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.

Keywords:

• somatic mutation
• GPI
• survival
• hemolysis
• MDS
• anemia

Disclosure

ALL and ICY have received research funding from Alexion Pharmaceuticals in the past but none at the time of the preparation of this manuscript. ICY is a member of the Canadian PNH Network which is sponsored in part by Alexion Pharma Canada. No professional writing services were employed. Alexion Pharma (or its employees) was (were) not involved at any point in any aspect of the manuscript, from conception to submission. FAA reports no conflicts of interest in this work.