Early Versus Delayed Add-on Therapy in Generalized Myasthenia Gravis: A Multicenter Real-World Cohort Study

ObjectiveThis 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. MethodsIn 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. ResultsThe EIT group (n = 36) showed more pronounced and consistent clinical improvement. Significant differences emerged in maximum MG-ADL (p{square}={square}0.013) and QMG (p{square}={square}0.002) reductions. Patient-acceptable symptom states (MG-ADL [≤]{square}2, QMG [≤]{square}7) were more often reached with EIT (p{square}={square}0.038, p{square}={square}0.006). QMG worsening occurred only in the LIT group (n = 117) (p{square}={square}0.021). Prednisone declined more steeply in EIT patients (p{square}={square}0.001), alongside a trend toward reduced pyridostigmine use. InterpretationInitiating 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. Summary for Social Media If PublishedO_ST_ABSWhat is the current knowledge on the topic?C_ST_ABSComplement and FcRn inhibitors have demonstrated efficacy in patients with AChR antibody-positive generalized myasthenia gravis (gMG) and are approved as add-on therapies in treatment-refractory disease. However, data guiding the optimal timing for their initiation in the treatment course remain limited. What question did this study address?This study investigated whether earlier initiation of add-on therapy improves clinical outcomes in AChR antibody-positive gMG. It compared patients escalated within 24 months of diagnosis to those treated later. What does this study add to our knowledge?Earlier treatment escalation was associated with significantly greater clinical improvements in MG-ADL and QMG scores, fewer symptom deteriorations, and steeper reductions in corticosteroid and pyridostigmine use, suggesting a potential benefit of timely intervention. How might this potentially impact the practice of neurology?The results support consideration of earlier escalation in the gMG treatment pathway. They may prompt re-evaluation of current stepwise approaches in favor of more proactive strategies. Suggested social media postEarlier add-on therapy in AChR+ gMG linked to better outcomes and lower treatment burden - real-world data suggest a benefit from timely escalation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/25340299v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@16fb592org.highwire.dtl.DTLVardef@f9997eorg.highwire.dtl.DTLVardef@cc52fcorg.highwire.dtl.DTLVardef@5c3e99_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO 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. C_FIG