Use of therapeutic drug monitoring (TDM) to individualize biologic therapy is a logical strategy, given the variable drug clearance and multiple factors influencing pharmacokinetics. However, prospective studies in adults have not demonstrated improved efficacy with TDM implemented following induction phase of infliximab treatment. We implemented TDM during induction in children with IBD, aiming to pre-emptively personalize maintenance dosing given previously documented wide variability of infliximab levels observed early post induction in paediatric patients.Methods:
Beginning in May 2016, children with IBD at participating sites in the Canadian Children IBD Network, when prescribed 3-dose infliximab induction therapy via either standard or intensified regimen, had pre-infusion trough level measured by ELISA at the time of third dose. An algorithm incorporating this trough level and the interval between doses 2 and 3 was used to determine timing and dose of first maintenance infusion, aiming to provide a trough level of 5 to 10 μg/mL when tested before dose 4. Induction regimens were at the discretion of the treating physician, but often intensified among patients with severe UC. Influence of patient demographics and baseline disease activity (physician global assessment and wPCDAI or PUCAI) on early trough levels was assessed.Results:
From May to August 2016 at 6 participating sites, 47 children (mean age 12.4 years, 62% male, 55% CD, 45% UC/IBD-U) received 3-dose infliximab induction. The CD patients (22% L1; 22% L2; 50% L3) infused in standard fashion at weeks 0, 2, 6 with mean dose of 5.5 mg/kg and with concomitant immunomodulation (93% methotrexate; 7% azathioprine) had a median pre-dose 3 IFX level of 11.9 μg/mL (IQR: 8.5–27.2). UC/IBD-U patients (18%steroid-dependent, 82% steroid-refractory) received more drug (mean 6.8 mg/kg across 3 doses) and via an intensified regimen (i.e., 3 doses within 4 weeks) in 34%. Pre-dose 3 IFX levels (median 13.5 μg/mL; IQR: 4.9–24.3) were comparable to CD despite use of higher doses. 25% of UC/IBD-U patients versus 11% of CD patients had infliximab trough level less than 5 μg/mL at time of dose 3.Conclusions:
Variability in infliximab exposure is evident early during induction. Patients with UC cleared drug more rapidly, requiring higher per kg dosing and a more intensive regimen to achieve comparable drug levels post induction. Ongoing monitoring of trough levels achieved prior to dose 4 in this cohort will determine whether early TDM with personalized dosing more consistently ensures adequate drug exposure.