Real-world effectiveness and safety of zilucoplan in patients with anti-AChR myasthenia gravis: A retrospective cohort study in France

ObjectivesTo evaluate the effectiveness and safety of zilucoplan in the real-world treatment setting in France.MethodsThis retrospective cohort study evaluated patients with generalized anti-AChR myasthenia gravis (MG) failing current therapy enrolled in the French early access program (EAP) for zilucoplan. Patients were evaluated at enrollment and at Months 1, 3 and 6 with the MG-ADL score, the Myasthenic Muscle Score (MMS-Garches), and the MG-quality of life questionnaire (MG-QoL15r). MG crises and on-treatment adverse events were documented. MG medication use was compared between the six months before and after enrollment.ResultsForty-eight patients were enrolled and treated with zilucoplan (mean age: 56.2 years; 50.9% men). Thirty patients achieved six months follow-up before the EAP ended. Three patients discontinued zilucoplan due to lack of efficacy. Mean MG-ADL score decreased from 7.4 ± 4.4 to M0 to 2.5 ± 2.7 at M6 (<i>p</i> < 0.0001). 9/43 patients achieved minimal symptom expression at M3 and 12/30 at M6. Mean MMS-Garches score was 67.5 ± 20.0 at M0 and 87.5 ± 13.2 at M6 (<i>p</i> < 0.0001). Mean MG-QoL15r score was 18.2 ± 8.6 at M0 and 8.7 ± 8.3 at M6 (<i>p</i> = 0.0156). 15 patients experienced adverse events, leading to discontinuation in four cases. The mean oral corticosteroid dose decreased from 28.8 ± 11.8 mg to 17.9 ± 11.8 (<i>p</i> <i>=</i> 0.001). Six patients experienced MG crises on treatment, compared to 22 in the six months preceding enrollment. treatment.DiscussionFollowing initiation of zilucoplan treatment, we observed an improvement in MG symptoms and a reduction in MG crises and in exposure to oral corticosteroids. Overall, zilucoplan was well-tolerated with no major adverse events reported.Trial registration informationThe study was registered in the clinicaltrials.gov trial registry under the number NCT06815133 (https://clinicaltrials.gov/study/NCT06815133) on February 4^th, 2025.