Complement Inhibition Therapy in Myasthenic Crisis-A Multicentre Retrospective Analysis of 17 Cases From Germany.

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.