Background

Recently, increasing evidence has demonstrated the rapid beneficial effect of monoclonal antibodies blocking the terminal complement protein C5 in refractory generalized myasthenia gravis (gMG); therefore, they have emerged as a promising option for fast-acting therapy (FT).

Case Report

We describe the case of a 21-year-old female with a 4-year history of non-thymomatous anti-acetylcholine receptor antibody (anti-AChR Ab) positive refractory gMG (Myasthenia Gravis Foundation of America [MGFA] class V) who responded to complement C5 inhibitor within the first week, achieving minimal symptom expression within 2 months. This rapid-onset efficacy challenged the existing understanding of antibody-mediated destruction of AChR, where instant restoration of neuromuscular junction neurotransmission from recovery of the destroyed postsynaptic membrane of the motor endplate and reduction in the number of AChR receptors is theoretically not possible with membrane attack complex inhibition.

Conclusion

The rapid target attainment effect of complement inhibition can be considered as an additional novel indication for conventional FT.
Key Words: Refractory generalized myasthenia gravis; Complement inhibition; AChR antibody; Eculizumab; Myasthenic crisis

1. Suh, J., Goldstein, J. M., & Nowak, R. J. (2013). Clinical characteristics of refractory myasthenia gravis patients. The Yale Journal of Biology and Medicine, 86(2), 255–260.
2. Howard, J. F., Jr., Utsugisawa, K., Benatar, M., Murai, H., Barohn, R. J., Illa, I., Jacob, S., Vissing, J., Burns, T. M., Kissel, J. T., Muppidi, S., Nowak, R. J., O'Brien, F., Wang, J. J., Mantegazza, R., & REGAIN Study Group. (2017). Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): A phase 3, randomised, double-blind, placebo-controlled, multicentre study. The Lancet Neurology, 16(12), 976–986. https://doi.org/10.1016/S1474-4422(17)30369-1
3. Vu, T., Meisel, A., Mantegazza, R., Annane, D., Katsuno, M., Aguzzi, R., Larkin, M., Boroojerdi, B., O'Brien, F., & Howard, J. F., Jr. (2022). Terminal complement inhibitor ravulizumab in generalized myasthenia gravis. NEJM Evidence, 1(5), Article EVIDoa2100066. https://doi.org/10.1056/EVIDoa2100066
4. Howard, J. F., Jr., Bresch, S., Genge, A., Hewamadduma, C., Hinton, J., Hussain, Y., Juntas-Morales, R., Kaminski, H. J., Korves, C. T., Santos, E., Utsugisawa, K., Vu, T., Boroojerdi, B., de la Borderie, G., Duda, P. W., Farzaneh-Far, R., Vandendries, E., & RAISE Study Group. (2023). Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): A randomised, double-blind, placebo-controlled, phase 3 study. The Lancet Neurology, 22(5), 395–406. https://doi.org/10.1016/S1474-4422(23)00080-7
5. Rossini, E., Morino, S., Garibaldi, M., Leonardi, L., Tufano, L., Lauletta, A., & Antonini, G. (2025). Emergent role of complement inhibitors in myasthenic crisis: Understanding why, when and how. Clinical Neurology and Neurosurgery, 256, Article 109011. https://doi.org/10.1016/j.clineuro.2025.109011
6. Gerischer, L., Doksani, P., Hoffmann, S., & Meisel, A. (2025). New and emerging biological therapies for Myasthenia Gravis: A focussed review for clinical decision-making. BioDrugs, 39(2), 185–213. https://doi.org/10.1007/s40259-025-00695-1
7. Koneczny, I., & Herbst, R. (2019). Myasthenia gravis: Pathogenic effects of autoantibodies on neuromuscular architecture. Cells, 8(7), Article 671. https://doi.org/10.3390/cells8070671
8. Rother, R. P., Rollins, S. A., Mojcik, C. F., Brodsky, R. A., & Bell, L. (2007). Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nature Biotechnology, 25(11), 1256–1264. https://doi.org/10.1038/nbt1344
9. Howard, J. F., Jr., Nowak, R. J., Wolfe, G. I., Freimer, M. L., Vu, T. H., Hinton, J. L., Jr., Benatar, M., Duda, P. W., Farzaneh-Far, R., Kaminski, H. J., & Zilucoplan MG Study Group. (2020). Clinical effects of the self-administered subcutaneous complement inhibitor zilucoplan in patients with moderate to severe generalized myasthenia gravis. JAMA Neurology, 77(5), 582–592. https://doi.org/10.1001/jamaneurol.2019.5125
10. Yanagidaira, M., Nishida, Y., & Yokota, T. (2020). Temporal correlation between serum CH50 level and symptom severity of myasthenia gravis during eculizumab therapy. Clinical Neurology and Neurosurgery, 189, Article 105630. https://doi.org/10.1016/j.clineuro.2019.105630
11. Muppidi, S., Utsugisawa, K., Benatar, M., Murai, H., Barohn, R. J., Illa, I., Jacob, S., Vissing, J., Burns, T. M., Kissel, J. T., Nowak, R. J., Andersen, H., Casasnovas, C., de Bleecker, J. L., Vu, T. H., Mantegazza, R., O'Brien, F., Wang, J. J., & Howard, J. F., Jr. (2019). Long-term safety and efficacy of eculizumab in generalized myasthenia gravis. Muscle & Nerve, 60(1), 14–24. https://doi.org/10.1002/mus.26447
12. Vu, T. H., Mantegazza, R., Annane, D., Katsuno, M., Meisel, A., Nicolle, M. W., O'Brien, F., Larkin, M., Boroojerdi, B., & Howard, J. F., Jr. (2025). Long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis: Final results from the phase 3 CHAMPION MG open-label extension. European Journal of Neurology, 32(1), Article e70158. https://doi.org/10.1111/ene.70158
13. Bruneau, E., Sutter, D., Hume, R. I., & Akaaboune, M. (2005). Identification of nicotinic acetylcholine receptor recycling and its role in maintaining receptor density at the neuromuscular junction in vivo. The Journal of Neuroscience, 25(43), 9949–9959. https://doi.org/10.1523/JNEUROSCI.3161-05.2005
14. Howard, J. F., Jr. (2018). Myasthenia gravis: The role of complement at the neuromuscular junction. Annals of the New York Academy of Sciences, 1412(1), 113–128. https://doi.org/10.1111/nyas.13522
15. Vilquin, J. T., Bayer, A. C., Le Panse, R., & Berrih-Aknin, S. (2019). The muscle is not a passive target in myasthenia gravis. Frontiers in Neurology, 10, Article 1343. https://doi.org/10.3389/fneur.2019.01343