Landemaine Amandine, Petitcollin Antoine, Brochard Charlène, Miard Céline, Dewitte Marie, Le Balc'h Eric, Grainville Thomas, Bellissant Eric, Siproudhis Laurent, Bouguen Guillaume
CHU Rennes, University of Rennes, Rennes, France.
CHU Rennes, University of Rennes, INSERM, CIC1414, France.
Clin Gastroenterol Hepatol. 2021 Feb;19(2):288-295.e4. doi: 10.1016/j.cgh.2020.03.018. Epub 2020 Mar 19.
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.
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).
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.
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.
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。我们旨在评估接受英夫利昔单抗治疗的患者发生感染的相关因素，包括药代动力学特征。
我们收集了209例IBD患者（102例男性；平均年龄39岁；159例患有克罗恩病；54例接受联合治疗）的数据，这些患者于2016年11月至2017年4月在法国接受英夫利昔单抗维持治疗方案。数据从每次输注就诊时收集（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）估算英夫利昔单抗的暴露量；基于AUC总和（ΣAUC）估算6个月期间的个体暴露量。
英夫利昔单抗的平均谷浓度为5.46 mg/L，平均ΣAUC为3938±1427 mg·d/L。在640次输注就诊中共收集到215例感染；123例患者（59%）至少发生1次感染。多因素分析后与感染独立相关的因素为吸烟（比值比[OR]，2.05；P = .046）、IBD发作（OR，2.71；P = .006）以及英夫利昔单抗的高ΣAUC（高于3234 mg·d/L）（OR，2.02；P = .02）。发生感染的患者ΣAUC更高（P = .04），且与感染次数相关（P = .04）。单独的英夫利昔单抗谷浓度与感染无关。
接受英夫利昔单抗治疗的患者中近三分之二发生了感染；风险与药物暴露的累积增加呈个体相关，但与英夫利昔单抗谷浓度无关。
