Research progress on molecular targeted drug therapy for myasthenia gravis_West China Medical Journal

Authors：

YUAN Man ^1,2 , KAN Hongjiao ^1,2 , CHEN Yunna ^2,3 , ZHAO Kaijie ^1,2 , SUN Xiuting ^1,2 ,  ZHANG Xiaoyan ²

1. The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P. R. China;
2. Department of Neurology, 940th Hospital of Chinese People’s Liberation Army Joint Logistic Support Force, Lanzhou, Gansu 730050, P. R. China;
3. Medical Department of Northwest Minzu University, Lanzhou, Gansu 730030, P. R. China;

Corresponding author：

ZHANG Xiaoyan, Email: zhangxiaoyan060110@163.com

Keywords：

Myasthenia gravis; neonatal Fc receptor; cytokine; complement

DOI：

10.7507/1002-0179.202402048

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Myasthenia gravis (MG) is a common antibody mediated, cell-mediated, and complement dependent neuromuscular junction immune disease. The treatment mainly includes drug therapy (symptomatic therapy, non-specific immunosuppressive therapy, targeted immunotherapy), immune regulation (intravenous injection of human immunoglobulin and plasma exchange), and thymectomy. With the continuous deepening of research on MG treatment, targeted immune regulation of B cells, complement system, and neonatal Fc receptors has become a current research hotspot in the treatment of MG. Compared with traditional immunosuppressants, MG patients have better tolerance to new biological agents. This article elaborates on the research of MG targeted therapy related drugs and summarizes their efficacy and safety in MG treatment, aiming to find more treatment options.

Citation： YUAN Man, KAN Hongjiao, CHEN Yunna, ZHAO Kaijie, SUN Xiuting, ZHANG Xiaoyan. Research progress on molecular targeted drug therapy for myasthenia gravis. West China Medical Journal, 2024, 39(5): 818-824. doi: 10.7507/1002-0179.202402048 Copy

1.	Chen J, Tian DC, Zhang C, et al. Incidence, mortality, and economic burden of myasthenia gravis in China: a nationwide population-based study. Lancet Reg Health West Pac, 2020, 5: 100063.
2.	Dalakas MC. Immunotherapy in myasthenia gravis in the era of biologics. Nat Rev Neurol, 2019, 15(2): 113-124.
3.	Guptill JT, Soni M, Meriggioli MN. Current treatment, emerging translational therapies, and new therapeutic targets for autoimmune myasthenia gravis. Neurotherapeutics, 2016, 13(1): 118-131.
4.	Dalakas MC. Treating myasthenia on consensus guide: helpful and challenging but still unfinished business. Neurology, 2016, 87(4): 350-351.
5.	Melzer N, Ruck T, Fuhr P, et al. Clinical features, pathogenesis, and treatment of myasthenia gravis: a supplement to the guidelines of the German Neurological Society. J Neurol, 2016, 263(8): 1473-1494.
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.
7.	Santos E, Bettencourt A, Duarte S, et al. Refractory myasthenia gravis: characteristics of a portuguese cohort. Muscle Nerve, 2019, 60(2): 188-191.
8.	Menon D, Bril V. Pharmacotherapy of generalized myasthenia gravis with special emphasis on newer biologicals. Drugs, 2022, 82(8): 865-887.
9.	Zeng R, Glaubitz S, Schmidt J. Antibody therapies in autoimmune inflammatory myopathies: promising treatment options. Neurotherapeutics, 2022, 19(3): 911-921.
10.	常婷, 李柱一. 重症肌无力的治疗: 期待靶向免疫治疗时代的到来. 中华神经科杂志, 2022, 55(4): 271-279.
11.	Butcher MJ, Zhu J. Recent advances in understanding the Th1/Th2 effector choice. Fac Rev, 2021, 10: 30.
12.	McCombe JA, Pittock SJ. Anti-complement agents for autoimmune neurological disease. Neurotherapeutics, 2022, 19(3): 711-728.
13.	Meng QF, Zhang XX, Zhang Z, et al. Therapeutic potential of artesunate in experimental autoimmune myasthenia gravis by upregulated T regulatory cells and regulation of Th1/Th2 cytokines. Pharmazie, 2018, 73(9): 526-532.
14.	Fichtner ML, Jiang R, Bourke A, et al. Autoimmune pathology in myasthenia gravis disease subtypes is governed by divergent mechanisms of immunopathology. Front Immunol, 2020, 11: 776.
15.	Ehrenstein MR, Wing C. The BAFFling effects of rituximab in lupus: danger ahead?. Nat Rev Rheumatol, 2016, 12(6): 367-372.
16.	Vesperinas-Castro A, Cortés-Vicente E. Rituximab treatment in myasthenia gravis. Front Neurol, 2023, 14: 1275533.
17.	Li T, Zhang GQ, Li Y, et al. Efficacy and safety of different dosages of rituximab for refractory generalized AChR myasthenia gravis: a meta-analysis. J Clin Neurosci, 2021, 85: 6-12.
18.	Yang X, Zhang W, Chang X, et al. Promising efficacy of low-dose rituximab in muscle specific kinase antibody positive myasthenia gravis. Neurosci Lett, 2024, 818: 137561.
19.	Nair SS, Jacob S. Novel immunotherapies for myasthenia gravis. Immunotargets Ther, 2023, 12: 25-45.
20.	Rüter J, Antonia SJ, Burris HA, et al. Immune modulation with weekly dosing of an agonist CD40 antibody in a phase I study of patients with advanced solid tumors. Cancer Biol Ther, 2010, 10(10): 983-993.
21.	GomezMancilla B, Meriggioli MN, Genge A, et al. Efficacy and safety of iscalimab, a novel anti-CD40 monoclonal antibody, in moderate-to-severe myasthenia gravis: a phase 2 randomized study. J Clin Neurosci, 2024, 119: 76-84.
22.	Chen H, Qiu Y, Yin Z, et al. Efficacy and safety of the innovative monoclonal antibodies in adults with generalized myasthenia gravis: a Bayesian network analysis. Front Immunol, 2023, 14: 1280226.
23.	Russell A, Yaraskavitch M, Fok D, et al. Obinutuzumab plus chlorambucil in a patient with severe myasthenia gravis and chronic lymphocytic leukemia. J Neuromuscul Dis, 2017, 4(3): 251-257.
24.	Waters MJ, Field D, Ravindran J. Refractory myasthenia gravis successfully treated with ofatumumab. Muscle Nerve, 2019, 60(6): E45-E47.
25.	Frampton JE. Inebilizumab: first approval. Drugs, 2020, 80(12): 1259-1264.
26.	李清峰, 郁莉斐. 被误诊为重症肌无力 3 例病例分析. 中华实用儿科临床杂志, 2021, 36(3): 222-224.
27.	Jia D, Zhang F, Li H, et al. Responsiveness to tocilizumab in anti-acetylcholine receptor-positive generalized myasthenia gravis. Aging Dis, 2024, 15(2): 824-830.
28.	Hewett K, Sanders DB, Grove RA, et al. Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis. Neurology, 2018, 90(16): e1425-e1434.
29.	Dhillon S. Telitacicept: first approval. Drugs, 2021, 81(14): 1671-1675.
30.	Shi F, Xue R, Zhou X, et al. Telitacicept as a BLyS/APRIL dual inhibitor for autoimmune disease. Immunopharmacol Immunotoxicol, 2021, 43(6): 666-673.
31.	Xie J, Fan X, Su Y, et al. Pharmacokinetic characteristics, safety, and tolerability of telitacicept, an injectable recombinant human B-lymphocyte stimulating factor receptor-antibody fusion protein, in healthy Chinese subjects. Clin Pharmacol Drug Dev, 2022, 11(11): 1273-1283.
32.	Zhang Z, Wang Z, Du X, et al. Refractory generalized myasthenia gravis treated successfully with telitacicept: two cases report. J Neurol, 2024, 271(1): 584-588.
33.	Munafo A, Priestley A, Nestorov I, et al. Safety, pharmacokinetics and pharmacodynamics of atacicept in healthy volunteers. Eur J Clin Pharmacol, 2007, 63(7): 647-656.
34.	Gilhus NE, Tzartos S, Evoli A, et al. Myasthenia gravis. Nat Rev Dis Primers, 2019, 5(1): 30.
35.	Christadoss P, Tüzün E, Li J, et al. Classical complement pathway in experimental autoimmune myasthenia gravis pathogenesis. Ann N Y Acad Sci, 2008, 1132: 210-219.
36.	Howard JF Jr. Myasthenia gravis: the role of complement at the neuromuscular junction. Ann N Y Acad Sci, 2018, 1412(1): 113-128.
37.	Huda R. Inflammation and autoimmune myasthenia gravis. Front Immunol, 2023, 14: 1110499.
38.	Mantegazza R, Vanoli F, Frangiamore R, et al. Complement inhibition for the treatment of myasthenia gravis. Immunotargets Ther, 2020, 9: 317-331.
39.	Howard JF Jr, Barohn RJ, Cutter GR, et al. A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis. Muscle Nerve, 2013, 48(1): 76-84.
40.	Howard JF Jr, 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.
41.	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.
42.	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, 270(8): 3862-3875.
43.	Vu T, Meisel A, Mantegazza R, et al. Summary of research: terminal complement inhibitor ravulizumab in generalized myasthenia gravis. Neurol Ther, 2023, 12(5): 1435-1438.
44.	Howard JF Jr, 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.
45.	Howard JF Jr, Bresch S, Genge A, et al. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Neurol, 2023, 22(5): 395-406.
46.	Genge A, Leite MI, Bresch S, et al. Long-term safety, efficacy & self-injection satisfaction with zilucoplan in myasthenia gravis: RAISE-XT interim analysis. J Neurol Sci, 2023: 455.
47.	陈元懿, 赵重波. 新生儿 Fc 受体拮抗剂治疗全身型重症肌无力的现状和前景. 中国临床神经科学, 2023, 31(4): 452-458.
48.	Saccà F, Pane C, Espinosa PE, et al. Efficacy of innovative therapies in myasthenia gravis: a systematic review, meta-analysis and network meta-analysis. Eur J Neurol, 2023, 30(12): 3854-3867.
49.	Di Stefano V, Alonge P, Rini N, et al. Efgartigimod beyond myasthenia gravis: the role of FcRn-targeting therapies in stiff-person syndrome. J Neurol, 2024, 271(1): 254-262.
50.	Wang Y, Zhong X, Wang H, et al. Batoclimab as an add-on therapy in neuromyelitis optica spectrum disorder patients with acute attacks. Eur J Neurol, 2023, 30(1): 195-203.
51.	Wang S, Wang Q, Jin L, et al. Efgartigimod is a new option for the treatment of thymoma associated myasthenia gravis: a case report. Int J Surg Case Rep, 2024, 115: 109241.
52.	Sivadasan A, Bril V. Clinical efficacy and safety of efgartigimod for treatment of myasthenia gravis. Immunotherapy, 2023, 15(8): 553-563.
53.	Howard JF Jr, Bril V, Burns TM, et al. Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis. Neurology, 2019, 92(23): e2661-e2673.
54.	Howard JF Jr, Bril V, Vu T, et al. Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol, 2021, 20(7): 526-536.
55.	Dewilde S, Qi CZ, Phillips G, et al. Association between Myasthenia Gravis-Activities of Daily Living (MG-ADL) and EQ-5D-5L utility values: the additional effect of efgartigimod on utilities. Adv Ther, 2023, 40(4): 1818-1829.
56.	Saccà F, Barnett C, Vu T, et al. Efgartigimod improved health-related quality of life in generalized myasthenia gravis: results from a randomized, double-blind, placebo-controlled, phase 3 study (ADAPT). J Neurol, 2023, 270(4): 2096-2105.
57.	Bril V, Howard JF Jr, Karam C, et al. Effect of efgartigimod on muscle group subdomains in participants with generalized myasthenia gravis: post hoc analyses of the phase 3 pivotal ADAPT study. Eur J Neurol, 2024, 31(1): e16098.
58.	Frangiamore R, Rinaldi E, Vanoli F, et al. Efgartigimod in generalized myasthenia gravis: a real-life experience at a national reference center. Eur J Neurol, 2024, 31(4): e16189.
59.	Hoy SM. Rozanolixizumab: first approval. Drugs, 2023, 83(14): 1341-1347.
60.	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.
61.	Bril V, Drużdż A, Grosskreutz J, et al. Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study. Lancet Neurol, 2023, 22(5): 383-394.
62.	Yan C, Duan RS, Yang H, et al. Therapeutic effects of batoclimab in chinese patients with generalized myasthenia gravis: a double-blinded, randomized, placebo-controlled phase II study. Neurol Ther, 2022, 11(2): 815-834.
63.	Benatar M, Wiendl H, Nowak R, et al. Batoclimab as induction and maintenance therapy in patients with myasthenia gravis: rationale and study design of a phase 3 clinical trial. BMJ Neurol Open, 2024, 6(1): e000536.
64.	Antozzi C, Guptill J, Bril V, et al. Safety and efficacy of nipocalimab in patients with generalized myasthenia gravis: results from the randomized phase 2 vivacity-MG study. Neurology, 2024, 102(2): e207937.
65.	Bhandari V, Bril V. FcRN receptor antagonists in the management of myasthenia gravis. Front Neurol, 2023, 14: 1229112.
66.	Granit V, Benatar M, Kurtoglu M, et al. Safety and clinical activity of autologous RNA chimeric antigen receptor T-cell therapy in myasthenia gravis (MG-001): a prospective, multicentre, open-label, non-randomised phase 1b/2a study. Lancet Neurol, 2023, 22(7): 578-590.
67.	Tian DS, Qin C, Dong MH, et al. B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis. EMBO Mol Med, 2024, 16(4): 966-987.
68.	Huda R. New approaches to targeting B cells for myasthenia gravis therapy. Front Immunol, 2020, 11: 240.
69.	Weyne J, Ni Y, DelGizzi R, et al. A randomized, double-blind, placebo-controlled phase 1 study of the pharmacokinetics and pharmacodynamics of REGN3918, a human antibody against complement factor C5, in healthy volunteers. Blood, 2018, 132(Suppl 1): 1039.

1. Chen J, Tian DC, Zhang C, et al. Incidence, mortality, and economic burden of myasthenia gravis in China: a nationwide population-based study. Lancet Reg Health West Pac, 2020, 5: 100063.
2. Dalakas MC. Immunotherapy in myasthenia gravis in the era of biologics. Nat Rev Neurol, 2019, 15(2): 113-124.
3. Guptill JT, Soni M, Meriggioli MN. Current treatment, emerging translational therapies, and new therapeutic targets for autoimmune myasthenia gravis. Neurotherapeutics, 2016, 13(1): 118-131.
4. Dalakas MC. Treating myasthenia on consensus guide: helpful and challenging but still unfinished business. Neurology, 2016, 87(4): 350-351.
5. Melzer N, Ruck T, Fuhr P, et al. Clinical features, pathogenesis, and treatment of myasthenia gravis: a supplement to the guidelines of the German Neurological Society. J Neurol, 2016, 263(8): 1473-1494.
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.
7. Santos E, Bettencourt A, Duarte S, et al. Refractory myasthenia gravis: characteristics of a portuguese cohort. Muscle Nerve, 2019, 60(2): 188-191.
8. Menon D, Bril V. Pharmacotherapy of generalized myasthenia gravis with special emphasis on newer biologicals. Drugs, 2022, 82(8): 865-887.
9. Zeng R, Glaubitz S, Schmidt J. Antibody therapies in autoimmune inflammatory myopathies: promising treatment options. Neurotherapeutics, 2022, 19(3): 911-921.
10. 常婷, 李柱一. 重症肌无力的治疗: 期待靶向免疫治疗时代的到来. 中华神经科杂志, 2022, 55(4): 271-279.
11. Butcher MJ, Zhu J. Recent advances in understanding the Th1/Th2 effector choice. Fac Rev, 2021, 10: 30.
12. McCombe JA, Pittock SJ. Anti-complement agents for autoimmune neurological disease. Neurotherapeutics, 2022, 19(3): 711-728.
13. Meng QF, Zhang XX, Zhang Z, et al. Therapeutic potential of artesunate in experimental autoimmune myasthenia gravis by upregulated T regulatory cells and regulation of Th1/Th2 cytokines. Pharmazie, 2018, 73(9): 526-532.
14. Fichtner ML, Jiang R, Bourke A, et al. Autoimmune pathology in myasthenia gravis disease subtypes is governed by divergent mechanisms of immunopathology. Front Immunol, 2020, 11: 776.
15. Ehrenstein MR, Wing C. The BAFFling effects of rituximab in lupus: danger ahead?. Nat Rev Rheumatol, 2016, 12(6): 367-372.
16. Vesperinas-Castro A, Cortés-Vicente E. Rituximab treatment in myasthenia gravis. Front Neurol, 2023, 14: 1275533.
17. Li T, Zhang GQ, Li Y, et al. Efficacy and safety of different dosages of rituximab for refractory generalized AChR myasthenia gravis: a meta-analysis. J Clin Neurosci, 2021, 85: 6-12.
18. Yang X, Zhang W, Chang X, et al. Promising efficacy of low-dose rituximab in muscle specific kinase antibody positive myasthenia gravis. Neurosci Lett, 2024, 818: 137561.
19. Nair SS, Jacob S. Novel immunotherapies for myasthenia gravis. Immunotargets Ther, 2023, 12: 25-45.
20. Rüter J, Antonia SJ, Burris HA, et al. Immune modulation with weekly dosing of an agonist CD40 antibody in a phase I study of patients with advanced solid tumors. Cancer Biol Ther, 2010, 10(10): 983-993.
21. GomezMancilla B, Meriggioli MN, Genge A, et al. Efficacy and safety of iscalimab, a novel anti-CD40 monoclonal antibody, in moderate-to-severe myasthenia gravis: a phase 2 randomized study. J Clin Neurosci, 2024, 119: 76-84.
22. Chen H, Qiu Y, Yin Z, et al. Efficacy and safety of the innovative monoclonal antibodies in adults with generalized myasthenia gravis: a Bayesian network analysis. Front Immunol, 2023, 14: 1280226.
23. Russell A, Yaraskavitch M, Fok D, et al. Obinutuzumab plus chlorambucil in a patient with severe myasthenia gravis and chronic lymphocytic leukemia. J Neuromuscul Dis, 2017, 4(3): 251-257.
24. Waters MJ, Field D, Ravindran J. Refractory myasthenia gravis successfully treated with ofatumumab. Muscle Nerve, 2019, 60(6): E45-E47.
25. Frampton JE. Inebilizumab: first approval. Drugs, 2020, 80(12): 1259-1264.
26. 李清峰, 郁莉斐. 被误诊为重症肌无力 3 例病例分析. 中华实用儿科临床杂志, 2021, 36(3): 222-224.
27. Jia D, Zhang F, Li H, et al. Responsiveness to tocilizumab in anti-acetylcholine receptor-positive generalized myasthenia gravis. Aging Dis, 2024, 15(2): 824-830.
28. Hewett K, Sanders DB, Grove RA, et al. Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis. Neurology, 2018, 90(16): e1425-e1434.
29. Dhillon S. Telitacicept: first approval. Drugs, 2021, 81(14): 1671-1675.
30. Shi F, Xue R, Zhou X, et al. Telitacicept as a BLyS/APRIL dual inhibitor for autoimmune disease. Immunopharmacol Immunotoxicol, 2021, 43(6): 666-673.
31. Xie J, Fan X, Su Y, et al. Pharmacokinetic characteristics, safety, and tolerability of telitacicept, an injectable recombinant human B-lymphocyte stimulating factor receptor-antibody fusion protein, in healthy Chinese subjects. Clin Pharmacol Drug Dev, 2022, 11(11): 1273-1283.
32. Zhang Z, Wang Z, Du X, et al. Refractory generalized myasthenia gravis treated successfully with telitacicept: two cases report. J Neurol, 2024, 271(1): 584-588.
33. Munafo A, Priestley A, Nestorov I, et al. Safety, pharmacokinetics and pharmacodynamics of atacicept in healthy volunteers. Eur J Clin Pharmacol, 2007, 63(7): 647-656.
34. Gilhus NE, Tzartos S, Evoli A, et al. Myasthenia gravis. Nat Rev Dis Primers, 2019, 5(1): 30.
35. Christadoss P, Tüzün E, Li J, et al. Classical complement pathway in experimental autoimmune myasthenia gravis pathogenesis. Ann N Y Acad Sci, 2008, 1132: 210-219.
36. Howard JF Jr. Myasthenia gravis: the role of complement at the neuromuscular junction. Ann N Y Acad Sci, 2018, 1412(1): 113-128.
37. Huda R. Inflammation and autoimmune myasthenia gravis. Front Immunol, 2023, 14: 1110499.
38. Mantegazza R, Vanoli F, Frangiamore R, et al. Complement inhibition for the treatment of myasthenia gravis. Immunotargets Ther, 2020, 9: 317-331.
39. Howard JF Jr, Barohn RJ, Cutter GR, et al. A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis. Muscle Nerve, 2013, 48(1): 76-84.
40. Howard JF Jr, 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.
41. 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.
42. 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, 270(8): 3862-3875.
43. Vu T, Meisel A, Mantegazza R, et al. Summary of research: terminal complement inhibitor ravulizumab in generalized myasthenia gravis. Neurol Ther, 2023, 12(5): 1435-1438.
44. Howard JF Jr, 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.
45. Howard JF Jr, Bresch S, Genge A, et al. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Neurol, 2023, 22(5): 395-406.
46. Genge A, Leite MI, Bresch S, et al. Long-term safety, efficacy & self-injection satisfaction with zilucoplan in myasthenia gravis: RAISE-XT interim analysis. J Neurol Sci, 2023: 455.
47. 陈元懿, 赵重波. 新生儿 Fc 受体拮抗剂治疗全身型重症肌无力的现状和前景. 中国临床神经科学, 2023, 31(4): 452-458.
48. Saccà F, Pane C, Espinosa PE, et al. Efficacy of innovative therapies in myasthenia gravis: a systematic review, meta-analysis and network meta-analysis. Eur J Neurol, 2023, 30(12): 3854-3867.
49. Di Stefano V, Alonge P, Rini N, et al. Efgartigimod beyond myasthenia gravis: the role of FcRn-targeting therapies in stiff-person syndrome. J Neurol, 2024, 271(1): 254-262.
50. Wang Y, Zhong X, Wang H, et al. Batoclimab as an add-on therapy in neuromyelitis optica spectrum disorder patients with acute attacks. Eur J Neurol, 2023, 30(1): 195-203.
51. Wang S, Wang Q, Jin L, et al. Efgartigimod is a new option for the treatment of thymoma associated myasthenia gravis: a case report. Int J Surg Case Rep, 2024, 115: 109241.
52. Sivadasan A, Bril V. Clinical efficacy and safety of efgartigimod for treatment of myasthenia gravis. Immunotherapy, 2023, 15(8): 553-563.
53. Howard JF Jr, Bril V, Burns TM, et al. Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis. Neurology, 2019, 92(23): e2661-e2673.
54. Howard JF Jr, Bril V, Vu T, et al. Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol, 2021, 20(7): 526-536.
55. Dewilde S, Qi CZ, Phillips G, et al. Association between Myasthenia Gravis-Activities of Daily Living (MG-ADL) and EQ-5D-5L utility values: the additional effect of efgartigimod on utilities. Adv Ther, 2023, 40(4): 1818-1829.
56. Saccà F, Barnett C, Vu T, et al. Efgartigimod improved health-related quality of life in generalized myasthenia gravis: results from a randomized, double-blind, placebo-controlled, phase 3 study (ADAPT). J Neurol, 2023, 270(4): 2096-2105.
57. Bril V, Howard JF Jr, Karam C, et al. Effect of efgartigimod on muscle group subdomains in participants with generalized myasthenia gravis: post hoc analyses of the phase 3 pivotal ADAPT study. Eur J Neurol, 2024, 31(1): e16098.
58. Frangiamore R, Rinaldi E, Vanoli F, et al. Efgartigimod in generalized myasthenia gravis: a real-life experience at a national reference center. Eur J Neurol, 2024, 31(4): e16189.
59. Hoy SM. Rozanolixizumab: first approval. Drugs, 2023, 83(14): 1341-1347.
60. 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.
61. Bril V, Drużdż A, Grosskreutz J, et al. Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study. Lancet Neurol, 2023, 22(5): 383-394.
62. Yan C, Duan RS, Yang H, et al. Therapeutic effects of batoclimab in chinese patients with generalized myasthenia gravis: a double-blinded, randomized, placebo-controlled phase II study. Neurol Ther, 2022, 11(2): 815-834.
63. Benatar M, Wiendl H, Nowak R, et al. Batoclimab as induction and maintenance therapy in patients with myasthenia gravis: rationale and study design of a phase 3 clinical trial. BMJ Neurol Open, 2024, 6(1): e000536.
64. Antozzi C, Guptill J, Bril V, et al. Safety and efficacy of nipocalimab in patients with generalized myasthenia gravis: results from the randomized phase 2 vivacity-MG study. Neurology, 2024, 102(2): e207937.
65. Bhandari V, Bril V. FcRN receptor antagonists in the management of myasthenia gravis. Front Neurol, 2023, 14: 1229112.
66. Granit V, Benatar M, Kurtoglu M, et al. Safety and clinical activity of autologous RNA chimeric antigen receptor T-cell therapy in myasthenia gravis (MG-001): a prospective, multicentre, open-label, non-randomised phase 1b/2a study. Lancet Neurol, 2023, 22(7): 578-590.
67. Tian DS, Qin C, Dong MH, et al. B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis. EMBO Mol Med, 2024, 16(4): 966-987.
68. Huda R. New approaches to targeting B cells for myasthenia gravis therapy. Front Immunol, 2020, 11: 240.
69. Weyne J, Ni Y, DelGizzi R, et al. A randomized, double-blind, placebo-controlled phase 1 study of the pharmacokinetics and pharmacodynamics of REGN3918, a human antibody against complement factor C5, in healthy volunteers. Blood, 2018, 132(Suppl 1): 1039.

West China Medical Journal

Research progress on molecular targeted drug therapy for myasthenia gravis

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content