Background: In the ADAPT study, treatment with efgartigimod (a human IgG1 antibody Fc-fragment that reduces pathogenic autoantibody and total IgG levels through neonatal Fc receptor blockade) resulted in clinically meaningful improvements in acetylcholine receptor autoantibody positive (AChR-Ab+) patients with generalized myasthenia gravis (gMG).
Objectives: Assess efficacy of efgartigimod in subgroups of AChR-Ab+ patients (n=129) with gMG.
Methods: Efgartigimod (EFG) 10 mg/kg or placebo (PBO) was administered intravenously in cycles of 4 weekly infusions, with subsequent cycles initiated based on clinical evaluation. Efficacy was assessed using Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. Responder status was defined as ≥2-point (MG-ADL) and ≥3-point (QMG) improvement for ≥4 consecutive weeks (with first improvement ≤1 week after last infusion). The proportion of responders was assessed for patients sub-grouped by clinical characteristics such as time from diagnosis, thymectomy status, and concomitant medications.
Results: In patients <3 years from diagnosis, 78.6% EFG (n=11/14) vs 23.5% PBO (n=4/17) patients were MG-ADL responders (between group difference 55.0%, 95% CI, 25.6–84.5). In non-thymectomized patients, 85.0% EFG (n=17/20) achieved responder status vs 32.4% PBO (n=11/34; between group difference 52.6%, 95% CI, 30.5–74.8). The proportion of responders among patients receiving only concomitant acetylcholinesterase inhibitors was 84.6% EFG (n=11/13) vs 16.7% PBO (n=1/6; between group difference 67.9%, 95% CI, 32.3–100.0) and among patients receiving any corticosteroid was 63.0% EFG (n=29/46) vs 29.4% PBO (n=15/51; between group difference 33.6%, 95% CI, 14.9–52.4). Results for other subgroups, along with the proportion of QMG responders, also consistently favored EFG. Common adverse events (mostly mild/moderate) in both treatment arms were headache, nasopharyngitis, nausea, diarrhea, and upper respiratory/urinary tract infection. Conclusion: Efgartigimod treatment resulted in consistent improvements across subgroups, including patients with early disease, reinforcing the efficacy of efgartigimod across a broad gMG population.