Utility of regular infliximab levels in pediatric Crohn's disease

Abstract

Introduction: Infliximab (IFX) has an established role in treating Crohn's disease. Serum trough IFX levels and anti-drug antibodies are increasingly used to optimize drug dosing in those losing response (LOR) and, in some adult studies, to predict and manage potential LOR. We report performance of routine IFX levels in children and the value of regular levels for guiding management. Methods: Retrospective chart review of children with Crohn's disease receiving IFX in a tertiary pediatric centre. Patient age, clinical phenotype, duration of therapy, IFX level, biomarkers and changes in management were recorded. Standard induction and maintenance therapy regimes were employed. Remission was defined as clinically well with normal CRP (<5) and FC (<200). Results: 117 IFX levels were recorded in 46 patients from January 2014 to March 2016. 43/46 (93%) children were on combination therapy with immunosuppression (IS) and only 2 developed IFX antibodies. 43 episodes of relapse (clinical, CRP >5, FC >200) were documented and IFX levels at this time were significantly lower (mean 4.6 μg/mL) than those in remission (mean 6.6, p=0.02). 17/43 (40%) in relapse had IFX levels <3.0 vs. 16/74 (22%) in remission with IFX levels <3.0. 27/117 (23%) of IFX levels led directly to a change in management: 15 episodes of treatment escalation, 7 of de-escalation and 5 changes to adalimumab. Of 15 escalations in treatment, 5 resulted in complete clinical and biochemical improvement to normal. 6/7 treatment de-escalations remained in remission with therapeutic IFX levels. 19 children had IFX levels at completion of induction (mean 8.5) significantly higher than those during maintenance (mean 5.5, p <0.01). All 9 children with post-induction IFX level >7 remained in clinical and biochemical remission over the following 6-12 months. 3 children had post-induction IFX levels <3, 2 failed to go into remission and 1 relapsed at 12 months. Conclusions: IFX trough levels help guide optimal management of IFX in children, including escalation and de-escalation of dosing, or change to adalimumab. They have some utility as a biomarker, with higher levels associated with ongoing clinical and biochemical remission. High post-induction IFX levels >7 predict a favourable 6-12 month response and low post-induction levels <3 predict a poor response or early relapse. Study numbers are small, but results are consistent with the emerging literature.L6128916632016-11-10 <br />