AIM: To explore if patient global assessment (PGA) is associated with inflammation over time and if associations are explained by other measures of disease activity and function in patients with idiopathic inflammatory myopathies (IIM). METHODS: PGA and systemic inflammatory markers prospectively collected over five years were retrieved from the International MyoNet registry for 1200 patients with IIM. Associations between PGA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and creatine kinase (CK) were analyzed using mixed models. Mediation analysis was used to test if the association between PGA and inflammatory markers during the first year of observation could be explained by measures of disease activity and function. RESULTS: PGA improved, and inflammatory markers decreased during the first year of observation. In the mixed models, high levels of inflammatory markers were associated with worse PGA in both men and women across time points during five years of observation. In men, but not in women, the association between elevated ESR, CRP and poorer PGA was explained by measures of function and disease activity. With a few exceptions, the association between improved PGA and reduced inflammatory markers was partially mediated by improvements in all measures of function and disease activity. CONCLUSION: Increased levels of systemic inflammation are associated with poorer PGA in patients with IIM. In addition to known benefits of lowered inflammation, these findings emphasize the need to reduce systemic inflammation to improve subjective health in patients with IIM. Furthermore, the results demonstrate the importance of incorporating PGA as an outcome measure in clinical practice and clinical trials.

Department of Biomedical Sciences Humanitas University 20072 Pieve Emanuele Milan Italy

Department of Gastroenterology Dermatology and Rheumatology Karolinska University Hospital Stockholm Sweden

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

Department of Medical Sciences Section of Rheumatology Uppsala University Uppsala Sweden

Department of Medicine Division of Rheumatology Karolinska Institutet Solna Stockholm Sweden

Department of Rheumatology and Immunology Inselspital Bern University Hospital University of Bern Bern CH 3010 Switzerland

Department of Rheumatology Oslo University Hospital Oslo Norway

Department of Rheumatology Salford Royal Hospital Northern Care Alliance NHS Foundation Trust Manchester Academic Health Science Centre Salford United Kingdom

Division of Clinical Immunology Faculty of Medicine University of Debrecen Debrecen Hungary

Division of Musculoskeletal and Dermatological Sciences School of Biological Sciences Faculty of Biology Medicine and Health Centre for Musculoskeletal Research Manchester Academic Health Science Centre The University of Manchester Manchester United Kingdom

Division of Rheumatology and Clinical Immunology IRCCS Humanitas Research Hospital 20089 Rozzano Milan Italy

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

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

Manchester Centre for Clinical Neurosciences Northern Care Alliance NHS Foundation Trust Salford United Kingdom

National Institute for Health Research Manchester Biomedical Research Centre Manchester University NHS Foundation Trust The University of Manchester Manchester United Kingdom

Universidad de Guadalajara Centro Universitario de Ciencias de la Salud Departamento de Biología Molecular y Genómica Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético Guadalajara Mexico

Women's Health and Health Professional Theme Medical Unit Occupational Therapy and Physical Therapy Karolinska University Hospital Stockholm Sweden

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$a Lodin, Karin $u Department of Medicine, Division of Rheumatology, Karolinska Institutet, Solna, Stockholm, Sweden; Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: Karin.lodin@regionstockholm.se

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$a Patient global assessment and inflammatory markers in patients with idiopathic inflammatory myopathies - A longitudinal study / $c K. Lodin, F. Espinosa-Ortega, M. Dastmalchi, J. Vencovsky, H. Andersson, H. Chinoy, JB. Lilleker, SK. Shinjo, B. Maurer, Z. Griger, A. Ceribelli, J. Torres-Ruiz, VD. Mercado M, D. Leonard, H. Alexanderson, IE. Lundberg, MyoNet Registry Study Group

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$a AIM: To explore if patient global assessment (PGA) is associated with inflammation over time and if associations are explained by other measures of disease activity and function in patients with idiopathic inflammatory myopathies (IIM). METHODS: PGA and systemic inflammatory markers prospectively collected over five years were retrieved from the International MyoNet registry for 1200 patients with IIM. Associations between PGA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and creatine kinase (CK) were analyzed using mixed models. Mediation analysis was used to test if the association between PGA and inflammatory markers during the first year of observation could be explained by measures of disease activity and function. RESULTS: PGA improved, and inflammatory markers decreased during the first year of observation. In the mixed models, high levels of inflammatory markers were associated with worse PGA in both men and women across time points during five years of observation. In men, but not in women, the association between elevated ESR, CRP and poorer PGA was explained by measures of function and disease activity. With a few exceptions, the association between improved PGA and reduced inflammatory markers was partially mediated by improvements in all measures of function and disease activity. CONCLUSION: Increased levels of systemic inflammation are associated with poorer PGA in patients with IIM. In addition to known benefits of lowered inflammation, these findings emphasize the need to reduce systemic inflammation to improve subjective health in patients with IIM. Furthermore, the results demonstrate the importance of incorporating PGA as an outcome measure in clinical practice and clinical trials.

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$a Dastmalchi, Maryam $u Department of Medicine, Division of Rheumatology, Karolinska Institutet, Solna, Stockholm, Sweden; Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden

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$a Chinoy, Hector $u National Institute for Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, The University of Manchester, Manchester, United Kingdom; Department of Rheumatology, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, United Kingdom; Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom

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$a Lilleker, James B $u Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom; Manchester Centre for Clinical Neurosciences, Northern Care Alliance NHS Foundation Trust, Salford, United Kingdom

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$a Shinjo, Samuel Katsuyuki $u Division of Rheumatology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil

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$a Ceribelli, Angela $u Division of Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Milan, Italy

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