Eculizumab as a promising treatment in thymoma-associated myasthenia gravis

Vélez-Santamaría, Valentina; Nedkova, Velina; Díez, Laura; Homedes, Christian; Alberti, M.; Casasnovas, Carlos

doi:10.1177/1756286420932035

Cited by 11 publications

(9 citation statements)

References 9 publications

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“…To date, Eculizumab act as one of the complement system inhibitors, it is the only approved drug for FDA (Soliris; Alexion Pharmaceuticals Inc., Cheshire, CT, USA). Eculizumab effectively treats paroxysmal nocturnal hemoglobinuria [ 37 , 38 ], atypical hemolytic-uremic syndrome [ 37 , 39 , 40 ], transplant-associated thrombotic microangiopathies [ 36 , 41 ], and autoimmune neuromuscular disorders [ 42 ]. Treatment with eculizumab has recently been reported in four severe COVID-19 related ARDS cases in Italy [ 43 ].…”

Section: The Therapeutic Perspective Of Complement Inhibitors In Sarsmentioning

confidence: 99%

An update: the emerging evidence of complement involvement in COVID-19

Chen

2021

Med Microbiol Immunol

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The current outbreak of coronavirus disease 2019 (COVID-19) has affected people around the world. Typically, COVID-19 originates in the lung, but lately it can extend to other organs and lead to tissue injury and multiorgan failure in severe patients, such as acute respiratory distress syndrome (ARDS), kidney failure and sepsis or systemic inflammation. Given that COVID-19 has been detected in a range of other organs, the COVID-19-associated disease is an alert of aberrant activation of host immune response which drives un-controlled inflammation that affects multiple organs. Complement is a vital component of innate immunity where it forms the first line of defense against potentially harmful microbes, but its role in COVID-19 is still not clear. Notably, the abnormal activation and continuous deposits of complement components were identified in the pre-clinical samples from COVID-19 patients, which have been confirmed in animal models. Recent evidence has revealed that the administration of complement inhibitors leads to relieve inflammatory response in ARDS. Hence, we speculate that the targeting complement system could be a potential treatment option for organ damage in COVID-19 patients.

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Section: The Therapeutic Perspective Of Complement Inhibitors In Sarsmentioning

confidence: 99%

An update: the emerging evidence of complement involvement in COVID-19

Chen

2021

Med Microbiol Immunol

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“…ImmunoTargets and Therapy 2020:9 64 Mohebnasab et al 65 Kerboua et al 70 Liu et al 71 Complement activation products C3a, C5a, sC5b9…”

Section: Dovepressmentioning

confidence: 99%

Section: Complement Inhibition In Mg Therapeuticsmentioning

confidence: 99%

“…However, recent evidences of case reports demonstrate that eculizumab represents a valid therapeutic approach also for thymoma-associated MG, which strongly associates with treatment-refractory disease. 65,66 Ravulizumab Ravulizumab (Ultomiris) is another recombinant humanized monoclonal antibody developed by Alexion Pharmaceuticals that binds the complement protein C5 with high affinity. Ravulizumab was primarily tested and then approved for PNH in the USA, following positive results of two phase III clinical trials, on December 2018.…”

mentioning

confidence: 99%

“…• Mohebnasab et al 65 Willrich et al 68 Wijnsma et al; 69 Kerboua et al 70 Yanagidaira et al 72 Howard et al 63…”

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<p>Complement Inhibition for the Treatment of Myasthenia Gravis</p>

Mantegazza

Vanoli

Frangiamore

et al. 2020

ITT

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Generalized myasthenia gravis (gMG) is a rare autoimmune disorder affecting the neuromuscular junction (NMJ). Approximately 80–90% of patients display antibodies directed against the nicotinic acetylcholine receptor (AChR). A major drive of AChR antibody-positive MG pathology is represented by complement activation. The role of the complement cascade has been largely demonstrated in patients and in MG animal models. Complement activation at the NMJ leads to focal lysis of the post-synaptic membrane, disruption of the characteristic folds, and reduction of AChR. Given that the complement system works as an activation cascade, there are many potential targets that can be considered for therapeutic intervention. Preclinical studies have confirmed the efficacy of complement inhibition in ameliorating MG symptoms. Eculizumab, an antibody directed towards C5, has recently been approved for the treatment of AChR antibody-positive gMG. Other complement inhibitors, targeting C5 as well, are currently under phase III study. Complement inhibitors, however, may present prohibitive costs. Therefore, the identification of a subset of patients more or less prone to respond to such therapies would be beneficial. For such purpose, there is a critical need to identify possible biomarkers predictive of therapeutic response, a field not yet sufficiently explored in MG. This review aims to give an overview of the complement cascade involvement in MG, the evolution of complement-inhibiting therapies and possible biomarkers useful to tailor and monitor complement-directed therapies.

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RETRACTED ARTICLE: MiR-522-3p inhibits proliferation and activation by regulating the expression of SLC31A1 in T cells

Wang

Sun

et al. 2021

Cytotechnology

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Eculizumab as a promising treatment in thymoma-associated myasthenia gravis

Cited by 11 publications

References 9 publications

An update: the emerging evidence of complement involvement in COVID-19

An update: the emerging evidence of complement involvement in COVID-19

<p>Complement Inhibition for the Treatment of Myasthenia Gravis</p>

RETRACTED ARTICLE: MiR-522-3p inhibits proliferation and activation by regulating the expression of SLC31A1 in T cells

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