[Future directions in the management of warm autoimmune hemolytic anemia]

Warm autoimmune hemolytic anemia (wAIHA) is an autoimmune disorder in which autoantibodies target the patient's own red blood cells. It can be classified as either idiopathic (primary) or secondary and is characterized by the presence of pan-reactive immunoglobulin G (IgG) autoantibodies that recognize epitopes on erythrocyte membrane proteins such as band 3 and Rh polypeptides. Spontaneous remission is rare, and corticosteroids are commonly used as first-line therapy. Rituximab and splenectomy are effective second-line treatments; however, there is no consensus on the optimal therapeutic approach for patients with wAIHA that is refractory to second-line therapy. New therapeutic agents for wAIHA include neonatal Fc receptor (FcRn) inhibitors, spleen tyrosine kinase (SyK) inhibitors, B cell-targeted therapies, and anti-CD38 monoclonal antibodies. Nipocalimab, a fully human IgG1 monoclonal antibody targeting FcRn, is expected to be effective in wAIHA by reducing the half-life of pathogenic IgG autoantibodies. Fostamatinib, an SyK inhibitor approved for the treatment of chronic immune thrombocytopenia in adults, demonstrated a significantly higher rate of sustained hemoglobin responses compared to placebo in the global, randomized, double-blind, placebo-controlled phase 3 FORWARD trial. The efficacy of Sovleplenib, another SyK inhibitor, was also demonstrated in a randomized, double-blind, placebo-controlled phase 2 trial.