Association between infliximab drug and antibody levels and therapy outcome in pediatric inflammatory bowel diseases

Objectives: While infliximab pharmacokinetics are associated with therapy outcome in adult inflammatory bowel disease (IBD) population, limited data are available in pediatric patients. We aimed to define the relationship between infliximab trough and antibodies' levels (IFX-TL, ATI) and clinical, biomarker remission. Methods: IFX-TL and ATI were routinely obtained between 2011 and 2017. Associations with clinical and inflammatory (C-reactive protein, CRP) endpoints were studied throughout the first year of infliximab therapy. Results: A total of 63 patients (50 Crohn disease, 13 ulcerative colitis, median follow-up 16 months, median 8samples/patient) were included, and 773 sera-samples were analyzed. Sera of patients in clinical remission had higher median IFX-TLs than sera of those with active disease (4 vs 2.25 mg/mL, P< 0.0001). In addition, patients with normal CRP had a higher median IFX-TL than those with elevated CRP (P = 0.02). Moreover, IFX-TL > 9.2mg/mL at week 2 predicted clinical remission by week 14 (sensitivity 71.4%, specificity 81.2%, area under curve (AUC) = 0.73, P = 0.02) and IFX-TL > 2.2 mg/mL at week 6 predicted infliximab retention beyond 1 year of treatment (sensitivity 88.9%, specificity 100.0%, AUC = 0.974, P< 0.0001). Conclusions: A significant association between IFX-TL and ATI and clinical and biomarker remission status in pediatric IBD patients was demonstrated, including a temporal association between week 2, 6 levels and outcome of induction and between week 6 and 14 levels and remission at 1 year of therapy. These findings suggest that therapeutic drug monitoring may be considered for management guidance among pediatric IBD patients.