Současné a budoucí terapeutické možnosti léčby generalizované formy myasthenia gravis

Česká verzia

Authors: M. Týblová
Authors place of work: Neurologická klinika a Centrum klinických neurověd, 1. LF UK a VFN v Praze
Published in the journal: Cesk Slov Neurol N 2023; 86(2): 100-106
Category: Review Article
doi: https://doi.org/10.48095/cccsnn2023100

Summary

Myasthenia gravis is a rare chronic autoimmune disease affecting the neuromuscular junction. Basic therapeutic procedures include lifestyle regimen, cholinesterase inhibitor symptomatic and immunomodulatory treatment, and thymectomy in indicated cases. We can influence myasthenia gravis immunopathogenesis acutely with plasmapheresis or intravenous immunoglobulins or orally with long-term corticoid and/or immunosuppressive treatment. In recent years, various biological treatments have been expanding, including C5 complement inhibitors and blockers of neonatal Fc receptors. First approved in the Czech Republic are eculizumab and efgartigimod. Eculizumab is indicated for seropositive refractory generalized myasthenia gravis. Efgartigimod is approved as add on therapy for the standard treatment of adult patients with generalized myasthenia gravis who are positive for antibodies against the acetylcholine receptor.

Keywords:

glucocorticoids – Complement inhibitors – immunomodulation – generalized myasthenia gravis – neonatal Fc receptors

Zdroje

1. Jaretzki A, Barohn RJ, Ernstoff RM et al. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology 2000; 55 (1): 16–23. doi: 10.1212/wnl.55.1.16.

2. Tannemaat MR, Verschuuren J. Emerging therapies for autoimmune myasthenia gravis: towards treatment without corticosteroids. Neuromuscul Disord 2020; 30 (2): 111–119. doi: 10.1016/j.nmd.2019.12.003.

3. Lascano AM, Lalive PH. Update in immunosuppressive therapy of myasthenia gravis. Autoimmun Rev 2021; 20 (1): 102712. doi: 10.1016/j.autrev.2020.102712.

4. Harris L, Allman PH, Sheffield R e t al. Cutter, longitudinal analysis of disease burden in refractory and nonrefractory generalized myasthenia gravis in the United States. J Clin Neuromuscul Dis 2020; 22 (1): 11–21. doi: 10.1097/CND.0000000000000301.

5. Rath J, Brunner I, Tomschik M et al. Frequency and clinical features of treatment-refractory myasthenia gravis. J Neurol 2020; 267 (4): 1004–1011. doi: 10.1007/s00415-019-09667-5.

6. Narayanaswami P, Sanders DB, Wolfe G et al. International consensus guidance for management of myasthenia gravis: 2020 update. Neurology 2021; 96 (3): 114–122. doi: 10.1212/WNL.0000000000011124.

7. Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 2011; 335 (1): 2–13. doi: 10.1016/j.mce.2010.04.005.

8. Negi V-S, Elluru S, Sibéril S et al. Intravenous immunoglobulin: an update on the clinical use and mechanisms of action. J Clin Immunol 2007; 27 (3): 233–245. doi: 10.1007/s10875-007-9088-9.

9. Tesar V, Jelínková E, Jirsa M et al. Soluble adhesive molecules and cytokines in patients with myasthenia gravis treated with plasmapheresis. Cas Lek Cesk 1998; 137 (21): 654–659.

10. Howard JF, Nowak RJ, Wolfe GI et al. Clinical effects of the self-administered subcutaneous complement inhibitor zilucoplan in patients with moderate to severe generalized myasthenia gravis: results of a phase 2 randomized, double-blind, placebo-controlled, multicenter clinical trial. JAMA Neurol 2020; 77 (5): 582–592. doi: 10.1001/jamaneurol.2019.5125.

11. Howard 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, double-blind, placebo-controlled, multicentre study. Lancet Neurol 2017; 16: 12): 976–986. doi: 10.1016/S1474-4422 (17) 30 369-1.

12. Alhaidar MK, Abumurad S, Soliven B et al. Current treatment of myasthenia gravis. J Clin Med 2022; 11 (6): 1597. doi: 10.3390/jcm11061597.

13. Habib AA. The therapeutic potential for FcRn blockade in myasthenia gravis- antibodies and antibody clearance. Neurol Rev 2020; 2020: 1–5.

14. Heo Y-A. Efgartigimod: first approval. Drugs 2022; 82 (3): 341–348. doi: 10.1007/s40265-022-01678-3.

15. Bril V, Benatar M, Andersen H et al. Efficacy and safety of rozanolixizumab in moderate to severe generalized myasthenia gravis: a phase 2 randomized control trial. Neurology 2021; 96 (6): e853–e865. doi: 10.1212/WNL.0000000000011108.

16.Maggi L, Mantegazza R. Treatment of myasthenia gravis: focus on pyridostigmine. Clin Drug Investig 2011; 31 (10): 691–701. doi: 10.2165/11593300-000000000-00000.

17. Howard J, Bril V, Vu T et al. Efficacy, safety, and tolerability of efgartigimod in patients with generalized myasthenia gravis: analysis of the phase 3 ADAPT study (4520). Neurology 2021; 96 (Suppl 15): 4520.

18. McKeage K. Ravulizumab: first global approval. Drugs 2019; 79 (3): 347–352. doi: 10.1007/s40265-019-010 68-2.

19. Kanai T, Uzawa A, Kawaguchi N et al. Predictive score for oral corticosteroid-induced initial worsening of seropositive generalized myasthenia gravis. J Neurol Sci 2019; 396: 8–11. doi: 10.1016/j.jns.2018.10.018.

20. Sghirlanzoni A, Peluchetti D, Mantegazza R et al. Myasthenia gravis: prolonged treatment with steroids. Neurology 1984; 34 (2): 170–174. doi: 10.1212/wnl.34. 2.170.

21. Johns TR. Long-term corticosteroid treatment of myasthenia gravis. Ann N Y Acad Sci 1987; 505: 568–583. doi: 10.1111/j.1749-6632.1987.tb51325.x.

22. Mantegazza R, Bonanno S, Camera G et al. Current and emerging therapies for the treatment of myasthenia gravi.s Neuropsychiatr Dis Treat 2011; 7: 151–160. doi: 10.2147/NDT.S8915.

23. Heckmann JM, Rawoot A, Bateman K et al. A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis. BMC Neurol 2011; 11: 97. doi: 10.1186/1471-2377-11-97.

24. Hart IK, Sathasivam S, Sharshar T. Immunosuppressive agents for myasthenia gravis. Cochrane Database Syst Rev 2007; 17 (4): CD005224. doi: 10.1002/14651858.CD005224.pub2.

25. Yoshikawa H, Kiuchi T, Saida T et al. Randomised, double-blind, placebo-controlled study of tacrolimus in myasthenia gravis. J Neurol Neurosurg Psychiatry 2011; 82 (9): 970–977. doi: 10.1136/jnnp-2011-300148.

26. Lebrun C, Bourg V, Tieulie N et al. Successful treatment of refractory generalized myasthenia gravis with rituximab. Eur J Neurol 2009; 16 (2): 246–250. doi: 10.1111/j.1468-1331.2008.02399.x.

27. Vial T, Descotes J. Immunosuppressive drugs and cancer. Toxicology 2003; 185 (3): 229–240. doi: 10.1016/S0300-483X (02) 00612-1.

28. Fonseca V, Havard CW. Long term treatment of myasthenia gravis with azathioprine. Postgrad Med J 1990; 66 (772): 102–105. doi: 10.1136/pgmj.66.772. 102.

29. Meriggioli NM, Ciafaloni E, Al-Hayk KA et al. Mycophenolate mofetil for myasthenia gravis: an analysis of efficacy, safety, and tolerability. Neurology 2003; 611 (10): 1438–1440. doi: 10.1212/01.WNL.0000094122.889 29.0B.

30. Chaudhry V, Cornblath DR, Griffin JW et al. Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular diseases. Neurology 2001; 56 (1): 94–96. doi: 10.1212/WNL.56.1.94.

31. Fan Z, Li Z, Shen F et al. Favorable effects of tacrolimus monotherapy on myasthenia gravis patients. Front Neurol 2020; 11: 594152. doi: 10.3389/fneur.2020.594 152.

32. Horáková M, Martinka I, Voháňka S et al. Srovnávací studie pacientů s myastenií České a Slovenské republiky. Cesk Slov Neurol N 2019; 82/115 (1): 171–175. doi: 10.14735/amcsnn2019171.

33. Tindall RS, Phillips JT, Rollins JA et al. A clinical therapeutic trial of cyclosporine in myasthenia gravis. Ann N Y Acad Sci 1993; 681: 539–551. doi: 10.1111/j.1749-6632.1993.tb22937.x.

34. Ciafaloni E, Nikhar NK, Massey JM et al. Retrospective analysis of the use of cyclosporine in myasthenia gravis, Neurology 2000; 55 (3): 448–450. doi: 10.1212/WNL.55.3.448.

35. Skeie GO, Apostolski S, Evoli A et al. Guidelines for treatment of autoimmune neuromuscular transmission disorders. Eur J Neurol 2010; 17 (7): 893–902. doi: 10.1111/j.1468-1331.2010.03019.x.

36. Pasnoor M, He J, Herbelin L et al. A randomized controlled trial of methotrexate for patients with generalized myasthenia gravis. Neurology 2016; 87 (1): 57–64. doi: 10.1212/WNL.0000000000002795.

37. Heatwole C, Ciafaloni E. Mycophenolate mofetil for myasthenia gravis: a clear and present controversy. Neuropsychiatr Dis Treat 2008; 4 (6): 1203–1209. doi: 10.2147/ndt.s3309.

38. Sanders DB. A trial of mycophenolate mofetil with prednisone as initial immunotherapy in myasthenia gravis. Neurology 2008; 71 (6): 394–399. doi: 10.1212/01.wnl.0000312373.67493.7f.

39. Hehir MK, Hobson-Webb LD, Benatar M et al. Rituximab as treatment for anti-MuSK myasthenia gravis. Neurology 2017; 89 (10): 1069–1077. doi: 10.1212/WNL.00000 00000004341.

40. Tandan R, Hehir MK, Waheed W et al. Rituximab treatment of myasthenia gravis: a systematic review. Muscle Nerve 22017; 56 (2): 185–196. doi: 10.1002/mus.25 597.

41. Nelson RP, Pascuzzi RM, Kessler K et al. Rituximab for the treatment of thymoma-associated and de novo myasthenia gravis: 3 cases and review. J Clin Neuromuscul Dis 2009; 10 (4): 170–177. doi: 10.1097/CND. 0b013e31819a8403.

42. Nelke C, Schroeter C, Stascheit F et al. Eculizumab versus rituximab in generalised myasthenia gravis. J Neurol Neurosurg Psychiatry 2022; 93 (5): 548–554. doi: 10.1136/jnnp-2021-328665.

43. Sánchez-Tejerina D, Sotoca J, Llaurado A et al. New targeted agents in myasthenia gravis and future therapeutic strategie. J Clin Med 2022; 11 (21): 6394. doi: 10.3390/jcm11216394.

44. Triantafyllou NI, Grapsa EI, Kararizou E et al. Periodic therapeutic plasma exchange in patients with moderate to severe chronic myasthenia gravis non-responsive to immunosuppressive agents: an eight year follow-up. Ther Apher Dial 2009; 13 (3): 174–178. doi: 10.1111/j.1744-9987.2009.00684.x.

45. Haas M, Mayr N, Zeitlhofer J et al. Long-term treatment of myasthenia gravis with immunoadsorption. J Clin Apher 2002; 17 (2): 84–87. doi: 10.1002/jca.10 023.

46. Achiron A, Barak Y, Miron S et al. Immunoglobulin treatment in refractory myasthenia gravis. Muscle Nerve 2000; 23) 4): 551–555. doi: 10.1002/ (SICI) 1097-4598 (200004) 23: 4<551:: AID-MUS14>3.0.CO; 2-O.

47. Hilkevich O, Drory VE, Chapman J et al. The use of intravenous immunoglobulin as maintenance therapy in myasthenia gravis. Clin Neuropharmacol 2001; 24 (3): 173–176. doi: 10.1097/00002826-200105000-00 010.

48. Sanders DB, Wolfe GI, Benatar M et al. International consensus guidance for management of myasthenia gravis: executive summary. Neurology 2019; 87 (4): 419–425. doi: 10.1212/WNL.0000000000002790.

49. Horáková M, Voháňka S. Škály a dotazníky používané u myastenia gravis. Neurol praxi 2017; 18 (5): 3001–304. doi: 10.36290/neu.2017.035.

50. Howard JF, Bril V, Burns TM et al. Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis. Neurology 2019; 92 (23): e2661–e2673. doi: 10.1212/WNL.0000000000007600.

51. Menon D, Barnett C, Bril V. Novel treatments in myasthenia gravis. Front Neurol 2020; 11: 538. doi: 10.3389/ fneur.2020.00538.

52. Ndegwa S, Mierzwinski-Urban M. Emerging drugs for generalized myasthenia gravis. Can J Heal Technol 2022; 2 (2): 1–31. doi: 10.51731/cjht.2022.270.

53. Ward ES, Gelinas D, Dreesen E et al. Clinical significance of serum albumin and implications of FcRn inhibitor treatment in IgG-mediated autoimmune disorders. Front Immunol 2022; 13: 892534. doi: 10.3389/fimmu.2022.892 534.