Eculizumab in the management of paroxysmal nocturnal hemoglobinuria: patient selection and special considerations

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant clonal disorder resulting from somatic mutation in the PIG-A gene leading to a deficiency of the membrane-anchoring molecule glycosylphosphatidylinositol. The lack of expression of two glycosylphosphatidylinositol-anchored proteins involved in the regulation of the complement system renders PNH erythrocytes susceptible to complement-mediated lysis. Clinical manifestations include thromboembolic disease, chronic kidney injury, pulmonary hypertension, smooth muscle dysfunction, and chronic hemolysis. Until recently, treatment was mainly supportive with most patients suffering from significant morbidity and shortened survival compared to age-matched controls. The development of eculizumab, a humanized monoclonal antibody directed against the terminal complement protein C5, has resulted in dramatic improvements of survival and reduction in complications. In this paper, we review some special considerations pertaining to the use of eculizumab for PNH.