Dados do Trabalho

Título

Avalglucosidase alfa improves health-related quality of life (HRQoL) in patients with Late-Onset Pompe Disease (LOPD) vs. alglucosidase alfa: Patient-reported outcome measures (PROMs) from the phase 3 COMET trial

Resumo

The phase 3 COMET trial (NCT02782741) assessed PROMs in treatment-naïve adult LOPD patients receiving avalglucosidase alfa (AVAL, n=51) or alglucosidase alfa (ALGLU, n=49). PROMs comprised generic measures (12-item Short-Form Health Survey [SF-12], Patient Global Impression of Change [PGIC]), EuroQoL-5D-5L [EQ-5D-5L]), and LOPD-specific measures (Pompe Disease Symptom Scale [PDSS], Pompe Disease Impact Scale [PDIS], and Rasch-Built Pompe-Specific Activity [R-PAct]) that cover various domains: breathing, mobility, fatigue, disease-related symptoms, upper extremity weakness, pain, morning headache, daily activities, physical functioning, and mental health. Change from baseline to Week 49 was analyzed using mixed models for repeated measures. AVAL was numerically better than ALGLU across all domains except for pain/discomfort (EQ-5D-5L) and mood (PDIS). Between-group difference was nominally significant (p-value <0.05) for PGIC questions: daily activities (least squares mean difference vs. ALGLU (95% confidence interval [CI]): 0.57 [0.08, 1.06]), disease-related symptoms (0.78 [0.31, 1.25]), mobility (0.65 [0.18,1.12]); and EQ-5D mobility (–0.31 [–0.62, 0.00]). Post-hoc responder analyses numerically favored AVAL vs. ALGLU for all PROMs. Proportion of responders was nominally significantly greater (p<0.05) for all PGIC questions (daily activities [62.0% vs. 37.0%], disease-related symptoms [74.0% vs. 49.0%], ability to breathe [66.0% vs. 41.0%] and mobility [66.0% vs. 29.0%]), EQ-5D-5L (usual activities [54.0% vs. 30.6%]), and PDSS (shortness of breath [26.0% vs. 4.1%], overall fatigue [22.0% vs. 2.0%], fatigue/pain [18.0% vs. 4.1%], and morning headache [22.0% vs. 4.1%]). Cumulative distribution functions showed a clear separation in favor of AVAL for full range of thresholds in PDSS (shortness of breath, overall fatigue, and fatigue/pain) and PDIS (difficulty in performing daily activities). These LOPD-specific PROMs provide further support for greater therapeutic benefit of AVAL over ALGLU, including the most relevant LOPD domains - mobility, usual activities, and breathing. This dataset confirms meaningful impact of AVAL on LOPD patient’s quality of life.