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Objectives Cutaneous manifestations are common in systemic lupus erythematosus (SLE) and substantially contribute to disease burden. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) provides a standardized measure of skin activity. Although biologic therapies have demonstrated efficacy in randomized trials, real-world comparative data on their impact on cutaneous disease remain heterogeneous. This study aimed to compare changes in skin activity, assessed by CLASI, among patients receiving biologic agents or standard-of-care (SoC) therapy.Methods The study included 116 patients with SLE (95 women/21 men; median age 34.0 [26.0-41.0] years) followed for 6 months. Treatment groups included rituximab, belimumab, anifrolumab, and SoC. Changes in CLASI (δCLASI) were compared across therapy groups, and associations with glucocorticoid (GC) dose were assessed using linear regression analysis.Results Of 116 patients with SLE, 72 (62%) had active cutaneous involvement at baseline ( table 1). Differences in cutaneous disease activity were observed across treatment groups. Patients receiving rituximab and SoC demonstrated smaller δCLASI values, reflecting lower baseline skin activity, whereas those treated with belimumab or anifrolumab showed greater reductions consistent with higher initial involvement. Median GC doses varied significantly between groups, being highest among rituximab-treated patients and lowest in the anifrolumab group. In a linear regression model including therapy type and GC dose, the model explained approximately 8% of the variance in δCLASI (R2 = 0.08). Anifrolumab was the only therapy independently associated with significant improvement in cutaneous activity (β = –4.52, p = 0.028), while belimumab showed a non-significant negative trend (p = 0.19). Higher GC doses were not associated with better skin outcomes (p = 0.15).Abstract PO:10:256 Table 1Comparison of ACLASI and glucocorticoid dose across therapy groupsConclusions Rituximab and SoC were associated with the most pronounced clinical improvement in cutaneous activity. However, in multivariable analysis, anifrolumab emerged as the only therapy independently linked to skin improvement, whereas higher GC doses did not enhance response. These findings highlight the heterogeneity of cutaneous outcomes and suggest a potential steroid-sparing role for targeted therapy in SLE.