Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening disease with symptoms of hemolysis and thrombosis. Current therapies for this complement-mediated disease rely predominantly on inhibition of the C5 complement protein. However, data on treatment responses and quality of life in C5-inhibitor (C5i)-treated PNH patients are scarce. The objective of this study was to determine C5i treatment effects on clinical parameters, PNH symptoms, quality of life, and resource use for PNH patients. This cross-sectional study surveyed 122 individuals in the USA receiving treatment for PNH with C5-targeted monoclonal antibodies, eculizumab (ECU) or ravulizumab (RAV). Despite most patients receiving C5i therapy for ≥ 3 months (ECU 100%, n = 35; RAV 95.4%, n = 83), many patients remained anemic with hemoglobin levels ≤ 12 g/dL in 87.5% (n = 28/32) and 82.9% (n = 68/82) of ECU and RAV recipients, respectively. A majority of patients on ECU (88.6%; n = 31/35) and RAV (74.7%; n = 65/87) reported fatigue symptoms. Among PNH patients receiving C5i therapy for ≥ 12 months, some still reported thrombotic events (ECU, 10.0%, n = 1/10; RAV, 23.5%, n = 4/17) and required transfusions within the past year (ECU, 52.2%, n = 12/23; RAV, 22.6%, n = 7/31). Other patient-reported PNH symptoms included breakthrough hemolysis, shortness of breath, and headaches. Patients reported scores below the average population norms on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scales. Overall, this study found that PNH patients receiving ECU or RAV therapy demonstrated a significant burden of illness, highlighting the need for improved PNH therapies.
Highlights
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, and life-threatening disease characterized by the chronic lysis of red blood cells (RBCs) and a high propensity for thrombosis [1]
This study indicates that the symptoms of PNH experienced by these patients are significant enough to have an impact on quality of life (QoL) and work productivity
The observed burden of illness among patients with PNH receiving ECU or RAV therapy may be a result of the effect that C5i has on the two distinct pathways of hemolysis that occur during PNH
Summary
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, and life-threatening disease characterized by the chronic lysis of red blood cells (RBCs) and a high propensity for thrombosis [1]. PNH is caused by a somatic mutation in the phosphatidylinositol glycan class A gene (PIG-A) in hematopoietic cells [2, 3]. This gene encodes for a protein that enables cells to synthesize glycosylphosphatidylinositol (GPI) anchors, which are covalently linked protein modifications to anchor proteins on the cell surface [2, 3]. IVH occurs when RBCs are directly lysed due to the activation of the alternative complement pathway [5]. This involves the formation of complexed complement proteins such as C3 convertase, C5 convertase, and the membrane attack complex (MAC).
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