Long-Term Effectiveness and Safety of Proactive Therapeutic Drug Monitoring of Infliximab in Paediatric Inflammatory Bowel Disease: A Real-World Study

Abstract

Background: This study evaluated the long-term effectiveness and safety of a multidisciplinary early proactive therapeutic drug monitoring (TDM) program combined with Bayesian forecasting for infliximab (IFX) dose adjustment in a real-world dataset of paediatric patients with inflammatory bowel disease (IBD).

Methods: A descriptive, ambispective, single-centre study of paediatric patients with IBD who underwent IFX serum concentration measurements between September 2015 and September 2023. The patients received reactive TDM before September 2019 (n = 17) and proactive TDM thereafter (n = 21). We analysed for clinical, biological, and endoscopic remission; treatment failure; hospitalisations; emergency visits; and adverse drug reactions. The IFX doses were adjusted to maintain trough concentrations ≥ 5 µg/mL, with specific targets for proactive TDM.

Results: Of the 38 patients, 21 had Crohn's disease (CD), 16 ulcerative colitis (UC), and 1 undetermined IBD. The mean (standard deviation) IFX trough concentrations were 6.83 (5.66) µg/mL (reactive) and 12.38 (9.24) µg/mL (proactive) (p = 0.08). No statistically significant differences between groups were found in remission rates or treatment failure. The proactive group had fewer hospitalisations (14.29% vs. 23.53%; p = 0.47) and shorter median hospitalisation days (6 vs. 19; p = 0.50), although the difference was not statistically significant. The number of patients with adverse reactions (infusion related reactions and infections) was higher in the proactive group (38.10% vs. 23.53%; p = 0.34) but the difference was not significantly different.

Conclusions: Proactive TDM showed no significant differences in treatment outcomes compared to reactive TDM. However, the results in both the reactive and proactive TDM groups were not worse than those reported in other studies. Further studies with larger samples are needed to optimize the treatment strategies for pediatric IBD patients.

Keywords: children; inflammatory bowel diseases; infliximab; therapeutic drug monitoring.

Figure 1

Dosing regimen of infliximab (IFX) according to the types of inflammatory bowel disease. CD = Crohn’s disease; UC = ulcerative colitis.

Figure 2

Reasons for intensifications or de-intensifications of infliximab: (1) Cmin outside the established range during both induction and maintenance according to the institutional protocol; (2) high clinical biomarkers (CRP > 0.5 mg/dL and/or FC > 250 mg/kg) and/or clinical non-response (PCDAI and PUCAI > 10); (3) Cmin outside the established range combined with high biomarkers and/or clinical non-response; (4) immunosuppression withdrawal; (5) Cmin outside the established range plus antibody development; (6) change in target levels due to a change in the disease. Cmin = trough concentration; CRP = C-reactive protein; FC = faecal calprotectin; PCDAI = Paediatric Crohn’s Disease Activity Index; PUCAI = Paediatric Ulcerative Colitis Activity Index.

Figure 3

Kaplan–Meier cumulative probability curves for treatment failure with infliximab in children with inflammatory bowel disease undergoing proactive or reactive therapeutic drug monitoring (TDM).

Figure 4

Kaplan–Meier cumulative probability curves for treatment failure with infliximab in children with inflammatory bowel disease according to severe or non-severe very early onset inflammatory bowel disease (VEOIBD).