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Objectives: RAISE (NCT04115293) was a randomized, multicenter, double‐blind, placebo‐controlled phase III study of zilucoplan, a macrocyclic peptide and complement component 5 inhibitor with a dual mechanism of action, in patients with acetylcholine receptor autoantibody‐positive generalized myasthenia gravis (MG). RAISE showed clinically meaningful and statistically significant improvements in MG‐specific outcomes in the overall population. Here, we assess efficacy and safety of zilucoplan in patients with generalized myasthenia gravis in the Japanese patients enrolled in RAISE. Methods: Adults with acetylcholine receptor autoantibody‐positive generalized MG (MGFA disease class II–IV) were randomized 1:1 to daily self‐administered subcutaneous zilucoplan 0.3 mg/kg or placebo injections for 12 weeks. The primary efficacy endpoint was change from baseline to week 12 in the MG Activities of Daily Living score. Safety was assessed by the incidence of treatment‐emergent adverse events. Efficacy and safety outcomes of a Japanese subgroup were prespecified. Results: Overall, 16 Japanese patients were randomized to zilucoplan 0.3 mg/kg (n = 7) or placebo (n = 9). There was a clinically meaningful improvement in the MG Activities of Daily Living score at week 12 for zilucoplan versus placebo in the Japanese population, with least squares mean difference of −4.26 (95% confidence interval −7.40, −1.12), which was comparable with the overall population. The incidence of treatment‐emergent adverse events was similar in both treatment arms, with 57.1% and 55.6% of patients in the zilucoplan and placebo groups, respectively, experiencing treatment‐emergent adverse events. Conclusions: In a subgroup of Japanese patients, zilucoplan showed clinically meaningful improvement in MG‐specific outcomes with a favorable safety profile, consistent with the overall RAISE population. [ABSTRACT FROM AUTHOR]

The primary purpose of the Japanese myasthenia gravis registry (JAMG‐R) has been to research and promote high‐quality medical care for MG patients in Japan. We reviewed the findings of surveys performed by JAMG‐R over an ~10‐y period. The first goal for favorable quality of life (QOL) is a status of minimal manifestations (MM) or better with an oral prednisolone (PSL) dose of 5 mg/d or less (MM‐5 mg). Early and aggressive use of nonoral fast‐acting treatment together with low‐dose oral PSL (the "EFT strategy") is recommended to reduce disease severity with minimal oral steroid use so that the MM‐5 mg target can be met as soon as possible. We conducted the fourth largest multicenter survey ever in 2021, obtaining detailed clinical information from 1710 consecutive MG patients all over Japan, and compared the 2021 surveys with those from 2012 and 2015. The frequency of patients treated with EFT strategies showed a gradual increase, reaching 39% of the total MG patients in the 2021 survey. The current and maximum dose of PSL and the number of days at high‐dose (>20 mg/d) PSL showed decreases. Survey results indicate that as EFT strategies have spread, the percentage of patients on MM‐5 mg has increased. We again confirmed that MM‐5 mg was associated with favorable QOL in the 2021 survey. Recent data regarding COVID‐19 suggests that it did not seriously impact the MG population in Japan; unfortunately, refractory MG, observed in 21% of patients, is still an unresolved problem. [ABSTRACT FROM AUTHOR]

The revised Japanese clinical guidelines for myasthenia gravis (MG) and Lambert–Eaton myasthenic syndrome (LEMS) were published in 2022. The notable points in these guidelines (GLs) are as follows: (i) these are the first Japanese GLs to include a description of LEMS; (ii) diagnostic criteria of MG are revised to lessen the incidence of false negative patients; (iii) MG is divided into six clinical subtypes; (iv) a high‐dose oral steroid regimen with escalation and de‐escalation schedule is not recommended by the GLs; (v) the GLs promote the early fast‐acting treatment strategy initially proposed in the previous GLs; (vi) refractory MG is defined; (vii) the use of molecular targeted drugs is included; (viii) diagnostic criteria of LEMS are proposed; and (ix) treatment algorithms for both MG and LEMS are presented. These new GLs are expected to improve the patients' quality of life and will serve to bridge the present era with the molecular targeted treatment eras. [ABSTRACT FROM AUTHOR]

Introduction: Eculizumab, 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. Methods: This 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. Results: Data 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 (<50/≥50 y); baseline age (18 to <40/≥40 to <65/≥65 y); Myasthenia Gravis Foundation of America disease classification (IIa/IIb/IIIa/IIIb/IVa/IVb/V); or baseline MG‐ADL score (<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. Conclusion: Eculizumab was well tolerated and effective in treating AChR Ab+ gMG across a broad spectrum of adult Japanese patients with difficult‐to‐control gMG. [ABSTRACT FROM AUTHOR]

Anti‐striational antibodies (StrAbs) have been described as serum immunoglobulins that react with cross‐striations of skeletal muscle in patients with myasthenia gravis (MG). StrAbs were expected to be useful biomarkers of MG; however, because of their low specificity, the diagnostic utility of StrAbs has been limited. The main autoantigens of StrAbs include titin, ryanodine receptor and Kv1.4. MG patients with StrAbs tend to suffer from bulbar symptoms and myasthenic crisis. The most remarkable finding regarding the clinical significance of StrAbs is their association with myositis concomitant with MG. Myocarditis is a lethal complication in MG patients, but it is treatable by immunotherapy. Patients with myocarditis usually show rapid deterioration, with serious arrhythmias and severe heart failure. As myocarditis often develops in patients with myositis accompanied by MG, MG with myositis and/or myocarditis is an important subset of patients. MG is one of the immune‐related adverse events associated with immune checkpoint inhibitors. MG with myositis and/or myocarditis is an infrequent subset of patients in the usual clinical settings; however, it is more common in patients with immune‐related adverse events. Anti‐titin and anti‐Kv1.4 antibodies were preferentially detected in patients with MG with myositis and/or myocarditis, and in patients with late‐onset and thymoma‐associated MG. The detection of StrAbs provides more specific and useful clinical information for the classification and management of MG patients, and identifies diagnostic biomarkers of serious immune‐related adverse events in cancer patients treated with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

A new version of the Japanese clinical guidelines for myasthenia gravis is under development. The current version was published in 2014, in which the top priority in treatment was to maintain patients' health‐related quality of life. The treatment goal was to achieve a post‐intervention status of minimal manifestations or better (according to the Myasthenia Gravis Foundation of America classification), with an oral prednisolone dose of 5 mg/day or less. The guidelines recommend minimizing the oral prednisolone dose, starting calcineurin inhibitors early in the course of treatment, and effectively treating patients with an early fast‐acting treatment regimen. Since the release of the 2014 version, the therapeutic tendencies in myasthenia gravis have been gradually changing in Japan, with an observed increase in the number of patients that achieved the treatment goal. Therefore, it is conceivable that the rationale of the 2014 guidelines was appropriate to treat patients with myasthenia gravis and that it should be taken over by the new guidelines. Meanwhile, the anti‐complement antibody (eculizumab) has been approved, and although off‐label in Japan, the effect of the anti‐CD20 antibody rituximab has been reported repeatedly. Many other agents are currently undergoing clinical trials. In the new guidelines, the treatment strategy should be demonstrated clearly, including these most recent developments. [ABSTRACT FROM AUTHOR]

Our multicenter studies have repeatedly shown that disease severity and oral steroid dose are major independent factors negatively impacting health‐related quality of life (QOL) in patients with myasthenia gravis (MG). Even if pharmacological remission is achieved, QOL is low in patients taking oral prednisolone >10 mg/day. Disease severity tends to affect QOL by decreasing personal activities, whereas insufficiently reduced steroids affects QOL by decreasing social activities. MG patients often experience unemployment and decreased income, and many patients report reduced social positivity. More effort is required to reduce both the severity and dose of oral steroids. QOL in patients with minimal manifestations (MM) or better status who are treated with prednisolone at ≤5 mg/day (MM‐or‐better‐5 mg) is almost identical to that in patients achieving complete stable remission. Early achievement of MM‐or‐better‐5 mg is now recommended as a target for MG treatment in Japan. However, our studies suggested that the percentage of patients achieving MM‐or‐better‐5 mg was not high in 2010 and 2012 (<40% of generalized MG patients), and was not considered to be increased by physician skill in steroid dosing. In Japan, treatment strategies are now being reconsidered to further increase treatment success, placing a focus on helping MG patients resume a normal lifestyle by achieving the target as soon as possible. An initial attempt to achieve early MM‐or‐better‐5 mg for some period through aggressive use of non‐oral fast‐acting therapies can be more important for patient QOL, even if long‐term stability cannot be provided. [ABSTRACT FROM AUTHOR]

Objectives: Most patients with myasthenia gravis (MG) undergo thoracic imaging at initial diagnosis. However, the follow‐up protocol is unclear. The objective of the present study was to clarify the follow‐up status and main findings of thoracic imaging in patients with MG. Methods: A total of 649 patients with disease duration ≥1 year were included in the study. The follow‐up rate and time from the initial scan to the latest thoracic imaging were evaluated. The rate of abnormality and details of abnormal findings in both non‐thymomatous MG and thymoma‐associated MG were investigated. Results: The follow‐up thoracic imaging rate of 145 patients with thymoma‐associated MG was 71.7%, whereas just 46.2% of 504 patients with non‐thymomatous MG underwent follow‐up imaging. Abnormal findings were detected in 8.6% of patients with non‐thymomatous MG and 26.0% of those with thymoma‐associated MG. Abnormal findings included cancer, lung infection and lymph node swelling in the former, and relapse or increased size of thymoma in the latter. Conclusions: Frequent follow up by thoracic imaging is necessary in patients with MG. The follow‐up thoracic imaging rate of patients with thymoma‐associated MG was 71.7%, whereas only 46.2% of patients with non‐thymomatous MG underwent follow‐up imaging. Abnormal findings were detected in 8.6% of patients with non‐thymomatous MG and 26.0% of those with thymoma‐associated MG. Frequent follow‐up by thoracic imaging is necessary in patients with MG. [ABSTRACT FROM AUTHOR]

Dermatomyositis (DM) is an idiopathic inflammatory myopathy, which not only affects skeletal muscle and skin, but it is also associated with arthritis/arthralgia, interstitial lung disease and cancer. The diagnostic criteria for myositis that Bohan and Peter formulated in 1975, which are often still used now, depend on the presence of a characteristic skin rash for classification of DM; without it, a diagnosis of polymyositis is given. However, advances in understanding the etiology of idiopathic inflammatory myopathies over the past few decades are impressive, encompassing discovery of myositis-specific/associated autoantibodies and development of muscle pathology, and enable us to classify them more precisely based on the underlying etiology. Correlations between clinical phenotypes and DM-specific autoantibodies (anti-Mi-2, TIF-1, NXP2, MDA5 and SAE) have been mostly elucidated, suggesting the diagnostic utility of autoantibody measurement. Advances in muscle pathology include analysis at the molecular level, such as the detection of myxovirus resistance protein A in myofibers, which can be used as a sensitive and specific pathological marker of DM. Today, a multidisciplinary approach - autoantibody profiling and pathological assessment, as well as clinical evaluation - is cardinal for a diagnosis of DM. The present review consolidates current knowledge about autoantibodies and muscle pathology in terms of diagnostic practice of DM. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathies ( IIM) are a heterogeneous group of subacute, chronic or acute systemic immune-mediated diseases of the skeletal muscles. Recently, research has shown the utility of adding new classifications of myopathies, mainly based on their pathology and the presence of specific autoantibodies. In addition, developments in genetics have helped reveal the genetic background of IIM. The human leukocyte antigen genomic region has been consistently shown to be the strongest genetic risk factor for IIM. The present review summarizes the previous and current literature on human leukocyte antigen analysis of IIM, as well as future directions for research. [ABSTRACT FROM AUTHOR]

Objectives Calcineurin inhibitors ( CNI) are approved for the treatment of myasthenia gravis ( MG) in Japan. However, the extent to which CNI have been effective remains unclear. Here we report data regarding CNI use and outcomes of MG. Methods We evaluated 640 consecutive MG patients by a multicenter survey. Patients not receiving any immune treatment were excluded, and cross-sectional and retrospective data of 515 patients receiving immune treatment with ( n = 312) or without ( n = 203) CNI were analyzed. Results Compared with patients treated without CNI, those treated with CNI had a higher frequency of MG Foundation of America Class III-V and higher severity disease at the worst clinical condition, and also had current higher severity, worse quality of life and higher daily doses of prednisolone, despite taking equivalent prednisolone dosages during the course of treatment. Achieving a treatment target was less frequent in the group treated with CNI. Onset age was not different between the two groups. Duration before CNI use after starting corticosteroids was 4.4 ± 6.3 years. Among those treated with CNI, late-onset MG patients achieved a more favorable current condition than did those with early-onset and thymoma-associated MG, whereas there was no such difference without CNI treatment. Conclusions CNI were given to severely ill MG patients with no attempt to select those more likely to respond, and failed to exert a strong impact on MG therapy. CNI should be given aggressively to patients with factors known to enhance susceptibility to these drugs, such as higher age at onset and early-stage disease. [ABSTRACT FROM AUTHOR]

Objective Myasthenia gravis ( MG) is classified as early-onset MG ( EOMG; age at onset ≤49 years), late-onset MG ( LOMG; age at onset ≥50 years) or thymoma-associated MG ( TAMG) (E-L-T classification). To clarify the characteristics of each group in the E-L-T classification in Japan, we carried out multicenter analyses of MG. Methods A total of 640 adult patients from 11 MG centers participated in the study. Age at onset, sex, clinical symptoms, frequency of crisis, thymic pathology, positivity of autoantibodies against acetylcholine receptor ( AChR) and muscle-specific receptor tyrosine kinase (Mu SK), selected treatment, Cushingoid appearance and post-intervention status were evaluated in each group. Results EOMG, LOMG and TAMG accounted for 44%, 33%, and 23% of the patients, respectively. Females predominated in the EOMG group (77%), whereas there was no sex difference in the LOMG group. The frequency of ocular MG was the highest in the LOMG group ( EOMG 15%, LOMG 38%, TAMG 12%). Bulbar symptoms and crisis were most frequent in the TAMG group. Anti- AChR antibody was always positive in patients with TAMG ( EOMG 70%, LOMG 78%, TAMG 99%), whereas anti-Mu SK antibody was never positive in TAMG patients, and more frequently detected in EOMG patients than in LOMG patients. Thymectomy was carried out in 51% of EOMG patients, 26% of LOMG patients and 97% of TAMG patients. Immunotherapy was carried out most aggressively in TAMG patients, and least aggressively in LOMG patients. Minimal manifestations or better with prednisolone ≤5 mg were achieved only in one-third of EOMG and TAMG patients. Conclusion Thymoma-associated MG required the most aggressive immunotherapy, followed by early-onset MG. [ABSTRACT FROM AUTHOR]

Our anti‐SRP and anti‐HMGCR ELISAs demonstrated excellent sensitivity and specificity compared to the previous methods. [ABSTRACT FROM AUTHOR]

Highlights from the article: Alternative to steroid therapy for myasthenia gravis and myositis occurring as immune-related adverse events We experienced a case of generalized myasthenia gravis and myositis occurring as immune-related adverse events that was curable without steroid therapy, only through the discontinuation of immune checkpoint inhibitor. Immunotherapy with immune checkpoint inhibitors has dramatically changed the treatment landscape for patients with cancer.

The article presents a case study of several patients diagnosed with skin manifestations including alopecia areata, vitiligo and pemphigus. Topics discussed include Thymoma-associated myasthenia gravis (T-MG)associated with skin inflammation in patient, loss of hair with Alopecia areata and Vitiligo characterized by appearance of white macules in the skin. It also mentions that Myasthenia Gravis (MG) was improved by thymomectomy and immunotherapy.