Gerischer L, Stein M, Schneider A, Tangen H, Loris J, Glaubitz S, Zschüntzsch J, Oy UH, Schubert C, Heesen C, Schlag M, Hagenacker T, Oeztuerk M, Ruck T, Doksani P, Dusemund C, Herdick M, Herzig-Nichtweiß J, Mergenthaler P, Stascheit F, Suboh A, Schwarz L, Hoffmann S, Meisel A, Lehnerer S.
Introduction: Generalized myasthenia gravis (gMG) may progress to life-threatening myasthenic crises (MC) requiring mechanical ventilation. Standard therapy includes intravenous immunoglobulins (IVIg), plasmapheresis (PLEX), immunoadsorption (IA), and high-dose corticosteroids. This study aimed to evaluate the real-world effectiveness of complement-inhibitors (C5-I) in patients refractory to the standard treatment of MC (termed therapy-refractory MC). Methods: This multicentre, retrospective study included patients with acetylcholine-receptor-antibody positive (AChR-ab+) gMG experiencing MC or severe exacerbations (MGFA IVb/V) treated with eculizumab or ravulizumab in the intensive or intermediate care unit (ICU/IMC). The primary outcome was the proportion of patients discharged from ICU/IMC within six weeks after C5-I initiation (German Clinical Trials Registry; DRKS00032104). Results: Among 17 identified cases, seven had thymoma-associated MG (TAMG) and 10 had late-onset MG; median age was 77 years. Five patients required non-invasive and 12 invasive ventilation; nine underwent tracheotomy. Therapies included IVIg, PLEX, IA, and corticosteroids. Rituximab was added in two cases. Twelve patients received eculizumab and five ravulizumab. Median hospitalization before C5-I initiation was 32 days (IQR 22-50) and median ICU-stay was 17 days (IQR 4.5-35) thereafter. Fourteen patients (82%) reached the primary outcome. Two patients died due to bacterial sepsis; no meningococcal infection was observed. Conclusion: In MC or severe exacerbations insufficiently responsive to standard treatment with IVIg and PLEX/IA, add-on C5-I therapy may represent an effective therapeutic approach. Importantly, TAMG, a subtype typically excluded from interventional trials yet often requiring more intensive therapy, also demonstrated clinical improvement. These findings warrant further systematic evaluation of C5-I as adjunctive therapy for AChR-ab+ therapy-refractory MC.Eur J Neurol. 2026 Apr;33(4):e70596
Link to Pubmed