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

• Published in: European journal of haematology 2023-07, Vol.111 (1), p.72-83
• Main Authors: Panse, Jens, Wilson, Koo, Fishman, Jesse, Wojciechowski, Piotr, Wdowiak, Marlena, Horneff, Regina, Patriquin, Christopher J., Oliver, Monika, Hakimi, Zalmai
• Format: Article
• Language: English
• Subjects: FACIT‐fatigue; Fatigue; functional assessment of chronic illness therapy‐fatigue; health related quality of life; Hematological diseases; Hemoglobin; paroxysmal nocturnal haemoglobinuria; PEGASUS; Quality of life
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/ejh.13969

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.