Disentangling Temporal Factors in Organ Damage Accrual in Systemic Lupus Erythematosus: Onset-Age, Onset-Era, and Aging in the Japanese LUNA Registry

Abstract Objectives To disentangle the contributions of three temporal factors—onset-age, onset-era, and aging—to organ damage in systemic lupus erythematosus (SLE). Methods We analyzed 1228 patients with SLE from a nationwide registry in Japan whose disease onset occurred between 1990–2019 at ≤50 years of age. Organ damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) between 2020–2023. Negative binomial and logistic regression models estimated the independent associations of onset-age (<20 years [early-onset SLE: EOSLE] vs. 20–50 years), onset-era (5-year ordinal categories), and current age with SDI outcomes, adjusting for sex and comorbidities. Pairwise interactions among the temporal factors were examined. Results EOSLE (count ratio 1.35; 95%CI 1.05–1.75), past onset-eras (count ratio 1.10; 95%CI 1.03–1.18), and older age (count ratio 1.02; 95%CI 1.01–1.03) were independently associated with higher SDI. EOSLE and older age were also associated with SDI ≥1, while past onset-eras were associated with greater 1-year increases in SDI. There was no evidence of interactions among the three temporal factors. Conclusions Onset-age, onset-era, and aging each exert distinct impact on organ damage in SLE. Recognizing these temporal aspects may strengthen risk stratification and individualized long-term care.