Document Type : Original Article

Authors

1 Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran Department of Neurology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

2 Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Neuromuscular Research Center, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Neuromuscular Research Center, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Neuromuscular Research Center, Tehran University of Medical Sciences, Tehran, Iran Department of Neurology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background: This retrospective cohort study was conducted to evaluate the efficacy and tolerance of rituximab (RTX) for the management of myasthenia gravis (MG).
Methods: This retrospective cross-sectional study was conducted on 61 patients with refractory and non-refractory MG who received RTX. The Myasthenia Gravis Activities of Daily Living (MG-ADL) profile was used to assess MG symptoms and their effects on daily activities at the start of RTX and in the last follow-up. The Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS) scale has been used as an outcome measure after treatment with RTX in the 12th month and the last follow-up.
Results: The mean age of the patients was 40.31 ± 13.53 years (range: 15-78 years). Of 61 patients, eight (13.1%) were double seronegative, 29 (47.5%) had anti-acetylcholine receptor (AChR+) antibody, and 24 (39.3%) had anti-muscle-specific tyrosine kinase antibody (MuSK+). According to the mean rank table, the results of this study showed that the drug was more effective in improving the symptoms of MuSK+ patients compared to the other two groups (P = 0.006). The mean MG-ADL was 4.86 ± 1.83 before treatment and 1.51 ± 2.02 in the last follow-up visit. Paired t-test showed a significant association between MG-ADL before and after treatment in the last visit [t(55): 11.30, 95% confidence interval (CI): 2.79-3.99, P = 0.001)].
Conclusion: This retrospective study showed a considerable effect of RTX as induction therapy in patients with MG, especially those with MuSk+ MG.

Keywords

  1. Collongues N, Casez O, Lacour A, Tranchant C, Vermersch P, de Seze J, et al. Rituximab in refractory and non-refractory myasthenia: A retrospective multicenter study. Muscle Nerve 2012; 46(5): 687-91.
  2. Silvestri NJ, Wolfe GI. Treatment-refractory myasthenia gravis. J Clin Neuromuscul Dis 2014; 15(4): 167-78.
  3. Sanders DB, Wolfe GI, Benatar M, Evoli A, Gilhus NE, Illa I, et al. International consensus guidance for management of myasthenia gravis: Executive summary. Neurology 2016; 87(4): 419-25.
  4. Deenen JC, Horlings CG, Verschuuren JJ, Verbeek AL, van Engelen BG. The epidemiology of neuromuscular disorders: A comprehensive overview of the literature. J Neuromuscul Dis 2015; 2(1): 73-85.
  5. Blum S, Gillis D, Brown H, Boyle R, Henderson R, Heyworth-Smith D, et al. Use and monitoring of low dose rituximab in myasthenia gravis. J Neurol Neurosurg Psychiatry 2011; 82(6): 659-63.
  6. Hoch W, McConville J, Helms S, Newsom-Davis J, Melms A, Vincent A. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med 2001; 7(3): 365-8.
  7. Lindberg C, Bokarewa M. Rituximab for severe myasthenia gravis--experience from five patients. Acta Neurol Scand 2010; 122(4): 225-8.
  8. Stieglbauer K, Pichler R, Topakian R. 10-year-outcomes after rituximab for myasthenia gravis: Efficacy, safety, costs of inhospital care, and impact on childbearing potential. J Neurol Sci 2017; 375: 241-4.
  9. Gilhus NE, Verschuuren JJ. Myasthenia gravis: Subgroup classification and therapeutic strategies. Lancet Neurol 2015; 14(10): 1023-36.
  10. Topakian R, Zimprich F, Iglseder S, Embacher N, Guger M, Stieglbauer K, et al. High efficacy of rituximab for myasthenia gravis: A comprehensive nationwide study in Austria. J Neurol 2019; 266(3): 699-706.
  11. Jing S, Lu J, Song J, Luo S, Zhou L, Quan C, et al. Effect of low-dose rituximab treatment on T- and B-cell lymphocyte imbalance in refractory myasthenia gravis. J Neuroimmunol 2019; 332: 216-23.
  12. Afanasiev V, Demeret S, Bolgert F, Eymard B, Laforet P, Benveniste O. Resistant myasthenia gravis and rituximab: A monocentric retrospective study of 28 patients. Neuromuscul Disord 2017; 27(3): 251-8.
  13. Singh AK, Vinayak M. Curcumin attenuates CFA induced thermal hyperalgesia by modulation of antioxidant enzymes and down regulation of TNF-alpha, IL-1beta and IL-6. Neurochem Res 2015; 40(3): 463-72.
  14. Lebrun C, Bourg V, Tieulie N, Thomas P. Successful treatment of refractory generalized myasthenia gravis with rituximab. Eur J Neurol 2009; 16(2): 246-50.
  15. Nelson RP, Jr., Pascuzzi RM, Kessler K, Walsh LE, Faught PP, Ramanuja S, 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): 170-7.
  16. Stieglbauer K, Topakian R, Schaffer V, Aichner FT. Rituximab for myasthenia gravis: three case reports and review of the literature. J Neurol Sci 2009; 280(1-2): 120-2.
  17. Zebardast N, Patwa HS, Novella SP, Goldstein JM. Rituximab in the management of refractory myasthenia gravis. Muscle Nerve 2010; 41(3): 375-8.
  18. Hehir MK, Hobson-Webb LD, Benatar M, Barnett C, Silvestri NJ, Howard JF, et al. Rituximab as treatment for anti-MuSK myasthenia gravis: Multicenter blinded prospective review. Neurology 2017; 89(10): 1069-77.
  19. Maddison P, McConville J, Farrugia ME, Davies N, Rose M, Norwood F, et al. The use of rituximab in myasthenia gravis and Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 2011; 82(6): 671-3.
  20. Stein B, Bird SJ. Rituximab in the treatment of MuSK antibody-positive myasthenia gravis. J Clin Neuromuscul Dis 2011; 12(3): 163-4.
  21. Sadnicka A, Reilly MM, Mummery C, Brandner S, Hirsch N, Lunn MP. Rituximab in the treatment of three coexistent neurological autoimmune diseases: Chronic inflammatory demyelinating polyradiculoneuropathy, Morvan syndrome and myasthenia gravis. J Neurol Neurosurg Psychiatry 2011; 82(2): 230-2.
  22. Nowak RJ, Dicapua DB, Zebardast N, Goldstein JM. Response of patients with refractory myasthenia gravis to rituximab: A retrospective study. Ther Adv Neurol Disord 2011; 4(5): 259-66.
  23. Anderson D, Phan C, Johnston WS, Siddiqi ZA. Rituximab in refractory myasthenia gravis: a prospective, open-label study with long-term follow-up. Ann Clin Transl Neurol 2016; 3(7): 552-5.
  24. Peres J, Martins R, Alves JD, Valverde A. Rituximab in generalized myasthenia gravis: Clinical, quality of life and cost-utility analysis. Porto Biomed J 2017; 2(3): 81-5.
  25. Koul R, Al FA, Abdwani R. Rituximab in severe seronegative juvenile myasthenia gravis: review of the literature. Pediatr Neurol 2012; 47(3): 209-12.
  26. Choi K, Hong YH, Ahn SH, Baek SH, Kim JS, Shin JY, et al. Repeated low-dose rituximab treatment based on the assessment of circulating B cells in patients with refractory myasthenia gravis. Ther Adv Neurol Disord 2019; 12: 1756286419871187.
  27. Grob D, Brunner N, Namba T, Pagala M. Lifetime course of myasthenia gravis. Muscle Nerve 2008; 37(2): 141-9.
  28. Lee CY, Lam CL, Pang SY, Lau KK, Teo KC, Chang RS, et al. Clinical outcome of generalized myasthenia gravis in Hong Kong Chinese. J Neuroimmunol 2015; 289: 177-81.
  29. Tandan R, Hehir MK, Waheed W, Howard DB. Rituximab treatment of myasthenia gravis: A systematic review. Muscle Nerve 2017; 56(2): 185-96.
  30. Brauner S, Eriksson-Dufva A, Hietala MA, Frisell T, Press R, Piehl F. Comparison between rituximab treatment for new-onset generalized myasthenia gravis and refractory generalized myasthenia gravis. JAMA Neurol 2020; 77(8): 974-81.