Department of Neurology/Movement Disorders, Loma Linda University, Loma Linda, CA 92354, USA.
Department of Neurology, The Permanente Medical Group, Greater Southern Alameda Area-San Leandro/Fremont, San Leandro, CA 94577, USA.
Toxins (Basel). 2024 Oct 15;16(10):442. doi: 10.3390/toxins16100442.
The first-line management of cervical dystonia (CD) symptoms is intramuscular injection of botulinum toxin type A (BoNTA). However, a comparison of safety among BoNTAs is difficult because, per regulatory authorities, units of BoNTA activity are not interchangeable. Dysphagia and muscle weakness are widely considered two key adverse events to monitor closely in the treatment of CD. This integrated analysis compared the safety of BoNTAs approved for CD in the US by evaluating relationships between the incidence of dysphagia and muscle weakness in prescribing information and the core neurotoxin content. Coefficients The coefficients of determination (R) and trendlines were estimated via regression-based lines of best fit. Adverse drug reaction (ADR) rates were strongly correlated with core neurotoxin amounts for conventional BoNTAs (slope coefficients: dysphagia = 0.048, R = 0.74; muscle weakness = 0.096, R = 0.82). The published ADR rates at approved doses for conventional BoNTAs were higher compared with DaxibotulinumtoxinA (DAXI; DAXXIFY, Revance Therapeutics, Inc., Nashville, TN, USA) by core neurotoxin content. The use of a core neurotoxin amount was found to be an effective method for comparing the safety of BoNTA products. Current clinical trials suggest that DAXI, a novel BoNTA formulation, provides a potentially wider safety margin compared with other approved BoNTAs for CD. The lower amount of core neurotoxin administered at approved doses compared with conventional BoNTAs may explain low on-target ADRs like muscle weakness, whereas reduced diffusion from the injection site is thought to be responsible for low off-target ADRs like dysphagia.
颈肌张力障碍 (CD) 症状的一线治疗是肉毒毒素 A 型 (BoNTA) 的肌肉内注射。然而，由于监管机构的规定，BoNTA 活性单位不可互换，因此比较 BoNTAs 的安全性比较困难。吞咽困难和肌肉无力被广泛认为是治疗 CD 时需要密切监测的两个关键不良事件。这项综合分析通过评估说明书中吞咽困难和肌肉无力的发生率与核心神经毒素含量之间的关系，比较了美国批准用于 CD 的 BoNTAs 的安全性。系数 通过基于回归的最佳拟合线来估计决定系数 (R) 和趋势线。对于传统 BoNTAs（斜率系数：吞咽困难=0.048，R=0.74；肌肉无力=0.096，R=0.82），不良药物反应 (ADR) 率与核心神经毒素量呈强相关。与 DaxibotulinumtoxinA (DAXI；DAXXIFY，Revance Therapeutics，Inc.，田纳西州纳什维尔) 相比，传统 BoNTAs 的批准剂量的公布 ADR 率更高。按核心神经毒素含量计算，使用核心神经毒素量是比较 BoNTA 产品安全性的有效方法。目前的临床试验表明，新型 BoNTA 制剂 DAXI 与其他批准用于 CD 的 BoNTA 相比，可能具有更宽的安全性边际。与传统 BoNTAs 相比，在批准剂量下给予的核心神经毒素量较少，可能解释了肌肉无力等低靶标 ADR，而从注射部位扩散减少则被认为是导致吞咽困难等低靶标 ADR 的原因。
