Pediatr. 2021 Sep 3;S0022-3476(21)00864-7. doi: 10.1016/j.jpeds.2021.08.079.Online ahead of print.

Karen van Hoeve ¹, Nasim Sadat Seyed Tabib ², Erwin Dreesen ³, Sophie Tops ⁴, Ilse Hoffman ⁵, Ann Gils ⁴, Marc Ferrante ⁶, Séverine Vermeire ⁷

Author information

¹Department of Pediatric Gastroenterology & Hepatology & Nutrition, University Hospitals Leuven, KU Leuven, Leuven, Belgium; TARGID, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium.

²TARGID, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium.

³Clinical Pharmacology and Pharmacotherapy Unit, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.

⁴Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.

⁵Department of Pediatric Gastroenterology & Hepatology & Nutrition, University Hospitals Leuven, KU Leuven, Leuven, Belgium.

⁶TARGID, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium; Department of Gastroenterology & Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.

⁷TARGID, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium; Department of Gastroenterology & Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. Electronic address: severine.vermeire@uzleuven.be.

Abstract

Objectives: To study infliximab (IFX) pharmacokinetics in children with inflammatory bowel disease (IBD) during induction therapy to predict outcome and explore if other covariates influenced outcome.

Study design: All children with IBD starting IFX therapy (5 mg/kg at weeks 0, 2, 6, and 12) for active luminal disease from May 2017 to May 2019 were included and followed prospectively. Patients were sampled at multiple timepoints during induction (trough concentrations and peak concentration at weeks 0, 2, 6, and 12, and intermediate concentration at weeks 1-4). IFX concentrations and cumulative drug exposure were correlated with outcome at 6 months. Endoscopic remission was defined as Simple Endoscopic Score for Crohn's Disease of <3 or Mayo endoscopic subscore of 0, and deep remission as endoscopic with clinical remission (Pediatric Ulcerative Colitis Activity Index/Pediatric Crohn's Disease Activity Index of <10).

Results: There were 252 serum induction concentrations obtained from 32 patients (81% on concomitant thiopurines). Children in endoscopic remission (all in deep remission) at 6 months had significantly higher drug concentrations from week 4 onward. A receiver operating characteristics curve analysis identified IFX trough concentrations at week 12 of ≥5.0 μg/mL and area under the curve at weeks 0-12 of ≥4056.0 μg∗day/mL as the minimal target to achieve endoscopic remission at 6 months (area under the receiver operating characteristics curve, 0.796 [95% CI, 0.62-0.97] and area under the receiver operating characteristics curve, 0.778 [95% CI, 0.61-0.94], respectively). In addition, our findings suggest that proteomic analysis may help to understand IFX response.

Conclusions: Higher IFX exposure during induction therapy in pediatric patients with IBD is associated with significantly better endoscopic and deep remission rates at 6 months. Drug concentrations differentiate remitters from nonremitters from week 4 after induction onward.