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

John G. Hanly; Murray B. Urowitz; Caroline Gordon; Sang Cheol Bae; Juanita Romero-Diaz; Jorge Sanchez-Guerrero; Sasha Bernatsky; Ann E. Clarke; Daniel J. Wallace; David A. Isenberg; Anisur Rahman; Joan T. Merrill; Paul R. Fortin; Dafna D. Gladman; Ian N. Bruce; Michelle Petri; Ellen M. Ginzler; Mary Anne Dooley; Rosalind Ramsey-Goldman; Susan Manzi; Andreas Jönsen; Graciela S. Alarcón; Ronald F. van Vollenhoven; Cynthia Aranow; Meggan Mackay; Guillermo Ruiz-Irastorza; Sam Lim; Murat Inanc; Kenneth C. Kalunian; Søren Jacobsen; Christine A. Peschken; Diane L. Kamen; Anca Askanase; Vernon Farewell

doi:10.1136/annrheumdis-2019-216150

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

John G. Hanly^*, Murray B. Urowitz, Caroline Gordon, Sang Cheol Bae, Juanita Romero-Diaz, Jorge Sanchez-Guerrero, Sasha Bernatsky, Ann E. Clarke, Daniel J. Wallace, David A. Isenberg, Anisur Rahman, Joan T. Merrill, Paul R. Fortin, Dafna D. Gladman, Ian N. Bruce, Michelle Petri, Ellen M. Ginzler, Mary Anne Dooley, Rosalind Ramsey-Goldman, Susan ManziAndreas Jönsen, Graciela S. Alarcón, Ronald F. van Vollenhoven, Cynthia Aranow, Meggan Mackay, Guillermo Ruiz-Irastorza, Sam Lim, Murat Inanc, Kenneth C. Kalunian, Søren Jacobsen, Christine A. Peschken, Diane L. Kamen, Anca Askanase, Vernon Farewell

^*Corresponding author for this work

Medicine, Rheumatology Division

Research output: Contribution to journal › Article › peer-review

58 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	356-362
Number of pages	7
Journal	Annals of the rheumatic diseases
Volume	79
Issue number	3
DOIs	https://doi.org/10.1136/annrheumdis-2019-216150
State	Published - Jan 8 2020

Funding

The corresponding author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive license (or nonexclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article (if accepted) to be published in Annals of the Rheumatic Diseases and any other BMJPGL products to exploit all subsidiary rights, as set out in our license (http://group.bmj.com/products/journals/ instructions-for-authors/licence-forms). 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\u2019s 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 Universit\u00E9 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\u2019s 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\u2019s 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\u2019s work was supported, in part, by the Centers for Disease Control and Prevention grant U01DP005119.

ASJC Scopus subject areas

Rheumatology
Immunology and Allergy
Immunology
General Biochemistry, Genetics and Molecular Biology

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10.1136/annrheumdis-2019-216150

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Hanly, J. G., Urowitz, M. B., Gordon, C., Bae, S. C., Romero-Diaz, J., Sanchez-Guerrero, J., Bernatsky, S., Clarke, A. E., Wallace, D. J., Isenberg, D. A., Rahman, A., Merrill, J. T., Fortin, P. R., Gladman, D. D., Bruce, I. N., Petri, M., Ginzler, E. M., Dooley, M. A., Ramsey-Goldman, R., ... Farewell, V. (2020). Neuropsychiatric events in systemic lupus erythematosus: a longitudinal analysis of outcomes in an international inception cohort using a multistate model approach. Annals of the rheumatic diseases, 79(3), 356-362. https://doi.org/10.1136/annrheumdis-2019-216150

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

abstract = "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.",

author = "Hanly, {John G.} and Urowitz, {Murray B.} and Caroline Gordon and Bae, {Sang Cheol} and Juanita Romero-Diaz and Jorge Sanchez-Guerrero and Sasha Bernatsky and Clarke, {Ann E.} and Wallace, {Daniel J.} and Isenberg, {David A.} and Anisur Rahman and Merrill, {Joan T.} and Fortin, {Paul R.} and Gladman, {Dafna D.} and Bruce, {Ian N.} and Michelle Petri and Ginzler, {Ellen M.} and Dooley, {Mary Anne} and Rosalind Ramsey-Goldman and Susan Manzi and Andreas J{\"o}nsen and Alarc{\'o}n, {Graciela S.} and {van Vollenhoven}, {Ronald F.} and Cynthia Aranow and Meggan Mackay and Guillermo Ruiz-Irastorza and Sam Lim and Murat Inanc and Kalunian, {Kenneth C.} and S{\o}ren Jacobsen and Peschken, {Christine A.} and Kamen, {Diane L.} and Anca Askanase and Vernon Farewell",

note = "Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2020.",

year = "2020",

month = jan,

day = "8",

doi = "10.1136/annrheumdis-2019-216150",

language = "English (US)",

volume = "79",

pages = "356--362",

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Hanly, JG, Urowitz, MB, Gordon, C, Bae, SC, Romero-Diaz, J, Sanchez-Guerrero, J, Bernatsky, S, Clarke, AE, Wallace, DJ, Isenberg, DA, Rahman, A, Merrill, JT, Fortin, PR, Gladman, DD, Bruce, IN, Petri, M, Ginzler, EM, Dooley, MA, Ramsey-Goldman, R, Manzi, S, Jönsen, A, Alarcón, GS, van Vollenhoven, RF, Aranow, C, Mackay, M, Ruiz-Irastorza, G, Lim, S, Inanc, M, Kalunian, KC, Jacobsen, S, Peschken, CA, Kamen, DL, Askanase, A & Farewell, V 2020, 'Neuropsychiatric events in systemic lupus erythematosus: a longitudinal analysis of outcomes in an international inception cohort using a multistate model approach', Annals of the rheumatic diseases, vol. 79, no. 3, pp. 356-362. https://doi.org/10.1136/annrheumdis-2019-216150

Neuropsychiatric events in systemic lupus erythematosus: a longitudinal analysis of outcomes in an international inception cohort using a multistate model approach. / Hanly, John G.; Urowitz, Murray B.; Gordon, Caroline et al.
In: Annals of the rheumatic diseases, Vol. 79, No. 3, 08.01.2020, p. 356-362.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Neuropsychiatric events in systemic lupus erythematosus

T2 - a longitudinal analysis of outcomes in an international inception cohort using a multistate model approach

AU - Hanly, John G.

AU - Urowitz, Murray B.

AU - Gordon, Caroline

AU - Bae, Sang Cheol

AU - Romero-Diaz, Juanita

AU - Sanchez-Guerrero, Jorge

AU - Bernatsky, Sasha

AU - Clarke, Ann E.

AU - Wallace, Daniel J.

AU - Isenberg, David A.

AU - Rahman, Anisur

AU - Merrill, Joan T.

AU - Fortin, Paul R.

AU - Gladman, Dafna D.

AU - Bruce, Ian N.

AU - Petri, Michelle

AU - Ginzler, Ellen M.

AU - Dooley, Mary Anne

AU - Ramsey-Goldman, Rosalind

AU - Manzi, Susan

AU - Jönsen, Andreas

AU - Alarcón, Graciela S.

AU - van Vollenhoven, Ronald F.

AU - Aranow, Cynthia

AU - Mackay, Meggan

AU - Ruiz-Irastorza, Guillermo

AU - Lim, Sam

AU - Inanc, Murat

AU - Kalunian, Kenneth C.

AU - Jacobsen, Søren

AU - Peschken, Christine A.

AU - Kamen, Diane L.

AU - Askanase, Anca

AU - Farewell, Vernon

PY - 2020/1/8

Y1 - 2020/1/8

N2 - 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.

AB - 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.

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DO - 10.1136/annrheumdis-2019-216150

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SN - 0003-4967

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JO - Annals of the rheumatic diseases

JF - Annals of the rheumatic diseases

IS - 3

ER -

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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