Division of Pulmonary, Critical Care and Sleep Medicine, NYU Grossman School of Medicine, and the André Cournand Pulmonary Physiology Laboratory, Bellevue Hospital, New York, NY, USA.
Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
J Neurol. 2024 Aug;271(8):5433-5446. doi: 10.1007/s00415-024-12489-9. Epub 2024 Jun 19.
Chronic respiratory insufficiency from progressive muscle weakness causes morbidity and mortality in late-onset Pompe disease (LOPD). Previous Pompe Registry (NCT00231400) analyses for ≤ 5 years' alglucosidase alfa treatment showed a single linear time trend of stable forced vital capacity (FVC) % predicted.
To assess longer term Pompe Registry data, piecewise linear mixed model regression analyses estimated FVC% predicted trajectories in invasive-ventilator-free patients with LOPD aged ≥ 5 years. We estimated annual FVC change 0-6 months, > 6 months-5 years, and > 5-13 years from treatment initiation, adjusting for baseline age, sex, and non-invasive ventilation.
Among 485 patients (4612 FVC measurements; 8.3 years median follow-up), median ages at symptom onset, diagnosis, and alglucosidase alfa initiation were 34.3, 41.1, and 44.9 years, respectively. FVC% increased during the first 6 months' treatment (slope 1.83%/year; 95% confidence interval: 0.66, 3.01; P = 0.0023), then modestly declined -0.54%/year (-0.79, -0.30; P < 0.0001) during > 6 months-5 years, and -1.00%/year (-1.36, -0.63; P < 0.0001) during > 5-13 years. The latter two periods' slopes were not significantly different from each other (P = 0.0654) and were less steep than published natural history slopes (-1% to -4.6%/year). Estimated individual slopes were ≥ 0%/year in 96.1%, 30.3%, and 13.2% of patients during the 0-6 month, > 6 month-5 year, and > 5-13 year periods, respectively.
These real-world data indicate an alglucosidase alfa benefit on FVC trajectory that persists at least 13 years compared with published natural history data. Nevertheless, unmet need remains since most individuals demonstrate lung function decline 5 years after initiating treatment. Whether altered FVC trajectory impacts respiratory failure incidence remains undetermined.
This study was registered (NCT00231400) on ClinicalTrials.gov on September 30, 2005, retrospectively registered.
进展性肌肉无力导致的慢性呼吸功能不全是晚发性庞贝病（LOPD）患者发病和死亡的主要原因。之前的庞贝病登记研究（NCT00231400）分析了接受为期≤5 年阿糖苷酶α治疗的患者，结果显示用力肺活量（FVC）占预计值的百分比呈单一线性时间趋势稳定。
为了评估更长期的庞贝病登记数据，我们对年龄≥5 岁、无侵入性通气的 LOPD 患者进行了分段线性混合模型回归分析，以评估 FVC 占预计值的轨迹。我们根据基线年龄、性别和无创通气调整了 0-6 个月、>6 个月-5 年和>5-13 年治疗开始时的 FVC 年变化率。
在 485 名患者（4612 次 FVC 测量；中位随访 8.3 年）中，症状发作、诊断和阿糖苷酶α开始治疗的中位年龄分别为 34.3、41.1 和 44.9 岁。治疗的前 6 个月 FVC 百分比增加（斜率 1.83%/年；95%置信区间：0.66，3.01；P=0.0023），然后在>6 个月-5 年期间适度下降-0.54%/年（-0.79，-0.30；P<0.0001），在>5-13 年期间下降-1.00%/年（-1.36，-0.63；P<0.0001）。后两个时期的斜率与彼此之间没有显著差异（P=0.0654），并且比已发表的自然史斜率（-1%至-4.6%/年）更平缓。在 0-6 个月、>6 个月-5 年和>5-13 年期间，分别有 96.1%、30.3%和 13.2%的患者的个体斜率≥0%/年。
与已发表的自然史数据相比，这些真实世界的数据表明阿糖苷酶α治疗在 FVC 轨迹上具有持续至少 13 年的获益。然而，由于大多数患者在开始治疗 5 年后仍存在肺功能下降，因此仍存在未满足的需求。FVC 轨迹的改变是否会影响呼吸衰竭的发生率仍有待确定。
该研究于 2005 年 9 月 30 日在 ClinicalTrials.gov 上注册（NCT00231400），为回顾性注册。
