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* = Presenting author

P297 Utility of post-induction trough level measurement in planning infliximab maintenance therapy for pediatric IBD

C. Popalis*, P.C. Church, K. Frost, J. Johnstone, T. Walters, A.M. Griffiths

The University of Toronto, Hospital for Sick Children, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Toronto, Canada

Background

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.

Methods

Beginning September 2013 at SickKids Hospital, Toronto 51 children and adolescents (median age 14.9 yrs; 30 CD; 21 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.

Results

30 CD patients infused in standard fashion (weeks 0,2,6) with mean dose of 5.3 mg/kg across the 3 doses had week 12 median trough levels of 9.7 (IQR 4.8 -12.8). All but one received concomitant immunemodulation during induction. Nine (30%) CD patients had week 12 trough level of <5.0µg/ml, suggesting that standard q8 weekly maintenance regimen beginning at week 14 would have been suboptimal.

21 UC patients (9 steroid dependent;12 steroid refractory) received higher infliximab doses (mean of 3 doses 6.2mg/kg, p=0.001 vs CD),often given more intensively (3 doses within 4 weeks in 17). UC patients were given first maintenance dose 4 weeks following 3rd induction dose, but median trough levels of 10.2 (IQR 4.8-14.0) were similar to those achieved among CD patients 6 weeks post 3rd infusion (Wilcoxon p=0.80).

Although similar in age, gender and baseline disease activity, CD and UC patients differed with respect to concomitant steroid therapy (CD:40%; UC:100%, Fisher's exact p<0.0001) and immunomodulation (CD:96.7%; UC:4.8%, Fisher's exact p< 0.0001) during induction.

24/28 children treated for CD, excluding those with a primary indication of perianal disease, compared with 7/21 treated for UC achieved steroid-free clinical remission post induction. 9/12 of the UC patients with continuing active disease had adequate trough levels (>3).

Conclusion

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.