OP0277 EVALUATING THE IMPACT OF CHILDHOOD-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS T2T TARGET ATTAINMENT: MITIGATING FLARES AND NEW DAMAGE ACCRUAL
Authors: C. Sarker, A. L. Jorgensen, M. W. Beresford, E. MD Smith
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease. Globally, there is a growing interest in the application of Treat-to-Target (T2T) strategies for managing both cSLE and adult-onset SLE (aSLE). The T2T approach promotes systematic and prompt management of disease activity, aiming to prevent organ damage and enhance health-related quality of life. The International cSLE T2T Task Force developed age-appropriate cSLE target definitions, including Childhood Lupus Low Disease Activity State (cLLDAS), cSLE clinical remission on (cCR) and off-corticosteroids (cCR-0), endorsed by the Paediatric Rheumatology European Society (PReS) [1]. These targets intentionally maintain alignment with the aSLE target definitions to facilitate life-course research, whilst promoting discontinuation of corticosteroids through pursuit of the second remission target (cCR-0). <h3>Objectives:</h3> To validate the new cSLE T2T endpoints, examining the influence of target attainment on the occurrence of new damage and severe flares. In addition, to compare the efficacy of cSLE-specific targets against those established for aSLE. <h3>Methods:</h3> Longitudinal data from UK JSLE Cohort Study participants aged &lt;18 years at the time of diagnosis, with ≥4 ACR criteria for SLE were utilised. Attainment of paediatric-specific targets (cLLDAS, cCR and cCR-0) [1] and corresponding aSLE targets (LLDAS [2], DORIS 2021 Remission [3]) were assessed. The paediatric-specific adaptations to T2T target definitions relate to prednisolone dosing, which introduced a weight-based cut-off, and stable immunosuppression where additional qualifiers relate to weight, side-effects, and adherence have been added. Univariable and multivariable Prentice-Williams-Peterson (PWP) gap-time models investigated the impact of target attainment on hazard of new damage and severe flare longitudinally. New damage was defined by an increase of SLICC-SDI score by ≥1 unit. Severe flare was defined by a BILAG score of A or B in any organ domain. <h3>Results:</h3> cLLDAS, cCR and cCR-0 were attained in 290/430 (67%), 249/430 (58%) and 202/430 (47%) of patients followed up for a median of 46 months [IQR 18-63], respectively. Median time to cLLDAS, cCR and cCR-0 attainment was 18.4 [8.7, 31.7], 20.4 [10.3, 35.7] and 23.4 [11.7, 36.0] months, respectively. Attainability and time to target was comparable between corresponding cSLE and aSLE targets respectively (Table 1). The risk of severe flare was reduced substantially in those reaching cLLDAS (HR 0.18 [0.14, 0.23, p&lt;0.001), cCR (HR 0.18 [0.13, 0.23], p&lt;0.001) and cCR-0 (HR 0.17 [0.13, 0.23], p&lt;0.001). Disease duration of &gt;1 year and being of White British ethnicity was associated with reduced hazards of severe flare, whereas increasing SDI score during follow-up was associated with increased hazards of severe flare. Hazards of severe flare were comparable between corresponding cSLE and aSLE targets (Table 2). Attainment of each target was also associated with reduced hazard of new damage (cLLDAS HR 0.22 [0.11, 0.44], cCR HR 0.25 [0.13, 0.49], cCR-0 HR 0.30 [0.15, 0.60], all p&lt;0.05). <h3>Conclusion:</h3> This is the first study validating new cSLE specific T2T endpoints, comparing them directly to corresponding aSLE targets. We have demonstrated that achievement of cLLDAS, cCR and cCR-0 is beneficial, leading to reductions in the risk of severe flare and new damage. Future work should utilise international cohort data to undertake sensitivity analyses investigating whether current cSLE specific T2T endpoints can be improved further, using a data driven approach. <h3>REFERENCES:</h3> [1] Smith E, et al. PReS-endorsed international childhood lupus T2T task force definition of cLLDAS. Clinical Immunology. 2023;250:109296. [2] Franklyn K, et al. Definition and initial validation of a LLDAS. Annals of the rheumatic diseases. 2016;75(9):1615-21. [3] Van Vollenhoven R, et al. A framework for remission in SLE: consensus findings from a large international task force on DORIS. Annals of the rheumatic diseases. 2017;76(3):554-61. <h3>Acknowledgements:</h3> The authors of the study would like to acknowledge all patients and their families for their participation in the UK JSLE Cohort Study. Specifically, we are grateful to all the support given by all principal investigators and the entire multi-disciplinary team within each of the paediatric centres who are part of the UK JSLE Study Group (https://www.liverpool.ac.uk/translational-medicine/research/ukjsle/jsle/). This study was supported by the UK's 'Experimental Arthritis Treatment Centre for Children' (supported by Versus Arthritis, the University of Liverpool and Alder Hey Children's NHS Foundation Trust), and the Medical Research Foundation. <h3>Disclosure of Interests:</h3> <b>None declared.</b>