Journal of Neurology

, Volume 262, Issue 5, pp 1115–1119 | Cite as

Efficacy and safety of rituximab for myasthenia gravis: a systematic review and meta-analysis

  • Raffaele Iorio
  • Valentina Damato
  • Paolo Emilio Alboini
  • Amelia Evoli


Myasthenia gravis is an autoimmune disorder of the neuromuscular junction caused by circulating antibodies specif ic for the post-synaptic acetylcholine receptor or, in a minority of cases, for the muscle-specific tyrosine-kinase and the low-density lipoprotein receptor-related protein 4. A wide range of symptomatic and immunosuppressive treatments is currently available for MG patients with variable outcome. However, most immunosuppressive treatments are characterized by delayed onset of action and in some cases are not sufficient to induce stable remission of the disease. Rituximab (RTX) is a chimaeric monoclonal antibody specific for the CD20 B-cell surface antigen. Recent studies have provided evidence that RTX may be an effective treatment for patients with myasthenia gravis (MG) who are refractory to standardized immunosuppressive therapy. We performed a systematic review and a meta-analysis of the efficacy and safety of RTX in myasthenia gravis considering the potential predictive factors related to patients’ response to RTX in this disease.


Rituximab Myasthenia gravis Immunotherapy Antibodies 


Conflicts of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Meriggioli MN, Sanders DB (2012) Muscle antibodies in myasthenia gravis: beyond diagnosis? Expert Rev Clin Immunol 8:427–438PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Verschuuren JJ, Huijbers MG, Plomp JJ et al (2013) Pathophysiology of myasthenia gravis with antibodies to the acetylcholine receptor, muscle-specific kinase and low-density lipoprotein receptor-related protein 4. Autoimmun Rev 12:918–923CrossRefPubMedGoogle Scholar
  3. 3.
    Skeie GO, Apostolski S, Evoli A et al (2010) Guidelines for treatment of autoimmune neuromuscular transmission disorders. Eur J Neurol 17:893–902CrossRefPubMedGoogle Scholar
  4. 4.
    Drachman DB, Adams RN, Hu R, Jones RJ, Brodsky RA (2008) Rebooting the immune system with high-dose cyclophosphamide for treatment of refractory myasthenia gravis. Ann N Y Acad Sci 1132:305–314PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Reff ME, Carner K, Chambers KS et al (1994) Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83:435–445PubMedGoogle Scholar
  6. 6.
    Gürcan HM, Keskin DB, Stern JN, Nitzberg MA, Shekhani H, Ahmed AR (2009) A review of the current use of rituximab in autoimmune diseases. Int Immunopharmacol 9:10–25CrossRefPubMedGoogle Scholar
  7. 7.
    Iorio R, Pittock SJ (2014) Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies. Clin Exp Neuroimmunol 5:175–187CrossRefGoogle Scholar
  8. 8.
    Iorio R, Assenza G, Tombini M, Colicchio G, Della Marca G, Benvenga A, Damato V, Rossini PM, Vollono C, Plantone D, Marti A, Batocchi AP, Evoli A (2014) The detection of neural autoantibodies in patients with antiepileptic-drug-resistant epilepsy predicts response to immunotherapy. Eur J Neurol. doi: 10.1111/ene.12529 PubMedGoogle Scholar
  9. 9.
    Zaja F, Russo D, Fuga G, Perella G, Baccarani M (2000) Rituximab for myasthenia gravis developing after bone marrow transplant. Neurology 55:1062–1063CrossRefPubMedGoogle Scholar
  10. 10.
    Wylam M, Anderson P, Kuntz NL, Rodriguez V (2003) Successful treatment of refractory myasthenia gravis using Rituxomab: a pediatric case report. J Pediatr 143:674–677CrossRefPubMedGoogle Scholar
  11. 11.
    Gajra A, Vajpayee N, Grethlein SJ (2004) Response of myasthenia gravis to rituximab in a patient with non-hodgkin lymphoma. Am J Hematol 77:196–197CrossRefPubMedGoogle Scholar
  12. 12.
    Takagi K, Yoshida A, Iwasaki H, Inoue H, Ueda A (2005) Anti-CD20 antibody (Rituximab) therapy in a myasthenia gravis patient with follicular lymphoma. Ann Hematol 84:548–550CrossRefPubMedGoogle Scholar
  13. 13.
    Lin PT, Martin BA, Weinacker AB, So YT (2006) High-dose cyclophosphamide in refractory myasthenia gravis with MuSK antibodies. Muscle Nerve 33:433–435CrossRefPubMedGoogle Scholar
  14. 14.
    Hain B, Jordan K, Deschauer M, Zierz S (2006) Successful treatment of Musk-antibody positive myasthenia gravis with Rituximab. Muscle Nerve 33:575–580CrossRefPubMedGoogle Scholar
  15. 15.
    Thakre M, Inshasi J, Marashi M (2007) Rituximab in refractory MuSK antibody myasthenia gravis. J Neurol 254:968–969CrossRefPubMedGoogle Scholar
  16. 16.
    Chan A, Lee DH, Linker R, Mohr A, Toyka KV, Gold R (2007) Rescue therapy with anti-CD20 treatment in neuroimmunologic breakthrough disease. J Neurol 254(11):1604–1606CrossRefPubMedGoogle Scholar
  17. 17.
    Baek WS, Bashey A, Sheean GL (2007) Complete remission induced by rituximab in refractory, seronegative, muscle-specific, kinase-positive myasthenia gravis. J Neurol Neurosurg Psychiatry 78:771PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Kerkeni S, Marotte H, Miossec P (2008) Improvement with Rituximab in a patient with both rheumatoid arthritis and myasthenia gravis. Muscle Nerve 38:1343–1345CrossRefPubMedGoogle Scholar
  19. 19.
    StroberJ MD, Cowan MJ, Horn BN (2009) Allogeneic hematopoietic cell transplantation for refractory myasthenia gravis. Arch Neurol 66:659–661Google Scholar
  20. 20.
    Stieglbauer K, Topakian R, Schäffer V, Aichner FT (2009) Rituximab for myasthenia gravis. Three case reports and review of the literature. J Neurol Sci 280:120–122CrossRefPubMedGoogle Scholar
  21. 21.
    Tzaribachev N, Schedel J, Koetter I, Kuemmerle-Deschner JB (2009) Rituximab for the treatment of refractory pediatric autoimmune diseases: a case series. Cases J 2:6609PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Masroujeh R, Otrock ZK, Yamout B, Jabbour MN, Bazarbachi A (2010) Myasthenia gravis developing in a patient with CNS lymphoma. Int J Hematol 91:522–524CrossRefPubMedGoogle Scholar
  23. 23.
    Sadnicka A, Reill MM, Mummery C, Brandner S, Hirsch N, Lunn MP (2011) Rituximab in the treatment of three coexistent neurological autoimmune diseases: chronic inflammatory demyelinating polyradiculoneuropathy, Morvan syndrome and myasthenia gravis. J Neurol Neurosurg Psychiatry 82:230–232CrossRefPubMedGoogle Scholar
  24. 24.
    Lau AYL, Chan AYY, Mok VCT (2011) Refractory bulbar and respiratory dysfunction in a young Chinese woman with seronegative, muscle-specific tyrosine kinase antibody–positive myasthenia gravis: response to cyclophosphamide and rituximab treatment. Hong Kong Med J 17:77–79PubMedGoogle Scholar
  25. 25.
    Kuntzer T, Carota A, Novy J, Cavassini M, Du Pasquier RA (2011) Rituximab is successful in an HIV-positive patient with Musk myasthenia gravis. Neurology 76:757–758CrossRefPubMedGoogle Scholar
  26. 26.
    Koul R, Al Futaisi A, Abdwani R (2012) Rituximab in severe seronegative juvenile myasthenia gravis: review of the literature. Pediatr Neurol 47:209–212CrossRefPubMedGoogle Scholar
  27. 27.
    Jakubikova M, Pitha J, Latta J, Ehler E, Schutzner J (2013) Myasthenia gravis, Castleman disease, pemphigus and anti-phospholipid syndrome. Muscle Nerve 47:447–451CrossRefPubMedGoogle Scholar
  28. 28.
    Renard D, Cornillet L, Castelnovo G (2013) Myocardial infarction after rituximab infusion. Neuromuscul Disord 23:599–601CrossRefPubMedGoogle Scholar
  29. 29.
    Yi JS, Decroos EC, Sanders DB, Weinhold KJ, Guptill JT (2013) Prolonged B-cell depletion in MuSK myasthenia gravis following rituximab treatment. Muscle Nerve 48:992–993PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Sun F, Ladha SS, Yang L, Liu Q, Shi SX, Su N, Bomprezzi R, Shi FD (2014) Interleukin-10 producing-B cells and their association with responsiveness to rituximab in myasthenia gravis. Muscle Nerve 49:487–494CrossRefPubMedGoogle Scholar
  31. 31.
    Jaretzki A, Barohn RB, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, Sanders DB (2000) Myasthenia gravis: recommendations for clinical research standards. Neurology 55:16–23CrossRefPubMedGoogle Scholar
  32. 32.
    Stasi R, Cooper N, Del Poeta G, Stipa E, Laura Evangelista M, Abruzzese E, Amadori S (2008) Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab. Blood 112:1147–1150CrossRefPubMedGoogle Scholar
  33. 33.
    Leandro MJ, Becerra-Fernandez E (2011) B-cell therapies in established rheumatoid arthritis. Best Pract Res Clin Rheumatol 25:535–548CrossRefPubMedGoogle Scholar
  34. 34.
    Cobo-Ibáñez T, Loza-Santamaría E, Pego-Reigosa JM, Marqués AO, Rúa-Figueroa I, Fernández-Nebro A, Cáliz RC, López Longo FJ, Muñoz-Fernández S (2014) Efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus: a systematic review. Semin Arthritis Rheum (Epub ahead of print)Google Scholar
  35. 35.
    Leandro MJ, Cambridge G, Ehrenstein MR, Edwards JC (2006) Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis. Arthritis Rheum 54(2):613–620CrossRefPubMedGoogle Scholar
  36. 36.
    Sfikakis PP, Souliotis VL, Fragiadaki KG, Moutsopoulos HM, Boletis JN, Theofilopoulos AN (2007) Increased expression of the FoxP3 functional marker of regulatory T cells following B cell depletion with rituximab in patients with lupus nephritis. Clin Immunol 123:66–73CrossRefPubMedGoogle Scholar
  37. 37.
    Catzola V, Battaglia A, Buzzonetti A, Fossati M, Scuderi F, Fattorossi A, Evoli A (2013) Changes in regulatory T cells after rituximab in two patients with refractory myasthenia gravis. J Neurol 260:2163–2165CrossRefPubMedGoogle Scholar
  38. 38.
    Benucci M, Manfredi M, Puttini PS, Atzeni F (2010) Predictive factors of response to rituximab therapy in rheumatoid arthritis: what do we know today? Autoimmun Rev 9:801–803CrossRefPubMedGoogle Scholar
  39. 39.
    Hultin LE, Hausner MA, Hultin PM, Giorgi JV (1993) CD20 (pan-B cell) antigen is expressed at a low level on a subpopulation of human T lymphocytes. Cytometry 14:196–204CrossRefPubMedGoogle Scholar
  40. 40.
    Huang H, Benoist C, Mathis D (2010) Rituximab specifically depletes short-lived autoreactive plasma cells in a mouse model of inflammatory arthritis. Proc Natl Acad Sci USA 107:4658–4663PubMedCentralCrossRefPubMedGoogle Scholar
  41. 41.
    Winter O, Dame C, Jundt F, Hiepe F (2012) Pathogenic long-lived plasma cells their survival niches in autoimmunity, malignancy, and allergy. J Immunol 189:5105–5111CrossRefPubMedGoogle Scholar
  42. 42.
    Díaz-Manera J, Martínez-Hernández E, Querol L, Klooster R, Rojas-García R, Suárez-Calvet X, Muñoz-Blanco JL, Mazia C, Straasheijm KR, Gallardo E, Juárez C, Verschuuren JJ, Illa I (2012) Long-lasting treatment effect of rituximab in MuSK myasthenia. Neurology 78:189–193CrossRefPubMedGoogle Scholar
  43. 43.
    HERMES Trial Group, Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH (2008) B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 358(7):676–688CrossRefGoogle Scholar
  44. 44.
    Mahévas M, Michel M, Weill JC, Reynaud CA (2013) Long-lived plasma cells in autoimmunity: lessons from B-cell depleting therapy. Front Immunol 4:494PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Raffaele Iorio
    • 1
  • Valentina Damato
    • 2
  • Paolo Emilio Alboini
    • 2
  • Amelia Evoli
    • 2
  1. 1.Don Carlo Gnocchi ONLUS FoundationMilanItaly
  2. 2.Institute of Neurology, Department of Geriatrics, Neurosciences and OrthopedicsCatholic UniversityRomeItaly

Personalised recommendations