Effectiveness and Safety of Eculizumab in Highly Active AChR+gMG and Its Therapeutic Response in Different Subtypes of gMG

Background: Eculizumab had been approved for anti-acetylcholine receptor antibody-positive (AChR+) refractory myasthenia gravis (MG), but its effect on the broader group of highly active generalized myasthenia gravis (gMG) in clinical practice has not been fully uncovered. Methods: We conduct a retrospective multi-center cohort study with prospectively collected data to explore the effectiveness and safety of eculizumab in highly active patients in clinical practice. Results: Thirty-three patients from 4 research centers were included in our study treated with eculizumab. This study contains 1 early onset MG (EOMG), 13 late-onset MG (LOMG), and 19 thymoma-associated MG (TAMG) patients. At week 12, the mean Myasthenia Gravis Activities of Daily Living (MG-ADL) score decreased by 7.97 ± 3.96 points and Quantitative Myasthenia Gravis (QMG) score decreased by 12.88±5.82 points,13 (40%) patients achieved minimal symptom expression (MSE) and 78.7% patients were ADL responders (the improvement of MG-ADL score ≥3 points and lasted for at least 4weeks). The improvement was sustained for 24 weeks. Overall, four patients had experienced myasthenic crisis (MC), and the time to wean from mechanical ventilation (MV) was 6.33±3.21 days. In muscle subdomains analysis, QMG score decreased more obviously in the ocular group (66%) and bulbar group (49%) than in other muscle groups at week 4. Moreover, subgroup analysis showed that the TAMG and LOMG groups exhibited a similar degree of therapeutic effect in symptom control and ADL response. The mean prednisone dose was reduced by 12.84±20.36 mg/day at week 24. Patients in our study showed well tolerance to eculizumab, and none of them experienced meningococcal infections. Conclusion: Our study confirmed the safety and effectiveness of eculizumab in highly active gMG patients with reducing steroid dose. TAMG and MC may be suitable indications for treatment with eculizumab. All the muscle groups achieved improvements, especially for the extraocular muscles.