Complement Inhibitors in Generalized Myasthenia Gravis: Comparison of Administration Schedules, Efficacy, and Safety

Background: Eculizumab, Ravulizumab, and Zilucoplan are inhibitors of terminal complement protein C5 (C5IT) approved for the treatment of generalized Myasthenia Gravis (gMG). The aim of this study is to compare the administration schedules, efficacy, and safety of these new biological therapies in a real-life setting. Methods: We enrolled 31 patients with gMG who received C5IT (Eculizumab: 7 patients; Ravulizumab: 11 patients; Zilucoplan: 13 patients). We gathered demographic, clinical data by the difference between scores at baseline (T0) and after follow-up for the MG-ADL, QMG, and MGC scales. Results: All C5IT demonstrated similar clinical efficacy, resulting in a statistically significant reduction in clinical scales scores for the MG-ADL (F = 14.7; p < 0.001), QMG (F = 14.78; p < 0.001), and MGC (F = 9.466; p < 0.001), with no significant differences among drugs (p > 0.05). No significant differences were highlighted in terms of MSE (p > 0.05). There was a decrease in the mean dose of steroid taken by patients in all three treatment groups (Eculizumab: -37%; Ravulizumab: -62%; Zilucoplan: -37%, at W34 compared to baseline). No myasthenic crises requiring hospitalization occurred during follow-up. Most of the reported adverse events were mild to moderate; the more severe events included one case of Stevens-Johnson syndrome (Ravulizumab) and episodes of pneumonia (Eculizumab, Ravulizumab). Conclusions: The comparison of C5IT did not bring out significant differences in terms of clinical efficacy and safety, representing a valid therapeutic option when traditional therapies fail to control disease symptoms.