Minimal Symptom Expression in Generalized Myasthenia Gravis: A Valuable Patient-Centric Treatment Goal.

INTRODUCTION: Generalized myasthenia gravis (gMG) is a chronic autoimmune neuromuscular disorder characterized by fluctuating muscle weakness and exertional fatigue, often requiring long-term immunosuppressive or biologic treatment. Although international guidelines recommend achieving minimal manifestations as the primary treatment goal, the lack of a standardized measurement approach has limited its application in clinical settings and trials. Minimal Symptom Expression (MSE), defined as a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 0 or 1, has recently emerged as a practical, patient-centric endpoint that reflects minimal functional burden and aligns with regulatory priorities around patient-reported outcomes. RESULTS: This position paper examines the rationale for MSE as a clinically meaningful, actionable treatment target in gMG. We summarize the strengths of the underlying MG-ADL scale and highlight phase 3 trial data showing that MSE is attainable with biologic therapies, including complement and neonatal Fc receptor inhibitors. Data also suggest that achieving MSE correlates with improvements in physician-assessed outcomes and quality of life metrics. However, inconsistencies in how sustained MSE is defined and reported limit comparability across trials. CONCLUSION: MSE, as a patient-centric endpoint, can be used alongside clinician-assessed measures and safety measures to support an integrated treatment goal that encompasses both efficacy and tolerability for the treatment of gMG. Future research should further define the clinical utility of MSE and sustained MSE and incorporate stakeholder input to validate MSE as a part of an integrated treatment goal in both clinical trials and real-world clinical practice.

Duke Scholars

Author Jeffrey Guptill Neurology, Neuromuscular Disease