Objectives 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.
Methods 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.
Results 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).
Conclusions 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.
- systemic lupus erythematosus
- autoimmune diseases
- outcomes research
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Handling editor Josef S Smolen
Contributors All authors contributed to drafting and reviewing the manuscript and approved the final version for publication. JGH has access to all data and analyses. Study conception and design: JGH, MU, CG, S-CB, JR-D, JS-G, SB, AEC, DJW, DI, AR, JTM, PRF, DDG, INB, MP, EMG, MAD, RR-G, SM, GSA, RvV, CA, KK, VF. Acquisition of data, and analysis and interpretation of data: JGH, MU, CG, S-CB, JR-D, JS-G, SB, AEC, DJW, DI, AR, JTM, PRF, DDG, INB, MP, EMG, MAD, RR-G, SM, AJ, GSA, RvV, CA, MM, GR-I, SL, MI, KK, SJ, CP, DLK, AA, VF.
Funding Core funding for this investigator-initiated study was provided to JGH by the Canadian Institutes of Health Research (grant MOP-88526). Other sources of funding supported activities at individual SLICC sites: S-CB’s work was supported in part by NRF-2017M3A9B4050335, Republic of Korea. CG is 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. The Hopkins Lupus Cohort is supported by the NIH (grant AR43727 and 69572). The Montreal General Hospital Lupus Clinic is partially supported by the Singer Family Fund for Lupus Research. AEC holds The Arthritis Society Chair in Rheumatic Diseases at the University of Calgary. PRF holds a tier 1 Canada Research Chair on Systemic Autoimmune Rheumatic Diseases at Université Laval. INB is a National Institute for Health Research (NIHR) Senior Investigator and is supported by Arthritis Research UK, the NIHR Manchester Biomedical Centre and the NIHR/Wellcome Trust 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. SJ is supported by the Danish Rheumatism Association (A3865) and the Novo Nordisk Foundation (A05990). RR-G’s work was supported by the NIH (grants 5UL1TR001422-02, formerly 8UL1TR000150 and UL-1RR-025741, K24-AR-02318, and P60AR064464 formerly P60-AR-48098). MAD’s work was supported by the NIH grant RR00046. GR-I is supported by the Department of Education, Universities and Research of the Basque Government. DI and AR are supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. SL’s work was supported, in part, by the Centers for Disease Control and Prevention grant U01DP005119.
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.
Patient consent for publication Not required.
Ethics approval The Nova Scotia Health Authority central zone Research Ethics Board and each of the participating centres’ research ethics review boards approved the study.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable as all data relevant to the study are included in the article of in supplementary files.
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