ravulizumab in myasthenia gravis

Last edited 05/2022 and last reviewed 05/2022

Generalized myasthenia gravis (gMG) is a rare autoimmune disorder affecting the neuromuscular junction (NMJ) (1)

• approximately 80-90% of patients display antibodies directed against the nicotinic acetylcholine receptor (AChR)
  • a major drive of AChR antibody-positive MG pathology is represented by complement activation
  • role of the complement cascade has been largely demonstrated in patients and in MG animal models
  • complement activation at the NMJ leads to focal lysis of the post-synaptic membrane, disruption of the characteristic folds, and reduction of AChRs
    • binding of anti-AChR antibodies leads to activation of the classical complement cascade, formation of the terminal complement complex (membrane attack complex), and consequent destruction of the postsynaptic membrane of the neuromuscular junction
      
      
• Ravulizumab
  • is a humanized monoclonal antibody that specifically binds with high affinity to the human terminal complement protein C5, preventing disruption of neuromuscular transmission, presumably by inhibiting membrane attack complex-mediated destruction of the neuromuscular junction
  • has demonstrated rapid and sustained improvements in both patient- and clinician-reported outcomes and had a side effect and adverse-event profile that did not limit treatment in adults with anti-AChR antibody-positive gMG (2)

Reference:

• Mantegazza R, Vanoli F, Frangiamore R, Cavalcante P. Complement Inhibition for the Treatment of Myasthenia Gravis. Immunotargets Ther. 2020;9:317-331. Published 2020 Dec 15. doi:10.2147/ITT.S261414
• Vu T et al. Terminal Complement Inhibitor Ravulizumab in Generalized Myasthenia Gravis NEJM Evid 2022; 1 (5). DOI:https://doi.org/10.1056/EVIDoa2100066