Improvement of fatigue in generalised myasthenia gravis with zilucoplan

Abstract Background Fatigue is a debilitating symptom of myasthenia gravis (MG). The impact of fatigue on MG can be assessed by Quality of Life in Neurological Disorders (Neuro-QoL) Short Form Fatigue scale. Transformation of raw Neuro-QoL fatigue scores to T-scores is a known approach for facilitating clinical interpretation of clinically meaningful and fatigue severity thresholds. Methods In the Phase 3, double-blind, placebo-controlled RAISE study (NCT04115293), adults with acetylcholine receptor autoantibody-positive generalised MG (MG Foundation of America Disease Class II–IV) were randomised 1:1 to daily subcutaneous zilucoplan 0.3 mg/kg or placebo for 12 weeks. Patients completing RAISE could opt to receive zilucoplan 0.3 mg/kg in an ongoing, open-label extension study, RAISE-XT (NCT04225871). In this post-hoc analysis, we evaluated the long-term effect of zilucoplan on fatigue in RAISE patients who entered RAISE-XT. We report change in Neuro-QoL Short Form Fatigue T-scores and fatigue severity levels from RAISE baseline to Week 60. Results Mean Neuro-QoL Short Form Fatigue T-scores improved from baseline to Week 12 in the zilucoplan group ( n = 86) with a clinically meaningful difference versus placebo ( n = 88; least squares mean difference: − 3.61 (nominal p -value = 0.0060]), and these improvements continued further to Week 60. At Week 12, more patients on zilucoplan ( n = 34, 47.2%) experienced improvements in ≥ 1 fatigue severity level from baseline versus placebo ( n = 23, 28.4%; p = 0.017). At Week 60, most ( n = 55, 65.5%) patients had mild fatigue or none. Conclusion Treatment with zilucoplan demonstrated statistical and clinically meaningful improvements in fatigue scores and severity versus placebo during RAISE, which were sustained to Week 60 in RAISE-XT.