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Objectives A goal of SLE management is to achieve and maintain remission or low disease activity to minimize long-term organ damage accrual. LupusNet, the largest SLE federated data network, combines and harmonizes data from 5 existing SLE registries. This study assessed regional variability in frequency, severity, and accrual of damage in patients with SLE, as a function of disease activity, using LupusNet.Methods Data from 5019 patients with >/=3y of follow-up and >/=3 follow-up visits in 3 LupusNet registries, APLC (Asia Pacific), RELESSER (Europe), and Almenara (South America), were analyzed using a privacy-preserving federated data network approach. Disease activity was assessed using SLEDAI (recorded >/=1 time/year). Organ damage was measured using SLICC Damage Index (SDI score >0). High disease activity (HDA) was defined as SLEDAI score >8 at >/=1 visit. The proportion of patients experiencing HDA and the presence of organ damage were reported.Results At baseline, 34%, 41%, and 48% of patients had damage in APLC, RELESSER, and Almenara. At any time over the 3y follow up, 36% (APLC), 18% (RELESSER), and 24% (Almenara) of patients experienced HDA; after 3y, damage occurred in 44% (APLC), 23% (RELESSER), and 66% (Almenara), and was similar between patients with (32%-68%) and without (20%-66%) HDA across cohorts ( figure 1). However, renal, ocular, and skin damage were more prevalent in patients with versus without HDA (figure 2). Regional variations were evident, with renal and musculoskeletal damage consistently prominent across regions. Ocular damage was more prevalent in RELESSER; gastrointestinal damage was more prevalent in Almenara. Prevalence of organ damage was generally lower in APLC versus Almenara and RELESSER. Patients with SLEDAI >8 at more visits exhibited higher rates of proteinuria, haematuria, urinary casts, and pyuria versus patients without visits with SLEDAI >8. Low complement and high DNA binding were common irrespective of disease activity (figure 3).Abstract PO:07:180 Figure 1–3Conclusions This analysis revealed similar overall rates of damage between patients with and without HDA, although renal, ocular, and skin damage were more prevalent in patients with HDA. Regional variations in damage types underscore the complexity of SLE. Further research is needed to identify factors driving these disparities.