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)