Contributors to organ damage in childhood lupus: corticosteroid use and disease activity

Abstract

Objectives: Awareness of paediatric-specific predictors of damage in childhood lupus is needed to inform mitigation measures. The objective of this study was to ascertain how clinical and demographic variables correlate with damage accrual and identify predictors of damage.

Methods: This analysis included UK JSLE Cohort Study participants. Univariable and multivariable Prentice-Williams-Peterson models investigated how demographic and clinical factors influenced the hazards of new damage. Analyses were performed across the entire cohort, in patients with minimal disease activity marked by a time-adjusted average SLEDAI-2K score (AMS) of ≤2, in patients with low activity (AMS of ≤4), patients with moderate-to-high activity (AMS of >4) and patients with no CS use.

Results: Within the entire cohort (n = 430), factors associated with damage included: any methylprednisolone [hazard ratio, HR 2.20 (CI 1.33-3.62)], time-adjusted mean Physician's Global Assessment (PGA) [HR 2.87 (CI 1.48-5.56)] and AMS score [HR 1.13 (CI 1.03-1.24), all P < 0.05]. Within the low activity subgroup, any methylprednisolone [HR 2.61 (CI 1.04-6.53)] and time-adjusted mean PGA [HR 3.41 (CI 1.52-7.76)] were associated with damage (both P < 0.05). Within the moderate-to-high activity subgroup, any methylprednisolone [HR 2.29 (CI 1.31-4.00)], time-adjusted mean PGA [HR 2.66, (CI 1.20-5.87)] and AMS score [HR 1.15 (CI 1.03-1.29)] were predictive of damage (all P < 0.05). Baseline organ damage was predictive of subsequent damage accrual in the minimal disease activity subgroup [HR 1.33 (CI 1.78-8.08)] and the no CSs subgroup [HR 3.64 (CI 1.83-7.24), both P < 0.005].

Conclusion: Disease activity levels (AMS/PGA) and proxy indicators (methylprednisolone exposure, baseline damage) were found to be key predictors of damage accrual. This highlights the importance of practical strategies, such as treat-to-target, for reducing disease activity and long-term treatment toxicity.

Keywords: Childhood SLE; corticosteroids; damage; low disease activity; treat-to-target.

Graphical abstract

Figure 1.

Flow chart depiction of patients and visits with damage. Excluded patients only had a single study visit (AMS could not be calculated). AMS: Adjusted Mean SLEDAI-2K

Figure 2.

Graphical representation of damage events over the course of follow-up, patients who have been stratified according to Adjusted Mean SLEDAI-2K (AMS) score. Damage event is defined as the time point of first new damage development. (A) Damage events for patients with low disease activity (AMS ≤ 4) throughout the follow-up period. (B) Damage events for patients with moderate-to-high disease activity (AMS > 4) throughout the follow-up period. AMS: Adjusted Mean SLEDAI-2K

Figure 3.

Radar charts demonstrating the types of damage accrued. (A) Whole cohort damage types. (B) Moderate-to-high disease activity subgroup damage types. (C) Low disease activity subgroup damage types. (D) Minimal disease activity subgroup damage types. (E) No CSs subgroup damage types. Damage included: cardiovascular: pericarditis, valvular disease, myocardial infarction, angina, cardiomyopathy; skin: alopecia, panniculus, ulceration; renal: end-stage renal disease, eGFR of <50%, proteinuria; pulmonary: hypertension, fibrosis, shrinking lung, infarction; peripheral vascular; tissue loss, venous thrombosis; ocular; retinal change, cataract; neuropsychiatric; cognitive impairment, seizures, cerebral vascular accident, neuropathy, transverse myelitis; musculoskeletal: arthritis, atrophy, osteoporosis, avascular necrosis, osteomyelitis, tendon rupture; gastrointestinal; infarction, mesenteric insufficiency, peritonitis, stricture, pancreatic insufficiency; other: diabetes, malignancy, gonadal failure