Idiopathic inflammatory myopathies as a damage-data-endotype continuum: A roadmap to precision trials and computable...

Idiopathic inflammatory myopathies (IIM) are heterogeneous immune-mediated diseases characterized by muscle inflammation that coexists with variable trajectories of lung, skin, cardiac involvement, and malignancy association. Although modern classification criteria and serology have improved phenotyping, evidence remains limited in its applicability across cohorts and trials because broad diagnostic labels obscure major differences in autoantibodies, organ-risk trajectories, disease stage, and outcome selection. We propose a community roadmap that redefines IIM as a damage-data-endotype continuum integrating: (i) tissue damage programs (alarmins/DAMPs, mitochondrial stress/redox imbalance, regeneration-fibrosis transitions), (ii) tissue niches (muscle, lung, skin, heart, vascular-stromal compartment), (iii) immune effector axes (interferon/JAK programs, complement/Fc biology, B cell-plasma cell persistence, cytotoxic T-cell/immunosenescence signatures), and (iv) multi-layered data (myositis autoantibodies, quantitative imaging, digital pathology, omics, and patient-reported/digital outcomes). We define actionable endotypes as the combination of autoantibody profile, dominant organ-risk trajectory, and dominant mechanistic axis, and map these endotypes to therapy classes, measurable biomarker sets, and sensitivity-optimized endpoints. Finally, we propose a minimum dataset (basic and enhanced) to harmonize registries and facilitate adaptive/platform trials, thereby supporting robust machine-learning models with external validation and drift monitoring. This roadmap aims to standardize evidence generation across IIM, accelerate precision trials, and provide a shared, falsifiable research agenda for the next phase of the field.