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P337 Early infliximab clearance predicts remission in children with Crohn’s Disease

Chung, A.(1);Carroll, M.(1);Almeida, P.(1);Petrova, A.(1);Mould, D.(2);Wine, E.(1);Huynh, H.(1);

(1)University of Alberta, Faculty of Medicine and Dentistry, Edmonton, Canada;(2)Projections Research Inc, Pharmacology, Phoenixville, United States; Edmonton Pediatric IBD Clinic (EPIC)

Background

Recent studies suggest pediatric Crohn’s Disease (CD) patients have higher infliximab clearance (IFX CL) for body weight and lower serum IFX when dosing by weight. Our aim was to determine if IFX CL calculated based on therapeutic drug monitoring (TDM) data predicts long term outcome.

Methods

Retrospective study of CD patients seen at the Stollery Children’s hospital from Jan 2013-Jul 2019. Anthropometric, lab, IFX TDM & disease data were collected for those having >2 serum IFX levels. IFX CL was calculated using non linear mixed effects modelling. The data was fit to a 2-compartment model with linear elimination. Outcomes were defined at 4, 9 & 15 months. Remission is defined as wPCDAI<12.5, CRP<4 & steroid-free for 4 months. Subjects that underwent intestinal surgery or ceased IFX due to refractory CD are non-responders. Logistic regression was used to determine early predictors (at baseline or end of induction) associated with remission at 4, 9 & 15 months. The variables evaluated were: IFX CL, IFX trough level, sex, age, PARIS classification, CRP, ESR, Alb, Hgb, weight, BSA, BMI, previous anti-TNF & immunomodulator use.

Results

85 subjects were included, with a median follow up of 670 days (IQR: 304,1105). See table 1 for baseline characteristics. Regression analysis showed early IFX CL was the only significant early predictor of remission for every timepoint. Baseline IFX CL and end of induction IFX CL, measured in L/h, were associated with 15-month remission with an OR of 0.606 (95%CI: 0.394,0.931; p=0.022) and 0.373 (95%CI: 0.207,0.669; p=0.001) respectively. Similar results obtained at 4 & 9 months. ROC analysis of remission was done using only early IFX CL. A baseline IFX CL of 5.83 L/h predicted 15-month remission with a sensitivity & specificity of 0.649 & 0.667 (AUC=0.701). End of induction IFX CL of 6.06 L/h predicted 15-month remission with a sensitivity & specificity of 0.676 & 0.611 (AUC=0.709). Similar results obtained at 4 & 9 months.

Table 1

nMedian(IQR)
Age12.7(10.1,14.6)
Sex(M:F)50:35
Weight(kg)37.4(28.0,49.8)
BMI16.1(14.6,19.9)
wPCDAI42.5(15,65)
Previous Adalimumab12
Ceased IFX due to refractory CD5
Intestinal Surgery due to refractory CD10
Paris Behavior
Non stricturing, non-penetrating66
Stricturing16
Penetrating3
Perianal40
Paris Location
Terminal ileum10
Colonic20
Ileocolonic55

Conclusion

In all timepoints, early IFX CL was a strong predictor of later remission compared to dose intensity, frequency, IFX levels and wPCDAI & CRP at end of induction. This suggests early IFX CL is a marker of early biological response to IFX. Early dose optimization is required in those with high IFX CL to ensure optimal response with adequate drug exposure. This will facilitate early change in treatment for those with inadequate response.

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