The following is a summary of “Trough Concentration Response in Infliximab and Adalimumab Treated Children With Inflammatory Bowel Disease Following Treatment Adjustment: A Pharmacokinetic Model,” published in the May 2023 issue of Gastroenterology and Nutrition by Levy, et al.
For a study, researchers sought to assess the trough concentration (TC) response to adjustments of anti-tumor necrosis factor (TNFα) therapy in pediatric patients with inflammatory bowel diseases (IBD).
Pediatric patients with IBD who were receiving anti-TNFα agents and had sequential monitoring of TC before and after treatment adjustments were included. Patients with positive anti-drug antibodies or concurrent changes in immunomodulatory treatment were excluded from the analysis.
The cohort consisted of 86 patients with a median age at diagnosis of 13.2 years. Among them, 48% were females, and 72% had Crohn’s disease (CD). For patients receiving infliximab, there were 201 interval changes and 26 dose increases. The increase in TC following a dose increase could not be reliably predicted due to significant variability (P = 0.9). However, for every 10% decrease in dosing interval, TC increased by 1.6 µg/mL or 57.2% (P = 0.014). The presence of perianal disease was associated with a reduced response. Conversely, for every 10% increase in dosing interval, TC decreased by 0.66 µg/mL or 4.2%. Patients diagnosed with CD exhibited a diminished response to interval increases. In the case of adalimumab, there were 31 interval decreases and 12 interval increases among 28 patients. Interval decreases resulted in a significant increase in median TC from 4.5 (3.5–5.3) µg/mL to 8.1 µg/mL (1.8-fold change), while interval increases led to a 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). An increase in delta TC was associated with younger age and the absence of perianal disease (P = 0.001).
Adjustments in TC following treatment modifications can be predicted in a nearly linear manner for adalimumab, whereas the response to infliximab adjustments is more variable. The findings highlighted the importance of individualized treatment strategies in pediatric patients with IBD receiving anti-TNFα therapy.