OBJECTIVES/GOALS: * Patients with skin of color (SOC) are disproportionately affected by systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). In this study, we aim to address this disparity and characterize the real-world efficacy and tolerability of anifrolumab in CLE patients using validated disease activity instruments. METHODS/STUDY POPULATION: This single-center, prospective observational cohort study includes SLE patients with severe or refractory CLE who have received ≥ 1 dose of anifrolumab. Cutaneous disease activity is assessed periodically at 2, 6, 9, 12, and 18 months using the Cutaneous Lupus Disease Area and Severity Index (CLASI). Adverse events and concurrent treatments are also routinely evaluated. To date, 22 patients have been enrolled, with 6-month follow-up data available for 15. At the time of anifrolumab initiation, 95% of participants had discoid LE (DLE), 60% had mucosal DLE, and 13% had subacute CLE. Nine patients identified as SOC, two as White, and four did not report race/ethnicity. RESULTS/ANTICIPATED RESULTS: A Friedman test showed statistically significant changes over time in CLASI activity score (CLASI-A) (χ2(2) =20, p<0.0001) (Figure 1) and CLASI damage score (CLASI-D) (χ2(2) =9.5789, p=0.0083) (Figure. To estimate effect sizes, we employed linear mixed models, which demonstrated statistically significant reductions in the CLASI-A score from baseline by an average of 14 points at 2 months (p<0.001) and 18 points at 6 months (p<0.001); notably, a reduction in CLASI-A of 4 is considered clinically meaningful. At 2 months, 20% of patients experienced a 50% or more reduction in CLASI, which increased to 60% of patients at 6 months. Patients on systemic corticosteroids could taper off. Adverse events were minimal and did not lead to treatment discontinuation. Fig. 1:[blob:https://acts.slayte.com/045319b4-7272-4351-a771-78ba9ee57f5c] Fig. 2:[blob:https://acts.slayte.com/67df7653-0cd8-4e8e-a3e1-d5c565b19dce] DISCUSSION/SIGNIFICANCE: As SOC patients with CLE have significant potential for permanent pigmentary alternations, early treatment is imperative. Effective treatments for refractory CLE are elusive. Our study represents the largest single-center cohort of CLE patients treated with anifrolumab and suggests that it is a promising therapeutic option for patients with SOC.