Trough Concentration Response in Infliximab and Adalimumab Treated Children With Inflammatory Bowel Disease Following Treatment Adjustment: A Pharmacokinetic Model

Abstract

Objectives: In patients with inflammatory bowel diseases (IBD), data on trough concentration (TC) response to adjustments of anti-tumor necrosis factor (TNFα) are scarce. Methods: We included pediatric patients with IBD who were treated with anti-TNFα agents and had sequential monitoring of TC pre- and post-adjustment. Patients with positive anti-drug-antibodies or with concomitant change in immunomodulatory treatment were excluded. Results: For the entire cohort (86 patients), median age at diagnosis was 13.2 (interquartile range, 10.7–14.9) years [females, 48%; Crohn disease (CD), 72%]. For infliximab, 58 patients had 201 interval changes and 26 had dose increase. Increase in TC following dose increase could not be predicted due to significant variability (P = 0.9). For every 10% decrease in interval, TC was increased by 1.6 µg/mL or by 57.2% (P = 0.014). Perianal disease was associated with attenuated response. For every 10% increase in interval, TC was decreased by 0.66 µg/mL or by 4.2%. The diagnosis of CD was associated with reduced response to interval increase. For adalimumab, 28 patients had 31 and 12 events of interval decrease or increase, respectively. Interval decrease resulted in increased median TC from 4.5 (3.5–5.3) µg/mL to 8.1 (6.5–10.5) µg/mL (X1.8) while interval increase resulted in TC change from 15.5 (12.8–18.6) µg/mL to 9.7 (6.5–14.6) µg/mL (:1.6) (P < 0.001 for both). Increase in delta TC was associated with younger age, and with absence of perianal disease (P = 0.001). Conclusion: Changes in TC following treatment adjustment can be almost linearly predicted for adalimumab while response to infliximab adjustment are more variable.