[New treatment strategies for paroxysmal nocturnal hemoglobinuria: the guideline update and novel complement-targeting drugs]

Abstract

The 2022 update of the Japanese guidelines for paroxysmal nocturnal hemoglobinuria (PNH) introduced refined diagnostic criteria and a new classification of disease severity, marking a significant advance in the clinical approach to this condition. Notably, this revision articulated 10 clinical questions designed to provide a thorough framework for addressing key aspects of PNH management. This includes guidance on interpreting diagnostic flowcharts and broader clinical considerations such as treatment approaches and individual patient circumstances. Following the guideline update, innovative therapeutic agents, including the complement C3 inhibitor pegcetacoplan, the factor D inhibitor danicopan, a novel C5 inhibitor crovalimab and the factor B inhibitor iptacopan have been approved in Japan. Although consistent mitigation of intravascular hemolysis remains the principal therapeutic goal in PNH management, there is a recognized need to refine approaches for managing residual anemia and fatigue, with future strategies likely to be informed by emerging real-world evidence.

Keywords: Breakthrough hemolysis; Extravascular hemolysis; Paroxysmal nocturnal hemoglobinuria; Proximal complement inhibitors.