Treatment of myasthenia gravis with rituximab

a systematic review and meta analysis

Authors

DOI:

https://doi.org/10.63162/v66n68e25614

Keywords:

Meta-analysis, Myasthenia gravis, Neuromuscular junction diseases, Rituximab, Systematic review

Abstract

Objectives: Myasthenia Gravis (MG) is an autoimmune neuromuscular disease that is cha-racterized by muscle weakness and fatigue. Despite the availability of several therapeutic op-tions, some patients show inadequate response or intolerance to conventional treatments. In this context, rituximab emerges as a promising alternative. This study aims to analyse the effi-cacy and role of rituximab in the treatment of myasthenia gravis. Methodology: A systematic review and meta-analysis were conducted, involving searches in the databases PubMed, EMBASE, LILACS, Cochrane Library, and Web of Science until January 2024. Studies evaluating rituximab in any dosage and infusion regimen in patients with a clinical diagnosis of myasthenia gravis were included. Results: Of the 3188 articles initially identified, 34 studies met the inclusion criteria, totaling 725 participants. The results demonstrated that 65.7% of the patients achieved a status of mi-nimal manifestation or better on the Myasthenia Gravis Foundation of America Post-intervention Status (MGFA-PIS) scale. Additionally, the analysis revealed a significant re-duction in the dose of corticosteroids and improvements in the scores of the Quantitative Myasthenia Gravis (QMG), Myasthenia Gravis Activities of Daily Living (MG-ADL), and Myasthenia Gravis Quality of Life (MG-QoL15) scales, indicating improvement in symp-toms and quality of life. Conclusion: Rituximab proved to be an effective alternative for controlling Myasthenia Gra-vis, significantly improving symptoms and reducing the need for corticosteroids. However, further randomized and controlled studies are needed to definitively establish its safety and efficacy in the long term.

References

Dresser L, Wlodarski R, Rezania K, Soliven B. Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations. JCM. 2021 May 21;10(11):2235.

Gilhus NE, Tzartos S, Evoli A, Palace J, Burns TM, Verschuuren JJGM. Myasthenia gravis. Nat Rev Dis Primers. 2019 May 2;5(1):30.

Narayanaswami P, Sanders DB, Wolfe G, Benatar M, Cea G, Evoli A, Gilhus NE, Illa I, Kuntz NL, Massey J, Melms A, Murai H, Nicolle M, Palace J, Richman D, Verschuuren J. International Consensus Guidance for Management of Myasthenia Gravis: 2020 Update. Neurology. 2021 Jan 19;96(3):114-122.

Tandan R, Potter C, Bradshaw D. Pilot trial of rituximab in myasthenia gravis. NEUROLOGY. 2008 Mar 11;70(11):A301–A301.

Afanasiev V, Demeret S, Bolgert F, Eymard B, Laforêt P, Benveniste O. Resistant myasthenia gravis and rituximab: A monocentric retrospec¬tive study of 28 patients. Neuromuscul Disord. 2017 Mar;27(3):251–8.

Nowak RJ, Coffey CS, Goldstein JM, Dimachkie MM, Benatar M, Kissel JT, Wolfe GI, Burns TM, Freimer ML, Nations S, Granit V, Smith AG, Ri¬chman DP, Ciafaloni E, Al-Lozi MT, Sams LA, Quan D, Ubogu E, Pearson B, Sharma A, Yankey JW, Uribe L, Shy M, Amato AA, Conwit R, O’Connor KC, Hafler DA, Cudkowicz ME, Barohn RJ; NeuroNEXT NN103 BeatMG Study Team. Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibo¬dy-Positive Generalized Myasthenia Gravis: The BeatMG Study. Neurology. 2022 Jan 25;98(4):e376-e389.

Beecher G, Anderson D, Siddiqi ZA. Rituximab in refractory myasthenia gravis: Extended prospective study results. Muscle Nerve. 2018 Sep;58(3):452–5.

Blum S, Gillis D, Brown H, Boyle R, Henderson R, Heyworth-Smith D, Hogan P, Kubler P, Lander C, Limberg N, Pillans P, Prain K, Staples C, Walsh M, McCombe P, Wong R. Use and monitoring of low dose rituximab in myasthenia gravis. J Neurol Neurosurg Psychiatry. 2011 Jun;82(6):659-63.

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 Aug 1;77(8):974–81.

Caballero-Ávila M, Álvarez-Velasco R, Moga E, Rojas-Garcia R, Turon-Sans J, Querol L, Olivé M, Reyes-Leiva D, Illa I, Gallardo E, Cortés-Vicente E. Rituximab in myasthenia gravis: efficacy, associated infections and risk of induced hypogammaglobulinemia. Neuromuscul Disord. 2022 Aug;32(8):664-671.

Choi K, Hong YH, Ahn SH, Baek SH, Kim JS, Shin JY, Sung JJ. Repeated low-dose rituximab treatment based on the assessment of circulating B cells in patients with refractory myasthenia gravis. Ther Adv Neurol Disord. 2019 Sep 18;12:1756286419871187.

Collongues N, Casez O, Lacour A, Tranchant C, Vermersch P, de Seze J, Lebrun C. Rituximab in refractory and non-refractory myasthenia: a retrospective multicenter study. Muscle Nerve. 2012 Nov;46(5):687-91.

Cortés-Vicente E, Rojas-Garcia R, Díaz-Manera J, Querol L, Casasnovas C, Guerrero-Sola A, Muñoz-Blanco JL, Bárcena-Llona JE, Márquez-In¬fante C, Pardo J, Martínez-Fernández EM, Usón M, Oliva-Nacarino P, Sevilla T, Illa I. The impact of rituximab infusion protocol on the long-term outcome in anti-MuSK myasthenia gravis. Ann Clin Transl Neurol. 2018 Jun;5(6):710–6.

Dos Santos A, Noury JB, Genestet S, Nadaj-Pakleza A, Cassereau J, Baron C, Videt D, Michel L, Pereon Y, Wiertlewski S, Magot A. Efficacy and safety of rituximab in myasthenia gravis: a French multicentre real-life study. Eur J Neurol. 2020 Nov;27(11):2277- 85.

Doughty CT, Suh J, David WS, Amato AA, Guidon AC. Retrospective analysis of safety and outcomes of rituximab for myasthenia gravis in patients ≥65 years old. Muscle Nerve. 2021 Dec;64(6):651–6.

Du Y, Li C, Hao YF, Zhao C, Yan Q, Yao D, Li L, Zhang W. Individualized regimen of low-dose rituximab monotherapy for new-onset AChR-po¬sitive generalized myasthenia gravis. J Neurol. 2022 Aug;269(8):4229-40.

Fatehi F, Moradi K, Okhovat AA, Shojatalab G, Sedighi B, Boostani R, Sarraf P, Haghi Ashtiani B, Ghasemi M, Moussavi S, Anjidani N, Nafissi S. Zytux in Refractory Myasthenia Gravis: A Multicenter, Open-Labeled, Clinical Trial Study of Effectiveness and Safety of a Rituximab Biosimilar. Front Neurol. 2021 Aug 26;12:682622.

Göl MF, Kara F, Boz M, Mutlu A, Karakullukçu S, Boz C. [Effects of rituximab on prognosis in myasthenia gravis: A single-center experience from Turkey]. Ideggyogy Sz. 2022 Sep 30;75(9–10):351–9.

Heckmann JM. A single low-dose rituximab infusion in severe chronic refractory myasthenia gravis in resource-limited settings. J Neurol Sci. 2022 Nov 15;442:120394.

Hehir MK, Hobson-Webb LD, Benatar M, Barnett C, Silvestri NJ, Howard JF Jr, Howard D, Visser A, Crum BA, Nowak R, Beekman R, Kumar A, Ruzhansky K, Chen IA, Pulley MT, LaBoy SM, Fellman MA, Greene SM, Pasnoor M, Burns TM. Rituximab as treatment for anti-MuSK myasthenia gravis: Multicenter blinded prospective review. Neurology. 2017 Sep 5;89(10):1069-77.

Kefalopoulou ZM, Veltsista D, Germeni A, Lykouras D, Tsiamaki E, Chroni E. Rituximab as a sole steroid-sparing agent in generalized myas¬thenia gravis: Long-term outcomes. Neurol Sci. 2023 Oct 13;

Li H, Huang Z, Jia D, Xue H, Pan J, Zhang M, Shi K, Shi FD, Zhang C. Low-dose rituximab treatment for new-onset generalized myasthenia gravis. J Neuroimmunol. 2021 May 15;354:577528.

Lindberg C, Bokarewa M. Rituximab for severe myasthenia gravis--experience from five patients. Acta Neurol Scand. 2010 Oct;122(4):225–8.

Litchman T, Roy B, Kumar A, Sharma A, Njike V, Nowak RJ. Differential response to rituximab in anti-AChR and anti-MuSK positive myasthe¬nia gravis patients: a single-center retrospective study. J Neurol Sci. 2020 Apr 15;411:116690.

López-Hernández JCS, Galnares-Olalde JA, Gómez-Figueroa E, Jorge de Sarachaga A, Vargas-Cañas ES. Rituximab in Refractory Myasthenia Gravis: Experience in a Single Healthcare Center in Mexico. Cureus. 2021 Feb 8;13(2):e13226.

Lu J, Zhong H, Jing S, Wang L, Xi J, Lu J, Zhou L, Zhao C. Low-dose rituximab every 6 months for the treatment of acetylcholine receptor-po¬sitive refractory generalized myasthenia gravis. Muscle Nerve. 2020 Mar;61(3):311–5.

Maddison P, McConville J, Farrugia ME, Davies N, Rose M, Norwood F, Jungbluth H, Robb S, Hilton-Jones D. The use of rituximab in myas¬thenia gravis and Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry. 2011 Jun;82(6):671 –3.

Marino M, Basile U, Spagni G, Napodano C, Iorio R, Gulli F, Todi L, Provenzano C, Bartoccioni E, Evoli A. Long-Lasting Rituximab-Induced Reduction of Specific-But Not Total-IgG4 in MuSK-Positive Myasthenia Gravis. Front Immunol. 2020 May 5;11:613.

Mathew T, Thomas K, K John S, Venkatesh S, Nadig R, Badachi S, Souza DD, Sarma G, Parry GJ. Effective Early Treatment of AChR Antibo¬dy-Positive Myasthenia Gravis with Rituximab; the Experience from a Neuroimmunology Clinic in a Developing Country. J Cent Nerv Syst Dis. 2021 May 17;13:11795735211016080.

Meng X, Zeng Z, Wang Y, Guo S, Wang C, Wang B, Guo S. Efficacy and Safety of Low-Dose Rituximab in Anti-MuSK Myasthenia Gravis Pa¬tients: A Retrospective Study. Neuropsychiatr Dis Treat. 2022 May 3;18:953–64.

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 Jun;2(3):81–5.

Roda RH, Doherty L, Corse AM. Stopping oral steroid-sparing agents at initiation of rituximab in myasthenia gravis. Neuromuscul Disord. 2019 Jul;29(7):554–61.

Piehl F, Eriksson-Dufva A, Budzianowska A, Feresiadou A, Hansson W, Hietala MA, Håkansson I, Johansson R, Jons D, Kmezic I, Lindberg C, Lindh J, Lundin F, Nygren I, Rostedt Punga A, Press R, Samuelsson K, Sundström P, Wickberg O, Brauner S, Frisell T. Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis: The RINOMAX Randomized Clinical Trial. JAMA Neurol. 2022 Nov 1;79(11):1105–12.

Sahai SK, Maghzi AH, Lewis RA. Rituximab in late-onset myasthenia gravis is safe and effective. Muscle Nerve. 2020 Sep;62(3):377–80.

Shivaram S, Nagappa M, Varghese N, Seshagiri DV, Duble S, Siddappa SA, Hesarur N, Sinha S, Taly AB. Rituximab in Myasthenia Gravis- Ex¬perience from a Low- and Middle-Income Country (LMIC) Setting. Neurol India. 2022 Sep-Oct;70(5):1931–41.

Singh N, Goyal V. Rituximab as induction therapy in refractory myasthenia gravis: 18 month follow-up study. J Neurol. 2019 Jul;266(7):1596–600.

Topakian R, Zimprich F, Iglseder S, Embacher N, Guger M, Stieglbauer K, Langenscheidt D, Rath J, Quasthoff S, Simschitz P, Wanschitz J, Win¬disch D, Müller P, Oel D, Schustereder G, Einsiedler S, Eggers C, Löscher W. High efficacy of rituximab for myasthenia gravis: a comprehensive nationwide study in Austria. J Neurol. 2019 Mar;266(3):699-706.

Yang X, Zhang W, Chang X, Li Z, Du R, Guo J. Promising efficacy of Low-Dose rituximab in Muscle specific kinase antibody positive Myasthe¬nia Gravis. Neurosci Lett. 2024 Jan 1;818:137561.

Zhao C, Pu M, Chen D, Shi J, Li Z, Guo J, Zhang G. Effectiveness and Safety of Rituximab for Refractory Myasthenia Gravis: A Systematic Review and Single-Arm Meta-Analysis. Front Neurol. 2021 Oct 13;12:736190.

Kaegi C, Wuest B, Schreiner J, Steiner UC, Vultaggio A, Matucci A, Crowley C, Boyman O. Systematic Review of Safety and Efficacy of Rituxi¬mab in Treating Immune-Mediated Disorders. Front Immunol. 2019 Sep 6;10:199.

Randall KL. Rituximab in autoimmune diseases. Aust Prescr. 2016 Aug 1;39(4):131–4.

Kimby E. Tolerability and safety of rituximab (MabThera®). Cancer Treatment Reviews. 2005 Oct;31(6):456–73.

Published

2025-08-14

Issue

Section

Revisão sistemática

How to Cite

1.
Cavalcante GH, Rossano Cavalcante Álvaro, Liberato De Oliveira LP, Sisterolli Diniz D, Mendonça H. Treatment of myasthenia gravis with rituximab: a systematic review and meta analysis. Rev Goiana Med [Internet]. 2025 Aug. 14 [cited 2026 May 19];66(68):e25614. Available from: https://www.amg.org.br/osj/index.php/RGM/article/view/614