients, the median (interquartile range) age at onset was 71 (68–77) years, and the follow-up duration was 27 (27-29) months. Most patients were types I (28%) and III (40%) according to the MG Foundation of America (MGFA) classification. In the Tac group, tacrolimus treatment was maintained for 36 (27-38) months. The dosage at the final evaluation was 1.0 (1.0–1.75) mg/day, and the last blood concentration test was 4.25 (2.85–5.7) ng/ml. A total of 43% reached remission, and 37% improved based on MGFA postintervention status (MGFA-PIS). For the 9 patients, newly diagnosed at enrollment within this group, MG activities of daily living (MG-ADL) decreased significantly from 3 (2-5) to 2 (1-2) (p = 0.041). Regarding the 13 patients, coadministering Wuzhi capsules the tacrolimus concentration increased from 2.75 (1.4–3.8) ng/ml to 5.95 (5.1–7.0) ng/ml (p = 0.012). No significant differences in outcomes were observed between tacrolimus treatment without and with corticosteroids or between the Tac group and the control group. A total of 93% had at least one comorbidity. ADRs related to tacrolimus emerged in 25% (9/36) of patients, most of which were not serious and reversible.ConclusionsTacrolimus is effective and safe in treating VLOMG. Tacrolimus monotherapy without corticosteroids can be used as an initial and maintenance treatment for VLOMG. Wuzhi capsules work well in elevating tacrolimus concentrations in this population.

The Myasthenia Gravis Activities of Daily Living score and associated factors to distinguish the refractory phase in generalized myasthenia gravis patients with 5 years or more disease duration

Associated factors of the Myasthenia Gravis Activities of Daily Living (MG-ADL) score were investigated in 55 patients who had had generalized MG for more than 5 years. In multivariate analysis, correlates of the MG-ADL score at the last follow-up were the total number of fast-acting treatments (FTs) (standardized regression coefficient 0.617，P < 0.001) and Myasthenia Gravis Foundation of America (MGFA) classification (standardized regression coefficient 0.227，P = 0.032) (F = 32.7，P < 0.001). In patients with a score of 5 or more on MG-ADL at the last follow-up, tendency as follows were seen: 1) early-onset (P = 0.002), 2) longer duration (P = 0.014), 3) high frequency of MGFA classification V (P = 0.017), 4) high frequency of the total number of FTs (P < 0.001), and 5) higher dose of prednisolone at the last follow-up (P = 0.003). MGFA V, early-onset without depending on E-L-T classification, or difficulty of reduction for high doses of prednisolone can be the target of novel treatment for MG, and future prospective study will be expected.

Rest or 30 min walk as exercise intervention (RESTOREX) in myasthenia gravis: A randomized controlled trial

Introduction There is a lack of evidence about the usefulness of exercise or rest in myasthenia gravis (MG). This study is aimed to evaluate the efficacy and safety of exercise or rest in MG. Methods In a single-center open-labeled randomized controlled trial, the patients with mild to moderate MG were randomized to 30-min walk or rest in addition to the standard treatment. The primary endpoint was 50% improvement in the MG Quality of Life (MG-QOL15), and secondary endpoints were change in the Myasthenic Muscle Score (MMS), MG Activities of Daily Living (MGADL), grip strength, dose of acetylcholine esterase inhibitor and prednisone, 6-min walk test (6MWT), decrement in trapezius on the low-rate repetitive nerve stimulation test, and adverse events. The outcomes were defined at 3 months, by >50% improvement in these outcome parameters. Results Forty patients with MG were randomized to the exercise or rest arm. The 2 arms were matched for demographic and clinical parameters. The patients in the exercise arm had significantly better QOL evidenced by MG-QOL15 (p = 0.02). The secondary endpoints, distance covered in 6MWT (p = 0.007), were also better in the exercise arm without any adverse event. Conclusion Regular exercise for 30 min in mild and moderate MG improves quality of life and walking distance compared to rest and is safe. Clinical trial registration The clinical trial registration number is CTRI/2019/11/021869.