Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry

Abstract

Paroxysmal nocturnal hemoglobinuria is a rare, acquired disease associated with hemolytic anemia, bone marrow failure, thrombosis, and, frequently, poor quality of life. The International PNH Registry is a worldwide, observational, non-interventional study collecting safety, effectiveness, and quality-of-life data from patients with a confirmed paroxysmal nocturnal hemoglobinuria diagnosis or detectable paroxysmal nocturnal hemoglobinuria clone, irrespective of treatment. In addition to evaluating the long-term safety and effectiveness of eculizumab in a global population, the registry aims to improve diagnosis, optimize patient management and outcomes, and enhance the understanding of the natural history of paroxysmal nocturnal hemoglobinuria. Here we report the characteristics of the first 1610 patients enrolled. Median disease duration was 4.6 years. Median granulocyte paroxysmal nocturnal hemoglobinuria clone size was 68.1% (range 0.01-100%). Overall, 16% of patients had a history of thrombotic events and 14% a history of impaired renal function. Therapies included anticoagulation (31%), immunosuppression (19%), and eculizumab (25%). Frequently reported symptoms included fatigue (80%), dyspnea (64%), hemoglobinuria (62%), abdominal pain (44%), and chest pain (33%). Patients suffered from poor quality of life; 23% of patients had been hospitalized due to paroxysmal nocturnal hemoglobinuria-related complications and 17% stated that paroxysmal nocturnal hemoglobinuria was the reason they were not working or were working less. This international registry will provide an ongoing, valuable resource to further the clinical understanding of paroxysmal nocturnal hemoglobinuria.

Figure 1.

LDH concentration. (A) Median LDH concentration at enrollment by PNH clone size and diagnosis. (B) Percentage of patients with LDH <1.5×ULN or ≥1.5×ULN by PNH clone size. Only includes patients who had not received eculizumab in the 12 months prior to study enrollment.

Figure 2.

Thrombosis and red blood cell transfusion history. (A) Percentage of patients with a history of thrombosis by PNH clone size and LDH level at enrollment. (B) Percentage of patients receiving red blood cell transfusion in the year prior to enrollment by PNH clone size and diagnosis. Only includes patients who had not received eculizumab in the 12 months prior to study enrollment.

Figure 3.

Patient-reported PNH symptoms. (A) Patient-reported symptoms by PNH clone size. (B) Patient-reported symptoms by LDH level. Only includes patients who had not received eculizumab in the 12 months prior to study enrollment. *Statistically significant. ^†Male patients only; n=62, 68, and 222. ^‡Male patients only; n=82 and 134.