P510 Infliximab in the Very Young: It is All about the Dosing – a Multi-Centre Study
Journal of Crohn's and colitis(2019)
摘要
Infliximab (IFX) is administered intravenously using weight-based dose (5 mg/kg) in paediatric and adult inflammatory bowel disease (IBD) patients. However, previous IFX pharmacokinetic (PK) data suggest this results in lower mean serum IFX concentrations in paediatric compared with adult CD patients, especially in young patients. We hypothesise that young children need a more intensive treatment regimen than the current weight-based dose administration. To assess IFX PK, based on existing therapeutic drug monitoring (TDM) data in a population of paediatric IBD patients below age of 10 and to compare these to paediatric IBD patients above age of 10. TDM data were collected retrospectively in 15 European and Canadian centres. Children treated with IFX between 2004–2016 were included, if IFX was started as IBD treatment below 10 year and PK data were available. These data were compared with a control group of paediatric IBD patients above age of 10 with PK data of IFX treated paediatric IBD patients in the Erasmus MC-Sophia Children’s Hospital. One-hundred and sixty paediatric IBD patients were eligible for the study (110 < 10 year; 50 >10 year). Median age IFX treatment was started was 8.3 years [IQR 6.9–8.9] in the young patients (YP), in the older patient (OP) group this was 14.3 [IQR 12.6–15.6]. In 49% of the YP trough levels were below therapeutic range (<3 μg/ml) at 14 weeks. The median interval between IFX infusions was significantly shorter (median interval days 49[39–56] vs. 56[55–56]; p < .001), while the dose (median dose 8 [5–10] mg/kg vs. 5 [5–8.5] mg/kg; p = 0.013) was significantly higher in the YP than OP at 1 year of scheduled IFX maintenance treatment. Moreover, significantly more YP developed antibodies to infliximab (ATI) during follow-up (44% in YP vs. 8.7 in OP, p = 0.004) compared with the OP group, while overall duration of response to IFX was not significantly different between both age groups (after 2 years 53%(n = 29) in YP vs. 63%(n = 26) in OP; p = 0.24). To achieve therapeutic IFX trough levels in young paediatric IBD patients (<10 years) a more intensive treatment schedule is required. Sub therapeutic IFX levels may be the explanation for development of more ATI’s in young patients compared with the older ones. Despite more ATI formation, duration of IFX therapy was comparable for both age groups. IFX dosing in YP is frequently suboptimal. We recommend to start with a higher dose IFX and an induction schedule with shorter intervals between infusions, beside use of early TDM to further personalise IFX treatment in young IBD patients.
更多查看译文
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要