Azathioprine vs. Methotrexate Effectiveness in the Treatment of Generalized Myasthenia Gravis (MG)

Authors

  • Sadaf Iftikhar Department of Neurology, King Edward Medical University (KEMU), Mayo Hospital, Lahore, Pakistan
  • Asfand Kousar Department of Neurology, King Edward Medical University (KEMU), Mayo Hospital, Lahore, Pakistan
  • Aysha Ghayyur Department of Medicine, Allama Iqbal Medical College (AIMC), Jinnah Hospital, Lahore, Pakistan
  • Saman Shahid Department of Sciences & Humanities, National University of Computer & Emerging Sciences (NUCES), FAST Lahore Campus, Lahore, Pakistan
  • Adina Qaiser Department of Physiology, Khawaja Safdar Medical College, Sialkot Pakistan

DOI:

https://doi.org/10.36552/pjns.v28i2.978

Keywords:

: Azathioprine, Methotrexate, Generalized Myasthenia Gravis, Myasthenia Gravis Foundation of America (MGFA)

Abstract

Objective: The current study investigated the effectiveness of Azathioprine versus Methotrexate in the treatment of generalized MG.

Methodology: An observational, open-label retrospective study was conducted in the Department of Neurology, Mayo Hospital, Lahore, Pakistan. All generalized MG patients with positive acetylcholine receptor antibodies (MGFA class II, III, or IV) aged >16 years, were included. Group 1 (n=31) was taking the combination of oral Prednisolone and Azathioprine (AZA) and group 2 (n=31) was taking the combination of Prednisolone and Methotrexate (MTX). The clinical response was assessed by Myasthenia gravis activities of daily living (MG-ADL) score at the 3rd, 6th, 9th, 12th, & 18th months.

Results: At 3rd month follow-up, the mean MG-ADL score was 2.97 (AZA) vs. 3.39 (MTX), after the 6th month, the score was 0.48(AZA) vs. 1.13 (MTX) (p-value=0.009), after the 9th month: the score was 0.26 (AZA), vs. 0.97(MTX) (p-value=0.002), after the 12th month, the score was 0.29 (AZA) vs. 0.74 (MTX) (p-value=0.079), after 15th month, the score was 0.16(AZA) vs. 0.65(MTX) (p-value=0.009) and after 18th month, the score was 0.42(AZA) vs. 0.52(MTX) (p-value=0.703).

Conclusion: Azathioprine is significantly more efficacious from the 6th, 9th, 12th and after the 15th-month follow-up as compared to Methotrexate in the treatment of MG; however, on the 18th-month follow-up, both steroid-sparing drugs were equally effective. There appears to be no difference in the effectiveness of Azathioprine versus Methotrexate in the treatment of generalized MG.

References

Tamparo CD. Diseases of the human body. 6th ed, FA Davis; 2016 Feb 3.

Isbister CM, Mackenzie PJ, Anderson D, Wade NK, Oger J. Co-occurrence of multiple sclerosis and myasthenia gravis in British C olumbia. Multiple Sclerosis Journal. 2003;9(6):550-3.

doi.org/10.1191/1352458503ms964oa

Liu CJ, Chang YS, Teng CJ, Chen TJ, Ou SM, Tzeng CH, Wang SJ. Risk of extrathymic cancer in patients with myasthenia gravis in Taiwan: a nationwide population?based study. European Journal of Neurology. 2012;19(5):746-51.

doi.org/10.1111/j.1468-1331.2011.03621.x

Oh SJ, Dhall R, Young A, Morgan MB, Lu L, Claussen GC. Statins may aggravate myasthenia gravis. Muscle & Nerve: Official Journal of the American Association of Electrodiagnostic Medicine. 2008;38(3):1101-7. doi.org/10.1002/mus.21074

Chan KH, Lachance DH, Harper CM, Lennon VA. Frequency of seronegativity in adult?acquired generalized myasthenia gravis. Muscle & nerve. 2007;36(5):651-8. doi.org/10.1002/mus.20854

Jowker AA, Goldenberg WD, Lorenzo N. Myasthenia Gravis. 2022. Available from:

https://emedicine.medscape.com/article/1171206-overview

Godoy DA, Mello LJ, Masotti L, Napoli MD. The myasthenic patient in crisis: an update of the management in Neurointensive Care Unit. Arquivos de Neuro-Psiquiatria. 2013;71:627-39.

doi.org/10.1590/0004-282X20130108

Gajdos P, Chevret S, Toyka KV. Intravenous immunoglobulin for myasthenia gravis. Cochrane Database of Systematic Reviews. 2008;1-24. Available from: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002277.pub3/pdf/full

Keller DM. Late-Onset Myasthenia Gravis Linked to Higher Cancer Risk. Medscape Medical News. Jul 2 2013.

Jayam Trouth A, Dabi A, Solieman N, Kurukumbi M, Kalyanam J. Myasthenia gravis: a review. Autoimmune diseases. 2012;2012.

doi.org/10.1155/2012/874680

Bosch EP, Subbiah BA, Ross MA. Cholinergic crisis after conventional doses of anticholinesterase medications in chronic renal failure. Muscle & nerve. 1991;14(10):1036-7. PMID: 1944406

Samuelsson A, Towers TL, Ravetch JV. Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science. 2001;291(5503):484-6. doi.org/10.1126/science.291.5503.484

Psaridi-Linardaki L, Trakas N, Mamalaki A, Tzartos SJ. Specific immunoadsorption of the autoantibodies from myasthenic patients using the extracellular domain of the human muscle acetylcholine receptor ?-subunit. Development of an antigen-specific therapeutic strategy. Journal of neuroimmunology. 2005;159(1-2):183-91.

doi.org/10.1016/j.jneuroim.2004.10.002

Barth D, Nouri MN, Ng E, Nwe P, Bril V. Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology. 2011;76(23):2017-23.

doi.org/10.1212/WNL.0b013e31821e5505

Robinson J, Eccher M, Bengier A, Liberman J. Costs and charges for plasma exchange (PLEX) versus intravenous immunoglobulin (IVIg) in the treatment of neuromuscular disease. Neurology (PD6. 008). PD6 Muscle Disease/Neuromascular Junction, 2012. doi.org/10.1212/WNL.78.1_MeetingAbstracts.PD6.008

Chaudhry V, Cornblath DR, Griffin JW, O’brien R, Drachman DB. Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular diseases. Neurology. 2001;56(1):94-6.

doi.org/10.1212/WNL.56.1.94

Ciafaloni E, Massey JM, Tucker–Lipscomb B, Sanders DB. Mycophenolate mofetil for myasthenia gravis: an open-label pilot study. Neurology.

;56(1):97-9. doi.org/10.1212/WNL.56.1.97

Meriggioli MN, Ciafaloni E, Al-Hayk KA, Rowin J, Tucker-Lipscomb B, Massey JM, Sanders DB. Mycophenolate mofetil for myasthenia gravis: an analysis of efficacy, safety, and tolerability. Neurology. 2003;61(10):1438-40.

doi.org/10.1212/01.WNL.0000094122.88929.0B

Spring PJ, Spies JM. Myasthenia gravis: options and timing of immunomodulatory treatment. Bio Drugs. 2001;15(3):173-83.

doi.org/10.2165/00063030-200115030-00004

Tindall RS, Phillips JT, Rollins JA, Wells LI, Hall K. A clinical therapeutic trial of cyclosporine in myasthenia gravis. Annals of the New York Academy of Sciences. 1993;681:539-51.

doi.org/10.1111/j.1749-6632.1993.tb22937.x

Heckmann JM, Rawoot A, Bateman K, Renison R, Badri M. A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis. BMC neurology. 2011;11:1-9. doi.org/10.1186/1471-2377-11-97

Wolfe GI, Herbelin L, Nations SP, Foster B, Bryan WW, Barohn RJ. Myasthenia gravis activities of daily living profile. Neurology. 1999;52(7):1487-1489. doi.org/10.1212/WNL.52.7.1487.

Romi F, Skeie GO, Aarli JA, Gilhus NE. The severity of myasthenia gravis correlates with the serum concentration of titin and ryanodine receptor antibodies. Archives of neurology. 2000;57(11):1596-600.

doi.org/10.1001/archneur.57.11.1596

Mehndiratta MM, Pandey S, Kuntzer T. Acetylcholinesterase inhibitor treatment for myasthenia gravis. Cochrane Database of Systematic Reviews. 2014(10).

doi.org/10.1002/14651858.CD006986.pub3

Sathasivam S. Steroids and immunosuppressant drugs in myasthenia gravis. Nature clinical practice Neurology. 2008;4(6):317-27.

doi.org/10.1038/ncpneuro0810

Muscle Study Group. A trial of mycophenolate mofetil with prednisone as initial immunotherapy in myasthenia gravis. Neurology. 2008;71(6):394-9. doi.org/10.1212/01.wnl.0000312373.67493.7f

Sanders D, Hart IK, Mantegazza R, Shukla SS, Siddiqi ZA, De Baets MH, Melms A, Nicolle MW, Solomons N, Richman DP. An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis. Neurology. 2008;71(6):400-6. doi.org/10.1212/01.wnl.0000312374.95186.cc

Zinman L, Ng E, Bril V. IV immunoglobulin in patients with myasthenia gravis: a randomized controlled trial. Neurology. 2007;68(11):837-41. doi.org/10.1212/01.wnl.0000256698.69121.45

Pasnoor M, He J, Herbelin L, Burns TM, Nations S, Bril V, Wang AK, Elsheikh BH, Kissel JT, Saperstein D, Shaibani JA. A randomized controlled trial of methotrexate for patients with generalized myasthenia gravis. Neurology. 2016;87(1):57-64. doi: 10.1212/WNL.0000000000002795

Gilhus NE, Owe JF, Hoff JM, Romi F, Skeie GO, Aarli JA. Myasthenia gravis: a review of available treatment approaches. Autoimmune diseases. 2011 Oct 5;2011. doi.org/10.4061/2011/847393

Evoli A, Bianchi MR, Riso R, Minicuci GM, Batocchi AP, Servidei S, Scuderi F, Bartoccioni E. Response to therapy in myasthenia gravis with anti?MuSK antibodies. Annals of the New York Academy of Sciences. 2008;1132(1):76-83.

doi.org/10.1196/annals.1405.012

Conti-Fine BM, Milani M, Kaminski HJ. Myasthenia gravis: past, present, and future. The Journal of

clinical investigation. 2006;116(11):2843-54.

doi.org/10.1172/JCI29894

Palace J, Newsom-Davis J, Lecky BR, Myasthenia Gravis Study Group. A randomized double?blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Neurology. 1998;50(6):1778-83. doi.org/10.1212/WNL.50.6.1778

Menon D, Bril V. Pharmacotherapy of generalized myasthenia gravis with special emphasis on newer biologicals. Drugs. 2022;82(8):865-87.

doi.org/10.1007/s40265-022-01726-y

Di L, Shen F, Wen X, Lu Y, Zhu W, Wang M, Da Y. A Randomized Open-Labeled Trial of Methotrexate as a Steroid-Sparing Agent for Patients with Generalized Myasthenia Gravis. Frontiers in Immunology. 2022;13.

doi.org/10.3389/fimmu.2022.839075

Narayanaswami P, Sanders DB, Wolfe G, Benatar M, Cea G, Evoli A, Gilhus NE, Illa I, Kuntz NL, Massey J, Melms A. International consensus guidance for management of myasthenia gravis: 2020 update. Neurology. 2021;96(3):114-22.

doi.org/10.1212/WNL.0000000000011124

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2024-06-13

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