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There are substantial disease and health-related quality-of-life (HRQoL) burdens for many patients with myasthenia gravis (MG), especially for those whose disease symptoms are not well controlled. HRQoL measures such as the Myasthenia Gravis Quality of Life 15-item revised (MG-QOL15r) and EuroQoL 5-Dimensions 5-Levels (EQ-5D-5L) are vital for evaluating the clinical benefit of therapeutic interventions in patients with MG, as they assess the burden of disease and the effectiveness of treatment, as perceived by patients. The phase 3 ADAPT study (NCT03669588) demonstrated that efgartigimod—a novel neonatal Fc receptor inhibitor—was well tolerated and that acetylcholine receptor antibody–positive (AChR-Ab+) participants who received efgartigimod had statistically significant improvements in MG-specific clinical scale scores. The ancillary data reported here, which cover an additional treatment cycle, show that these participants had similar significant improvements in HRQoL measures, the MG-QOL15r and EQ-5D-5L utility and visual analog scales, and that these improvements were maintained in the second treatment cycle. Positive effects on HRQoL were rapid, seen as early as the first week of treatment in both treatment cycles, and maintained for up to 4 weeks in the follow-up–only portion of treatment cycles. The pattern of improvements in HRQoL paralleled changes in immunoglobulin G level, and correlational analyses show that improvements were consistent across HRQoL measures and with clinical efficacy measures in the ADAPT study. The substantial and durable improvements in HRQoL end points in this study demonstrate the broader benefit of treatment with efgartigimod beyond relief of immediate signs and symptoms of gMG.

Introduction AIMS Myasthenia Gravis (MG) is an autoimmune neuromuscular disease in which patients suffer from recurrent exacerbation. There are insufficient data measuring the effects of the resources employed before and during acute exacerbation on subsequent disease outcomes. This study aims to identify factors which lead to lengthened hospital stay. Methods This is a retrospective chart review of acute MG exacerbations requiring hospitalization. Exacerbations were identified using ICD-9/ICD-10 codes and considered the following variables: age and Myasthenia Gravis Foundation of America (MGFA) class at initial MG diagnosis, age and MGFA class at exacerbation, sex, thymectomy, cause of exacerbation, treatment regimen at time of exacerbation, inpatient treatment regimen, length of hospital stay (LOS), intubation, use of noninvasive ventilation, complications, and disposition. Results Seventy patients with 141 hospitalizations were identified. Crisis management characterized by intubation and plasmapheresis positively correlated with LOS (both p (p p Discussion Plasmapheresis, intubation, and male sex were associated with increased LOS in acute MG exacerbation. Intubation appears to be the strongest predictor of LOS. Those with previous thymectomy had shorter hospital stays. The role of thymectomy in the acute setting merits further analysis.

ObjectiveAssess number needed to treat (NNT) and costs required to achieve improvements in symptoms and functional activities with targeted therapies for myasthenia gravis (MG).BackgroundNNT and cost per improved efficacy can help inform comparative clinical efficacy and cost-effectiveness across MG treatments.Design/MethodsRelative to conventional therapy (CT), NNTs and annual costs for achieving one point improvement in Quantitative Myasthenia Gravis score (QMG), one additional patient with minimal clinically important difference (MCID) in QMG (i.e., = 3 points improvement), and one additional patient achieving minimal symptom expression (MSE; Myasthenia Gravis-Activities of Daily Living score of 0 or 1) were estimated for efgartigimod (EFG), intravenous immunoglobulin (IVIg), and eculizumab (ECU). All treatments were used in conjunction with CT. Costs per improved outcome (CPR) were compared between EFG, IVIg, and ECU. Efficacy evaluated at week 4 of respective phase 3 randomized trials (ADAPT [NCT03669588],NCT02473952, REGAIN [NCT01997229]. Annual drug acquisition and administration costs (2021 USD) were considered.ResultsCompared with CT, mean NNTs to achieve one point improvement and MCID in QMG were 0.19 and 2.03 for EFG, 0.52 and 7.14 for IVIg, and 0.56 and 6.25 for ECU. NNTs to achieve an additional patient with MSE was 3.46 for EFG and 8.13 for ECU. Compared to EFG, the mean annual CPR to achieve one point improvement and MCID in QMG were higher for IVIg (Difference [95% confidence interval] = $36,130 [$14,024, $58,237] per point improvement in QMG; $661,561 [$0, $1,546,275] per one patient with MCID in QMG) and ECU ($340,659 [$158,038, $523,280]; $3,838,718 [$1,470,740, $6,206,695]). Cost to achieve one additional patient with MSE was $4,761,649 [$2,859,671, $6,663,626] higher for ECU compared with EFG.ConclusionsEvidence indicates more favorable treatment benefit and economic value for EFG with fewer NNT and lower cost required to achieve improved outcomes compared to other treatments.

ObjectiveTo evaluate real-world utilization patterns of intravenous immunoglobulin (IVIg) among patients with generalized myasthenia gravis (gMG) over 3 years post-IVIg initiation.BackgroundgMG is a rare autoimmune neuromuscular disorder with no known cure. Although IVIg is the most commonly used add-on therapy after standard of care treatments in gMG, it is currently unclear whether it is more commonly used as a “one-off” treatment to manage exacerbations, or as maintenance therapy aimed at reducing or replacing steroid use.Design/MethodsPatients with gMG who initiated IVIg treatment were identified from a US claims database (Symphony Health, an ICON plc Company, Integrated Dataverse [IDV]®, January 1, 2014-December 31, 2019). The frequency of subsequent IVIg treatment and associated cost during the first 12 months post-IVIg initiation were analyzed. Usage patterns of concomitant gMG treatments during the year preceding and 3 years post-IVIg initiation were compared.ResultsAmong 1225 patients with gMG who initiated IVIg treatment, 706 patients (57.6%) received 1 to 5 IVIg treatment courses (intermittent IVIg users), and 519 patients (42.4%) received = 6 IVIg treatment courses (chronic IVIg users) within the subsequent year. Mean annual medical cost per patient was nearly 2.5-fold higher for chronic vs intermittent IVIg users ($161,478 vs $64,888, p < 0.001). Usage frequency of other immunotherapy treatments did not decrease over the follow-up period, even for patients who continued annual chronic IVIg for 3 consecutive years post-initiation.ConclusionsNearly half of patients with gMG received chronic and multiple IVIg treatment courses within the first year once initiating IVIg treatment, indicating higher usage than expected. For all IVIg initiators, usage frequency of other immunotherapy treatments did not decrease over 3 years despite IVIg initiation.

Background: Management of myasthenia gravis (MG), a rare immunoglobulin G autoantibody–mediated neuromuscular junction disorder, is driven by physician experience. To gain insight into current practices and physician needs, neurologists’ use of guidelines and disease activity evaluations to manage MG was assessed. Methods: In November and December of 2020, a quantitative, cross-sectional, 51-item, online survey–based study was used to collect data from 100 community neurologists, from 31 US states, who treat MG. Differences across ratio variables were analyzed via Chi-square and t tests, at a significance level of P

ObjectiveTo describe the efgartigimod treatment regimens and response among 6 US-based patients with generalized myasthenia gravis (gMG) enrolled in an Expanded Access Program (EAP).BackgroundFor 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/MethodsIn 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 (>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.ResultsAs 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).ConclusionsWe report on 6 patients with gMG who received efgartigimod as part of an EAP. Detailed patient narratives will be presented.

While the clinical manifestations of myasthenia gravis (MG) are well understood, its humanistic impact is not. The objective of this systematic literature review (SLR) was to provide a comprehensive understanding of the humanistic burden of MG with regards to psychological symptoms and health-related quality of life (HRQoL) according to patients and caregivers.A systematic search was conducted on December 27, 2019, in MEDLINE and Embase to identify English-language studies that were published from January 1, 2009-December 27, 2019 and presented relevant information on the humanistic burden among adults with MG and their caregivers. Title/abstract and full-text screening was performed by two investigators, with any discrepancies resolved by a third investigator.Sixty-seven publications were included in the SLR. Compared with the general population, patients with MG experienced worse HRQoL. Studies reporting on psychological symptoms of MG, including depression, anxiety, fatigue, and sleep, were heterogeneous in terms of the scales and instruments used to assess patients, as well as the patient populations themselves. However, in general those with more severe symptoms and hospitalization days had worse depression and anxiety, and fatigue and sleep improved with disease remission and/or improvement. Scores were worse for females compared with males and where evaluated, HRQoL scores generally improved following treatment.While the literature demonstrates that symptoms associated with MG get better with disease improvement and remission, additional options in efficacious therapy that adequately address the disease-related symptoms and also improve HRQoL may contribute to beneficial outcomes in a greater number of patients with MG.

Background: The development of better treatments for brain diseases of the elderly will necessitate more sensitive and efficient means of repeatedly assessing an individual’s neurocognitive status. Aim: To illustrate the development of an assessment combining episodic memory and working memory tasks with simultaneous electroencephalography and evoked potential (EP) brain function measures. Methods: Data from matched groups of elderly subjects with mildly impaired episodic verbal memory on neuropsychological tests and those with no objective signs of impairment were used for scale development. An exploratory multivariate divergence analysis selected task performance and neurophysiological variables that best recognized impairment. Discriminant validity was then initially assessed on separate impaired and unimpaired groups. Results: Decreased response accuracy and parietal late positive component EP amplitude in the episodic memory task best characterized impaired subjects. Sensitivity in recognizing impairment in the validation analysis was 89% with 79% specificity (area under the curve = 0.94). Retest reliability was 0.89 for the unimpaired and 0.74 for the impaired validation groups. Conclusion: These promising initial results suggest that with further refinement and testing, an assessment combining cognitive task performance with simultaneous neurofunctional measures could eventually provide an important benefit for clinicians and researchers.

This report reviews the case of a young woman who has livedo rettcularts and cerebrovascular disease A skin biopsy specimen taken from normal skin showed endarteritis obliterans This finding, in combination with the clinical findings, confirmed the diagnosis of Sneddon's syndrome.

Studies were conducted with the putative delta-opioid receptor antagonist lCl 154,129 (lCl) and the putative mu-receptor antagonist beta-funaltrexamine (beta-FNA) to investigate their ability to block the acute opioid-like effects of a single electroconvulsive shock (ECS). lCl, but not beta-FNA, attenuated the increase in hot-plate escape latencies seen following ECS. From these data, we conclude that ECS activates endogenous opioids which act upon delta rather than mu receptors to result in an increase in hot-plate escape latencies.