Background & Aims

Infliximab increases the risk of infection in patients with inflammatory bowel diseases (IBD), but there is controversy over the relationship between drug concentration and infections. We aimed to assess factors associated with infection in infliximab-treated patients, including pharmacokinetic features.

Methods

We collected data from 209 patients with IBD (102 men; mean age, 39 y; 159 with Crohn’s disease; 54 received combination therapy) who received an infliximab maintenance regimen from November 2016 through April 2017 in France. Data were collected from each infusion visit (total of 640 infusions). Infliximab exposure was estimated based on the area under the curve (AUC) of drug concentration in pharmacokinetic models; individual exposures over the 6-month period were estimated based on the sum of the AUC (ΣAUC).

Results

The mean infliximab trough level was 5.46 mg/L, and the mean ΣAUC was 3938 ± 1427 mg.d/L. A total of 215 infections were collected from the 640 infusion visits; 123 patients (59%) had at least 1 infection. Factors independently associated with infection after multivariate analysis were smoking (odds ratio [OR], 2.05; P = .046), IBD flare (OR, 2.71; P = .006), and a high ΣAUC of infliximab (above 3234 mg x d/L) (OR, 2.02; P = .02). The ΣAUC was higher in patients with an occurrence of infection (P = .04) and correlated with the number of infections (P = .04). Trough concentration of infliximab alone was not associated with infection.

Conclusions

Almost two-thirds of patients treated with infliximab developed an infection; risk was individually correlated with cumulative increase in drug exposure, but not infliximab trough level.

中文翻译：

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英夫利昔单抗的累积暴露，但不是谷浓度，与感染率相关。

背景与目标

英夫利昔单抗会增加炎症性肠病 (IBD) 患者的感染风险，但药物浓度与感染之间的关系存在争议。我们旨在评估与英夫利昔单抗治疗患者感染相关的因素，包括药代动力学特征。

方法

我们从 2016 年 11 月至 2017 年 4 月在法国接受英夫利昔单抗维持方案的 209 名 IBD 患者（102 名男性；平均年龄 39 岁；159 名克罗恩病患者；54 名接受联合治疗）收集了数据。从每次输注访问中收集数据（总共 640 次输注）。根据药代动力学模型中药物浓度的曲线下面积 (AUC) 估计英夫利昔单抗的暴露量；根据 AUC (ΣAUC) 的总和估算 6 个月期间的个人暴露量。

结果

平均英夫利昔单抗谷浓度为 5.46 mg/L，平均 ΣAUC 为 3938 ± 1427 mg.d/L。从 640 次输液就诊中总共收集了 215 次感染；123 名患者 (59%) 至少有 1 次感染。多变量分析后与感染独立相关的因素是吸烟（比值比 [OR]，2.05；P  = .046）、IBD 发作（OR，2.71；P  = .006）和英夫利昔单抗的高 ΣAUC（高于 3234 mg xd/ L) (OR, 2.02; P  = .02)。发生感染的患者的 ΣAUC 较高 ( P  = .04) 并与感染次数相关 ( P  = .04)。单独使用英夫利昔单抗的谷浓度与感染无关。

结论

几乎三分之二接受英夫利昔单抗治疗的患者发生感染；风险分别与药物暴露的累积增加相关，但与英夫利昔单抗的谷水平无关。