Utility of recording regular infliximab levels in pediatric Crohn's disease

Abstract

Introduction: Infliximab (IFX) has an established role in treating Crohn's disease (CD). Serum trough IFX levels (TLIs) and anti-drug antibodies (ADAs) are increasingly used to optimize drug dosing in those with loss of response (LOR) and to predict and manage potential LOR. We report the performance of routine TLIs in children and their value in guiding management. Methods: We conducted a retrospective chart review of children with CD receiving IFX in a tertiary pediatric center. Patient age, clinical phenotype, duration of therapy, TLI (μg/mL), biomarkers, and changes in management were recorded. Standard induction and maintenance therapy regimens were employed. Remission was defined as Pediatric Crohn's Disease Activity Index (PCDAI) ≤ 10, C-reactive protein ≤ 5, fecal calprotectin ≤ 200 and no active endoscopic disease. Results: A total of 209 TLIs were recorded in 60 patients from January 2014 to May 2017. Of the 60 children, 56 (93%) were receiving combination therapy with an immunomodulator, and five (8%) developed ADAs. There were 72 episodes of relapse documented, with TLIs (mean, 4.6) significantly lower than in those in remission (mean, 6.5; P < 0.0001). Of the 72 in relapse, 36 (50%) had a TLI < 3 versus 25/137 (28%) in remission (P < 0.0001). Seven of 72 (10%) in relapse had a TLI > 7 versus 47/137 (34%) in remission (P = 0.0001). Forty-three of 209 TLIs (21%) directly led to a change in management in 31/60 children (52%): 21 episodes of treatment escalation, 12 of de-escalation, and 10 changes to adalimumab. Of the 21 escalations in treatment, 10 had complete clinical and biochemical improvement to normal, six had partial improvement in PCDAI and/or biomarkers, and five had no improvement, requiring a change to adalimumab. Of the 12 de-escalations, seven remained in complete remission with therapeutic TLIs over the following 12 months, and five had an episode of relapse. At completion of induction, 31 children had TLIs (mean, 8.6) significantly higher than those during maintenance therapy (mean, 5.0; P < 0.0001). Seventeen of 31 children had a postinduction TLI > 7, with 15/17 achieving clinical and biochemical remission that continued for the duration of therapy. Five of 31 children had a post-induction TLI < 3, with four requiring early escalation due to failed induction or early relapse. Conclusions: Routine TLIs have a high utility for guiding optimal management of IFX in children, including escalation and de-escalation of dosing or change to adalimumab. At time of sampling, TLIs < 3 are associated with relapse, and TLIs > 7 are strongly associated with clinical and biochemical remission. Post-induction TLI > 7 predicts a favorable sustained response, and post-induction TLI < 3 predicts poor response or early relapse. Routine TLI monitoring in children with CD is useful for clinical decision making and should therefore be standard clinical practice.L6180063372017-08-31 <br />