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

Area of Science:

• Neurology
• Immunology
• Critical Care Medicine

Background:

• Generalized myasthenia gravis (gMG) can escalate to life-threatening myasthenic crises (MC), necessitating mechanical ventilation.
• Standard treatments for MC include IVIg, PLEX, IA, and corticosteroids, but some patients remain refractory.
• Complement inhibitors (C5-I) are emerging as a therapeutic option for severe, refractory cases.

Purpose of the Study:

• To evaluate the real-world effectiveness of complement inhibitors (C5-I) in patients with therapy-refractory myasthenic crises (MC).
• To assess C5-I as an add-on therapy in acetylcholine-receptor-antibody positive (AChR-ab+) gMG patients unresponsive to standard treatments.

Main Methods:

• A multicentre, retrospective study involving AChR-ab+ gMG patients experiencing MC or severe exacerbations (MGFA IVb/V).
• Patients were treated with eculizumab or ravulizumab in intensive or intermediate care units.
• The primary outcome was the proportion of patients discharged from ICU/IMC within six weeks of C5-I initiation.

Main Results:

• Of 17 patients, 82% (14/17) achieved the primary outcome of discharge within six weeks.
• Patients included those with thymoma-associated MG (TAMG) and late-onset MG, with a median age of 77 years.
• Two deaths occurred due to bacterial sepsis; no meningococcal infections were reported.

Conclusions:

• Add-on C5-I therapy is an effective approach for MC or severe exacerbations refractory to standard treatments like IVIg and PLEX/IA.
• Clinical improvement was observed in thymoma-associated MG (TAMG) patients, a group often excluded from trials.
• Further systematic evaluation of C5-I as adjunctive therapy for AChR-ab+ therapy-refractory MC is warranted.