The Combination of Predictive Factors of Pharmacokinetic Origin Associates with Enhanced Disease Control during Treatment of Pediatric Crohn's Disease with Infliximab.
The Combination of Predictive Factors of Pharmacokinetic Origin Associates with Enhanced Disease Control during Treatment of Pediatric Crohn's Disease with Infliximab.
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DOI：
10.3390/pharmaceutics15102408
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发表时间：
2023-09-30
期刊：
影响因子：
5.4
通讯作者：
Dervieux T
中科院分区：
文献类型：
--
作者：
Dubinsky MC;Rabizadeh S;Panetta JC;Spencer EA;Everts-van der Wind A;Dervieux T
英夫利西单抗（IFX）浓度是克罗恩病（CD）治疗中药代动力学（PK）来源的预测因子（PF）。我们评价了清除率，另一种PK来源的PF，单独或与浓度组合。他们从两个队列进行评估，第一个设计为接受标准剂量（n = 37），第二个设计为主动靶向治疗IFX浓度（n = 108）。使用均相迁移率变动测定法测量浓度。使用贝叶斯先验的非线性混合效应方法估计清除率。基于C-反应蛋白的临床缓解（在没有症状的情况下<3 mg/L）用于疾病控制结果测量。采用重复事件分析法分析了由于时间、IFX浓度和清除率等因素导致的疾病控制的纵向变化。计算目标函数值的变化（CNOOFV），以比较浓度和清除率。结果表明，较低的基线清除率和主动给药与诱导期间增强的疾病控制相关（p < 0.01）。在第二、第三和第四次输注时测量的较高IFX浓度和较低清除率在维持期间产生改善的疾病控制（p < 0.032）。在维持治疗期间，清除率与疾病控制的相关性优于浓度（OFV =-19.2; p < 0.001），在存在两种PK来源的PF的情况下，两者联合使用进一步降低OFV（p < 0.001），并显著提高临床产量。我们得出结论，IFX浓度和清除率的组合是更好的预测治疗结果相比，单独一个。
Infliximab (IFX) concentrations are a predictive factor (PF) of pharmacokinetic (PK) origin in the treatment of Crohn’s disease (CD). We evaluated Clearance, another PF of PK origin, either alone or in combination with concentrations. They were evaluated from two cohorts, the first designed to receive standard dosing (n = 37), and the second designed to proactively target therapeutic IFX concentrations (n = 108). Concentrations were measured using homogeneous mobility shift assay. Clearance was estimated using the nonlinear mixed effects methods with Bayesian priors. C-reactive protein-based clinical remission (<3 mg/L in the absence of symptoms) was used for the disease control outcome measure. Longitudinal changes in disease control due to factors including time, IFX concentration, and Clearance were analyzed using repeated event analysis. Change in objective function value (∆OFV) was calculated to compare concentration and Clearance. The results indicated that lower baseline Clearance and proactive dosing associated with enhanced disease control during induction (p < 0.01). Higher IFX concentrations and lower Clearance measured at the second, third, and fourth infusion yielded improved disease control during maintenance (p < 0.032). During maintenance, the association with disease control was better with Clearance than with concentrations (∆OFV = −19.2; p < 0.001), and the combination of both further minimized OFV (p < 0.001) with markedly improved clinical yield in the presence of both PF of PK origin. We conclude that the combination of IFX concentration and Clearance are better predictors of therapeutic outcome compared with either one alone.
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影响因子：
2.9
作者：
Papamichael K;Jairath V;Zou G;Cohen B;Ritter T;Sands B;Siegel C;Valentine J;Smith M;Vande Casteele N;Dubinsky M;Cheifetz A
通讯作者：
Cheifetz A
影响因子：
29.4
作者：
Vande Casteele, Niels;Ferrante, Marc;Vermeire, Severine
通讯作者：
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影响因子：
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作者：
Vande Casteele, Niels;Jeyarajah, Jenny;Sandborn, William J.
通讯作者：
Sandborn, William J.
影响因子：
35.7
作者：
Kennedy, Nicholas A.;Heap, Graham A.;Ahmad, Tariq
通讯作者：
Ahmad, Tariq
DOI：
10.1016/j.cgh.2020.03.072
发表时间：
2021-03
期刊：
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
影响因子：
--
作者：
Battat R;Hemperly A;Truong S;Whitmire N;Boland BS;Dulai PS;Holmer AK;Nguyen NH;Singh S;Vande Casteele N;Sandborn WJ
通讯作者：
Sandborn WJ