CLINICAL BURDEN OF PNH PATIENTS WITH HEMOGLOBIN BETWEEN ≥10 AND <12 G/DL: RESULTS FROM A MULTINATIONAL REAL-WORLD STUDY
Jörg Schubert et al
Klinik für Innere Medizin II - Elblandklinikum Riesa, Weinbergstraße, Germany
Background
- Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare clonal hematopoietic stem cell disorder which renders red blood cells sensitive to complement-mediated destruction. PNH is characterized by hemolytic anemia, bone marrow failure, and thrombosis.
- Common manifestations include fatigue, dyspnea, and chest/abdominal pain. Disease modifying treatments include terminal complement inhibitor therapies (Ci) which target complement 5 (C5i) and proximal Cis which target complement 3 (C3i), factor B or D.
- Improvements in hemoglobin (Hb) above 10 g/dL are viewed as beneficial, yet patients with Hb levels between ≥10 and <12 g/dl still face meaningful burden on their daily living. The aim of the study is to understand the burdens of PNH in patients with Hb levels between ≥10 and <12 g/dl.
Methods
- Data were drawn from the Adelphi PNH II Disease Specific Programme™, a real-world cross–sectional survey of physicians and their PNH patients, conducted across Canada, France, Germany, Italy, Japan, Spain and United Kingdom from November 2023–January 2025. Physicians provided data on demographics, clinical symptoms, treatment, and PNH-related hospitalizations.
- Patients voluntarily provided self-reported data on symptoms, Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue and work productivity and activity impairment (WPAI) questionnaires. Data were analyzed descriptively; missing data were not imputed.
Results
- Eighty physicians provided data for 234 PNH patients with Hb levels between ≥10 and <12 g/dl. Patients had a median (interquartile range; IQR) age of 48.0 (37.0–60.0) years, 56.4% were male and 59.9% were in full/part time employment.
- The median (IQR) time since PNH diagnosis was 2.2 (0.9–4.5) years. Of patients prescribed treatment at the time of survey (n=217), the majority were prescribed Ci (85.7%), with 79.3% and 6.5% prescribed C5 and C3 inhibitor treatment, respectively. Patients (n=181) had been prescribed Ci for a median (IQR) duration of 1.6 (0.7–2.8) years.
- Among patients diagnosed since at least a year (n=160), 16.9% had at least one PNH-related hospitalization in the 12 months prior to survey, mostly due to infection (44.4%), followed by treatment of PNH-related complications (22.2%), and thrombotic event (14.8%). Additionally, 48.1% were admitted via the emergency room and 92.6% had to stay in hospital overnight for a median (IQR) 5.0 (4.0–7.0) nights.
- Sixty-three patients provided self-reported data. The most common patient-reported symptom was tiredness (79.4%), followed by shortness of breath (47.6%), and lack of focus/brain fog (44.4%). Tiredness was also considered the most bothersome symptom by 61.2% of patients. The mean (standard deviation; SD) of FACIT-fatigue score was 38.5 (7.7). Via the WPAI, patients experienced a mean (SD) 25.1 (23.7) percentage overall work impairment (n=24), and mean (SD) 33.7 (25.2) percentage activity impairment (n=62).
Conclusion
- Overall, these findings highlight that even PNH patients with mild anemia (Hb levels between ≥10 and <12 g/dL) experience a significant burden on their daily living and working activities.
- A notable proportion also depend heavily on healthcare resources, reflecting the ongoing challenges associated with managing their condition.
- Addressing this unmet need is essential to closing gaps in care and ultimately improving patient outcomes.