Fatigue and health-related quality of life in paroxysmal nocturnal haemoglobinuria: A post hoc analysis of the pegcetacoplan PEGASUS trial data

Objectives: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, non-malignant haematological disorder associated with disabling fatigue and reduced health-related quality of life. Post hoc analysis of PEGASUS phase 3 trial (NCT03500549) characterised improvements in patient-reported fatigue measured by functional assessment of chronic illness therapy-fatigue (FACIT-fatigue) instrument item-level ratings for pegcetacoplan and eculizumab for the treatment of PNH.Methods: Item-level responder analysis was conducted on a =2-level change from baseline (CFB) clinically important response (CIR) for the FACIT-fatigue 13 individual items rated on a 5-level Likert scale. We evaluated =2-level change against the minimal clinically important difference (MCID) of the FACIT-fatigue total score (=5 points) and clinical parameters, haemoglobin (Hb; =1 g/dL) and normalised absolute reticulocyte count (ARC; 30-100 pg/cells). Logistic regressions estimated baseline-to-Week-16 FACIT-fatigue item-level transitional probabilities; Kaplan-Meier analysis estimated time to FACIT-fatigue item CIR.Results: Pegcetacoplan versus eculizumab was associated with significantly greater odds of Week 16 CIR across 8/13 items and on total score MCID (OR [CI] = 11.19 [3.73, 33.57]) and faster times to responses. The item-level CIR threshold also showed clinical relevance on Hb level and ARC normalization.Conclusions: Compared with eculizumab, pegcetacoplan was associated with clinically meaningful greater improvements on a majority of FACIT-fatigue items.