Neurol. praxi. 2024;25(5):362-366 | DOI: 10.36290/neu.2024.047

Complement inhibitors eculizumab and ravulizumab in the treatment of generalized myasthenia gravis (gMG)

MUDr. Ivan Martinka, PhD.
Centrum pre neuromuskulárne ochorenia, Neurologická klinika SZU a UNB, Nemocnica Ružinov, Bratislava

The current conventional treatment of generalized myasthenia gravis (gMG) has various pitfalls - later onset of effect of some drugs, occurrence of adverse effects limiting the treatment itself and the patient's quality of life, lack of effectiveness in a small group of patients. Therefore, new drugs are being developed that specifically affect parts of the immune system that are in a clear causal connection with the MG etiopathogenesis. The advantage of these drugs is their high efficiency and good safety profile. Complement inhibitors, which are used in the etiopathogenesis of MG with positivity of antibodies against the acetylcholine receptor (AChR), also appear as a promising therapeutic option. In our work, we describe the mechanism of action of eculizumab and ravulizumab, present the results of clinical studies and their drug profile.

Keywords: generalized myasthenia gravis, acetylcholine receptor, complement, eculizumab, ravulizumab.

Received: July 16, 2024; Revised: July 16, 2024; Accepted: July 22, 2024; Prepublished online: July 22, 2024; Published: November 19, 2024  Show citation

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Martinka I. Complement inhibitors eculizumab and ravulizumab in the treatment of generalized myasthenia gravis (gMG). Neurol. praxi. 2024;25(5):362-366. doi: 10.36290/neu.2024.047.
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    References

    1. Andersen H, Mantegazza R, Wang JJ, et al., REGAIN Study Group. Eculizumab improves fatigue in refractory generalized myasthenia gravis. Qual Life Res. 2019;28(8):2247-2254. doi: 10.1007/s11136-019-02148-2. Go to original source... Go to PubMed...
    2. Chamberlain JL, Huda S, Whittam DH, et al. Role of complement and potential of complement inhibitors in myasthenia gravis and neuromyelitis optica spectrum disorders: a brief review. J Neurol. 2021;268(5):1643-1664. doi: 10.1007/s00415-019-09498-4. Go to original source... Go to PubMed...
    3. Dhillon S. Eculizumab: A Review in Generalized Myasthenia Gravis. Drugs. 2018;78(3):367-376. Go to original source... Go to PubMed...
    4. European Medicines Agency. Soliris® (eculizumab) Summary of Product Characteristics. Dostupné na: https: //www.ema.europa.eu/en/documents/product-information/soliris-epar-product-information_en.pdf.
    5. European Medicines Agency. Ultomiris® (ravulizumab) Summary of Product Characteristics. Dostupné na: https://www.ema.europa.eu/sk/documents/product-information/ultomiris-epar-product-information_sk.pdf.
    6. Fakhouri F, Schwotzer N, Golshayan D, Frémeaux-Bacchi V. The Rational Use of Complement Inhibitors in Kidney Diseases. Kidney Int Rep. 2022;7(6):1165-1178. doi: 10.1016/j.ekir.2022.02.021. Go to original source... Go to PubMed...
    7. Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355(12):1233-43. doi: 10.1056/NEJMoa061648. Go to original source... Go to PubMed...
    8. Howard Jr JF. Myasthenia gravis: the role of complement at the neuromuscular junction. Ann N Y Acad Sci. 2018;1412(1):113-128. doi: 10.1111/nyas.13522. Go to original source... Go to PubMed...
    9. Howard Jr JF, Utsugisawa K, Benatar M, et al. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, doubleblind, placebo-controlled, multicentre study. Lancet Neurol. 2017;16(12):976-986. doi: 10.1016/S1474-4422(17)30369-1 Go to original source... Go to PubMed...
    10. Mantegazza R, O'Brien FL, Yountz M, Howard Jr JF, REGAIN Study Group. Consistent improvement with eculizumab across muscle groups in myasthenia gravis. Ann Clin Transl Neurol. 2020;7(8):1327-1339. doi: 10.1002/acn3.51121 Go to original source... Go to PubMed...
    11. Mantegazza R, Wolfe GI, Muppidi S, et al. Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension. Neurology. 2021;96(4):e610-e618. doi: 10.1212/WNL.0000000000011207. Go to original source... Go to PubMed...
    12. Meisel A, Annane D, Vu T, et al. Long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis: results from the phase 3 CHAMPION MG open-label extension. J Neurol. 2023 Aug;270(8):3862-3875. doi: 10.1007/s00415-023-11699-x Go to original source... Go to PubMed...
    13. Menon D, Barnett C, Bril V. Novel Treatments in Myasthenia Gravis. Front Neurol. 2020;11:538. doi: 10.3389/fneur.2020.00538. Go to original source... Go to PubMed...
    14. Muppidi S, Utsugisawa K, Benatar M, et al. Long-term safety and efficacy of eculizumab in generalized myasthenia gravis. Muscle Nerve. 2019;60(1):14-24. doi: 10.1002/mus.26447. Go to original source... Go to PubMed...
    15. Narayanaswami P, Sanders DB, Wolfe GI, et al. International Consensus Guidance for Management of Myasthenia Gravis: 2020 Update. Neurology. 2021;96(3):114-122. doi: 10.1212/WNL.0000000000011124. Go to original source... Go to PubMed...
    16. Pittock SJ, Berthele A, Fujihara K. Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019;381(7):614-625. doi: 10.1056/NEJMoa1900866. Go to original source... Go to PubMed...
    17. Špalek P. Myasténia gravis. Cesk Slov Neurol N. 2008;71/104(1):7-24.
    18. Špalek P. Intravenózny imunoglobulín v liečbe myasténie gravis. Neurológia. 2018;13:53-58.
    19. Vanoli F, Mantegazza R. Current drug treatment of myasthenia gravis. Curr Opin Neurol. 2023;36(5):410-415. doi: 10.1097/WCO.0000000000001196. Go to original source... Go to PubMed...
    20. Voháňka S. Farmakoterapie myasthenia gravis. Neurol. praxi. 2010;11(2):95-99.
    21. Vissing J, Jacob S, Fujita KP, et al., REGAIN Study Group. 'Minimal symptom expression' in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab. J Neurology. 2020;267(7):1991-2001. doi: 10.1007/s00415-020-09770-y. Go to original source... Go to PubMed...
    22. Vu T, Meisel A, Mantegazza R, et al. Terminal complement inhibitor ravulizumab in generalized myasthenia gravis. Neurol Ther. 2023;12(5):1435-1438. doi: 0.1007/s40120-023-00514-4. Go to original source... Go to PubMed...
    23. Vu T, Ortiz S, Katsuno M, et al. Ravulizumab pharmacokinetics and pharmacodynamics in patients with generalized myasthenia gravis. J Neurol. 2023;270(6):3129-3137. doi: 10.1007/s00415-023-11617-1. Go to original source... Go to PubMed...
    24. Vu T, Wiendl H, Katsuno M, et al. Ravulizumab in Myasthenia Gravis: A Review of the Current Evidence. Neuropsychiatr Dis Treat. 2023;19:2639-2655. doi: 10.2147/NDT.S374694. Go to original source... Go to PubMed...
    25. Wijnsma KL, Duineveld C, Wetzels JFM, van de Kar NCAJ. Eculizumab in atypical hemolytic uremic syndrome: strategies toward restrictive use. Pediatr Nephrol. 2019;34(11):2261-2277. doi: 10.1007/s00467-018-4091-3. Go to original source... Go to PubMed...
    26. Wolfe GI, Kaminski HJ, Aban IB, et al. Randomized Trial of Thymectomy in Myasthenia Gravis. N Engl J Med. 2016;375(6):511-22. doi: 10.1056/NEJMoa1602489. Go to original source... Go to PubMed...

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