Anifrolumab significantly reduces SLEDAI-2K by 7.8 points and circulating LDNs in real-world SLE patients

Systemic lupus erythematosus (SLE) is a chronic, progressive autoimmune disease characterized by systemic immune complex deposition, leading to diverse clinical manifestations. Despite its severity, SLE has historically had limited targeted treatment options compared to other autoimmune conditions like rheumatoid arthritis. Current standard-of-care often relies on broad immunosuppressants and glucocorticoids, which carry significant side effects and may not adequately control disease activity for all patients. A key driver in SLE pathogenesis is the type I interferon pathway, which is often overactive in patients. Targeting this pathway with agents like anifrolumab, an IFNAR1 antagonist, represents a promising strategy to address this underlying immunological dysregulation and improve patient outcomes.

Researchers conducted a longitudinal, multicenter, observational cohort study of 20 adult patients with active SLE to assess the real-world effectiveness and safety of anifrolumab. Patients received anifrolumab 300 mg intravenously every 4 weeks for 12 months. Individuals with active lupus nephritis or central nervous system involvement were excluded. Clinical and laboratory measures, including SLEDAI-2K, Physician Global Assessment, and daily prednisolone equivalents, were recorded at baseline and at months 3, 6, 9, and 12. Mechanistic assessments involved measuring chemokines, cytokines, low-density neutrophils (LDNs), and neutrophil extracellular trap degradation products at these time points.

Over the 12-month follow-up, anifrolumab treatment led to a significant reduction in disease activity. Mean SLEDAI-2K scores declined from 10.9±5.0 at baseline to 3.1 (95% CI 1.1 to 5.1; p<0.001). This substantial improvement translated into high response rates: SLE Responder Index-4 response was achieved in 64.7% of patients at month 12 (intention-to-treat analysis). By month 12, an impressive 86% of patients reached Lupus Low Disease Activity State, and 50% achieved Definition of Remission in SLE remission. Physician Global Assessment also significantly improved from 1.6 to 0.2 (95% CI 0.0 to 0.5; p<0.001).