Pan Yu-Wen, Tsai Meng-Che, Yang Chiao-Yu, Yu Wen-Hao, Wang Bow, Yang Yao-Jong, Chou Yen-Yin
Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 138, Shengli Rd., North Dist., Tainan City, Taiwan, ROC.
Department of Pediatrics, An-Nan Hospital, China Medical University, No. 66, Sec. 2, Changhe Rd., Annan Dist., Tainan City, Taiwan, ROC.
Mol Genet Metab Rep. 2023 Jan 31;34:100957. doi: 10.1016/j.ymgmr.2023.100957. eCollection 2023 Mar.
Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disease with multi-systemic involvement, with no disease-modifying treatment available. Olipudase alfa is an investigational enzyme product developed to replace the deficient acid sphingomyelinase in ASMD patients. Several clinical trials have reported promising safety and efficacy results in adult and pediatric patients. However, no data have been reported outside of the clinical trial setting yet. This study aimed to evaluate major outcomes in pediatric chronic ASMD patients receiving olipudase alfa in the real-world setting.
Two children with type A/B (chronic neuropathic) ASMD have received olipudase alfa treatment since May 2021. Clinical parameters, including height, weight, complete blood count, liver function tests, lipid profiles, biomarkers, abdominal ultrasonography with shear wave elastography, chest computed tomography, nerve conduction studies, neurodevelopmental evaluations, and six-minute walk tests, were checked at baseline and every three to six months in the first year of enzyme replacement therapy (ERT) to assess its efficacy and safety.
The two patients in our study started olipudase alfa treatment at the age of 5 years and 8 months and 2 years and 6 months. During the first year of treatment, both patients saw a reduction in their hepatic and splenic volumes as well as liver stiffness. Height z-score, weight z-score, lipid profiles, biomarker levels, interstitial lung disease scores, and bone mineral densities also improved over time. The six-minute walk test showed a gradual increase in walking distance in both patients. There were no obvious improvements or deterioration in neurocognitive function and peripheral nerve conduction velocities after treatment. No severe infusion-associated reactions were noted during the first year of treatment. One patient had two episodes of transient but significantly elevated liver enzymes during the dose-escalation phase. The patient was asymptomatic, and the impaired liver function resolved spontaneously within two weeks.
Our results provide real-world experience that olipudase alfa is safe and effective in improving major systemic clinical outcomes for pediatric chronic ASMD patients. Monitoring of liver stiffness by shear wave elastography is a noninvasive procedure that can monitor treatment efficacy during ERT.
酸性鞘磷脂酶缺乏症（ASMD）是一种累及多系统的溶酶体贮积病，目前尚无改善病情的治疗方法。奥利普酶α是一种研发用于替代ASMD患者体内缺乏的酸性鞘磷脂酶的研究性酶产品。多项临床试验报告了其在成人和儿童患者中的安全性和疗效结果令人鼓舞。然而，临床试验环境之外尚未有数据报道。本研究旨在评估在现实环境中接受奥利普酶α治疗的小儿慢性ASMD患者的主要结局。
自2021年5月起，两名A/B型（慢性神经病变型）ASMD患儿接受了奥利普酶α治疗。在酶替代疗法（ERT）的第一年，于基线时以及每三至六个月检查临床参数，包括身高、体重、全血细胞计数、肝功能检查、血脂谱、生物标志物、腹部超声剪切波弹性成像、胸部计算机断层扫描、神经传导研究、神经发育评估和六分钟步行试验，以评估其疗效和安全性。
我们研究中的两名患者分别在5岁8个月和2岁6个月时开始接受奥利普酶α治疗。在治疗的第一年，两名患者的肝脏和脾脏体积以及肝脏硬度均有所减小。身高Z评分、体重Z评分、血脂谱、生物标志物水平、间质性肺病评分和骨密度也随时间有所改善。六分钟步行试验显示两名患者的步行距离逐渐增加。治疗后神经认知功能和周围神经传导速度无明显改善或恶化。在治疗的第一年未观察到严重的输注相关反应。一名患者在剂量递增阶段出现两次短暂但明显升高的肝酶情况。该患者无症状，肝功能损害在两周内自发缓解。
我们的结果提供了现实世界中的经验，即奥利普酶α在改善小儿慢性ASMD患者的主要全身临床结局方面是安全有效的。通过剪切波弹性成像监测肝脏硬度是一种可在ERT期间监测治疗效果的非侵入性方法。
