The burden of illness in patients with paroxysmal nocturnal hemoglobinuria receiving treatment with the C5-inhibitors eculizumab or ravulizumab: results from a US patient survey

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.

Keywords: Burden of illness; Eculizumab; Fatigue; Paroxysmal nocturnal hemoglobinuria; Quality of life; Ravulizumab.

Fig. 1

Patient-reported clinical parameters and PNH symptoms. a Number of thrombotic events and transfusions reported by survey participants within the past 12 months. N reported here represents the number of individuals that had at least experienced a thrombotic event/transfusion once in their lifetime and who were on C5i treatment (ECU or RAV) for one or more years. b Most recent patient-reported Hb levels. N represents the number of survey participants that reported their most recent Hb levels (overall, n = 114). c Most frequently reported current PNH symptoms that were disclosed by ≥ 35% of total survey participants (N = 122). Abbreviations: C5i, C5-inhibitor; ECU, eculizumab; Hb, hemoglobin; n_E, n for ECU users; n_R, n for RAV users; PNH, paroxysmal nocturnal hemoglobinuria; RAV, ravulizumab; Tx, treatment

Fig. 2

FACIT-Fatigue and EORTC QLQ-C30 scores. Mean FACIT-Fatigue score gathered from patients with PNH receiving C5i therapy (N = 122) compared to FACIT-Fatigue score for the general US population [24]. Mean EORTC-QLQ-C30 scores for global health status and physical functioning recorded from C5i-treated patients with PNH (N = 122) compared to the EORTC QLQ-C30 scores representative of the general population [23]. Abbreviations: C5i, C5-inhibitor; ECU, eculizumab; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30; FACIT, Functional Assessment of Chronic Illness Therapy; RAV, ravulizumab