Juvenile-onset systemic lupus erythematosus in the treat-to-target era: recent advances in outcome assessment

Abstract Juvenile-onset systemic lupus erythematosus (jSLE) is a rare, severe multisystem autoimmune/inflammatory disease associated with early morbidity, cumulative treatment toxicity, and long-term organ damage. In this context, outcome assessment is central to both clinical care and research, yet remains particularly challenging because disease activity fluctuates over time and relevant outcomes extend beyond short-term disease control to include flare prevention, damage accrual, glucocorticoid toxicity, quality of life, and developmental impact. This review summarises recent advances in outcome assessment in jSLE, with particular emphasis on the treat-to-target (T2T) era. Traditional clinimetric instruments, including Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, British Isles Lupus Assessment Group (BILAG)-2004 and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index, are routinely used in clinical practice for disease activity and damage assessment, while paediatric flare and response criteria have been developed mainly for use in clinical trials. However, most interventional studies in jSLE still rely on adult-derived endpoints, reflecting the limited availability of validated paediatric-specific measures. Recent international collaborative work has led to the development of childhood-specific T2T targets, including childhood lupus low disease activity state (cLLDAS), childhood clinical remission on (cCR) and off (cCR-0) glucocorticoids. Across multiple cohorts, these states have proven achievable and, importantly, clinically meaningful, as their attainment is consistently associated with reduced disease flare risk and lower damage accrual. Emerging evidence also highlights factors impacting upon target attainment, including baseline disease burden, renal involvement, selected laboratory markers, and treatment exposure. At the same time, implementation remains challenging, and recent data suggest an important potential disconnect between clinician judgement and formal target attainment, underlining the need for structured, reproducible assessment in routine care. Looking forward, biomarker-informed monitoring, digital tools, and predictive modelling may help refine longitudinal assessment and support more timely treatment adaptation. Harmonisation with adult frameworks, together with continued development of paediatric-specific measures, may also facilitate earlier inclusion of children in clinical trials and improve access to novel therapies. Overall, outcome assessment in jSLE is shifting from isolated activity measurement towards a more integrated, target-driven and prognostically meaningful framework for paediatric patients across diverse clinical and research settings.