Paradoxical Findings in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with C5 Inhibitors: Suboptimal Disease Control Perceived As Satisfactory
Authors: Gaya Anna , Fuertes Luis Fernando Fernández , Ballesteros Andrés Mónica , De La Iglesia Íñigo Silvia , Del Orbe Barreto Rafael Andrés , Fernández Fuertes Fernando , Gonzalez Ana Pilar , Jarque Isidro , Lavilla Esperanza , Nuñez Vasquez Ramiro , Salido Eduardo José , Vahí Maria , Vallejo Carlos 
Published: December 2023

Introduction: The introduction of C5 inhibitors (C5i) for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) has resulted in lower morbidity and mortality rates. However up to 86% of patients still experience anemia and fatigue in 63% of them which may impact their quality of life (QoL). The SATURNO study aimed to assess PNH patient and physician satisfaction with C5i treatment, along with the impact of the disease and clinical outcomes.

Methods: A multicenter, observational, cross-sectional study conducted in PNH patients receiving C5i treatment for at least 3 months in Spain. Key clinical and laboratory data were collected, including red blood cells (RBC) transfusions, hemolytic crisis, hemoglobin (Hb), haptoglobin (Hp), lactate dehydrogenase (LDH), absolute reticulocyte count (ARC) and bilirubin. Patient satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM) and Visual Analog Scale (VAS). Physician satisfaction was measured using the TSQM general item and VAS. Fatigue and QoL were evaluated using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), respectively. The Work Productivity and Activity Impairment questionnaire (WPAI) was also used.

Results: A total of 56 patients and 13 physicians participated in the study. Median (IQR) age of patients was 54.0 (44.5; 63.5) years, 35.7% were female and median (IQR) duration of treatment with C5i was 6.6 (3.3; 11.6) years.

Overall, 94.6% of patients and 90.6% of physicians reported to be satisfied, very satisfied, or extremely satisfied with the treatment. Mean (SD) VAS score for patient satisfaction was 9.0 (1.2) and for physicians 7.9 (1.7) out of 10. Mean (SD) EORTC QLQ-C30 score was 71.7 (21.7) out of 100. Mean (SD) FACIT-F score was 39.7 (10.6) out of 52 and fatigue was reported by 55.2% of patients.

Clinical and laboratory parameters showed a significant proportion of patients exhibiting abnormal values. Hb and Hp were below the normal ranges in 67.9% and 65.1% of patients, respectively, whereas elevated LDH, ARC and indirect bilirubin were observed in 50.0%, 83.0% and 75.9% of them, respectively.

In the last 12 months, 30.9% of patients had received at least one RBC transfusion, with a mean (SD) number of 8.6 (8.4) RBC transfusions, and 33.9% experienced at least one hemolytic crisis with a mean (SD) of 4.9 (9.4).

Work productivity assessment revealed that 60.7% of patients were currently unemployed, a mean (SD) percentage of absenteeism of 5.7% (12.4) and presenteeism of 23.8% (26.0). Overall mean (SD) percentage of work productivity impairment was 25.6% (27.3). Activity impairment was reported by 36.4% (28.3) of patients.

Conclusions: The SATURNO study showed that although patients and physicians reported satisfaction with C5i treatment, this might be challenged. A substantial number of PNH patients treated with C5i still experience anemia, fatigue and abnormal laboratory values, indicative of ongoing hemolysis and suboptimal control. Moreover, patients with PNH had affected work productivity and a proportion of them were experiencing activity impairment. These findings highlight the need for comprehensive management strategies to address the impact of the disease on patients with PNH receiving C5i treatment.