Prior adalimumab exposure alters infliximab pharmacokinetics and trough targets in pediatric Crohn's disease.

BACKGROUND: In patients with Crohn's disease (CD) treated with infliximab (IFX), the annual rate of loss of response is approximately 10%. This study aimed to compare patients who initiated primary IFX in the disease course with those who received IFX as a second-line biologic after a longer disease duration and greater prior treatment exposure. METHODS: This retrospective study reviewed medical records of children with Crohn's disease (CD) who received IFX therapy. Patients were classified according to prior adalimumab (ADL) exposure status, and IFX trough levels (TLs) and endoscopic outcomes were compared between groups. RESULTS: A total of 469 children with CD were included, including 372 in the biologic-naive group and 97 in the ADL-exposed group. There was no statistically significant difference in demographic data and disease severity at diagnosis between the two groups. However, at the time of IFX initiation, patients in group 2-who had a longer disease duration-were significantly older (P < .001) and had a higher body mass index than those in group 1 (P < .001). As the 1-year outcome of IFX therapy, the proportion achieving endoscopic remission (ER) did not differ significantly between group 1 and group 2 (61.3% vs 58.8%; P = .328). However, at the 1-year assessment, IFX TLs were significantly lower in group 2 than in group 1 (4.73 µg/mL vs 6.19 µg/mL, P = .003), and a significantly higher proportion of group 2 required dose intensification (41.2% vs 35.2%; P = .001). In a combined-cohort logistic regression, erythrocyte sedimentation rate, body mass index, IFX TLs, and dose intensification were significantly associated with ER. CONCLUSIONS: Prior ADL exposure was associated with lower IFX TLs despite comparable rates of ER when IFX was used as first- or second-line biologic therapy in pediatric CD. Patients with prior ADL exposure achieved ER at lower observed IFX TLs than biologic-naive patients, suggesting a potential difference in the exposure-response relationship according to prior ADL exposure status.