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. 2025 Jan;12(1):e200331.
doi: 10.1212/NXI.0000000000200331. Epub 2024 Nov 27.

Ravulizumab and Efgartigimod in Myasthenia Gravis: A Real-World Study

Frauke Stascheit  1 , Carla Daiane Ferreira de Sousa  1 , Annette Aigner  1 , Malina Behrens  1 , Christian W Keller  1 , Luisa Klotz  1 , Sophie Lehnerer  1 , Maike Stein  1 , Meret Herdick  1 , Paolo Doksani  1 , Lea M Gerischer  1 , Sarah Hoffmann  1 , Konstantinos Lazaridis  1 , John Tzartos  1 , Heinz Wiendl  1 , Andreas Meisel  1 , Jan D Lünemann  1
Affiliations

Ravulizumab and Efgartigimod in Myasthenia Gravis: A Real-World Study

Frauke Stascheit et al. Neurol Neuroimmunol Neuroinflamm. 2025 Jan.

Abstract

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.

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Conflict of interest statement

F. Stascheit received travel/accommodation/meeting expenses from Alexion Pharmaceuticals and argnx and received speaking honoria and honoria for attendance at advisory boards from Alexion Pharmaceuticals, argnx and UCB pharma; A. Aigner and M. Behrens reports no conflict of interests; C.W. Keller received travel, accommodation and meeting expenses from Alexion and UCB; L. Klotz received speaking honoraria and travel/meeting expenses from Argenx, Bayer, Biogen, Bristol-Myers Squibb, Genzyme, Grifols, Merck Serono, Novartis, Roche, Santhera and Teva. She participated in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Genzyme, Horizon, Janssen, Merck Serono, Novartis, Roche, Sandoz and Viatris; S. Lehnerer has received speakers honoraria from Alexion, argenx, Hormosan and UCB, honoraria for attendance at advisory boards from Alexion, argenx, Biogen, UCB and Roche, travel/accommodation/meeting expenses from Alexion Pharmaceuticals and argnx and research funding from Hormosan, Alexion, UCB and argnx; M. Stein has received speaking honoria and honoria for attendance at advisory boards from Argenx and Alexion Pharmaceuticals; M. Herdick has received speaker's honaria from argenx; P. Doksani and L. Gerischer reports no conflict of interest; S. Hoffmann has received speakers' honoraria from Alexion, argenx, UCB, Grifols and Roche, honoraria for attendance at advisory boards from Alexion, argenx and Roche and research funding from argenx and Janssen. S. Hoffmann is member of the medical advisory board of the German Myasthenia Society, DMG. K. Lazaridis reports no conflict of interest; J. Tzartos reports speaking honoria from Astra Zeneca and Medison Pharma; H. Wiendl received speaker honoraria from Alexion, Biogen, Bristol Myers Squibb, Genzyme, Merck, Neurodiem, Novartis, Ology, Roche, TEVA, and WebMD Global. He received honoraria for consulting services from Abbvie, Actelion, Argenx, BD, Bristol Myers Squibb, EMD Serono, Fondazione Cariplo, Gossamer Bio, Idorsia, Immunic, Immunovant, INmune Bio_Syneos Health, Janssen, Merck, NexGen, Novartis, Roche, Sanofi, Swiss MS Society, UCB and Worldwide Clinical Trials. His research is supported by the German Myasthenia Gravis Society; A. Meisel received speaker or consultancy honoraria or financial research support (paid to his institution) from Alexion Pharmaceuticals, argenx, Axunio, Destin, Grifols, Hormosan Pharma, Janssen, Merck, Octapharma, UCB, and Xcenda. He serves as medical advisory board chairman of the German Myasthenia Gravis Society; J.D. Lünemann has received speaker fees, research support, travel support, and/or served on advisory boards by Abbvie, Alexion, Argenx, Biogen, Merck, Moderna, Novartis, Roche, Sanofi and Takeda, and is member of the medical advisory board of the German Myasthenia Gravis Society. Go to Neurology.org/NN for full disclosures.

Figures

Figure 1
Figure 1. Clinical Response to Ravulizumab and Efgartigimod in Patients With AChR-Ab–Positive gMG
(A) Myasthenia gravis activities of daily living (MG-ADL) score in patients treated with ravulizumab (baseline, week 2, week 10) or efgartigimod (baseline, week 4, week 8). Indicated in gray are individual patients. Indicated in red are the median at baseline, median differences for follow-up along with the interquartile range; (B) Quantitative Myasthenia Gravis (QMG) score in individual patients treated with ravulizumab (baseline, week 2, week 10) or efgartigimod (baseline, week 4, week 8). (C) Bar chart for the distribution of minimal improvement in MG-ADL score from baseline to second follow-up (week 8 or week 10), separately for ravulizumab-treated and efgartigimod-treated patients. (D) Bar chart for the distribution of minimal improvement in QMG score from baseline to second follow-up (week 8 or week 10), separately for ravulizumab-treated and efgartigimod-treated patients. AChR-Ab = acetylcholine receptors-Ab; gMG = generalized MG.
Figure 2
Figure 2. Profiling Activated Complement Protein and IgG Levels Along With AChR-Specific Antibody Effector Functions on Treatment Initiation With Ravulizumab and Efgartigimod
(A) Serum complement C5a and (B) total igG protein levels were quantified at baseline, at 10 weeks after ravulizumab therapy, and 8 weeks after initiation of efgartigimod therapy. Only ravulizumab-treated patients presented with a significant decrease in terminal complement factors C5a (p = 0.00024). Only efgartigimod-treated patients presented with a significant decrease in total IgG levels (p = 0.03). Mean relative difference for total IgG levels in efgartigimod-treated patients is −22.0 and for ravulizumab-treated patients is 8.2. (C) Antibody-dependent complement deposition and (D) phagocytosis induced by isolated AChR-specific IgG quantified at baseline, at 10 weeks after ravulizumab therapy, and 8 weeks after initiation of efgartigimod therapy. Indicated in gray are individual patients. Indicated in red are the median at baseline and median differences for follow-up along with the interquartile range. AChR = acetylcholine receptor; IgG = immunoglobulin G.
See this image and copyright information in PMC

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