Abstract Background Infliximab (IFX) is widely used for treating pediatric inflammatory bowel disease (pIBD). Development of anti-infliximab antibodies (AbIFX) reduces treatment efficacy, accelerating drug clearance. This study evaluated factors impacting serum IFX levels, AbIFX positivity in pIBD, and aimed to identify the most appropriate IFX threshold for antibody testing. Methods Clinical and biochemical data, including inflammatory and disease-activity indices, were collected from pIBD patients followed at a tertiary referral center who underwent IFX and AbIFX measurements between May 2019 and September 2024. IFX and AbIFX were quantified by ELISA. AbIFX positivity was defined as 3 U/mL. Results A total of 374 paired IFX–AbIFX determinations from 55 patients (26 males; Crohn’s disease n = 41, ulcerative colitis n = 14) were analyzed. AbIFX were detected in at least one determination in 29% of patients, more frequently in Crohn’s disease (34%) than in ulcerative colitis (14%). At univariate analysis, IFX concentrations were significantly associated with BMI (r = 0.1425, p = 0.0058), ESR (r=-0.1673, p = 0.0028), CRP (r=-0.2801, p 0.0001) and albumin (r = 0.1309, p = 0.0156). In the multivariate linear regression model, adjusted for days since last infusion and dose (mg/kg), only ESR remained independently associated with IFX levels (B = –0.095, p = 0.011). At univariate analysis, AbIFX positivity correlated with disease activity (p = 0.036) and infusion reactions (p 0.0001). In the multivariate logistic regression, only infusion reactions remained an independent predictor of antibody positivity (OR = 22.8, p = 0.002). A moderate inverse correlation was observed between IFX and AbIFX levels (p 0.0001). ROC analysis (AUC = 0.790) identified a 3 µg/mL IFX threshold as the most accurate cut-off for predicting AbIFX positivity (sensitivity 77,6%, specificity 70,1%), outperforming the conventional 5 µg/mL threshold (sensitivity 79,6%, specificity 51,6%). Conclusion Systemic inflammation, reflected by elevated ESR, emerged as the main determinant of reduced IFX through levels. Antibody development was strongly associated with infusion-related reactions, likely representing the clinical expression of infliximab immunogenicity. A serum IFX threshold of 3 µg/mL appears to be a more accurate and clinically useful trigger for reflex antibody testing, supporting a personalized and cost-effective therapeutic drug-monitoring strategy in pediatric IBD. Conflict of interest: Dr. Gagliano, Chiara: No conflict of interest Carciofi, Annalisa: No conflict of interest Borgiani, Francesca: No conflicts of interest Olivetti, Linda: No conflict of interest Morelli, Renato: No conflict of interest Babini, Lucia: No conflict of interest Baldassari, Michela: No conflict of interest Calcinari, Alessandra: No conflict of interest Brusco, Mario: No conflict of interest Franceschini, Elisa: No conflict of interest Moretti, Marco: No conflict of interest Lionetti, Maria Elena: No conflict of interest Gatti, Simona: No conflict of interest
Gagliano et al. (Thu,) studied this question.