Myasthenia gravis: the future is here

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(12)

Published: June 16, 2024

Myasthenia gravis (MG) stands as a prototypical antibody-mediated autoimmune disease: it is dependent on T cells and characterized by the presence of autoantibodies targeting proteins located postsynaptic surface skeletal muscle, known neuromuscular junction. Patients with MG exhibit spectrum weakness, ranging from limited ocular muscle involvement to life-threatening respiratory failure. Recent decades have witnessed substantial progress in understanding underlying pathophysiology, leading delineation distinct subcategories within MG, including linked AChR or MuSK antibodies well age-based distinction, thymoma-associated, immune checkpoint inhibitor–induced MG. This heightened has paved way for development more precise targeted therapeutic interventions. Notably, FDA recently approved inhibitors complement IgG receptor FcRn, testament our improved comprehension autoantibody effector mechanisms In this Review, we delve into various subgroups stratified age, type, histology thymus neoplasms. Furthermore, explore both current potential emerging strategies, shedding light evolving landscape treatment.

Language: Английский

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Expert consensus recommendations for improving and standardising the assessment of patients with generalised myasthenia gravis

European Journal of Neurology, Journal Year: 2024, Volume and Issue: 31(7)

Published: March 24, 2024

Regular and consistent disease assessment could provide a clearer picture of burden in generalised myasthenia gravis (gMG) improve patient care; however, the use tools practice lacks standardisation. This modified Delphi approach was taken to review current evidence on tool gMG develop expert-derived consensus recommendations for good practice.

Language: Английский

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Rozanolixizumab in generalized myasthenia gravis: Pooled analysis of the Phase 3 MycarinG study and two open-label extensions

Journal of Neuromuscular Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Background: Myasthenia gravis (MG) is a chronic autoimmune disease causing fluctuating muscle weakness. The MycarinG study showed that rozanolixizumab, neonatal Fc receptor inhibitor, provided clinically meaningful improvements in MG outcomes patients with acetylcholine (AChR) and muscle-specific tyrosine kinase (MuSK) autoantibody-positive generalized (gMG). Objective: We assessed efficacy safety of 6-week rozanolixizumab treatment cycles gMG. Methods: Following MycarinG, eligible enrolled the open-label extension Phase 3 studies MG0004 (NCT04124965) to receive up 52 weekly infusions or MG0007 (NCT04650854) 6 (initiated on symptom worsening at investigators’ discretion). To assess effect repeated cyclical treatment, data were pooled across (first weeks) (interim analysis). Efficacy endpoints included change from baseline Gravis Activities Daily Living (MG-ADL), Composite (MGC) Quantitative (QMG) who received ≥2 symptom-driven cycles. Treatment-emergent adverse events (TEAEs) ≥1 cycle had an (up to) 8-week follow-up period. Results: At cut-off (July 8, 2022), 188/196 (95.9%) period (primary pool; MycarinG/MG0007) 127 (64.8%) MycarinG/MG0004 [first weeks]/MG0007). Consistent MG-ADL, MGC QMG scores, high response rates, observed end first subsequent TEAEs experienced by 169/188 (89.9%) mostly mild moderate. did not increase Conclusions: Repeated resulted consistent, MG-specific acceptable profile, supporting as option for adults AChR MuSK

Language: Английский

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Efficacy and safety of rozanolixizumab in patients with muscle-specific tyrosine kinase autoantibody-positive generalised myasthenia gravis: a subgroup analysis of the randomised, double-blind, placebo-controlled, adaptive phase III MycarinG study

Therapeutic Advances in Neurological Disorders, Journal Year: 2024, Volume and Issue: 17

Published: Jan. 1, 2024

Muscle-specific tyrosine kinase (MuSK) autoantibody-positive (Ab+) generalised myasthenia gravis (gMG) is a rare and frequently severe subtype of gMG.

Language: Английский

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Application of digital tools and artificial intelligence in the Myasthenia Gravis Core Examination

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 4, 2024

Advances in video image analysis and artificial intelligence provide opportunities to transform how patients are evaluated. In this study, we assessed the ability quantify Zoom recordings of a standardized neurological examination- Myasthenia Gravis Core Examination (MG-CE)-designed for telemedicine evaluations. We used (Zoom Video Communications) videos with myasthenia gravis (MG) who underwent MG-CE. Computer vision, combination methods, was develop algorithms analyze videos, focus on eye body motions. To assess examinations involving vocalization, signal processing such as natural language (NLP), were developed. A series developed automatically compute metrics total 51 MG assessed, recorded twice separate days, while 15 control subjects evaluated once. successfully quantified positions lids, eyes, arms respiratory based breath counts. The cheek puff exercise found have limited value quantification. Technical limitations included variations illumination, bandwidth, fact that recording conducted from examiner's side rather than patient's side. Several aspects MG-CE can be produce continuous measurements using standard recordings. Further development technology will enable trained non-physician healthcare providers conduct precise outside conventional clinical settings, including purpose trials.

Language: Английский

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Myasthenia gravis in 2025: five new things and four hopes for the future

Journal of Neurology, Journal Year: 2025, Volume and Issue: 272(3)

Published: Feb. 22, 2025

Abstract The last 10 years has brought transformative developments in the effective treatment of myasthenia gravis (MG). Beginning with randomized trial thymectomy that demonstrated efficacy nonthymomatous MG, several new approaches have completed successful clinical trials and regulatory launch. These modalities, including B cell depletion, complement inhibition, blockade neonatal Fc receptor, are now use, offering prospects sustained remission neuromuscular protection what is a long-term disease. In this review, we update our clinico-immunological review 2016 these important advances, examine their role algorithms, focus attention on key issues biomarkers for prognostication growing cohort older patients, both those disease, late-onset MG (‘LOMG’). We close by expressing four hopes next 5–10 years: improvements laboratory medicine to facilitate rapid diagnosis, strategies protection, more research into better understanding pathophysiology response individuals, potentially therapies aimed at delivering durable such as chimeric antigen receptor (CAR) T cells. Our postscript summarizes some emerging themes field serological online biomarkers, which may develop greater stature epoch.

Language: Английский

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Safety and efficacy of chronic weekly rozanolixizumab in generalized myasthenia gravis: the randomized open-label extension MG0004 study

Journal of Neurology, Journal Year: 2025, Volume and Issue: 272(4)

Published: March 19, 2025

In the Phase 3 MycarinG study (NCT03971422), six once-weekly subcutaneous infusions of rozanolixizumab significantly improved myasthenia gravis (MG)-specific outcomes versus placebo in patients with acetylcholine receptor or muscle-specific tyrosine kinase autoantibody-positive generalized MG (gMG). Following completion MycarinG, could enroll open-label extension MG0004 (NCT04124965) to receive chronic weekly rozanolixizumab. Patients were re-randomized 1:1 7 10 mg/kg for up 52 infusions. The primary endpoints occurrence treatment-emergent adverse events (TEAEs) and TEAEs leading discontinuation. After ≥6 visits/infusions switch MG0007 (NCT04650854) cyclic treatment. MG0004, 70 received (n = 35) 35). Mean treatment duration was 22.9 23.7 weeks, respectively, due rollover into MG0007. reported 60/70 (85.7%) patients; most mild/moderate. frequently headache (25/70 [35.7%]), diarrhea (13/70 [18.6%]) decreased blood immunoglobulin G (11/70 [15.7%]). There no opportunistic, serious severe infections, hypersensitivity injection-site reactions, any anaphylactic reactions albumin lipid abnormalities. Maximum mean reduction from baseline Activities Daily Living score 3.1 group 4.1 group. Chronic generally well tolerated, clinically relevant improvements across MG-specific maintained, supporting long-term use gMG. NCT04124965 (registered October 11, 2019).

Language: Английский

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Real-World Case Series of Ravulizumab Use in Patients with Myasthenia Gravis in Romania

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(4), P. 350 - 350

Published: March 28, 2025

Background and Objectives: Ravulizumab, a long-acting C5 complement inhibitor, was approved in the US Europe 2022 as an add-on therapy for standard treatment of AChR-positive generalized MG (gMG). We share our real-world experience with adult patients receiving this Romania. Materials Methods: Six gMG received ravulizumab through Early Access Program (January 2023-October 2024). Patient outcomes were assessed at start q8w using Quantitative (QMG), Activities Daily Living (MG-ADL), Quality Life 15-item revised (MG-QoL15r) scales. Results: Age disease onset ranged from 15 to 35 years. Four six women. Two had severity level IIa, four IIb according Myasthenia Gravis Foundation America (MGFA) classification. Five experienced rapid sustained improvements symptoms MG-ADL score reductions -3 -5 26 weeks post-ravulizumab (except those low baseline score: three one). QMG dropped (-2 12) during period, increased two (+2 +8), remained stable one (zero). Three showed improvement after ≥60 weeks. MG-QoL15r significantly (-22 -10) throughout period. One patient ravulizumab-associated adverse events (vomiting, diarrhea, chills) that resolved within 24 h following symptomatic management, episodes myasthenic exacerbations treatment, discontinued it. Conclusions: All cases presented here early-onset AChR antibody-positive, non-thymomatous MG. Despite differences duration underlying conditions, clinically meaningful symptoms, reduced corticosteroid doses observed all except adding plan.

Language: Английский

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Challenges navigating thymectomy with myasthenia gravis: A qualitative study of patient treatment experiences

Applied Nursing Research, Journal Year: 2025, Volume and Issue: unknown, P. 151961 - 151961

Published: May 1, 2025

Language: Английский

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Registered trials on novel therapies for myasthenia gravis: a cross-sectional study on ClinicalTrials.gov

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 24, 2024

Abstract Novel biologics in MG therapy research is on the rise. This aimed to investigate characteristics of registered trials novel therapies for myasthenia gravis ClinicalTrials.gov. cross-sectional study used a descriptive approach assess features included We found 62 from 2007 2023 The results showed yearly rise number (r = 0.76, p < 0.001). Following 2017, more industry-sponsored were conducted (91.5% [43] vs. 60% [9], 0.009), fewer released (10.6% [5] 0.001), and entered phase 3 (67.4% [31] 20% [2], most researched medications neonatal Fc receptor inhibitors (51.2% [21]), complement (39.0% [16]), B cell depletors (14.6% [6]). According website’s data, effective treating patients three (NCT03315130, NCT03669588, NCT00727194). provides valuable insights into profile gravis. More clinical studies are needed future prove value its application.

Language: Английский

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