Comprehensive approach to paroxysmal nocturnal hemoglobinuria for the correct identification of patients who may benefit from switching from iC5 to iCP – expert consensus opinion

Introduction: Paroxysmal nocturnal hemoglobinuria is a rare disease characterized by hemolytic anemia predominantly intravascular and cytopenias. Complement terminal C5 inhibitors (C5i) have significantly altered the treatment landscape. Objective: To facilitate the identification of patients with suboptimal response to C5i secondary to anemia and/or fatigue who may benefit from a therapeutic switch to proximal complement inhibitors (CPi). Material and methods: Narrative review with a collaborative methodology based on the clinical opinion of paroxysmal nocturnal hemoglobinuria experts, supported by scientific evidence. Results: First, diagnostic and treatment monitoring tests, differences between intravascular and extravascular hemolysis, and the utility of cytometric studies are detailed. A questionnaire for patients is proposed to identify the persistence of symptoms. Finally, the consequences of persistent anemia and/or chronic hemolysis are reviewed, along with recommendations for managing iron overload. Conclusions: Although C5i improves survival, treatment response is often suboptimal, which affects patients’ quality of life. This document provides tools to identify patients with clinically significant hemolysis who may benefit from an CPi.