OptiMyG

Myasthenia gravis (MG; OrphaCode 391490; ICD-10 G70.0) is a chronic autoimmune disease affecting the signal transmission between nerve and muscle, with an estimated prevalence of 1.5 to 2.5 per 10.000. Well-powered population-based studies of prevalence and incidence, as well as disease burden, including comorbidities are rare. Disease severity varies from milder forms to potentially life-threatening crises with respiratory failure, and clinical management is mainly based on empirical evidence, with a scarcity of reliable clinical predictors or biomarkers for disease subform stratification and long-term outcomes. Further, while smaller randomized trials suggest that thymectomy and B cell-depleting therapy early after disease onset are associated with improved medium-term outcomes in certain subgroups, the benefit-risk balance of induction treatments compared with chronic administration of corticosteroids and oral immune suppressants in the longer term are unknown. This has in turn translated into variable treatment practices within and between countries. Patient-reported outcomes (PROs) are increasingly used as important endpoints in randomized trials, however, they have mostly been tested in smaller cohorts, which restricts reliability and understanding of external validity. We here propose a comprehensive program to shed light on these important knowledge gaps. To this end we will perform a nationwide registry linkage study in Sweden to establish more precise prevalence/incidence rates and candidate clinical predictors of long-term outcomes, also including PRO outcomes and epidemiological questionnaire data on half the estimated nationwide prevalent MG population. These findings will be corroborated, extended and cross-compared in large and well-characterized cohorts from 5 countries across Europe reflecting different geographic areas, patient populations and treatment practices. Finally, using advanced immunological methods we will identify novel immunological markers for MG subform characterization and disease severity prediction to be validated in a multicenter prospective, observational study of new onset MG. The knowledge thus gained has the potential to change treatment practices with currently available interventions and to be informative for future intervention studies.