Switching treatment to cipaglucosidase alfa plus miglustat positively affects patient-reported outcome measures in patients with late-onset Pompe diseaseKishnani, Priya S. (Avtor) Byrne, Barry J. (Avtor) Claeys, Kristl G. (Avtor) Diaz-Manera, Jordi (Avtor) Dimachkie, Mazen M. (Avtor) Kushlaf, Hani (Avtor) Mozaffar, Tahseen (Avtor) Roberts, Mark (Avtor) Schoser, Benedikt (Avtor) Hummel, Noemi (Avtor) Koritnik, Blaž (Sodelavec pri raziskavi) Pompe diseasepatient-reported outcomeshealth-related quality of lifeSARS-Cov-2Background: Late-onset Pompe disease (LOPD), a rare autosomal recessive multisystemic disorder, substantially impacts patients’ day-to-day activities, outcomes, and health-related quality of life (HRQoL). The PROPEL trial compared cipaglucosidase alfa plus miglustat (cipa+mig) with alglucosidase alfa plus placebo (alg+pbo) in adult patients with LOPD over 52 weeks and showed improved motor and respiratory function in patients switching treatment from standard-of-care enzyme replacement therapy (ERT) to cipa+mig at baseline. This study evaluated the impact of cipa+mig on patient-reported outcomes (PROs), including HRQoL in ERT-experienced patients, using data from PROPEL. Methods: PROs evaluated included the Subject’s Global Impression of Change (SGIC), Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 20a, PROMIS Fatigue Short Form 8a, Raschbuilt Pompe-specific Activity (R-PAct), and European Quality of Life-5 Dimensions 5 Response Levels (EQ-5D-5L). The proportions of responders in the cipa+mig arm and the alg+pbo arm were compared via chi-squared or Fisher’s exact test (patient-level responder analysis), and least squares (LS) mean differences were calculated for change from baseline at Week 52 of the PRO measures (group-level analysis). Results: At Week 52, patient-level SGIC responder and group-level SGIC analyses favored cipa+mig compared with alg+pbo across all SGIC domains (e.g. 90 vs. 59% responders in the cipa+mig vs. the alg+pbo group for SGIC ability to move around; P=0.0005; and LS mean difference 0.385; P=0.02). Similarly, PROMIS Physical Function and Fatigue domains numerically favored cipa+mig in both analyses (e.g. 50 vs. 40% responders in the cipa+mig vs. alg+pbo arm for PROMIS Physical Function; P=0.37; and LS mean difference 3.1; P=0.11). R-PAct for both treatment groups was similar in the patient-level responder analysis, but numerically favored alg+pbo in the group-level analysis (35% responders in both arms; P=0.95; and LS mean difference −0.8; P=0.48). Self-care, usual activities, and depression anxiety domains of EQ-5D-5L numerically favored cipa+mig in both analyses (e.g. 20 vs. 12% responders in the cipa+mig vs. alg+pbo arm for EQ-5D-5L self-care; P=0.54; and LS mean difference −0.108; P=0.52). Conclusions: Overall, switching treatment from alglucosidase alfa to cipa+mig positively impacted PRO measurements during the double-blind period of PROPEL.20242026-02-26 14:16:04Neznano27881sl