Attainment of low disease activity and remission targets reduces the risk of severe flare and new damage in childhood lupus

Smith, E. M.D. et al. (2022) Attainment of low disease activity and remission targets reduces the risk of severe flare and new damage in childhood lupus. Rheumatology, 61(8), pp. 3378-3389. (doi: 10.1093/rheumatology/keab915) (PMID:34894234)

Abstract

Objectives: To assess the achievability and effect of attaining low disease activity (LDA) or remission in childhood (cSLE). Methods: Attainment of three adult-SLE derived definitions of LDA (LLDAS, LA, Toronto-LDA), and four definitions of remission (clinical-SLEDAI-defined remission on/off treatment, pBILAG-defined remission on/off treatment) was assessed in UK JSLE Cohort Study patients longitudinally. Prentice-Williams-Petersen-GAP recurrent event models assessed the impact of LDA/remission attainment on severe flare/new damage. Results: LLDAS, LA and Toronto-LDA targets were reached in 67%, 73% and 32% of patients, after a median of 18, 15 or 17 months, respectively. Cumulatively, LLDAS, LA and Toronto-LDA was attained for a median of 23%, 31% and 19% of total follow-up-time, respectively. Remission on-treatment was more common (61% cSLEDAI-defined, 42% pBILAG-defined) than remission off-treatment (31% cSLEDAI-defined, 21% pBILAG-defined). Attainment of all target states, and disease duration (>1 year), significantly reduced the hazard of severe flare (p< 0.001). As cumulative time in each target increased, hazard of severe flare progressively reduced. LLDAS attainment reduced the hazard of severe flare more than LA or Toronto-LDA (p< 0.001). Attainment of LLDAS and all remission definitions led to a statistically comparable reduction in the hazards of severe flare (p> 0.05). Attainment of all targets reduced the hazards of new damage (p< 0.05). Conclusions: This is the first study demonstrating that adult-SLE-derived definitions of LDA/remission are achievable in cSLE, significantly reducing risk of severe flare/new damage. Of the LDA definitions, LLDAS performed best, leading to a statistically comparable reduction in the hazards of severe flare to attainment of clinical-remission.

• Item Type: Articles
• Additional Information: This work was supported by the Wellcome Trust through a Wellcome Trust Institutional Strategic Support Fund [204822z16z], Equality and Diversity grant, awarded to ES by the Faculty of Health and Life Sciences, University of Liverpool’. Lupus UK provide financial support for co-ordination of the UK JSLE Cohort Study [grant numbers: LUPUS UK: JXR10500, JXR12309]. The study took place as part of the UK’s ‘Experimental Arthritis Treatment Centre for Children’ supported by Versus Arthritis (grant number ARUK-20621), the University of Liverpool, Alder Hey Children’s NHS Foundation Trust and the Alder Hey Charity, and based at the University of Liverpool and Alder Hey Children’s NHS Foundation Trust.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gardner-Medwin, Dr Janet
• Authors: Smith, E. M.D., Tharmaratnam, K., Al-Abadi, E., Armon, K., Bailey, K., Brennan, M., Ciurtin, C., Gardner-Medwin, J., Haslam, K. E., Hawley, D., Leahy, A., Leone, V., Malik, G., McLaren, Z., Pilkington, C., Ramanan, A. V., Rangaraj, S., Ratcliffe, A., Riley, P., Sen, E., Sridhar, A., Wilkinson, N., Hedrich, C. M., Jorgensen, A., and Beresford, M. W.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Rheumatology
• Publisher: Oxford University Press
• ISSN: 1462-0324
• ISSN (Online): 1462-0332
• Published Online: 11 December 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Rheumatology 61(8): 3378-3389
• Publisher Policy: Reproduced under a Creative Commons License