Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Gut Liver. 2022 Jan 15;16(1):71-80. doi: 10.5009/gnl20322.
BACKGROUND/AIMS: The efficacy of biologics for the treatment of Crohn's disease (CD) is affected by the drug concentrations. We aimed to evaluate the importance of albumin and globulin which are known to be associated with drug concentrations as prognostic biomarkers in CD.
In total, 121 pediatric patients with CD who had received anti-tumor necrosis factor (TNF)-α therapy were retrospectively examined between January 2010 and February 2019.
Relapse was observed in 48.8% of patients (59/121). The level of calprotectin (odds ratio, 2.13; p=0.03) and the albumin-to-globulin ratio (AGR) at 1 year after anti-TNF-α therapy (odds ratio, 0.0002; p=0.003) were associated with relapse. The AGR at 1 year after anti-TNF-α therapy was the only factor associated with the time-to-relapse (hazard ratio, 0.02; p<0.001). The optimal AGR cutoff value for the prediction of relapse was 1.47 (area under the curve, 0.916; p<0.001). The median infliximab trough level (TL) was lower in patients with AGRs <1.47 than in those with AGRs ≥1.47. Anti-drug antibody (ADA) concentrations were negatively correlated with the AGR at 1 year of anti-TNF-α therapy (r=-0.413, p=0.032).
AGR can be used to predict relapse. Patients with AGRs <1.47 at 1 year after anti-TNF-α therapy are more likely to have low drug TLs and develop ADAs, which increase the possibility of relapse than those with AGRs ≥1.47. Therefore, if the AGR at 1 year after anti-TNF-α therapy is less than 1.47, clinicians should monitor disease activity, assess the TLs of the anti-TNF-α agents, test for ADAs and determine the appropriate therapeutic strategies.
背景/目的：生物制剂治疗克罗恩病（CD）的疗效受药物浓度的影响。我们旨在评估白蛋白和球蛋白作为与药物浓度相关的预测生物标志物在 CD 中的重要性。
本研究共纳入 2010 年 1 月至 2019 年 2 月期间接受抗肿瘤坏死因子（TNF）-α治疗的 121 例儿科 CD 患者进行回顾性分析。
48.8%的患者（59/121）出现复发。抗 TNF-α治疗 1 年后的 calprotectin 水平（优势比，2.13；p=0.03）和白蛋白-球蛋白比值（AGR）（优势比，0.0002；p=0.003）与复发相关。抗 TNF-α治疗 1 年后的 AGR 是与复发时间相关的唯一因素（风险比，0.02；p<0.001）。预测复发的最佳 AGR 截断值为 1.47（曲线下面积，0.916；p<0.001）。AGR<1.47 的患者的 infliximab 谷浓度（TL）中位数低于 AGR≥1.47 的患者。抗 TNF-α治疗 1 年后的 ADA 浓度与 AGR 呈负相关（r=-0.413，p=0.032）。
AGR 可用于预测复发。抗 TNF-α治疗 1 年后 AGR<1.47 的患者更有可能出现药物 TL 较低和 ADA 产生，这比 AGR≥1.47 的患者更有可能导致复发。因此，如果抗 TNF-α治疗 1 年后的 AGR 小于 1.47，临床医生应监测疾病活动度，评估抗 TNF-α药物的 TL，检测 ADA，并确定适当的治疗策略。
