Clemente Bautista Susana, Segarra Cantón Óscar, Padullés-Zamora Núria, García García Sonia, Álvarez Beltrán Marina, Larrosa García María, Cabañas Poy Maria Josep, Sanz-Martínez Maria Teresa, Vázquez Ana, Gorgas Torner Maria Queralt, Miarons Marta
Pharmacy Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain.
Paediatric Gastroenterology and Clinical Nutrition Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain.
Pharmaceutics. 2024 Dec 10;16(12):1577. doi: 10.3390/pharmaceutics16121577.
This study evaluated the long-term effectiveness and safety of a multidisciplinary early proactive therapeutic drug monitoring (TDM) program combined with Bayesian forecasting for infliximab (IFX) dose adjustment in a real-world dataset of paediatric patients with inflammatory bowel disease (IBD).
A descriptive, ambispective, single-centre study of paediatric patients with IBD who underwent IFX serum concentration measurements between September 2015 and September 2023. The patients received reactive TDM before September 2019 (n = 17) and proactive TDM thereafter (n = 21). We analysed for clinical, biological, and endoscopic remission; treatment failure; hospitalisations; emergency visits; and adverse drug reactions. The IFX doses were adjusted to maintain trough concentrations ≥ 5 µg/mL, with specific targets for proactive TDM.
Of the 38 patients, 21 had Crohn's disease (CD), 16 ulcerative colitis (UC), and 1 undetermined IBD. The mean (standard deviation) IFX trough concentrations were 6.83 (5.66) µg/mL (reactive) and 12.38 (9.24) µg/mL (proactive) ( = 0.08). No statistically significant differences between groups were found in remission rates or treatment failure. The proactive group had fewer hospitalisations (14.29% vs. 23.53%; = 0.47) and shorter median hospitalisation days (6 vs. 19; = 0.50), although the difference was not statistically significant. The number of patients with adverse reactions (infusion related reactions and infections) was higher in the proactive group (38.10% vs. 23.53%; = 0.34) but the difference was not significantly different.
Proactive TDM showed no significant differences in treatment outcomes compared to reactive TDM. However, the results in both the reactive and proactive TDM groups were not worse than those reported in other studies. Further studies with larger samples are needed to optimize the treatment strategies for pediatric IBD patients.
本研究在儿科炎症性肠病（IBD）患者的真实世界数据集中，评估了多学科早期主动治疗药物监测（TDM）计划联合贝叶斯预测用于英夫利昔单抗（IFX）剂量调整的长期有效性和安全性。
对2015年9月至2023年9月期间接受IFX血清浓度测量的儿科IBD患者进行一项描述性、回顾性、单中心研究。2019年9月之前患者接受反应性TDM（n = 17），之后接受主动TDM（n = 21）。我们分析了临床、生物学和内镜缓解情况；治疗失败情况；住院情况；急诊就诊情况；以及药物不良反应。调整IFX剂量以维持谷浓度≥5μg/mL，并为主动TDM设定了特定目标。
38例患者中，21例患有克罗恩病（CD），16例患有溃疡性结肠炎（UC），1例患有未定型IBD。IFX谷浓度的平均值（标准差）在反应性组为6.83（5.66）μg/mL，在主动组为12.38（9.24）μg/mL（P = 0.08）。两组在缓解率或治疗失败方面未发现统计学上的显著差异。主动组的住院次数较少（14.29%对23.53%；P = 0.47），中位住院天数较短（6天对19天；P = 0.50），尽管差异无统计学意义。主动组中出现不良反应（输液相关反应和感染）的患者数量较多（38.10%对23.53%；P = 0.34），但差异无显著统计学意义。
与反应性TDM相比，主动TDM在治疗结果上无显著差异。然而，反应性和主动TDM组的结果均不劣于其他研究报告的结果。需要进行更大样本量的进一步研究，以优化儿科IBD患者的治疗策略。
