Initial Clearance of Infliximab is a predictor for long-time mucosal healing and biomarker response

Background Anti-tumor necrosis factor (TNF) alpha therapy poses a mainstay in the treatment of patients with Inflammatory Bowel Disease (IBD). Nevertheless, the pharmacokinetic of Infliximab (IFX) has a high inter- and intra-variability, which can result in loss of response. One possible cause of failure is high initial clearance consequently triggering anti-drug antibody (ADA) formation or result in IFX underexposure. Here, we are exploring initial clearance of IFX as predictor of maintenance outcome in patients with Crohn’s disease (CD).

Methods We developed a population pharmacokinetic model using data from a Phase 3 clinical trial of biosimilar CT-P13 and originator infliximab comparing efficacy and safety in moderately to severely active CD (CDAI of 220–450). Data from 220 patients with 1607 IFX serum concentrations were modeled. The model was qualified and the first estimated clearance for each patient was subsequently merged with patients’ baseline data together with selected endpoints. The data were fit as binary logistic regression analyses. Probability of outcome at week 54 versus predictors of interest (initial IFX clearance, age, IFX dose, disease duration, sex), along with 80 % confidence intervals (CI) were generated.

Results Initial IFX clearance was the only predictor for mucosal healing (SES-CD ≤2; p = 0.00070) at week 54. Initial IFX clearance as well as disease duration and age also predicted serum CRP within normal range at ( < 10 mg/L) at that visit. For clinical remission defined by CDAI < 150 no predictors were identified. Initial clearance was predictive of the development of ADAs at any time.

Conclusion Initial IFX clearance is the only independent predictor of maintenance mucosal healing and biomarker response, but not for clinical remission. Pro-active management of early rapid elimination of biologics might pose an opportunity of long-term inhibition of objective disease activity.

Publication History

Article published online:
01 September 2021