Generalised Myasthenia Gravis
The form of myasthenia gravis where muscle weakness extends beyond the eyes to affect limb, respiratory, and bulbar muscles. Generalised MG is the specific indication for zilucoplan. Approximately 85% of MG patients eventually develop generalised disease.
Technical Context
MGFA (Myasthenia Gravis Foundation of America) classification: Class I (ocular only), Class II (mild generalised — IIa predominantly limb/axial, IIb predominantly oropharyngeal/respiratory), Class III (moderate generalised), Class IV (severe generalised), Class V (requiring intubation ± mechanical ventilation). Approximately 85% of patients with initial ocular MG develop generalised disease within 2 years. Generalised MG significantly impacts quality of life: difficulty chewing/swallowing, dysarthria, limb weakness affecting daily activities, respiratory weakness (myasthenic crisis requiring ventilatory support occurs in approximately 15-20%). Treatment escalation: acetylcholinesterase inhibitors (pyridostigmine — symptomatic, first-line) → immunosuppressive therapy (corticosteroids, azathioprine, mycophenolate) → targeted therapies (complement inhibitors — zilucoplan, eculizumab, ravulizumab; FcRn inhibitors — efgartigimod, rozanolixizumab; anti-CD20 — rituximab). Zilucoplan's advantage: self-administered SC injection (vs IV infusion for eculizumab), lower cost, and peptide-based rather than antibody-based complement inhibition.