P451 Early infliximab trough levels in paediatric IBD patients predict sustained remission

Abstract

Background Therapeutic drug monitoring (TDM) is an approach to improve treatment effectiveness of anti-TNF therapy in Inflammatory Bowel Disease (IBD), but timing and threshold trough levels (TL) are still subject of investigation, especially in paediatric populations. The aims of our study were (1) to analyse induction – and post-induction infliximab TLs (respectively after 6 and 14 weeks) to predict sustained biochemical and clinical remission between 6 and 12 months in paediatric patients with IBD, and (2) to define paediatric threshold TLs at these timepoints. Methods We performed a retrospective study in 70 anti-TNF naïve paediatric IBD patients from two centres who were treated with an induction scheme of 5 mg/kg on 0, 2 and 6 weeks, and subsequently every approximately 8 weeks. We measured infliximab TLs at week 6 and 14 combined with (non)-invasive markers for disease activity. Patients were in sustained biochemical and clinical remission when they were asymptomatic and had normalised CRP and faecal calprotectin between 6 and 12 months after initiating therapy. Receiver operating characteristic (ROC) analysis was used to determine infliximab TL thresholds that best predicted sustained biochemical remission. Results Median infliximab TL at 6 and 14 weeks were higher for children in sustained remission versus children who were not (TL6 p=0.028 and TL14 p=0.028). Area under the ROC curve (AUROC) for infliximab TL6 and TL14 to predict sustained biochemical remission was 0.68 (95% Confidence Interval [CI] 0.53-0.83) and 0.67 (95%CI 0.53-0.82), respectively (Figure 1 and 2). The optimal infliximab thresholds were 13.2 mg/L and 6.9 mg/L for TL6 and TL14, respectively, yielding a sensitivity and specificity of 70% and 68% for TL6 and 57% and 76% for TL14. Figure 1 ROC curve of infliximab trough level at 6 weeks for predicting sustained remission between 6 months to 12 months. Figure 2 ROC curve of infliximab trough level at 14 weeks for predicting sustained remission between 6 months to 12 months. Conclusion In children with IBD treated with a regular infliximab induction scheme, infliximab TLs at week 6 and 14 both predicted sustained clinical and biochemical remission between 6 and 12 months after initiating therapy. TDM and early dose optimization may improve infliximab effectiveness and drug survival.