This paper describes a clinical observation of a patient with active systemic lupus erythematosus (SLE) primarily affecting the skin and joints and high immunological activity. Given the insufficient effectiveness of previous therapy, progression of the skin syndrome, and the inability to reduce the glucocorticosteroid (GCS) dose, the patient was initiated on anifrolumab (AFM) at a dose of 300 mg once every 4 weeks. After just 4 weeks, partial regression of the manifestations of acute cutaneous lupus erythematosus (ACLE) was observed: bullous and maculopapular lesions resolved, although facial erythema persisted. Complete resolution of the skin syndrome was noted three months after the start of therapy. By the sixth month of AFM therapy, a significant reduction in antinuclear factor (ANF) and anti-dsDNA antibody titers was observed, as well as low disease activity (SLEDAI-2K score 4 points), which allowed for a reduction in the glucocorticosteroid dose. Health-related quality of life was assessed using the LupusQol questionnaire, which revealed a significant improvement with AFM therapy. No adverse reactions were reported in this patient after the first or subsequent AFM infusions. Thus, by the 6th month after the start of therapy, it was possible to achieve low disease activity on therapy with hydroxychloroquine 400 mg/day, AFM 300 mg intravenously once every 4 weeks. At the same time, the prednisone dose was reduced to 10 mg/day. At the moment, AFM therapy according to the 300 mg IV drip scheme once every 4 weeks continues, the possibility of further reducing the dose of GCS is being considered.