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Myasthenia gravis (MG) is an antibody-mediated disorder of the neuromuscular junction affecting children and adults. MG is a treatable condition with most patients requiring immunosuppression for disease control and/or remission. Juvenile myasthenia gravis (JMG) is rare in comparison with adult-onset MG but given the same underlying pathophysiology, treatment strategies are similar to those in adults. Until recently, there were only a few randomised controlled trials (RCTs) for MG treatments in adults and none in children, and management strategies were primarily based on expert consensus. In addition, treatment options for refractory MG cases have been severely limited, resulting in poor long-term quality of life in such patients due to the significant disease burden. Recently, there have been several RCTs focussing on novel therapeutic strategies with potentially promising outcomes, suggesting a change in MG management over the coming years and access to more effective and faster-acting drugs for MG patients. This paper will review current and new MG treatments including efgartigimod, eculizumab, rozanolixizumab, ravulizumab, and zilucoplan, with a focus on juvenile myasthenia gravis.

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

Generalized myasthenia gravis (MG) with antibodies against the acetylcholine receptor is a chronic disease causing muscle weakness. Access to novel treatments warrants authoritative treatment recommendations. The Nordic countries have similar, comprehensive health systems, mandatory health registers, and extensive MG research. MG experts and patient representatives from the five Nordic countries formed a working group to prepare treatment guidance for MG based on a systematic literature search and consensus meetings. Pyridostigmine represents the first-line symptomatic treatment, while ambenonium and beta adrenergic agonists are second-line options. Early thymectomy should be undertaken if a thymoma, and in non-thymoma patients up to the age of 50-65 years if not obtaining remission on symptomatic treatment. Most patients need immunosuppressive drug treatment. Combining corticosteroids at the lowest possible dose with azathioprine is recommended, rituximab being an alternative first-line option. Mycophenolate, methotrexate, and tacrolimus represent second-line immunosuppression. Plasma exchange and intravenous immunoglobulin are used for myasthenic crises and acute exacerbations. Novel complement inhibitors and FcRn blockers are effective and fast-acting treatments with promising safety profiles. Their use depends on local availability, refunding policies, and cost-benefit analyses. Adapted physical training is recommended. Planning of pregnancies with optimal treatment, information, and awareness of neonatal MG is necessary. Social support and adaptation of work and daily life activities are recommended. Successful treatment of MG rests on timely combination of different interventions. Due to spontaneous disease fluctuations, comorbidities, and changes in life conditions, regular long-term specialized follow-up is needed. Most patients do reasonably well but there is room for further improvement. Novel treatments are promising, though subject to restricted access due to costs.

International guidelines on the treatment of myasthenia gravis (MG) have been published but are not tailored to the Belgian situation. This publication presents recommendations from a group of Belgian MG experts for the practical management of MG in Belgium. It includes recommendations for treatment of adult patients with generalized myasthenia gravis (gMG) or ocular myasthenia gravis (oMG). Depending on the MG-related antibody a treatment sequence is suggested with therapies that can be added on if the treatment goal is not achieved. Selection of treatments was based on the level of evidence of efficacy, registration and reimbursement status in Belgium, common daily practice and the personal views and experiences of the authors. The paper reflects the situation in February 2024. In addition to the treatment considerations, other relevant aspects in the management of MG are addressed, including comorbidities, drugs aggravating disease symptoms, pregnancy, and vaccination. As many new treatments might potentially come to market, a realistic future perspective on the impact of these treatments on clinical practice is given. In conclusion, these recommendations intend to be a guide for neurologists treating patients with MG in Belgium.

Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating weakness and early fatigability of ocular, skeletal and bulbar muscles. Despite being commonly considered a prototypic autoimmune disorder, MG is a complex and heterogeneous condition, presenting with variable clinical phenotypes, likely due to distinct pathophysiological settings related with different immunoreactivities, symptoms’ distribution, disease severity, age at onset, thymic histopathology and response to therapies. Current treatment of MG based on international consensus guidelines allows to effectively control symptoms, but most patients do not reach complete stable remission and require life-long immunosuppressive (IS) therapies. Moreover, a proportion of them is refractory to conventional IS treatment, highlighting the need for more specific and tailored strategies. Precision medicine is a new frontier of medicine that promises to greatly increase therapeutic success in several diseases, including autoimmune conditions. In MG, B cell activation, antibody recycling and NMJ damage by the complement system are crucial mechanisms, and their targeting by innovative biological drugs has been proven to be effective and safe in clinical trials. The switch from conventional IS to novel precision medicine approaches based on these drugs could prospectively and significantly improve MG care. In this review, we provide an overview of key immunopathogenetic processes underlying MG, and discuss on emerging biological drugs targeting them. We also discuss on future direction of research to address the need for patients’ stratification in endotypes according with genetic and molecular biomarkers for successful clinical decision making within precision medicine workflow.

Background To investigate the frequency and characterize the clinical features of treatment-refractory myasthenia gravis in an Austrian cohort. Methods Patient charts of 126 patients with generalized myasthenia gravis and onset between 2000 and 2016 were analyzed retrospectively. Patients were classified as treatment-refractory according to strict, predefined criteria. These mandated patients being at least moderately symptomatic (i.e., MGFA class III) or needing either maintenance immunoglobulins or plasma exchange therapy for at least 1 year in spite of two adequately dosed immunosuppressive drugs. Clinical features and outcome at last follow-up were compared to treatment-responsive patients. Results 14 out of 126 patients (11.1%) met these criteria of treatment-refractory myasthenia gravis. Treatment-refractory patients had more frequent clinical exacerbations and more often received rescue treatments or a further escalation of immunosuppressive therapies. They also remained more severely affected at last follow-up. An early onset of myasthenia gravis was associated with a higher risk for a refractory course. Conclusion A small subgroup of patients with generalized myasthenia gravis do not respond sufficiently to standard therapies. Refractory disease has considerable implications for both patients and health care providers and highlights an unmet need for new treatment options.

Muscle-specific kinase (MuSK) myasthenia gravis (MG) is relatively rare and has a higher incidence of myasthenic crisis compared with other subtypes. However, there is still a lack of effective treatment for refractory MuSK MG. We report the case of a 70-year-old female MuSK MG patient with recurrent fluctuations who stabilized on telitacicept in combination with anti-CD20 B-cell depletion therapy. This combination regimen deserves further investigation. Furthermore, we summarized the treatment protocols of 14 previously reported cases of MuSK MG.

Background This study aimed to describe treatment patterns in patients with myasthenia gravis (MG) in France. Methods A retrospective cohort analysis was performed using the French National Health Data System (SNDS) database between 2008 and 2019. MG patients were identified using ICD-10 codes during hospitalization and/or long-term disease. We defined two adult subpopulations: a prevalent MG population of patients alive on 31/12/2019 and an incident population of newly identified patients with MG in 2012 and 2013. Results Among the 22,079 prevalent patients, 53.1% ( n  = 11,498) received at least one chronic MG treatment in 2019. Among these treated patients, 52.5% received Acetylcholinesterase inhibitors (AChEIs) only, 10.2% were treated with corticosteroids (CS) ± AChEIs, 7.3% with non-steroidal immunosuppressive treatments (NSIST) and CS, 24.2% with NSIST w/o CS, and 5.8% received immunoglobulin and/or plasma exchange. Among the 2,661 incident patients, 84.6% received at least one chronic MG treatment over the 6-year follow-up period, and among them, 79.0% had at least one treatment category change. During the first semester of follow-up, 28.1% of patients were treated with an immunomodulator (CS, NSIST). Among patients starting treatment with immunomodulator, the proportion of those treated with CS decreased from 35.3% at initiation to 10.9% at 6 years. Conclusion This study illustrates the complexity of MG management. Significant CS sparing was observed over time. The frequent treatment changes especially in patients with an immunomodulator treatment reflect the high variability of the disease severity. The need for personalised treatment approaches in the management of MG to reduce the burden of disease remains.

Background Several innovative treatments are expected for myasthenia gravis (MG) in the coming years. Healthcare payers usually require cost-effectiveness analyses before reimbursement. We aimed to investigate resource utilization and direct medical costs for patients with MG treated with intravenous immunoglobulin (IVIg) to inform such analyses. Methods We identified patients with MG in the Norwegian Patient Registry based on at least two hospital encounters with an MG diagnosis (ICD-10 G70.0) from 1 Jan 2010 to 31 Dec 2021. IVIg treatment was identified by medical procedure and Anatomical Therapeutic Chemical (ATC) codes (RPGM05 and J06BA02). Using Diagnosis-Related Group (DRG) cost weights, we estimated direct medical costs for each year following the first MG diagnosis. Results Over the study period, 1083 patients were diagnosed with MG in Norway, of whom 155 (14.3%) were treated with IVIg. No significant differences in age or sex were observed between IVIg and non-IVIg patients. Compared with non-IVIg patients, IVIg-patients had 2.3 times higher direct medical costs during the first year after MG diagnosis (EUR 35,714 vs. EUR 15,457) and 3.1 times higher costs during the second year (EUR 19,119 vs. EUR 6256). In the fifth year after diagnosis, IVIg-patients still had higher costs and resource utilization than non-IVIg patients (EUR 9953 vs. EUR 5634). Conclusion IVIg treatment represents an important marker for high direct medical costs among patients with MG. The costs continue to be high during the first five years after MG diagnosis.

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