Early versus late add-on therapy in generalized myasthenia gravis: a multicenter real-world cohort study

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.

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.

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).

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.