Li Shangze, Huang Runcheng, Meng Yuanyuan, Liu Yijia, Qian Jiao, Zou Junjie, Yang Jun
Department of Orthopedics, The Second Affiliated Hospital (Changzheng Hospital), Naval Medical University, Shanghai, China.
Department of Endocrinology, The Second Affiliated Hospital (Changzheng Hospital), Naval Medical University, Shanghai, China.
Front Pharmacol. 2024 Aug 5;15:1420126. doi: 10.3389/fphar.2024.1420126. eCollection 2024.
Associated with enzyme deficiencies causing glycosaminoglycans (GAGs) accumulation, mucopolysaccharidosis type VI (MPS VI) is lysosomal storage disorder. In the treatment of MPS VI, galsulfase (Naglazyme) is commonly used as an enzyme replacement therapy (ERT). There remains a need for comprehensive real-world data on its safety and associated adverse events (AEs).
An analysis of the FDA Adverse Event Reporting System (FAERS) database will be conducted to identify potential risks and adverse reactions associated with galsulfase in real-life settings.
The FAERS database was used to extract data from Q2 2005 to Q4 2023. A total of 20,281,876 reports were analyzed after duplicate elimination, with 3,195 AE reports related to galsulfase identified. The association between galsulfase and AEs was investigated by utilizing four algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). The analysis focused on the timing of onset, signs of AEs, and clinical significance.
Twenty seven organ systems were involved, and significant system organ classes (SOCs) included respiratory, thoracic and mediastinal disorders, and infections and infestations. At the PT level, 72 PTs corresponding to 15 SOCs were identified, with some AEs not previously mentioned in the product label. AEs associated with galsulfase had a median onset time of 1,471 days, with over half of the cases occurred within the first 5 years of treatment initiation.
This investigation delivers an exhaustive and indicative assessment of galsulfase's safety profile, grounded in authentic, real-world evidence. The findings emphasis the importance of continuous safety surveillance and the emergence of new AEs. The identification of previously unreported urologic adverse events, such as glomerulonephritis membranous and nephritic syndrome, warrants further investigation. The study emphasizes the need for enhanced pharmacovigilance to ensure patient safety and the effectiveness of galsulfase treatment.
黏多糖贮积症VI型（MPS VI）是一种溶酶体贮积症，与导致糖胺聚糖（GAGs）积累的酶缺乏有关。在MPS VI的治疗中，加尔硫酸酯酶（Naglazyme）通常用作酶替代疗法（ERT）。仍需要关于其安全性和相关不良事件（AEs）的全面真实世界数据。
将对美国食品药品监督管理局不良事件报告系统（FAERS）数据库进行分析，以确定在现实环境中与加尔硫酸酯酶相关的潜在风险和不良反应。
使用FAERS数据库提取2005年第二季度至2023年第四季度的数据。在消除重复报告后，共分析了20281876份报告，确定了3195份与加尔硫酸酯酶相关的不良事件报告。利用四种算法研究加尔硫酸酯酶与不良事件之间的关联：报告比值比（ROR）、比例报告比值比（PRR）、贝叶斯置信传播神经网络（BCPNN）和多项目伽马泊松收缩器（MGPS）。分析重点关注发病时间、不良事件体征和临床意义。
涉及27个器官系统，重要的系统器官类别（SOCs）包括呼吸、胸和纵隔疾病以及感染和寄生虫感染。在首选术语（PT）层面上，确定了与15个SOCs相对应的72个PT，其中一些不良事件在产品标签中未曾提及。与加尔硫酸酯酶相关的不良事件的中位发病时间为1471天，超过一半的病例发生在开始治疗的前5年内。
本调查基于真实的现实世界证据，对加尔硫酸酯酶的安全性概况进行了详尽且具有指示性的评估。研究结果强调了持续安全监测以及新不良事件出现的重要性。鉴定出先前未报告的泌尿系统不良事件，如膜性肾小球肾炎和肾炎综合征，值得进一步研究。该研究强调需要加强药物警戒，以确保患者安全和加尔硫酸酯酶治疗的有效性。
