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Background: Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease. Globally, there is significant interest in the application of Treat-to-Target (T2T) strategies for managing both cSLE and adult-onset SLE (aSLE)1,2. The T2T approach promotes systematic and prompt management of disease activity, to prevent organ damage and enhance quality of life. The International cSLE T2T Task Force1 has developed the Childhood Lupus Low Disease Activity State (cLLDAS) definition through expert consensus, receiving endorsement from the Paediatric Rheumatology European Society (PReS)3. Childhood-LLDAS intentionally maintains alignment with the aSLE LLDAS definition to facilitate life-course research. Objectives: This study will perform sensitivity analyses on the cLLDAS definition by modelling adjustment of its criteria to assess whether potential revised definitions provide improved protection against severe flares and new damage in comparison to the original consensus definition, informing the development of cSLE T2T trials. Methods: Longitudinal data from UK JSLE Cohort Study participants under 18 at diagnosis were analysed for cLLDAS achievement. These included five criteria: (1) SLEDAI-2K ≤4 with no major organ activity, (2) no new lupus activity, (3) Physician Global Assessment ≤1, (4) prednisolone ≤0.15mg/kg/day (max 7.5mg/day), and (5) stable disease-modifying immunosuppressive drugs3. Nine modified cLLDAS definitions (Table 1) were examined, assessing their impact on reducing the hazards of subsequent severe flare (BILAG A or B score) and new damage (SLICC-SDI increase ≥1), using univariable and multivariable Prentice-Williams-Peterson (PWP) models. Two-sided t-tests were used to compare the hazard ratios (HRs) of the original and modified cLLDAS definitions obtained from multivariable PWP models. Results: Multivariable PWP models demonstrated that the risk of severe flare was substantially reduced in those reaching cLLDAS using the current definition (HR 0.18 0.14, 0.23, p0.05). Indeed, permutation 1 (removal of the criterion 'no new features of lupus activity compared with previous assessment') significantly increased the hazard ratio for new damage as compared to the original cLLDAS definition (HR 0.38 [0.24, 0.68, pConclusion: Achievement of the consensus-derived cLLDAS target, consistent with aSLE LLDAS definitions, significantly protects against severe flares and new damage in cSLE. This study has indicated that modification of the cLLDAS criteria, specifically lowering the SLEDAI-2K score cut-off to ≤3 and the PGA score cut-off to ≤0.5, may enhance this protective effect, further reducing severe flare risk. These changes, however, did not affect the risk of new damage, a key factor in long-term outcomes in cSLE. Further research, utilising international cohort's and prospective studies is crucial to validate T2T endpoints like cLLDAS and remission criteria, prior to undertaking a cSLE T2T trial. REFERENCES: 1 Smith EMD, et al. Ann Rheu Dis 2023; 82(6): 788-98. 2 Van Vollenhoven RF, et al. Ann Rheu Dis 2014; 73(6): 958-67. 3 Smith EMD, et al. Clin Immuno 2023; 250: DOI: 10.1016/j.clim.2023.109296.109296. Acknowledgements: The authors would like to acknowledge all patients and their families for participating in the UK JSLE Cohort Study. Specifically, the 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. Disclosure of Interests: None declared.
Smith et al. (Sat,) studied this question.