PT4:07 Anifrolumab as rescue therapy in life-threatening, infection-complicated SLE: a biomarker-guided case beyond trial criteria

Objectives Type I interferon (IFN) signalling is a central driver of systemic lupus erythematosus (SLE). Anifrolumab, an anti-IFNAR1 monoclonal antibody, improves outcomes in moderate–severe, trial-eligible patients, however, pivotal trials excluded severe organ-threatening phenotypes and advised against initiation during clinically significant active infection. Herein, we describe the use of anifrolumab in fulminant, refractory mucocutaneous SLE with respiratory compromise and recurrent infections.Methods A 45-year-old woman with known SLE (ANA/dsDNA-positive, hypocomplementaemic) previously manifesting with diffuse ulcerative mucocutaneous disease, alopecia, serositis, pulmonary/mesenteric vasculitis, inflammatory arthritis with Jaccoud’s and shrinking-lung syndrome presented with life-threatening disease despite recent Euro-Lupus cyclophosphamide and rituximab. She presented with haemodynamic compromise (SLEDAI-2K 15) with diffuse ulcerative mucocutaneous lesions (CLASI-A 28; figure 1). Her shrinking lung syndrome progressed and resulted in significant hypercapnia. Admission serology showed dsDNA >400 IU/mL (NR 400 to 17 IU/mL and complement levels normalised over the following 18 months. She remains on monthly Anifrolumab and continues in sustained clinical remission (having weaned off all other immunosuppressive agents and glucocorticoids) with a CLASI of 0.Abstract PT4:07 Figure 1Conclusions In severe, organ-threatening SLE complicated by infection and refractory to cyclophosphamide and rituximab, anifrolumab achieved profound clinical and serological recovery, concordant with CXCL10-flagged IFN-driven biology. This extends real-world use beyond trial populations and underscores biomarker-guided selection when cytotoxic options are unsafe. Clinically, anifrolumab warrants consideration as rescue therapy for high-risk, IFN-driven SLE with contraindications to further cytotoxic treatment.