OBJECTIVES: We evaluated improvements in patient-reported fatigue, as measured by FACIT-F item level scores to characterize response rates for pegcetacoplan versus eculizumab for the treatment of PNH.

METHODS: We posited that a ≥2-point change from baseline (CFB) at 16 weeks on each individual FACIT-F item indicated a clinically meaningful improvement in fatigue score. This threshold of CFB was validated with published clinically meaningful improvement (≥4-point) in FACIT-F total scores. With logistic regression analysis we then estimated the transitional probabilities among 5-level responses (from “not at all” to “very much”) of each FACIT-F item from baseline to Week 16. We further evaluated the transitional probabilities for pegcetacoplan and eculizumab using the corresponding natural logarithms of odds derived from the model.

RESULTS: 2-point CFB in FACIT-F item scores were associated with changes in FACIT-F mean total scores ranging from 15.8─20.7. Compared with eculizumab, pegcetacoplan was associated with significantly higher odds for clinically meaningful (≥2-point) improvements at Week 16 across 8/13 items and meaningful improvement (≥4-point) in FACIT-F total score (OR=11.19 [3.73:33.57]). The best-fitting logistic models for transition probabilities for FACIT-F item ratings indicated that patients receiving pegcetacoplan compared with eculizumab were significantly more likely (nominal P<0.05) to report complete resolution, more advanced improvement in functional items and/or had lower chance to maintain negative assessment for the following FACIT-F items: I feel weak all over; I feel listless; I feel tired; I have energy; I am too tired to eat; I am frustrated by being too tired; and I have limited social activity because I am tired. The ratings for these items also improved significantly from baseline (nominal P<0.05).

CONCLUSIONS: The present analysis indicated that treatment outcomes of pegcetacoplan compared with eculizumab manifested as consistently improved scores across the majority of FACIT-F items.