Refractory myasthenia gravis – clinical characteristics and possibilities of biological treatment
Authors:
J. Piťha 1,2
Authors place of work:
Neurologická klinika 1. LF UK a VFN Praha
1; MS Centrum Teplice, Neurologické oddělení, KZ a. s. – Nemocnice Teplice o. z.
2
Published in the journal:
Cesk Slov Neurol N 2019; 82(5): 490-495
Category:
Review Article
doi:
https://doi.org/10.14735/amcsnn2019490
Summary
Refractory myasthenia gravis, despite significant advances in the diagnosis and therapy of this autoimmune disease, is an important medical and socioeconomic problem. The article deals with the immunopathogenesis of myasthenia gravis, the characteristics of the disease, the clinical context in terms of risk groups of patients, the quantification of neurological deficits and the treatment options aimed at biological therapy.
The author declares he has no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
Přijato k recenzi: 9. 5. 2019
Přijato do tisku: 13. 8. 2019
Keywords:
myasthenia gravis – MuSK – refractory form – clinical characteristics
Zdroje
1. Meriggioli MN, Sanders DB. Muscle autoantibodies in myasthenia gravis: beyond diagnosis? Expert Rev Clin Immunol 2012; 8(5): 427–438. doi: 10.1586/ eci.12.34.
2. Berrih-Aknin S, Le Panse R. Myasthenia gravis: a comprehensive review of immune dysregulation and etiological mechanisms. J Autoimmun 2014; 52: 90–100. doi: 10.1016/ j.jaut.2013.12.011.
3. 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. doi: 10.1007/ s00415-016-8045-z.
4. Wang Z, Yan Y. Immunopathogenesis in myasthenia gravis and neuromyelitis optica. Front Immunol 2017; 8: 1785. doi: 10.3389/ fimmu.2017.01785.
5. Tuzun E, Huda R, Christadoss P. Complement and cytokine based therapeutic strategies in myasthenia gravis. J Autoimmun 2011; 37(2): 136–143. doi: 10.1016/ j.jaut.2011.05.006.
6. Sieb JP. Myasthenia gravis: an update for the clinician. Clin Exp Immunol 2014; 175(3): 408–418. doi: 10.1111/ cei.12217.
7. Huda R, Tuzun E, Christadoss P. Targeting complement system to treat myasthenia gravis. Rev Neurosci 2014; 25(4): 575–583. doi: 10.1515/ revneuro-2014-0021.
8. Rivner MH, Pasnoor M, Dimachkie MM et al. Muscle-specific tyrosine kinase and myasthenia gravis owing to other antibodies. Neurol Clin 2018; 36(2): 293–310. doi: 10.1016/ j.ncl.2018.01.004.
9. Yan M, Xing GL, Xiong WC et al. Agrin and LRP4 antibodies as new biomarkers of myasthenia gravis. Ann N Y Acad Sci 2018; 1413(1): 126–135. doi: 10.1111/ nyas.13573.
10. Yi JS, Guptill JT, Stathopoulos P et al. B cells in the pathophysiology of myasthenia gravis. Muscle Nerve 2018; 57(2): 172–184. doi: 10.1002/ mus.25973.
11. Jakubíková M, Piťha J. Současný pohled na imunopatogenezi myasthenia gravis. Cesk Slov Neurol N 2015; 78/ 111(6): 649–654.
12. Spillane J, Higham E, Kullmann DM. Myasthenia gravis. BMJ 2012; 345: e8497. doi: 10.1136/ bmj.e8497.
13. Li Y, Arora Y, Levin K. Myasthenia gravis: newer therapies offer sustained improvement. Cleve Clin J Med 2013; 80(11): 711–721. doi: 10.3949/ ccjm.80a.13044.
14. Sanders DB, Wolfe GI, Benatar M et al. International consensus guidance for management of myasthenia gravis: executive summary. Neurology 2016; 87(4): 419–425. doi: 10.1212/ WNL.0000000000002790.
15. Grob D, Brunner N, Namba T et al. Lifetime course of myasthenia gravis. Muscle Nerve 2008; 37(2): 141–149. doi: 10.1002/ mus.20950.
16. Carr AS, Cardwell CR, McCarron PO et al. A systematic review of population based epidemiological studies in myasthenia gravis. BMC Neurol 2010; 10: 46. doi: 10.1186/ 1471-2377-10-46.
17. Baggi F, Andreetta F, Maggi L et al. Complete stable remission and autoantibody specificity in myasthenia gravis. Neurology 2013; 80(2): 188–195. doi: 10.1212/ WNL.0b013e31827b907b.
18. Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol 2015; 14(10): 1023–1036. doi: 10.1016/ S1474-4422(15)00145-3.
19. Sudulagunta SR, Sepehrar M, Sodalagunta MB. Refractory myasthenia gravis – clinical profile, comorbidities and response to rituximab. Ger Med Sci 2016; 14: Doc12. doi: 10.3205/ 000239.
20. Jordan A, Freimer M. Recent advances in understanding and managing myasthenia gravis. F1000Res 2018; 7. pii: F1000 Faculty Rev-1727. doi: 10.12688/ f1000research.15973.1.
21. Schneider-Gold C, Hagenacker T, Melzer N et al. Understanding the burden of refractory myasthenia gravis. Ther Adv Neurol Disord 2019; 12: 1756286419832242. doi: 10.1177/ 1756286419832242.
22. Silvestri NJ and Wolfe GI. Treatment-refractory myasthenia gravis. J Clin Neuromuscul Dis 2014; 15(4): 167–178. doi: 10.1097/ CND.0000000000000034.
23. Suh J, Goldstein JM and Nowak RJ. Clinical characteristics of refractory myasthenia gravis patients. Yale J Biol Med 2013; 86(2): 255–260.
24. Zebardast N, Patwa HS, Novella SP et al. Rituximab in the management of refractory myasthenia gravis. Muscle Nerve 2010; 41(3): 375–378. doi: 10.1002/ mus.21521.
25. Mantegazza R, Antozzi C. When myasthenia gravis is deemed refractory: clinical signposts and treatment strategies. Ther Adv Neurol Disord 2018; 11: 1756285617749134. doi: 10.1177/ 1756285617749134.
26. Collongues N, Casez O, Lacour A et al. Rituximab in refractory and non-refractory myasthenia: a retrospective multicenter study. Muscle Nerve 2012; 46(5): 687–691. doi: 10.1002/ mus.23412.
27. Engel-Nitz NM, Boscoe A, Wolbeck R et al. Burden of illness in patients with treatment refractory myasthenia gravis. Muscle Nerve 2018; 58: 99–105. doi: 10.1002/ mus.26114.
28. Sorgun MH, Sener HO, Yucesan C et al. Intravenous immunoglobulin for prophylaxis of acute exacerbation in myasthenia gravis. Neurol Sci 2014; 35(6): 891–896. doi: 10.1007/ s10072-013-1621-4.
29. Nicolle MW, Rask S, Koopman WJ et al. Sleep apnea in patients with myasthenia gravis. Neurology 2006; 67(1): 140–142. doi: 10.1212/ 01.wnl.0000223515.15691.26.
30. Martínez-Lapiscina EH, Erro ME, Ayuso T et al. Myasthenia gravis: sleep quality, quality of life, and disease severity. Muscle Nerve 2012; 46(2): 174–180. doi: 10.1002/ mus.23296.
31. Nagane Y, Murai H, Imai T et al. Social disadvantages associated with myasthenia gravis and its treatment: a multicentre cross-sectional study. BMJ Open 2017; 7(2): e013278. doi: 10.1136/ bmjopen-2016-013278.
32. Benatar M, Sanders DB, Burns TM, Recommendations for myasthenia gravis clinical trials. Muscle Nerve 2012; 45(6): 909–917. doi: 10.1002/ mus.23330.
33. Jaretzki A 3rd, Barohn RJ, Ernstoff RM et al. Myasthenia gravis. Recommendations for clinical research standards. Ann Thorac Surg 2000; 70(1): 327–334.
34. Collongues N, Casez O, Lacour A et al. Rituximab in refractory and non-refractory myasthenia: a retrospective multicenter study. Muscle Nerve 2012; 46(5): 687–691. doi: 10.1002/ mus.23412.
35. Barohn RJ, McIntire D, Herbelin L et al. Reliability testing of the quantitative myasthenia gravis score. Ann N Y Acad Sci 1998; 841: 769–772.
36. Wolfe GI, Herbelin L, Nations SP et al. Myasthenia gravis activities of daily living profile. Neurology 1999; 52(7): 1487–1489.
37. Sanders DB, Tucker-Lipscomb B and Massey JM. A simple manual muscle test for myasthenia gravis: validation and comparison with the QMG score. Ann N Y Acad Sci 2003; 998: 440–444. doi: 10.1196/ annals.1254.057.
38. Burns TM, Conaway MR, Cutter GR et al. Construction of an efficient evaluative instrument for myasthenia gravis: the MG composite. Muscle Nerve 2008; 38(6): 1553–1562. doi: 10.1002/ mus.21185.
39. Chmelíková M, Voháňka S, Bednařík J. Myasthenia gravis composite – validace české verze. Cesk Slov Neurol N 2016; 79/ 112(5): 585–590.
40. Mullins LL, Carpentier MY, Paul RH et al. Disease-specific measure of quality of life for myasthenia gravis. Muscle Nerve 2008; 38(2): 947–956. doi: 10.1002/ mus.21016.
41. Horakova M, Vohanka S, Bednarik J. Validation of myasthenia gravis quality of life questionnaire – Czech version of MG-QOL15. Cesk Slov Neurol N 2017; 80/ 113(1): 66–69.
42. Drachman DB, Adams RN, Hu R et al. Rebooting the immune system with high-dose cyclophosphamide for treatment of refractory myasthenia gravis. Ann N Y Acad Sci 2008; 1132: 305–314. doi: 10.1196/ annals.1405.033.
43. Bryant A, Atkins H, Pringle CE. Myasthenia gravis treated with autologous hematopoietic stem cell transplantation. JAMA Neurol 2016; 73(6): 652–658. doi: 10.1001/ jamaneurol.2016.0113.
44. Dalakas MC. Immunotherapy in myasthenia gravis in the era of biologics. Nat Rev Neurol 2019; 15(2): 113–124. doi: 10.1038/ s41582-018-0110-z.
45. Glennie MJ, French RR, Cragg MS et al. Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol Immunol 2007; 44(16): 3823–3837. doi: 10.1016/ j.molimm.2007.06.151.
46. Wylam ME, Anderson PM, Kuntz NL et al. Successful treatment of refractory myasthenia gravis using rituximab: a pediatric case report. J Pediatr 2003; 143(5): 674–677. doi: 10.1067/ S0022-3476(03)00300-7.
47. Iorio R, Damato V, Alboini PE et al. Efficacy and safety of rituximab for myasthenia gravis: a systematic review and meta-analysis. J Neurol 2015; 262(5): 1115–1119. doi: 10.1007/ s00415-014-7532-3.
48. Tandan R, Hehir MK 2nd, Waheed W et al. Rituximab treatment of myasthenia gravis: a systematic review. Muscle Nerve 2017; 56(2): 185–196. doi: 10.1002/ mus.25597.
49. Topakian R, Zimprich F, Iglseder S et al. High efficacy of rituximab for myasthenia gravis: a comprehensive nationwide study in Austria. J Neurol 2019; 266(3): 699–706. doi: 10.1007/ s00415-019-09191-6. 16.
50. Cortés-Vicente E, Rojas-Garcia R, Díaz-Manera J et al. The impact of rituximab infusion protocol on the long-term outcome in anti-MuSK myasthenia gravis. Ann Clin Transl Neurol 2018; 5(6): 710–716. doi: 10.1002/ acn3.564.
51. Robeson KR, Kumar A, Keung B at al. Durability of the rituximab response in acetylcholine receptor autoantibody-positive myasthenia gravis. JAMA Neurol 2017; 74(1): 60–66. doi: 10.1001/ jamaneurol.2016.4190.
52. Nowak R, Barohn RJ, Goldstein JM et al. A phase II trial of Rituximab in myasthenia gravis. Presented on Annual Meeting of the American Academy of Neurology, May 2018, poster P.4.478. [online]. Available from URL: https: / / n.neurology.org/ content/ 90/ 24/ e2182/ tab-article-info.
53. A study evaluating the safety and efficacy of Rituximab in patients with myasthenia gravis (Rinomax). [online]. Available from URL: https: / / clinicaltrials.gov/ ct2/ show/ NCT02950155.
54. Carson KR, Evens AM, Richey EA et al. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports Project. Blood 2009; 113(20): 4834–4840. doi: 10.1182/ blood-2008-10-186999.
55. Berger JR, Malik V, Lacey S et al. Progressive multifocal leukoencephalopathy in rituximab treated rheumatic diseases: a rare event. J Neurovirol 2018; 24(3): 323–331. doi: 10.1007/ s13365-018-0615-7.
56. Schatz-Jakobsen JA, Zhang Y, Johnson K et al. Structural basis for eculizumab-mediated inhibition of the complement terminal pathway. J Immunol 2016; 197(1): 337–344. doi: 10.4049/ jimmunol.1600280.).
57. Howard JF Jr., Utsugisawa K, Benatar M et al. REGAIN Study Group. 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)30369-1.
58. 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.
59. Dhillon S. Eculizumab: a review in generalized myasthenia gravis. Drugs 2018; 78(3): 367–376. doi: 10.1007/ s40265-018-0889-3.
60. 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.
61. 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. doi: 10.1212/ WNL.0000000000007600.
62. Phase 2 study shows Rozanolixizumab is safe and effective in alleviating MG symptoms. [online]. Available from URL: https: / / myastheniagravisnews.com/ 2018/ 10/ 23/ phase-2- study-shows-rozanolixizumab-safe-effective-alleviating- mg-symptoms/ .
63. Trial of Orencia in patients with myasthenia gravis. [online]. Available from URL: https: / / clinicaltrials.gov/ ct2/ show/ NCT03059888).
64. Therapy of antibody-mediated autoimmune diseases by Bortezomib (TAVAB). [online]. Available from URL https: / / clinicaltrials.gov/ ct2/ show/ NCT02102594).
65. Howard JF, Kaminski HJ, Nowak RJ et al. RA101495, a subcutaneously administered peptide inhibitor of complement component 5 (C5) for the treatment of generalized myasthenia gravis (gMG): phase 1 results and phase 2 design. Neurology 2018; 90 (Suppl 15): S31.006. [online]. Available from URL: https: / / n.neurology.org/ content/ 90/ 15_Supplement/ S31.006.
66. Ristov J, Espie P, Ulrich P et al. Characterization of the in vitro and in vivo properties of CFZ533, a blocking and nondepleting anti-CD40 monoclonal antibody. Am J Transplant 2018; 18(12): 2895–2904. doi: 10.1111/ ajt.1487.
67. Safety and efficacy study of ravulizumab in aults with generalized myasthenia gravis. [online]. Available from URL: https://clinicaltrials.gov/ct2/show/NCT03920293.
Štítky
Paediatric neurology Neurosurgery NeurologyČlánok vyšiel v časopise
Czech and Slovak Neurology and Neurosurgery
2019 Číslo 5
- Advances in the Treatment of Myasthenia Gravis on the Horizon
- Memantine Eases Daily Life for Patients and Caregivers
- Spasmolytic Effect of Metamizole
Najčítanejšie v tomto čísle
- Treatment of insomnia in the context of neuropathic pain
- Compressive neuropathies as an occupational disease
- Changes of paraspinal muscle morphology in patients with chronic non-specific low back pain
- Endoscopic surgery for lumbar disc herniation – the first experience