Anifrolumab for Nonsystemic Cutaneous Lupus Erythematosus: Clinical Experience, Immunologic Insights, and Review of the Literature

<b>Objective:</b> Anifrolumab is approved for systemic lupus erythematosus (SLE). Its off-label use in non-systemic cutaneous lupus erythematosus (NSCLE) remains poorly characterized. We aimed to assess its effectiveness and safety in refractory NSCLE, supported by a literature review and exploratory immunologic analysis. <b>Methods:</b> This multicenter observational study included patients with NSCLE treated with anifrolumab. Skin disease was assessed using the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). CLASI scores at baseline were compared to months 1, 3, and 6. A narrative literature review was also conducted. In a subset of three patients, peripheral blood immunophenotyping was performed before and after treatment to explore immunologic surrogate markers associated with clinical response. <b>Results:</b> Fifteen patients (11 women; mean age 52.1 ± 11.7 years) were included. All had received topical corticosteroids and hydroxychloroquine. Most of them had failed multiple systemic therapies. Anifrolumab (300 mg IV every 4 weeks) was used in combination (<i>n</i> = 12) or as monotherapy (<i>n</i> = 3). All patients improved. Median CLASI-A decreased from 16 to 1 (<i>p</i> < 0.001); CLASI-D decreased from 5 to 4 (<i>p</i> < 0.001). The literature review identified 6 publications reporting 14 additional cases of NSCLE with similar outcomes and minimal adverse effects. Immunologic profiling pointed to an increase in intermediate and non-classical and decreased PD-1 expression in monocytes and NK cells after 12 weeks of treatment. <b>Conclusions</b>: Anifrolumab appears effective and relatively safe in refractory NSCLE. Preliminary immunologic data suggest changes in peripheral blood monocyte subsets and NK cells. However, these findings must be confirmed in prospective, controlled clinical trials.