OBJECTIVE: To study the trajectories of changes in damage over time and explore associations with autoantibody defined subgroups using a large international cohort of patients with idiopathic inflammatory myopathies (IIM). METHODS: Data from the MYONET registry, including patients who were tested for autoantibodies and had at least one assessment of damage using the Myositis Damage Index (MDI), were analyzed. Patients were sub-grouped according to their autoantibody profiles (myositis-specific, myositis-associated, or seronegative). The index date was defined as the time point for the first registered MDI assessment. The longitudinal trajectories of damage with autoantibody status as the main predictor were analyzed using linear mixed models. RESULTS: A total of 757 adult patients were included in this study. Each year of disease duration since diagnosis had an estimated MDI score increase of 0.16 units for the seronegative group (reference). Compared with the seronegative group as reference, patients with dermatomyositis-specific autoantibodies developed less damage per year of follow-up since diagnosis (average 0.08 less score, P = 0.04), whereas patients with anti-PM/Scl autoantibodies developed more damage per year of follow-up since diagnosis (average 0.28 higher score, P = 0.03) independent of sex and age at diagnosis. The seronegative subgroup and the immune-mediated necrotizing myopathy autoantibody subgroup had the strongest correlation between severity of muscle damage and HAQ-DI scores at five years of follow-up, rho=0.84, P < 0.001 and rho=0.72, P < 0.001, respectively. CONCLUSION: Our study is the first to describe patterns and trajectories of change in damage over time in relation to autoantibody defined subgroups in a large international multicenter cohort of patients with IIM. Patients with anti-PM/Scl scored a greater extent of damage, whereas patients with dermatomyositis-specific antibodies had less damage than seronegative patients. Severity in muscle damage had moderate to strong correlation with functional disability among the IMNM and seronegative subgroups with lower correlations for the other subgroups. These findings suggest that autoantibodies may be useful predictors of long-term damage.

Center for Rheumatology and Spine Diseases Copenhagen University Hospital Rigshospitalet Copenhagen Denmark; Department of Rheumatology Odense University Hospital Odense Denmark

Department of Clinical and Molecular Sciences Polytechnic University of Marche Torrette di Ancona Italy

Department of Immunology and Rheumatology Instituto Nacional de Ciencias Médicas y Nutrición Dr Salvador Zubirán Mexico City Mexico

Department of Neurology Amsterdam University Medical Center University of Amsterdam Amsterdam Neuroscience Amsterdam the Netherlands

Department of Rheumatology Oslo University Hospital Oslo Norway

División de Medicina Interna Servicio de Reumatología Hospital Civil Dr Juan 1 Menchaca Universidad de Guadalajara Guadalajara Jalisco Mexico

Division of Musculoskeletal and Dermatological Sciences School of Biological Sciences Faculty of Biology Medicine and Health Centre for Musculoskeletal Research The University of Manchester Manchester UK; Department of Rheumatology Salford Royal Hospital Northern Care Alliance NHS Foundation Trust Manchester Academic Health Science Centre Salford UK

Division of Musculoskeletal and Dermatological Sciences School of Biological Sciences Faculty of Biology Medicine and Health Centre for Musculoskeletal Research The University of Manchester Manchester UK; Manchester Centre for Clinical Neurosciences Northern Care Alliance NHS Foundation Trust Manchester Academic Health Science Centre Salford UK

Division of Rheumatology and Clinical Immunology IRCCS Humanitas Research Hospital Rozzano Milan Italy; Department of Biomedical Sciences Humanitas University Milan Italy

Division of Rheumatology Department of Medicine Solna Karolinska Institutet Stockholm Sweden; Department of Gastro Dermatology and Rheumatology Karolinska University Hospital Stockholm Sweden

Division of Rheumatology Department of Medicine Solna Karolinska Institutet Stockholm Sweden; Theme Women's Health and Health Professionals Medical Unit Allied Health Professionals Karolinska University Hospital Stockholm Sweden

Division of Rheumatology Faculdade de Medicina FMUSP Universidade de Sao Paulo Sao Paulo SP Brazil

Faculty of Medicine Division of Clinical Immunology University of Debrecen Hungary

Institute of Rheumatology and Department of Rheumatology 1st Medical Faculty Charles University Prague Czech Republic

Systemic Autoimmune Diseases Unit Vall d'Hebron Hospital Universitat Autonoma de Barcelona Spain

Zitelab Aps Copenhagen Denmark

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