Disease Control in Generalized Myasthenia Gravis

BACKGROUND AND OBJECTIVES: Generalized myasthenia gravis (gMG) is a chronic fluctuating neuromuscular disease. Some patients keep experiencing symptoms or adverse events (AEs) despite tailored therapeutic schemes. The aim of this study was to characterize adequately controlled gMG and describe patients' evolution and outcomes, including estimated direct health costs in a universal health care system. METHODS: Spanish expert neurologists developed a definition of adequately controlled gMG using Delphi methodology. This was applied to an existing cohort of patients recently diagnosed with gMG during 1998-2020 in a Spanish referral neuromuscular diseases' unit. Control status, clinical outcomes, AEs, and health care resource utilization (HCRU) were described biennially. RESULTS: We assessed 220 patients diagnosed with gMG (54.5% women; mean age at onset of 58 years; 84% anti-AChR, 6% anti-MuSK, 10% seronegative). Adequately controlled gMG was defined as achieving Myasthenia Gravis Foundation of America Post-Intervention Status classification of clinical stable remission, pharmacologic remission, or minimal manifestations stable for a year; having an MG-ADL score ≤2; experiencing no clinical exacerbations during the last year requiring a change in immunosuppressive therapy or rescue therapy; and having no or mild AE to therapies (100% of experts in agreement or total agreement). The proportion adequately controlled (AC) patients increased from 62.0% at 2 years after first visit to 81.9% after 8 years of follow-up. 47.3% of patients remained AC in every observation, and 17.7% remained not adequately controlled (NC) in every observation. No features were significantly associated with adequate control. AE-related drug interruption rates were higher in NC patients (ranging from 50% to 100% during the study). The mean cost per patient/year ranged from 2,718.6€ in the first biennial period to 843.1€ in the last biennial period for AC patients and from 10,190.1€ to 5,827.4€ for NC patients. DISCUSSION: Based on the new gMG control consensus definition, almost 1 in 5 patients do not reach disease control even after 8 years of evolution. Those patients lacked specific clinical features, underscoring the unpredictability of the gMG course. Burden of AE-related drug interruptions, HCRU, and costs per patients/year were higher among those patients NC. However, our study is unicentric and included patients from a referral unit, with a possible overrepresentation of NC patients.