P-125 YI Utility of Post-Induction Trough Level Measurement in Planning Infliximab Maintenance Therapy for Pediatric IBD

Abstract

Multicenter clinical trial data in adults and children with IBD demonstrate that efficacy of infliximab correlates with drug levels at trough. Trough levels of 3–7 µg/ml are targeted. We measured infliximab levels early following 3rd induction dose in pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC), aiming to optimize individual maintenance regimens. Beginning September 2013 at SickKids Hospital, Toronto 56 children and adolescents (median age 14.4 years; 30 CD; 26 UC) initiating infliximab therapy via a 3-dose induction regimen were given first maintenance dose earlier than the conventional 8 weeks following 3rd induction dose. Infliximab trough levels, measured by ELISA at time of first maintenance infusion, were compared between CD and UC. Influence of disease activity (assessed by physician global assessment and PCDAI or PUCAI), serum albumin and hsCRP at baseline on post-induction early trough levels were assessed. Response to induction regimen was assessed using PGA and PCDAI/PUCAI at time of first maintenance infusion. Thirty CD patients infused in standard fashion (weeks 0, 2, 6) with mean dose of 4.7 mg/kg across the 3 doses had week 12 median trough levels of 9.66 (IQR 4.8–12.8). All but 1 received concomitant immunomodulation during induction (5 AZA; 24 MTX [8 subcut; 16 oral]). Nine (30%) CD patients had week 12 trough level of <5.0 µg/ml, suggesting that standard q 8 weekly maintenance regimen beginning at week 14 would have been suboptimal. Twenty-six UC patients (14 steroid dependent; 12 steroid refractory) received higher infliximab doses (mean of 3 doses 6.17 mg/kg, P = 0.0003 versus CD), often given more intensively (3 doses within 4-5 weeks in 13). UC patients were given first maintenance dose 4 weeks following 3rd induction dose, but median trough levels of 10.10, (IQR 2.6–13.0) were similar to those achieved among CD patients 6 weeks post 3rd infusion. Although similar in age and baseline disease activity, CD and UC patients differed with respect to gender (males 67% CD versus 35% UC; chi sq P = 0.017); concomitant steroid therapy (CD: 40%; UC: 80%; Fisher's exact test P = 0.0002) and immunomodulation (93.67% CD versus 15.38% UC; chi sq P < 0.0001) during induction. 26/30 children treated for CD compared with 10/26 treated for UC achieved steroid-free clinical remission post induction as assessed by PGA and PCDAI/PUCAI. 8/14 of the UC patients with continuing active disease had adequate trough levels (>3). Early post-induction trough level testing is useful in assessing primary non-response to infliximab and in planning of optimal maintenance regimen. In this pediatric cohort, patients with UC cleared drug more rapidly, requiring higher per kg dosing and a more intensive regimen to achieve comparable drug levels post induction.