Serra López-Matencio Jose M, Pérez García Yaiza, Meca-Lallana Virginia, Juárez-Sánchez Raquel, Ursa Angeles, Vega-Piris Lorena, Pascual-Salcedo Dora, de Vries Annick, Rispens Theo, Muñoz-Calleja Cecilia
Servicio de Farmacia, Hospital Universitario de La Princesa, Madrid, Spain.
Servicio de Inmunología, Hospital de La Princesa, Madrid, Spain.
Front Neurol. 2021 Oct 7;12:716548. doi: 10.3389/fneur.2021.716548. eCollection 2021.
Plasma concentration of natalizumab falls above the therapeutic threshold in many patients who, therefore, receive more natalizumab than necessary and have higher risk of progressive multifocal leukoencephalopathy. To assess in a single study the individual and treatment characteristics that influence the pharmacokinetics and pharmacodynamics of natalizumab in multiple sclerosis (MS) patients in the real-world practice. Prospective observational study to analyse the impact of body weight, height, body surface area, body mass index, gender, age, treatment duration, and dosage scheme on natalizumab concentrations and the occupancy of α4-integrin receptor (RO) by natalizumab. Natalizumab concentrations ranged from 0.72 to 67 μg/ml, and RO from 26 to 100%. Body mass index inversely associated with natalizumab concentration (beta = -1.78; ≤ 0.001), as it did body weight (beta = -0.34; = 0.001), but not height, body surface area, age or gender Extended vs. standard dose scheme, but not treatment duration, was inversely associated with natalizumab concentration (beta = -7.92; = 0.016). Similar to natalizumab concentration, body mass index (beta = -1.39; = 0.001) and weight (beta = -0.31; = 0.001) inversely impacted RO. Finally, there was a strong direct linear correlation between serum concentrations and RO until 9 μg/ml (rho = 0.71; = 0.003). Nevertheless, most patients had higher concentrations of natalizumab resulting in the saturation of the integrin. Body mass index and dosing interval are the main variables found to influence the pharmacology of natalizumab. Plasma concentration of natalizumab and/or RO are wide variable among patients and should be routinely measured to personalize treatment and, therefore, avoid either over and underdosing.
在许多患者中，那他珠单抗的血浆浓度高于治疗阈值，因此这些患者接受了超过必要剂量的那他珠单抗，发生进行性多灶性白质脑病的风险更高。在一项单一研究中评估影响那他珠单抗在现实世界中多发性硬化症（MS）患者体内药代动力学和药效学的个体及治疗特征。前瞻性观察性研究，分析体重、身高、体表面积、体重指数、性别、年龄、治疗持续时间和给药方案对那他珠单抗浓度以及那他珠单抗对α4整合素受体占有率（RO）的影响。那他珠单抗浓度范围为0.72至67μg/ml，RO为26%至100%。体重指数与那他珠单抗浓度呈负相关（β = -1.78；P≤0.001），体重也是如此（β = -0.34；P = 0.001），但身高、体表面积、年龄或性别并非如此。延长给药方案与标准给药方案相比，而非治疗持续时间，与那他珠单抗浓度呈负相关（β = -7.92；P = 0.016）。与那他珠单抗浓度相似，体重指数（β = -1.39；P = 0.001）和体重（β = -0.31；P = 0.001）对RO有负面影响。最后，血清浓度与RO之间在9μg/ml之前存在强烈的直接线性相关性（ρ = 0.71；P = 0.003）。然而，大多数患者的那他珠单抗浓度较高，导致整合素饱和。体重指数和给药间隔是发现影响那他珠单抗药理学的主要变量。那他珠单抗的血浆浓度和/或RO在患者之间差异很大，应常规测量以实现个体化治疗，从而避免用药过量和不足。
