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Validating treat-to-target endpoints in childhood lupus: data-driven sensitivity analyses from the UK JSLE cohort study

Lookup NU author(s): Dr Ethan SenORCiD

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Abstract

© 2026 The Author(s).Objectives To conduct data-driven sensitivity analyses to evaluate whether refined definitions of childhood-onset systemic lupus erythematosus (cSLE) treat-to-target goals provide better protection against moderate-severe flares and new damage, compared with original consensus-derived targets. Methods The UK JSLE Cohort Study was utilized. Childhood-SLE target attainment was determined at each visit. Removal or transformation of cSLE target criteria ('variations') were investigated, for Childhood Lupus Low Disease Activity State (cLLDAS), cSLE Clinical Remission on Steroids (cCR) and cSLE Clinical Remission off Steroids (cCR-0). The impact of such variations on the hazards of subsequent moderate-severe flare and new damage was assessed, using Prentice-Williams-Peterson (PWP) models. Two-sided t-tests compared the hazard ratios (HRs) obtained from the PWP gap-time models for the original and varied cSLE target definitions. Results Two variations of cLLDAS demonstrated significantly better protection against moderate-severe flare, including transformation of SLEDAI-2K cut-off to ≤3 (HR 0.13 [0.09, 0.19], P < 0.001); and transformation of PGA cut-off to ≤0.25 (HR 0.14 [0.10, 0.20], P < 0.001). These variations in cLLDAS did not impact on the hazards of new damage. No variations of cCR and cCR-0 led to a significant improvement in hazards of moderate-severe flare/new damage (all P > 0.05). A modified version of cLLDAS, combining these two transformations was also assessed, demonstrating further improvement in protection against moderate-severe flare (HR 0.12 [0.08, 0.17], P < 0.001). Conclusions Refining the cLLDAS definition by lowering the SLEDAI-2K cut-off to ≤3 and PGA to ≤0.25 may enhance protection against moderate-severe flare, but not new damage. No variations of cCR or cCR-0 showed significant improvement.

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Author(s): Sarker C, Jorgensen AL, Tharmaratnam K, Al-Abadi E, Armon K, Bailey K, Bohm M, Brennan M, Ciurtin C, Gardner-Medwin J, Hawley DP, Kinder A, Leahy A, Malik G, Mclaren Z, Moraitis E, Mosley E, Ramanan AV, Rangaraj S, Ratcliffe A, Riley P, Rostron H, Sen ES, Hedrich CM, Beresford MW, Smith EMD

Publication type: Article

Publication status: Published

Journal: Rheumatology

Year: 2026

Volume: 65

Issue: 2

Print publication date: 01/02/2026

Online publication date: 20/01/2026

Acceptance date: 15/12/2025

Date deposited: 16/02/2026

ISSN (print): 1462-0324

ISSN (electronic): 1462-0332

Publisher: Oxford University Press

URL: https://doi.org/10.1093/rheumatology/keag015

DOI: 10.1093/rheumatology/keag015

Data Access Statement: Deidentified participant data and a data dictionary defining each field will be made available to others upon reasonable request to the Chief Investigator for the UK JSLE Cohort Study, Professor Michael W Beresford (m.w.beresford@liverpool.ac.uk), following completion of the UK JSLE Cohort study Data Access Application Form. This can be obtained from the UK JSLE Cohort Study co-ordinator (Robertsc@liverpool.ac.uk). Additional related documents (e.g. study protocol, statistical analysis plan, informed consent forms) are not routinely available but requests may be considered on a case-by-case basis.

PubMed id: 41557849

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