Abstract Background This study examined whether the timing of targeted add-on therapy initiation influences clinical outcomes in acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (gMG), based on the hypothesis that earlier escalation may improve treatment response by intervening before structural or immunological consolidation occurs. Methods In this multicenter, retrospective real-world cohort study, 153 patients with AChR antibody-positive gMG were included from eight German tertiary centers. All received either complement C5 inhibitors (eculizumab, ravulizumab) or the FcRn antagonist efgartigimod as add-on therapy. Patients were grouped by treatment initiation within 24 months of diagnosis (Early Intensified Treatment; EIT) or later (Late Intensified Treatment; LIT). MG-ADL, QMG, and MG-QoL15 scores, as well as daily corticosteroid and pyridostigmine doses, were assessed at baseline and at 1, 3, and 6 months. Results The EIT group ( n = 36) showed more pronounced and consistent clinical improvement. Significant differences emerged in maximum MG-ADL ( p = 0.013) and QMG ( p = 0.002) reductions. Patient-acceptable symptom states (MG-ADL ≤ 2, QMG ≤ 7) were more often reached with EIT ( p = 0.038, p = 0.006). QMG worsening occurred only in the LIT group ( n = 117) ( p = 0.021). Prednisone declined more steeply in EIT patients ( p = 0.001). Conclusion Initiating add-on therapy within two years of diagnosis was associated with stronger and more consistent clinical responses, fewer deteriorations, and a steeper reduction of treatment burden. These findings support timely escalation as a strategy to enhance both efficacy and tolerability in gMG care. Graphical abstract Impact of Early Versus Late Initiation of Targeted Therapy in AChR-Positive Generalized Myasthenia Gravis. This graphical abstract illustrates the design and main findings of a multicenter, retrospective cohort study conducted across eight specialized MG centers in Germany. The study included 153 patients with acetylcholine receptor antibody-positive (AChR) generalized myasthenia gravis who received targeted add-on treatment with complement inhibitors (C5-I; eculizumab or ravulizumab) or an FcRn inhibitor (FcRn-I; efgartigimod). Participants were stratified based on the timing of escalation: those who initiated treatment within 24 months of diagnosis (Early Intensified Treatment; EIT) and those who escalated later (Late Intensified Treatment; LIT). Clinical outcomes were assessed using MG-ADL and QMG scores over a six-month period. Patients in the EIT group demonstrated more robust improvements in both functional and strength-based measures, with higher rates of clinically meaningful response and symptom resolution. The data support the notion that earlier introduction of targeted therapies may enhance treatment efficacy and improve patient outcomes in real-world settings. This figure was created with BioRender.com.
Oeztuerk et al. (Sun,) studied this question.