Hemoglobin Improvement Correlates With Better HRQOL in Paroxysmal Nocturnal Hemoglobinuria

Post hoc analyses of the phase 3 PEGASUS trial found that clinical and hematological improvements were associated with better patient-reported fatigue and physical function outcomes in paroxysmal nocturnal hemoglobinuria, for an overall bettering of health-related quality of life (HRQOL).

Although the hematological symptoms of paroxysmal nocturnal hemoglobinuria (PNH) can improve with treatment, little is known about the correlation between laboratory improvements and patient-reported outcomes. In post hoc analyses from the phase 3 PEGASUS trial of pegcetacoplan vs eculizumab for PNH, researchers found that clinical and hematological improvements were associated with improvements in patient-reported fatigue and physical function outcomes.

PNH is a rare, chronic condition that leads to life-threatening hematological complications such as thrombosis, impaired bone marrow function, complement-mediated hemolysis, and anemia. Fatigue is the most common symptom in patients with PNH, which is also characterized by dyspnea, hemoglobinuria, pain, and other symptoms that affect health-related quality of life (HRQOL) and indicate disease progression. Thus, patient-reported outcomes (PROs) are an important aspect of managing PNH.

The main end point in the PEGASUS trial was hemoglobin level improvement in patients treated with pegcetacoplan vs eculizumab, and pegcetacoplan led to greater improvement compared with eculizumab. Secondary outcomes included the impact on PROs based on patient responses to the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and European Organization for Research and Treatment of Cancer Quality of Life Questionnare-C30 (EORTC QLQ-C30) during the study. The EORTC QLQ-C30 assesses a range of HRQoL aspects, including fatigue and physical function.

FACIT-F and EORTC QLQ-C30 scores were assessed weekly during the 16-week randomized controlled period of the study, as were hemoglobin levels, absolute reticulocyte count, and indirect bilirubin. For the post hoc analyses, PROs based on FACIT-F and EORTC QLQ-C30 responses were compared with the clinical and hematological measurements in the same period.

By week 16, 72.2% of patients treated with pegcetacoplan and 22.9% of patients given eculizumab achieved clinically meaningful improvements in FACIT-F score, defined as an increase of 5 or more points from baseline. FACIT-F score changes were moderately correlated with hemoglobin level measurements and less strongly correlated with absolute reticulocyte count and indirect bilirubin levels.

Patients treated with pegcetacoplan also demonstrated clinically meaningful improvements in several categories in the EORTC QLQ-C30, including global health status and QOL, physical functioning, role functioning, social functioning, fatigue, and dyspnea.

Across treatment groups, patients who experienced the greatest improvement in hemoglobin levels also saw the biggest reduction of fatigue based on FACIT-F scores. The greatest improvements in absolute reticulocyte count and indirect bilirubin levels also correlated with the more significant reductions in fatigue. The patients whose hemoglobin and other hematological levels improved the most also reported the most notable improvements according to EORTC QLQ-C30 responses. Therefore, the authors note that clinicians may want to consider treatment strategies geared to increasing hemoglobin levels specifically for patients with PNH.

Overall, the study results suggest that HRQOL outcomes correlate with clinical and hematological improvements in PNH.

“According to these results, PNH patients may experience PRO improvements in fatigue and other symptoms from pegcetacoplan at various hemoglobin levels, as treatment has been shown to lead to a reduction of transfusion requirements, and higher hemoglobin levels in the PEGASUS trial,” the authors wrote. “Further, based on these correlation results, measurement of change in fatigue may predict changes in hemoglobin, changes that may warrant clinical exploration of the PNH patient.”


Cella D, Sarda SP, Hsieh R, et al. Changes in hemoglobin and clinical outcomes drive improvements in fatigue, quality of life, and physical function in patients with paroxysmal nocturnal hemoglobinuria: post hoc analyses from the phase III PEGASUS study. Ann Hematol. Published online July 23, 2022. doi:10.1007/s00277-022-04887-8