Health-Related Quality of Life and Symptom-Specific Functional Impairment Among Patients Treated with Parenterally Administered Complement Inhibitors for Paroxysmal Nocturnal Hemoglobinuria

Abstract

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening, stem cell disorder that renders red blood cells vulnerable to complement-mediated hemolysis. This study describes the health-related quality of life (HRQoL) and symptom-specific functional impairment of patients with PNH in a real-world setting. Methods: US-based adults with PNH treated with a parenterally administered complement inhibitor (PACI) for ≥6 months completed an online, cross-sectional, observational survey; a subset of patients also participated in individual semi-structured qualitative interviews after completing the survey. The survey included the PROMIS® 29+2 Profile v2.1 (PROMIS 29+2) to measure HRQoL. The FACIT Fatigue, Neuro-QOL Item Bank v2.0 Cognitive Function Short Form, and PROMIS Item Bank v1.0 Dyspnea Functional Limitations 10a Short Form measured functional impairment associated with specific symptoms of PNH. For each patient with PNH who completed the online survey, up to 3 age- (+/- 3 years) and sex-matched adults without PNH also completed the survey. The HRQoL and functional impairment of the PNH sample was compared to that of general population (GP) sample using independent samples t-tests or Mann-Whitney tests. To further explore the experiences of patients with PNH, the association between HRQoL/functional impairment and fatigue severity was investigated. Patients with PNH were grouped according to their self-reported fatigue severity over the past 7 days (very mild or mild vs moderate, severe, or very severe [no patients reported no fatigue]). Differences in scores across these 2 groups were tested. Data from the qualitative interviews were coded using thematic analysis to explore key concepts related to HRQoL and impairment due to PNH symptoms. Data collection began in March 2023; results are based on interim data. Results: Demographic characteristics of the study samples (PNH survey sample: N=31, GP survey sample: N=62, PNH interview sample: N=10) are shown in Table 1. Patients were treated for PNH with eculizumab, pegcetacoplan, or ravulizumab, with an average duration of current PACI treatment of 3.4 years. Compared to the age and sex-matched GP sample, patients with PNH had significantly higher median scores on the PROMIS 29+2 fatigue domain (GP: 48.70 vs PNH: 57.10, p=0.041) and PROMIS Dyspnea Functional Limitations short form (GP: 40.70 vs PNH: 48.60, p=0.036), indicating that patients with PNH experience more fatigue and dyspnea limitations than the GP sample. Patients with PNH also had significantly lower median scores on the PROMIS 29+2 ability to participate in social roles/activities domain (GP: 53.50 vs PNH: 44.20, p=0.013), indicating greater role/activity limitations among patients with PNH. Compared to the GP sample, patients with PNH had numerically lower (i.e., worse) median PROMIS 29+2 cognitive functioning domain scores (GP: 50.00 vs PNH: 46.30, p=0.058) and FACIT Fatigue scores (GP: 39.50 vs PNH: 30.00, p=0.057). Within the PNH sample, statistically significant associations (p<0.05) were observed between fatigue severity and HRQoL/functional impairment for all outcomes except for the PROMIS 29+2 sleep disturbance and cognitive functioning domains (Table 2). Patients with more severe fatigue had worse HRQoL and more functional impairment than patients with less severe fatigue. Interview participants described fatigue-related functional impairments in their physical, social, and cognitive functioning. Fatigue made daily activities (e.g., cooking, cleaning, going for a walk) difficult and sometimes impossible. Planning social activities in advance was also challenging as patients could not predict how they would feel on any given day, and often found they had to miss, postpone, or cancel social engagements. Finally, patients described experiencing “brain fog” including difficulty concentrating, forgetfulness, and delayed cognitive processing. Conclusions: Despite receiving treatment for PNH, patients experienced deficits in areas of HRQoL related to fatigue, participation in social roles, cognitive function, and functional limitations due to dyspnea, relative to a sample of GP adults. During follow-up interviews, patients emphasized the deep and broad impacts that fatigue and cognitive functioning had, making daily activities and their social lives very difficult.