A Novel Use of Anifrolumab for a Novel Disease

OBJECTIVE: To explore the potential role of type-I interferon (IFN-I) signaling in autoimmune cytopenias outside the context of systemic lupus erythematosus (SLE), and to evaluate the clinical response to off-label anifrolumab in two patients with fatigue and immune-mediated cytopenias who did not meet established criteria for SLE. METHODS: We describe two older White male patients with fatigue and autoimmune cytopenias who did not meet established SLE criteria and were refractory to standard immunosuppressants. Both received off-label anifrolumab. RESULTS: Both patients experienced rapid and sustained improvement in fatigue and resolution of cytopenias following treatment, with continued benefit and no significant adverse effects. CONCLUSION: These cases suggest IFN-I signaling may underlie autoimmune cytopenias outside classic SLE. The positive response to anifrolumab raises the possibility of an atypical or distinct IFN-mediated autoimmune condition and supports broader investigation of IFN blockade in hematologic autoimmunity.