- |||||||||| Journal: Anti-MuSK positive myasthenia gravis with anti-Lrp4 and anti-titin antibodies. (Pubmed Central) - Apr 15, 2021
The patient developed MG crisis following a 10-year history of intermittent double vision with ptosis, and a 7-year history of dropped head. Our detailed clinical, laboratory, and therapeutic descriptions highlight its unique characteristics of anti-MuSK-antibody positive MG accompanied by anti-Lrp4 and anti-titin antibodies.
- |||||||||| prednisolone / Generic mfg.
Clinical, Journal, Checkpoint inhibition: A Case of Asymptomatic Immune Checkpoint Inhibitor-associated Myocarditis. (Pubmed Central) - Apr 15, 2021
High-dose prednisolone (PSL) is associated with a risk of MG exacerbation; therefore, PSL therapy was gradually increased from 5 mg/day to 20 mg/day, which resulted in the normalization of the TNI level, and no PSL-related side effects occurred. MG easily complicates myocarditis as an immune-related adverse event; thus, the treatment plan should be carefully considered.
- |||||||||| Soliris (eculizumab) / Alexion Pharma, efgartigimod IV (ARGX-113 IV) / argenx, Broteio
[VIRTUAL] Comparative Effectiveness and Safety of Efgartigimod in Generalized Myasthenia Gravis () - Apr 12, 2021 - Abstract #ISPOR2021ISPOR_1142;
Efgartigimod has a favorable comparative effectiveness and safety profile versus currently available gMG treatments. Limitations of this study include heterogeneity of study populations, differences in treatment administration, and small sample sizes across trials.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
[VIRTUAL] Cost-of-Illness for Adults with Generalized Myasthenia Gravis in the US () - Apr 12, 2021 - Abstract #ISPOR2021ISPOR_1092;
The 12-month period following a crisis event was also associated with high costs. CONCLUSIONS Beyond costs associated directly with crisis, use of immune-globulins, newly diagnosed status and the year prior to and following a crisis are a significant contributor to direct costs in adults with gMG in the US.
- |||||||||| mycophenolate mofetil / Generic mfg., azathioprine / Generic mfg.
[VIRTUAL] Conceptualization and Novel Budget Impact Analysis Framework for Treatments of Myasthenia Gravis () - Apr 12, 2021 - Abstract #ISPOR2021ISPOR_1075;
CONCLUSIONS : Future budget impact analysis for MG treatments should capture both direct pharmacy and medical costs including those related to disease exacerbations and treatment adverse effects. The framework includes all the identified core components essential to assessing the full budget impact of novel MG treatments on direct pharmacy and medical costs.
- |||||||||| [VIRTUAL] UPDATE ON IGG4 AUTOIMMUNE DISEASES: NEW FAMILY MEMBERS (HALL D) - Apr 11, 2021 - Abstract #AUTO2021AUTO_530;
IgG4 autoimmune diseases were found to be restricted to four distinct organs: 1) the central and peripheral nervous system, 2) the kidney, 3) the skin and mucous membranes and 4) the vascular system or soluble antigens in the blood circulation.ConclusionsIn conclusion, there are to date six class I (verified), five class II (likely) and ten class III IgG4 autoimmune diseases, of which five are class IIIa, with insufficient data and five class IIIb, which support pathogenic entities other than IgG4. The pathogenicity of IgG4 in IgG4 autoimmune diseases is associated with blocking of enzymatic activity or protein-protein interaction of their target antigen
- |||||||||| [VIRTUAL] THERAPEUTIC PLASMA EXCHANGE IN AUTOINMUNE NEUROLOGICAL DISEASES (HALL A) - Apr 11, 2021 - Abstract #AUTO2021AUTO_460;
Hypotension and hydroelectrolytic disorders were the main complications. After TPE, 99 (52.9%) patients showed improvement in the mRS scores and a statistical significance (p<0.05) was seen between the admission score and after TPE for every diagnosis except for CIDP.ConclusionsTPE has an adequate safety profile and improvement in functionality in treated patients reflects its effectiveness.
- |||||||||| [VIRTUAL] RISK FACTORS ASSOCIATED WITH MYASTHENIA GRAVIS IN THYMOMA PATIENTS: A LINK WITH ECTOPIC GERMINAL CENTERS (HALL B) - Apr 11, 2021 - Abstract #AUTO2021AUTO_448;
By immunohistochemistry, we found thymic GCs in the adjacent tissue of thymoma encircled by high endothelial venules (HEVs) that could favor peripheral cell recruitment. We also clearly associated MG symptoms with higher IFN-γ, IL-1β and sCD40L serum levels specifically in MGT compared to TOMA patients.ConclusionsAltogether, these analyses had allowed the clear identification of histological, in particular the presence of GCs, and biological parameters that would help to evaluate the probability of the outcome of MG post-operatively in thymoma patients.
- |||||||||| [VIRTUAL] BLOCKING THE IL-23/TH17 PATHWAY AMELIORATES MYASTHENIA GRAVIS SYMPTOMS IN AUTOIMMUNE MYASTHENIA GRAVIS MOUSE MODEL (HALL B) - Apr 11, 2021 - Abstract #AUTO2021AUTO_447;
More, increased muscle regeneration gene expression and significant muscular improvements were observed and correlated with amelioration of clinical symptoms and global disease score.ConclusionsAltogether these data suggest that an anti-IL-23 therapy could be beneficial in MG by acting on the thymic inflammatory state and on muscle physiology. The inhibition of IL-23 activates transduction pathways involved in antibody production and in muscle regeneration process favoring then disease amelioration.
- |||||||||| Clinical, Journal: Clinical and electrophysiological evaluation of myasthenic features in an alpha-dystroglycanopathy cohort (FKRP-predominant). (Pubmed Central) - Apr 10, 2021
A defective postsynaptic neuromuscular junction transmission was not identified in any of the patients carrying FKRP mutations but only in one mildly affected patient with GMPPB mutations (c.79 G>C, p.D27H and c.402+1G>A, splice site variant). We conclude that symptoms of fatigue with activity did not predict abnormal neuromuscular junction transmission on electrodiagnostic studies in this cohort and that, unlike GMPPB subgroup, a defective neuromuscular junction transmission does not appear to be present in patients with FKRP-associated muscular dystrophies.
- |||||||||| Clinical, Review, Journal: The epidemiology of myasthenia gravis. (Pubmed Central) - Apr 10, 2021
The incidence and prevalence of MG reported around the globe have been rising steadily and consistently over the past decades. Ethnic aspects, gender-related differences, and environmental risk factors have been described, implying that these might contribute to a specific phenotype, further suggesting that MG may be considered an umbrella term that covers several clinical entities.
- |||||||||| ondansetron/pyridostigmine (DAS-001) / DAS Therap
Enrollment open, Trial completion date, Trial primary completion date: Study of Pyridostigmine With Ondansetron in Subjects With Anti-AchR Positive Myasthenia Gravis (clinicaltrials.gov) - Apr 8, 2021
P2, N=24, Recruiting,
Applying the RNS test to limb muscles could be useful for predicting the conversion to generalized MG in patients with ocular onset. Not yet recruiting --> Recruiting | Trial completion date: Sep 2021 --> Apr 2022 | Trial primary completion date: Sep 2021 --> Apr 2022
- |||||||||| [VIRTUAL] EXPERIENCE OF 1,517 COVID-19 PEDIATRIC CASES IN ARGENTINA: MULTICENTER STUDY (Hall 02) - Apr 7, 2021 - Abstract #ESPID2021ESPID_129;
Not yet recruiting --> Recruiting | Trial completion date: Sep 2021 --> Apr 2022 | Trial primary completion date: Sep 2021 --> Apr 2022 In our study most cases were mild, had history of close contact with COVID-19 cases, PIMS was reported in 2% and COVID-19 lethality was 0.2%.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Review, Journal: Complement Inhibitor Therapy for Myasthenia Gravis. (Pubmed Central) - Apr 7, 2021
Second- and third-generation complement inhibitors are in development and approaching pivotal efficacy evaluations. This review will summarize the history and present the state of knowledge of this new therapeutic modality.
- |||||||||| Journal: Point Mutations of Nicotinic Receptor α1 Subunit Reveal New Molecular Features of G153S Slow-Channel Myasthenia. (Pubmed Central) - Apr 7, 2021
Introduction of L199T mutation to the C-loop in the vicinity of Ser 153 changed hydrogen bonds distribution, decreased acetylcholine potency (EC 2607 vs. 146 nM) of the double mutant and decay kinetics of acetylcholine-evoked cytoplasmic Ca rise (τ 14.2 ± 0.3 vs. 34.0 ± 0.4 s). These results shed light on molecular mechanisms of nAChR activation-desensitization and on the involvement of such mechanisms in channelopathy genesis.
- |||||||||| Review, Journal: Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics. (Pubmed Central) - Apr 7, 2021
Complement is a double-edged sword, since when dysregulated or overactivated it becomes the host's enemy, leading to tissue damage, organ failure, and, in worst case, death. A number of acute and chronic diseases are candidates for pharmacological treatment to avoid complement-dependent damage, ranging from the well established treatment for rare diseases to possible future treatment of large patient groups like the pandemic coronavirus disease 2019.
- |||||||||| Review, Journal: Central Role of T Follicular Helper Cells in Myasthenia Gravis. (Pubmed Central) - Apr 7, 2021
Recent studies have shown that the development and clinical progression of MG is closely associated with the abnormal function of follicular helper T (Tfh) cells. Thus, this article reviews the recently achieved research progress on the involvement of Tfh cells in MG immunopathogenesis and focuses on the role of Tfh cells and related-factors (IL-21, CXCL13, CXCR5, bcl-6 etc.) in germinal center formation and antibody production in MG immune response.
- |||||||||| Review, Journal: Conservation and Innovation: Versatile Roles for LRP4 in Nervous System Development. (Pubmed Central) - Apr 7, 2021
Additional findings indicate that LRP4 plays a role in disorders of the nervous system, including myasthenia gravis, amyotrophic lateral sclerosis, and Alzheimer's disease, demonstrating the need for further study to understand disease etiology. This review will highlight our current knowledge of how LRP4 functions in the nervous system, focusing on the diverse developmental roles and different modes this essential cell surface protein uses to ensure the formation of robust synaptic connections.
- |||||||||| Retrospective data, Review, Journal: Which Is the Best Treatment in Recurrent Thymoma? A Systematic Review and Meta-Analysis. (Pubmed Central) - Apr 7, 2021
This review will highlight our current knowledge of how LRP4 functions in the nervous system, focusing on the diverse developmental roles and different modes this essential cell surface protein uses to ensure the formation of robust synaptic connections. Surgical treatment after thymoma recurrence is associated with a significant better 5y OS; therefore, surgical resection should be preferred in all technically feasible cases.
- |||||||||| Clinical, Journal: GENOMIC AND EPIGENOMIC PREDICTORS FOR VARIOUS CLINICAL PHENOTYPES OF MYASTHENIA GRAVIS. (Pubmed Central) - Apr 7, 2021
Surgical treatment after thymoma recurrence is associated with a significant better 5y OS; therefore, surgical resection should be preferred in all technically feasible cases. Estimate the features of the formation of various variants of the immune response in thymus-independent and thymus-dependent myasthenia gravis is a necessary condition for targeted immunocorrection or surgery.
- |||||||||| Zilbrysq (zilucoplan) / UCB
Enrollment status, Trial completion date, Trial primary completion date: RAISE-XT: Open-Label Extension of Zilucoplan in Subjects With Generalized Myasthenia Gravis (clinicaltrials.gov) - Apr 5, 2021
P3, N=200, Enrolling by invitation,
The results were somewhat surprising, yet very robust, and thus raises the question if seronegative RA is in fact “more autoimmune” despite the absence of (identified) autoantibodies. Recruiting --> Enrolling by invitation | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023
- |||||||||| Remicade (infliximab) / Merck (MSD), Mitsubishi Tanabe, J&J, Enbrel (etanercept) / Pfizer, Amgen, efgartigimod IV (ARGX-113 IV) / argenx, Broteio
[VIRTUAL] Current and emerging therapies: what comes next? (Room Seville) - Apr 3, 2021 - Abstract #EAN2021EAN_297;
Contrasting data have been reported in the literature concerning the benefit of indirect B cells targeting agents, such as etanercept, infliximab, belimumab and bortezemib...Neonatal Fc receptor antagonists, including efgartigimod and rozanolixizumab, which reduce IgG plasma levels, blocking their recycling and increasing their clearance could be a promising therapeutic option in all forms of MG. Nevertheless, high cost, potential adverse events during chronic therapy, and production of anti-drug antibodies, could be some limitations of these new biologics which deserve to be considered.
- |||||||||| Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
[VIRTUAL] Old and new myasthenia gravis antibodies: what is our current phenotype understanding? (Room Seville) - Apr 3, 2021 - Abstract #EAN2021EAN_294;
LRP4 abs were shown to belong to the complement activating IgG1 subtype and to be able to disrupt agrinLRP4 signalling. With regard to the upcoming new therapeutic agents in MG the determination of ab IgGsubclass type has gained increasing relevance/implications for treatment strategies.
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