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Ann Rheum Dis. 2020 Jan 8. pii: annrheumdis-2019-216150. doi: 10.1136/annrheumdis-2019-216150. [Epub ahead of print]

Neuropsychiatric events in systemic lupus erythematosus: a longitudinal analysis of outcomes in an international inception cohort using a multistate model approach.

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Division of Rheumatology, Department of Medicine and Department of Pathology, Queen Elizabeth ll Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada
Center for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico.
Divisions of Rheumatology and Clinical Epidemiology, Department of medicine, McGill University, Montreal, Quebec, Canada.
Divisions of Rheumatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Cedars-Sinai/David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Centre for Rheumatology Research, Department of Medicine, University College, London, UK.
Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Division of Rheumatology, Department of Medicine, CHU de Québec, Université Laval, Quebec City, Quebec, Canada.
Arthritis Research UK Epidemiology Unit, Faculty of Biology Medicine and Health, Manchester Academic Health Sciences Centre, The University of Manchester, and NIHR Manchester Musculoskeletal Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Department of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY, USA.
Thurston Arthritis Research Centre, University of North Carolina, Chapel Hill, NC, USA.
Northwestern University and Feinberg School of Medicine, Chicago, IL, USA.
Lupus Center of Excellence, Allegheny Health Network, Pittsburgh, PA, USA.
Department of Clinical Sciences Lund, Rheumatology, Lund University, Lund, Sweden.
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Rheumatology and Clinical Immunology, University Medical Centres, Amsterdam, The Netherlands.
Feinstein Institute for Medical Research, Manhasset, NY, USA.
Autoimmune Diseases Research Unit, Department of Internal Medicine, BioCruces Bizkaia Health Research Institute, Hospital Universitario Cruces, University of the Basque Country, Barakaldo, Spain.
Emory University, Department of Medicine, Division of Rheumatology, Atlanta, Georgia, USA.
Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
UCSD School of Medicine, La Jolla, CA, USA.
Copenhagen Lupus and Vasculitis Clinic, 4242, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
University of Manitoba, Winnipeg, Manitoba, Canada.
Medical University of South Carolina, Charleston, South Carolina, USA.
Hospital for Joint Diseases, NYU, Seligman Centre for Advanced Therapeutics, New York, NY, USA.
MRC Biostatistics Unit, Cambridge Institute of Public Health, University of Cambridge, Cambridge, UK.



Using a reversible multistate model, we prospectively examined neuropsychiatric (NP) events for attribution, outcome and association with health-related quality of life (HRQoL), in an international, inception cohort of systemic lupus erythematosus (SLE) patients.


Annual assessments for 19 NP events attributed to SLE and non-SLE causes, physician determination of outcome and patient HRQoL (short-form (SF)-36 scores) were measured. Time-to-event analysis and multistate modelling examined the onset, recurrence and transition between NP states.


NP events occurred in 955/1827 (52.3%) patients and 592/1910 (31.0%) unique events were attributed to SLE. In the first 2 years of follow-up the relative risk (95% CI) for SLE NP events was 6.16 (4.96, 7.66) and non-SLE events was 4.66 (4.01, 5.43) compared with thereafter. Patients without SLE NP events at initial assessment had a 74% probability of being event free at 10 years. For non-SLE NP events the estimate was 48%. The majority of NP events resolved over 10 years but mortality was higher in patients with NP events attributed to SLE (16%) versus patients with no NPSLE events (6%) while the rate was comparable in patients with non-SLE NP events (7%) compared with patients with no non-SLE events (6%). Patients with NP events had lower SF-36 summary scores compared with those without NP events and resolved NP states (p<0.001).


NP events occur most frequently around the diagnosis of SLE. Although the majority of events resolve they are associated with reduced HRQoL and excess mortality. Multistate modelling is well suited for the assessment of NP events in SLE.


autoimmune diseases; epidemiology; outcomes research; systemic lupus erythematosus

Conflict of interest statement

Competing interests: RvV has received grants from BMS, GSK, Lilly, Pfizer, UCB Pharma, personal fees from AbbVie, AstraZeneca, Biotest, Celgene, GSK, Janssen, Lilly, Novartis, Pfizer, Servier, UCB, outside the submitted work.

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