A93 POST-INDUCTION INFLIXIMAB TROUGH LEVELS VARY WIDELY AND AID IN INDIVIDUALIZING INFLIXIMAB MAINTENANCE THERAPY FOR PEDIATRIC IBD

Abstract

Clinical trial data in patients with IBD shows that infliximab (IFX) efficacy correlates with trough drug levels. Absence of drug predisposes to antibody formation and secondary loss of response. We aimed to individualize IFX regimens through early post-induction drug levels in pediatric patients with Crohn’s disease (CD) and ulcerative colitis (UC). Starting September 2013 at SickKids Hospital, Toronto children/adolescents initiating IFX via a 3-dose induction regimen were given their first maintenance dose earlier than the conventional 8 weeks following 3rd induction dose. IFX trough levels, measured by ELISA at the time of first maintenance infusion were compared between CD and UC. The influence of baseline characteristics such as physician global assessment (PGA) of disease activity, albumin and hsCRP on trough levels pre-dose 4 was assessed. 125 patients with IBD (81 CD, 44 UC; 60% male) were identified (Table). CD and UC patients were similar in age, gender, disease duration, BMI, and hsCRP. However, UC patients had higher disease activity, lower albumin, and higher steroid use at baseline. 81 CD patients infused in standard fashion (weeks 0, 2, 6) had a median dose of 5.3 mg/kg (IQR 5.0–5.5) across 3 induction doses. They had median trough levels at week 12 of 9.3 mcg/mL (IQR 4.8–13.4). 65/81 (80%) received concomitant immunomodulator during induction. 22 (27%) CD patients had a week 12 trough level <5 mcg/mL, and 18 (22%) had a level <3 mcg/mL. 44 UC patients were induced more intensively, with many given 3 doses over 4–5 weeks. They also received higher doses (median 6.3 mg/kg over 3 induction doses) compared to CD (p<0.001). All UC patients were given their first maintenance dose 4 weeks following the 3rd induction dose. The median trough level of 10.2 mcg/mL (IQR 3.7–14.4) was similar to CD patients dosed 6 weeks after their 3rd infusion (Figure). Dose 4 trough levels were <7mcg/mL for 17 (37%) UC patients and <3mcg/mL for 9 (21%). Post-induction trough levels are variable for pediatric IBD patients. For many patients, standard maintenance infusions beginning at week 14 would result in suboptimal trough levels. In this cohort, patients with UC cleared drug more rapidly, requiring more intensive dosing to achieve comparable drug levels post induction. Baseline characteristics None