Novel Immunotherapies for Myasthenia Gravis

Nair, Sruthi S; Jacob, Saiju

doi:10.2147/itt.s377056

Cited by 27 publications

(10 citation statements)

References 114 publications

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“…Three main groups of biologics have been developed for clinical use, targeting the neonatal Fc receptor (FcRn), the complement cascade, and B cells [11]. The FcRn is a multifunctional Fc-gamma receptor [12,13] that during fetal life promotes the transplacental transfer of maternal antibodies to the fetus.…”

Section: Introductionmentioning

confidence: 99%

Efgartigimod in generalized myasthenia gravis: A real‐life experience at a national reference center

Frangiamore,

Rinaldi,

Vanoli

et al. 2024

Euro J of Neurology

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Background and purposeInhibition of the neonatal Fc receptor (FcRn) for IgG is a promising new therapeutic strategy for antibody‐mediated disorders. We report our real‐life experience with efgartigimod (EFG) in 19 patients with generalized myasthenia gravis (gMG) along a clinical follow‐up of 14 months.MethodsEFG was administered according to the GENERATIVE protocol (consisting of a Fixed period of two treatment cycles [given 1 month apart] of four infusions at weekly intervals, followed by a Flexible period of re‐cycling in case of worsening). Eight patients were positive for acetylcholine receptor antibody, four for muscle‐specific tyrosine kinase antibody, and two for lipoprotein‐related protein 4 antibody, and five were classified as triple negative. Efficacy of EFG was assessed by the Myasthenia Gravis Activities of Daily Living, Myasthenia Gravis Composite, and Quantitative Myasthenia Gravis scales.ResultsFifty‐three percent of patients needed three treatment cycles, 26% needed four, and 21% needed five along the 14‐month clinical follow‐up. Meaningful improvement was observed at the end of each cycle with the clinical scores adopted. EFG had a dramatic effect on disease course, as during the year before treatment eight of 19 patients (42%) were hospitalized, and 15 of 19 (79%) needed treatment with plasma exchange or immunoglobulins; three of 19 (16%) were admitted to the intensive care unit. During EFG, none of the patients was hospitalized and only one patient required plasma exchange and intravenous immunoglobulins. No major side effects or infusion‐related reactions occurred.ConclusionsWe observed that EFG was safe and modified significantly the course of the disease along a 14‐month follow‐up. Our experience strengthens the role of FcRn inhibition as an effective new tool for long‐term treatment of gMG.

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Section: Introductionmentioning

confidence: 99%

Efgartigimod in generalized myasthenia gravis: A real‐life experience at a national reference center

Frangiamore,

Rinaldi,

Vanoli

et al. 2024

Euro J of Neurology

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“…1 From an immunopathological point of view, autoimmune MG is a prototype autoimmune disorder mediated by B cells and dependent on T helper cells (Th) as the main culprits are autoantibodies directed against various components of the NMJ. 2 Although the pathogenesis of MG is well characterised and is one of the best understood autoimmune disorders, its causes have not been precisely elucidated. The general consensus is that MG, like many other autoimmune non-monogenic diseases, is a multi-factorial disorder, triggered through epigenetic mechanisms by several exogenous factors which bombard an individual genetically predisposed to autoimmunity.…”

Section: Introductionmentioning

confidence: 99%

Autoimmune myasthenia gravis and COVID-19. A case report-based review

et al. 2023

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A potential relationship between COVID-19 infection and new onset myasthenia gravis (MG) has been suggested by the coexistence of these two diseases in a number of reports. This study aimed to assess their relationship by reviewing case studies of COVID-19 followed by new onset MG published between 01 December 2019 and 30 June 2023 identified by a search of PubMed/Medline database. In addition, we reviewed evidence in favour and against a potential cause and effect association, and described possible mechanisms that would underpin such a relationship. We identified 14 publications that reported 18 cases. Analysis showed the following features: age 19–83 years; 10 men/8 women; median time interval between COVID-19 and MG (17, 5–56 days); autoimmune comorbidities (4); generalised MG (14); ocular MG (4); thymoma (3); antiacetylcholine receptor antibody (16); antimuscle-specific kinase antibodies (2). All patients improved following treatment. Proof of direct causality between the two conditions can only be established in time by confirming epidemiological increase in the incidence of MG or elucidating pathogenic mechanisms to substantiate a possible cause-effect association, or both.

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“…B cells play a key role in host defense by secreting antibodies, which are the components of the humoral adaptive immune system [ 48 ]. B-cell-specific surface antigens MS4A1 and CD19 are used as targets in many autoimmune diseases, including MG, with MS4A1 surface molecule (aka CD20) being the most reliable marker of B lymphocytes and CD19 is expressed on a broader group of cells [ 49 ]. MS4A1 is thought to function for B cell activation, proliferation, and differentiation and is associated with a variety of B cell surface molecules [ 50 , 51 , 52 ].…”

Section: Resultsmentioning

confidence: 99%

Delving into Molecular Pathways: Analyzing the Mechanisms of Action of Monoclonal Antibodies Integrated in IMGT/mAb-DB for Myasthenia Gravis

Golfinopoulou,

Giudicelli,

Manso

et al. 2023

Vaccines

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Background: Myasthenia Gravis (MG) is a rare autoimmune disease presenting with auto-antibodies that affect the neuromuscular junction. In addition to symptomatic treatment options, novel therapeutics include monoclonal antibodies (mAbs). IMGT®, the international ImMunoGeneTics information system®, extends the characterization of therapeutic antibodies with a systematic description of their mechanisms of action (MOA) and makes them available through its database for mAbs and fusion proteins, IMGT/mAb-DB. Methods: Using available literature data combined with amino acid sequence analyses from mAbs managed in IMGT/2Dstructure-DB, the IMGT® protein database, biocuration allowed us to define in a standardized way descriptions of MOAs of mAbs that target molecules towards MG treatment. Results: New therapeutic targets include FcRn and molecules such as CD38, CD40, CD19, MS4A1, and interleukin-6 receptor. A standardized graphical representation of the MOAs of selected mAbs was created and integrated within IMGT/mAb-DB. The main mechanisms involved in these mAbs are either blocking or neutralizing. Therapies directed to B cell depletion and plasma cells have a blocking MOA with an immunosuppressant effect along with Fc-effector function (MS4A1, CD38) or FcγRIIb engager effect (CD19). Monoclonal antibodies targeting the complement also have a blocking MOA with a complement inhibitor effect, and treatments targeting T cells have a blocking MOA with an immunosuppressant effect (CD40) and Fc-effector function (IL6R). On the other hand, FcRn antagonists present a neutralizing MOA with an FcRn inhibitor effect. Conclusion: The MOA of each new mAb needs to be considered in association with the immunopathogenesis of each of the subtypes of MG in order to integrate the new mAbs as a viable and safe option in the therapy decision process. In IMGT/mAb-DB, mAbs for MG are characterized by their sequence, domains, and chains, and their MOA is described.

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Novel Immunotherapies for Myasthenia Gravis

Cited by 27 publications

References 114 publications

Efgartigimod in generalized myasthenia gravis: A real‐life experience at a national reference center

Efgartigimod in generalized myasthenia gravis: A real‐life experience at a national reference center

Autoimmune myasthenia gravis and COVID-19. A case report-based review

Delving into Molecular Pathways: Analyzing the Mechanisms of Action of Monoclonal Antibodies Integrated in IMGT/mAb-DB for Myasthenia Gravis

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