Neuropsychiatric Events in Systemic Lupus Erythematosus: Predictors of Occurrence and Resolution in a Longitudinal Analysis of an International Inception Cohort

• Type of Material: Article
• Authors: John G Hanly, Queen Elizabeth II Health Sciences Centre and Dalhousie University; Caroline Gordon, University of Birmingham; Sang-Cheol Bae, Hanyang Univ Hosp Rheumat Dis; Juanita Romero-Diaz, nstituto Nacional de Ciencias Médicas y Nutrición; Jorge Sanchez-Guerrero, nstituto Nacional de Ciencias Médicas y Nutrición; Sasha Bernatsky, McGill University; Ann E Clarke, University of Calgary; Daniel J Wallace, Cedars Sinai Medical Center; David A Isenberg, University College London; Anisur Rahman, University College London; Joan T Merrill, Oklahoma Medical Research Foundation; Paul R Fortin, Laval University; Dafna D Gladman, Toronto Western Hospital; Murray B Urowitz, Toronto Western Hospital; Ian N Bruce, University of Manchester; Michelle Petri, Johns Hopkins University; Ellen M Ginzler, SUNY Downstate Medical Centre; MA Dooley, University of North Carolina; Rosalind Ramsey-Goldman, Northwestern University; Susan Manzi, Allegheny Health Network; Andreas Jonsen, Lund University; Graciela S Alarcón, University of Alabama Birmingham; Ronald F Vollenhoven, Amsterdam University Medical Centers; Cynthia Aranow, Feinstein Inst Med Res; Meggan Mackay, Feinstein Inst Med Res; Guillermo Ruiz-Irastorza, Hospital Universitario Cruces; Sung Lim, Emory University; Murat Inanc, Istanbul University; Kenneth C Kalunian, University of California San Diego; Soren Jacobsen, Copenhagen Univ Hosp; Christine A Peschken, University of Manitoba; Diane L Kamen, Medical University of South Carolina; Anca Askanase, NYU Langone Orthoped Hosp; Vernon Farewell, University of Cambridge
• Language: English
• Date: 2021-10-29
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021, American College of Rheumatology
• Final Published Version (URL): http://dx.doi.org/10.1002/art.41876
• Title of Journal or Parent Work: ARTHRITIS & RHEUMATOLOGY
• Volume: 73
• Issue: 12
• Start Page: 2293
• End Page: 2302
• Grant/Funding Information: Dr. Ruiz-Irastorza is supported by the Department of Education, Universities and Research of the Basque Government.; Dr Caroline Gordon was supported by Lupus UK, Sandwell and West Birmingham Hospitals NHS Trust and the National Institute for Health Research (NIHR)/Wellcome Trust Birmingham Clinical Research Facility. The views expressed are those of the authors(s) and not necessarily those of the NHS, the NIHR or the Department of Health.; Dr. Mary Anne Dooley’s work was supported by the NIH grant RR00046.; Dr. Paul R. Fortin holds a tier 1 Canada Research Chair on Systemic Autoimmune Rheumatic Diseases at Université Laval.; The Montreal General Hospital Lupus Clinic is partially supported by the Singer Family Fund for Lupus Research. Dr. Sasha Bernatsky holds a James McGill Research Chair.; Dr. Soren Jacobsen is supported by the Danish Rheumatism Association (non-commercial, A3865) and the Independent Research Fund Denmark (non-commercial, 0134-00473B).; Dr. Bruce is a National Institute for Health Research (NIHR) Senior Investigator and is supported by Versus Arthritis UK, the NIHR Manchester Biomedical Research Centre and the NIHR Manchester Clinical Research Facility. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.; The Hopkins Lupus Cohort is supported by the NIH (grant AR43727 and 69572).; Dr. Sang-Cheol Bae’s work was supported in part by NRF-2017M3A9B4050335, Republic of Korea.; Dr. Ramsey-Goldman’s work was supported by the NIH (grants 5UL1TR001422-02, formerly 8UL1TR000150 and UL-1RR-025741, K24-AR-02318, and P30 AR072579, formerly P60AR064464 and P60-AR-48098).; John G. Hanly (Canadian Institutes of Health Research grant MOP-88526); Dr. Clarke holds The Arthritis Society Chair in Rheumatic Diseases at the University of Calgary.; Dr Isenberg and Dr Rahman are supported by and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Center.
• Keywords: Life Sciences & Biomedicine; ANTIPHOSPHOLIPID ANTIBODIES; CRITERIA; OUTCOMES; Rheumatology; ADOLESCENTS; PREVALENCE; DISORDERS; DAMAGE; ASSOCIATION; DISEASE; Science & Technology; PROTEIN-S

Abstract

Objective: To determine predictors of change in neuropsychiatric (NP) event status in a large, prospective, international inception cohort of patients with systemic lupus erythematosus (SLE). Methods: Upon enrollment and annually thereafter, NP events attributed to SLE and non-SLE causes and physician-determined resolution were documented. Factors potentially associated with the onset and resolution of NP events were determined by time-to-event analysis using a multistate modeling structure. Results: NP events occurred in 955 (52.3%) of 1,827 patients, and 593 (31.0%) of 1,910 unique events were attributed to SLE. For SLE-associated NP (SLE NP) events, multivariate analysis revealed a positive association with male sex (P = 0.028), concurrent non-SLE NP events excluding headache (P < 0.001), active SLE (P = 0.012), and glucocorticoid use (P = 0.008). There was a negative association with Asian race (P = 0.002), postsecondary education (P = 0.001), and treatment with immunosuppressive drugs (P = 0.019) or antimalarial drugs (P = 0.056). For non-SLE NP events excluding headache, there was a positive association with concurrent SLE NP events (P < 0.001) and a negative association with African race (P = 0.012) and Asian race (P < 0.001). NP events attributed to SLE had a higher resolution rate than non-SLE NP events, with the exception of headache, which had comparable resolution rates. For SLE NP events, multivariate analysis revealed that resolution was more common in patients of Asian race (P = 0.006) and for central/focal NP events (P < 0.001). For non-SLE NP events, resolution was more common in patients of African race (P = 0.017) and less common in patients who were older at SLE diagnosis (P < 0.001). Conclusion: In a large and long-term study of the occurrence and resolution of NP events in SLE, we identified subgroups with better and worse prognosis. The course of NP events differs greatly depending on their nature and attribution.