Targeting the neonatal Fc receptor (FcRn) in hematologic conditions with a focus on warm autoimmune hemolytic anemia.

Abstract

Warm autoimmune hemolytic anemia (wAIHA) is the most prevalent form of autoimmune hemolytic anemia, where in most patients extravascular hemolysis is driven by immunoglobulin G (IgG) autoantibodies, with or without complement activation. While standard-of-care treatment with corticosteroids provides a high initial response rate, relapses are frequent, and most patients require additional immunosuppressive therapies. A high unmet medical need remains for patients with refractory or chronic relapsing wAIHA. Neonatal Fc receptor (FcRn) blockers are novel biologic therapies designed to provide a rapid, sustained decrease in circulating concentrations of IgG antibodies, including autoantibodies, and have been investigated in hematologic conditions like immune thrombocytopenia and hemolytic anemia of the fetus and newborn and other autoimmune conditions, such as generalized myasthenia gravis. FcRn blockade is currently under evaluation in patients with wAIHA to determine its potential as a safe, effective treatment option.