[New treatment strategies for paroxysmal nocturnal hemoglobinuria: drug selection in the era of novel complement inhibitors].

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder characterized by complement-mediated hemolysis, thrombosis, and bone marrow failure. Eculizumab (Ecu), a C5 inhibitor, blocks intravascular hemolysis (IVH) and improves prognosis. Ravulizumab and crovalimab have longer half-lives, and reduce treatment burden. Crovalimab is effective in patients with C5 polymorphism resistant to Ecu. Despite C5 inhibition, approximately 70% of patients remain anemic due to bone marrow failure and extravascular hemolysis (EVH) from C3 deposition. Upstream complement inhibition can address both IVH and EVH. Pegcetacoplan (C3 inhibitor) improves anemia better than Ecu. Danicopan (factor D inhibitor) and ipracopan (factor B inhibitor) also improve anemia and fatigue. Proximal inhibitors offer better anemia control but pose a risk of breakthrough hemolysis (BTH), especially under complement-amplifying conditions. In addition, long-term real-world infection data remain necessary. While IVH control has improved PNH prognosis, future therapies should focus on patients with persistent anemia or insufficient improvement in quality of life, and should aim to enhance hemoglobin levels and overall well-being while managing BTH for optimal care.