THERAPEUTIC DRUG MONITORING OF INFLIXIMAB DURING INDUCTION: A SINGLE-CENTER EXPERIENCE

Background: Anti-tumor necrosis factor (TNF) treatment in moderate to severe pediatric Inflammatory Bowel Disease (IBD) is effective; however, loss of response (LOR) to drug can be as high as 40%.Both primary and secondary LOR contribute to treatment failure.Evidence suggests that clinical and histologic remission rates are improved with prospective therapeutic drug monitoring (TDM) at Week 14. Limited data exists for TDM utility during induction.We aim to examine infliximab (IFX) levels achieved during standard induction and assess the relationship between induction and maintenance TDM and overall clinical remission rates.Methods: The study population consisted of all IBD patients receiving anti-TNF therapy with IFX at our institution between January 2015 and November 2017 who had documented IFX levels and anti-drug antibody (ADA) titers.Demographic data, primary diagnosis, sites of involvement, IFX levels and ADA titers were recorded retrospectively.Sample mean, standard deviation, and median were calculated for the patient's current age and at diagnosis of IBD.Data was stratified by IFX levels achieved during induction of IFX.Though TDM was performed by all providers, decisions regarding dose optimization were at the discretion of the treating physician.All data analyses were performed by using SAS Enterprise Guide 7.1.Results: A total of 148 patients met inclusion criteria.Among our population, 80.3% identified as Hispanic and 65% were male.The mean patient age was 14.9 (range 2-23) years.The mean age at diagnosis was 12.6 (1.5-21) years.72.7% of our population had Crohn's disease (CD).CD phenotype was described as inflammatory in 48.2%, penetrating in 38.8%, and stenosing in 7.1%.Of patients receiving induction IFX at 5-7 mg/kg, mean IFX level at Week 6 was 18.9 (range 0-34) µg/mL.Of patients receiving induction IFX at 7.5-10 mg/kg, mean IFX level at Week 6 was 27.1 (range 0-34) µg/mL.Week 6 levels above 30 µg/mL were associated with higher IFX levels ( $ 5 µg/mL) during first maintenance TDM (63%).8.5% of our population had ADA (mean 18 U/ml, range 4.5-51.3U/ml) present at 6 weeks.Of patients with 12-month clinical data, 81% remained in clinical remission on IFX.76% of patients showing LOR to IFX at 12 months were secondary to ADA.Discussion: 81% of our population who underwent routine Week 6 TDM remained in clinical remission at 12 months.Patients with IFX levels greater than 30 µg/mL at Week 6 were found to have the highest TDM level during maintenance.Of patients who failed IFX, the majority showed secondary LOR due to formation of ADA.Our results indicate the likely benefit of early TDM assessment and an opportunity to improve clinical outcomes.Further study is needed to assess optimum IFX dose modification and correlate with clinical and endoscopic remission. Su2029