OBJECTIVES : Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease with the most prominent symptoms being hemolytic anemia, hemoglobinuria, thrombosis and fatigue. Complement C5 inhibition with eculizumab (Ecu) or ravulizumab (Ravu) is the current standard of care. Despite improvements in morbidity and mortality, some patients continue experiencing hemolysis and suboptimal quality of life (QoL). This study aimed at investigating the symptom burden of PNH in patients currently treated with a C5 inhibitor, globally.

METHODS : Adult patients with a self-reported diagnosis of PNH were recruited through patient advocacy groups in the United States (US) and Europe (EU: UK, France and Germany): Aplastic Anemia and MDS International Foundation, Patient Support, HPN France, and Stiftung Lichterzellen, respectively. Patients treated with Ecu or Ravu completed an online cross-sectional questionnaire. FACIT (Functional Assessment of Chronic Illness Therapy) was used to measure fatigue scores. Descriptive statistics are reported here.

RESULTS : A total of 122 adult patients in the US, and 71 in EU, were enrolled. Current medications included Ecu (EU:69%, US:29%) or Ravu (EU:31% US:71%); most patients were on treatment for ≥3 months: EU:98.6% US:96.7%. The most recent hemoglobin level was <12g/dL (mean±SD; EU:10.19±1.97, US:10.17±2.04) for the majority of patients (EU:85.7%, US:84.2%), indicating that most remained anemic. Among patients who ever received a red blood cell transfusion and were on treatment for ≥1 year, (EU:35.0%, US:35.2%) received ≥1 transfusion in the previous year, and 18% (EU) and 22% (US) received ≥4. Fatigue was the most commonly reported symptom (EU:63.4%, US:78.7%). FACIT scores (EU:35.0±13.7, US:32.1±13.4) were lower than in the general population (43.5) indicating higher levels of fatigue. Breakthrough hemolysis was experienced by US:40% and EU:39% patients.

CONCLUSIONS : Despite C5 treatment, PNH patients experience a substantial burden of illness. There is a significant unmet need for treatments with better clinical and hematological outcomes for PNH patients.