Frauke Stascheit, Carla Daiane Ferreira de Sousa, Annette Aigner, Malina Behrens, Christian W Keller, Luisa Klotz, Sophie Lehnerer, Maike Stein, Meret Herdick, Paolo Doksani, Lea M Gerischer, Sarah Hoffmann, Konstantinos Lazaridis, John Tzartos, Heinz Wiendl, Andreas Meisel, Jan D Lünemann
{"title":"Ravulizumab和Efgartigimod治疗肌萎缩症:一项真实世界研究","authors":"Frauke Stascheit, Carla Daiane Ferreira de Sousa, Annette Aigner, Malina Behrens, Christian W Keller, Luisa Klotz, Sophie Lehnerer, Maike Stein, Meret Herdick, Paolo Doksani, Lea M Gerischer, Sarah Hoffmann, Konstantinos Lazaridis, John Tzartos, Heinz Wiendl, Andreas Meisel, Jan D Lünemann","doi":"10.1212/NXI.0000000000200331","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>Biologics that target pathogenic antibodies (Abs) and their effector functions such as the complement inhibitor ravulizumab and the neonatal Fc receptor agonist efgartigimod have recently been approved for the treatment of acetylcholine receptor (AChR)-Ab-positive myasthenia gravis (MG), but comparative studies are lacking.</p><p><strong>Methods: </strong>In a prospective, exploratory real-world study, we assessed clinical efficacy, safety, and biological effects of ravulizumab and efgartigimod treatment initiation. Myasthenia Gravis-Activities of Daily Living and Quantitative Myasthenia Gravis scores were used as clinical endpoints. Ab effector functions were determined by AChR-Ab-dependent complement activation and phagocytosis assays and systemic complement activation profiling.</p><p><strong>Results: </strong>We observed similar moderate short-term efficacy of ravulizumab and efgartigimod in achieving clinical improvement. Ravulizumab reduced systemic terminal complement activation, but neither treatment showed significant effects on complement pathways proximal to C5 or functional capacities of AChR-Abs. Both treatment modalities were well tolerated with no serious adverse events reported.</p><p><strong>Discussion: </strong>Clinical benefits obtained with ravulizumab and efgartigimod can be remarkably heterogeneous in daily clinical practice. Neither treatment relevantly changed effector functions of pathogenic AChR-Abs, supporting the concept that durable disease control in MG requires continuous administration of both fast-acting agents.</p><p><strong>Classification of evidence: </strong>This study provides Class III evidence that in AChR-Ab-positive patients with generalized MG, ravulizumab and efgartigimod provide comparable modest improvement in MG functional scales.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200331"},"PeriodicalIF":7.8000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604103/pdf/","citationCount":"0","resultStr":"{\"title\":\"Ravulizumab and Efgartigimod in Myasthenia Gravis: A Real-World Study.\",\"authors\":\"Frauke Stascheit, Carla Daiane Ferreira de Sousa, Annette Aigner, Malina Behrens, Christian W Keller, Luisa Klotz, Sophie Lehnerer, Maike Stein, Meret Herdick, Paolo Doksani, Lea M Gerischer, Sarah Hoffmann, Konstantinos Lazaridis, John Tzartos, Heinz Wiendl, Andreas Meisel, Jan D Lünemann\",\"doi\":\"10.1212/NXI.0000000000200331\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>Biologics that target pathogenic antibodies (Abs) and their effector functions such as the complement inhibitor ravulizumab and the neonatal Fc receptor agonist efgartigimod have recently been approved for the treatment of acetylcholine receptor (AChR)-Ab-positive myasthenia gravis (MG), but comparative studies are lacking.</p><p><strong>Methods: </strong>In a prospective, exploratory real-world study, we assessed clinical efficacy, safety, and biological effects of ravulizumab and efgartigimod treatment initiation. Myasthenia Gravis-Activities of Daily Living and Quantitative Myasthenia Gravis scores were used as clinical endpoints. Ab effector functions were determined by AChR-Ab-dependent complement activation and phagocytosis assays and systemic complement activation profiling.</p><p><strong>Results: </strong>We observed similar moderate short-term efficacy of ravulizumab and efgartigimod in achieving clinical improvement. Ravulizumab reduced systemic terminal complement activation, but neither treatment showed significant effects on complement pathways proximal to C5 or functional capacities of AChR-Abs. Both treatment modalities were well tolerated with no serious adverse events reported.</p><p><strong>Discussion: </strong>Clinical benefits obtained with ravulizumab and efgartigimod can be remarkably heterogeneous in daily clinical practice. Neither treatment relevantly changed effector functions of pathogenic AChR-Abs, supporting the concept that durable disease control in MG requires continuous administration of both fast-acting agents.</p><p><strong>Classification of evidence: </strong>This study provides Class III evidence that in AChR-Ab-positive patients with generalized MG, ravulizumab and efgartigimod provide comparable modest improvement in MG functional scales.</p>\",\"PeriodicalId\":19472,\"journal\":{\"name\":\"Neurology® Neuroimmunology & Neuroinflammation\",\"volume\":\"12 1\",\"pages\":\"e200331\"},\"PeriodicalIF\":7.8000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604103/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurology® Neuroimmunology & Neuroinflammation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1212/NXI.0000000000200331\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurology® Neuroimmunology & Neuroinflammation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1212/NXI.0000000000200331","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/27 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Ravulizumab and Efgartigimod in Myasthenia Gravis: A Real-World Study.
Background and objectives: Biologics that target pathogenic antibodies (Abs) and their effector functions such as the complement inhibitor ravulizumab and the neonatal Fc receptor agonist efgartigimod have recently been approved for the treatment of acetylcholine receptor (AChR)-Ab-positive myasthenia gravis (MG), but comparative studies are lacking.
Methods: In a prospective, exploratory real-world study, we assessed clinical efficacy, safety, and biological effects of ravulizumab and efgartigimod treatment initiation. Myasthenia Gravis-Activities of Daily Living and Quantitative Myasthenia Gravis scores were used as clinical endpoints. Ab effector functions were determined by AChR-Ab-dependent complement activation and phagocytosis assays and systemic complement activation profiling.
Results: We observed similar moderate short-term efficacy of ravulizumab and efgartigimod in achieving clinical improvement. Ravulizumab reduced systemic terminal complement activation, but neither treatment showed significant effects on complement pathways proximal to C5 or functional capacities of AChR-Abs. Both treatment modalities were well tolerated with no serious adverse events reported.
Discussion: Clinical benefits obtained with ravulizumab and efgartigimod can be remarkably heterogeneous in daily clinical practice. Neither treatment relevantly changed effector functions of pathogenic AChR-Abs, supporting the concept that durable disease control in MG requires continuous administration of both fast-acting agents.
Classification of evidence: This study provides Class III evidence that in AChR-Ab-positive patients with generalized MG, ravulizumab and efgartigimod provide comparable modest improvement in MG functional scales.
期刊介绍:
Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.