Case Report: Zilucoplan in refractory myasthenic crisis and its prodromal stages: a novel therapeutic perspective

Myasthenic crisis (MC) represents life-threatening respiratory failure in myasthenia gravis (MG), while impending myasthenic crisis (iMC) denotes rapidly worsening weakness threatening ventilation however the condition is reversible with timely intervention. Complement inhibition has emerged as a targeted approach for acetylcholine receptor (AChR) antibody-positive MG. To date, evidence for Zilucoplan, a subcutaneous macrocyclic peptide C5 inhibitor, in acute settings remains limited. This study describes two Italian AChR-positive-MG patients experiencing severe, treatment-refractory exacerbations. One patient presented with overt MC requiring non-invasive ventilation, and the second with iMC and rapidly worsening bulbar dysfunction. Both patients received Zilucoplan 32.4 mg/day subcutaneously following failure of corticosteroids, intravenous immunoglobulin, and, in one case, multiple biologic agents. Zilucoplan provided rapid, robust, and durable improvement in refractory AChR-positive MG during both MC and iMC. Both patients maintained sustained remission with no adverse events under ongoing Zilucoplan therapy. Continuous complement blockade and easy-to-use subcutaneous administration may offer significant advantages for acute rescue and maintenance therapy. Early initiation could prevent progression from iMC to established MC. Larger prospective studies are warranted to define optimal use and timing of Zilucoplan in MG crisis management.