ERN-NMD Center of Messina for Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
Sanofi, Chilly-Mazarin, France.
Mol Genet Metab. 2024 Feb;141(2):108121. doi: 10.1016/j.ymgme.2023.108121. Epub 2023 Dec 27.
The Phase 3 COMET trial (NCT02782741) comparing avalglucosidase alfa and alglucosidase alfa included health-related quality of life (HRQoL) assessments in treatment-naïve patients with late-onset Pompe disease (LOPD). Here, we further characterize results from disease-specific and general patient-reported outcome (PRO) measures.
Adults who participated in the COMET trial receiving avalglucosidase alfa or alglucosidase alfa (both 20 mg/kg biweekly) during the 49-week double-blind treatment period were included in the analysis. Proportions of patients exceeding meaningful change thresholds at Week 49 were compared post hoc between treatment groups. PROs and their meaningful change thresholds included: Pompe Disease Severity Scale (PDSS; decrease 1.0-1.5 points), Pompe Disease Impact Scale (PDIS; decrease 1.0-1.5 points), Rasch-built Pompe-specific Activity Scale (R-PAct; change from unable to able to complete activity), 12-item Short Form Health Survey (SF-12; physical component summary [PCS] score: increase ≥6 points, mental component summary [MCS] score: increase ≥7 points), EuroQol 5 Dimension 5 Level (EQ-5D-5L; improvement of ≥1 category), and Patient Global Impression of Change (PGIC; any improvement).
The analysis included 99 adult patients (avalglucosidase alfa n = 50; alglucosidase alfa n = 49). Patients who received avalglucosidase alfa had significantly greater odds of achieving a meaningful change versus alglucosidase alfa for the PDSS Shortness of Breath (OR [95% CI] 11.79 [2.24; 62.18]), Fatigue/Pain (6.24 [1.20; 32.54]), Morning Headache (13.98 [1.71; 114.18]), and Overall Fatigue (5.88 [1.37; 25.11]) domains, and were significantly more likely to meet meaningful change thresholds across multiple PDSS domains (all nominal p < 0.05). A numerically greater proportion of patients in the avalglucosidase alfa group were able to complete selected activities of the R-PAct compared with the alglucosidase alfa group. Significantly greater proportions of patients who received avalglucosidase alfa achieved meaningful improvements for EQ-5D-5L usual activities dimension, EQ visual analog scale, and all four PGIC domains. The proportion of patients with improvements in SF-12 PCS and MCS was greater in the avalglucosidase alfa group versus alglucosidase alfa group, but was not significant (p > 0.05).
These analyses show that avalglucosidase alfa improves multiple symptoms and aspects of daily functioning, including breathing and mobility. This supports the clinical relevance of the effects of avalglucosidase alfa on HRQoL for patients with LOPD.
3 期 COMET 试验（NCT02782741）比较了依洛葡萄糖苷酶阿尔法和阿加糖酶阿尔法在晚发性庞贝病（LOPD）的初治患者中的疗效，包括健康相关生活质量（HRQoL）评估。在此，我们进一步描述了疾病特异性和一般患者报告结局（PRO）测量的结果。
纳入了在 49 周双盲治疗期间接受依洛葡萄糖苷酶阿尔法或阿加糖酶阿尔法（均为 20mg/kg 每两周一次）治疗的 COMET 试验成年患者。事后比较了两组患者在第 49 周时达到有意义的变化阈值的比例。PRO 及其有意义的变化阈值包括：庞贝病严重程度量表（PDSS；下降 1.0-1.5 分）、庞贝病影响量表（PDIS；下降 1.0-1.5 分）、基于 Rasch 构建的庞贝病特定活动量表（R-PAct；从无法完成活动变为能够完成活动）、12 项简短健康调查（SF-12；生理成分综合评分 [PCS]：增加≥6 分，心理成分综合评分 [MCS]：增加≥7 分）、欧洲五维健康量表 5 维度（EQ-5D-5L；改善≥1 个类别）和患者整体印象变化（PGIC；任何改善）。
分析纳入了 99 名成年患者（依洛葡萄糖苷酶阿尔法组 n=50；阿加糖酶阿尔法组 n=49）。与阿加糖酶阿尔法相比，接受依洛葡萄糖苷酶阿尔法治疗的患者在 PDSS 短气（OR [95%CI] 11.79 [2.24；62.18]）、疲劳/疼痛（6.24 [1.20；32.54]）、晨头痛（13.98 [1.71；114.18]）和总体疲劳（5.88 [1.37；25.11]）等领域达到有意义变化的可能性显著更高，并且在多个 PDSS 领域更有可能达到有意义的变化阈值（所有名义 p<0.05）。与阿加糖酶阿尔法组相比，依洛葡萄糖苷酶阿尔法组能够完成 R-PAct 中多项活动的患者比例更高。接受依洛葡萄糖苷酶阿尔法治疗的患者在 EQ-5D-5L 日常活动维度、EQ 视觉模拟量表和所有四个 PGIC 维度上的改善更显著。与阿加糖酶阿尔法组相比，依洛葡萄糖苷酶阿尔法组患者的 SF-12 PCS 和 MCS 改善比例更高，但无统计学意义（p>0.05）。
这些分析表明，依洛葡萄糖苷酶阿尔法改善了多种症状和日常功能，包括呼吸和移动能力。这支持了依洛葡萄糖苷酶阿尔法对 LOPD 患者 HRQoL 的影响具有临床意义。
