Changes in serum trough levels of infliximab during treatment intensification but not in anti-infliximab antibody detection are associated with clinical outcomes after therapeutic failure in Crohn's disease

J Crohns Colitis. 2015 Mar;9(3):238-45. doi: 10.1093/ecco-jcc/jjv004. Epub 2015 Jan 9.


Background and aims: Intensification of the infliximab (IFX) regimen is recommended if the treatment effect is inadequate. However, the rationale for this is not well defined as the underlying mechanisms vary. The aim of this study was to explore the association between changes in serum IFX and anti-IFX antibodies (Abs) after IFX intensification and clinical outcomes.

Methods: We performed a post hoc analysis of a randomized clinical trial including 42 Crohn's disease patients with IFX treatment failure, all treated with an intensified IFX regimen (5mg/kg every 4 week) for 12 weeks. Trough serum IFX and anti-IFX Ab concentrations were measured by a homogeneous mobility shift binding assay (HMSA) and a functional cell-based reporter gene assay (RGA) at treatment failure and the end of the trial.

Results: Twenty-one patients (50%) regained clinical response on the intensified IFX regimen. The increase in serum trough levels of IFX during treatment intensification was higher among responders than non-responders (RGA, 8.8 versus 3.0 μg/mL, p = 0.035; HMSA, 9.9 versus 4.7 μg/mL, p = 0.040), and differentiated patients by clinical outcome (RGA, area under receiver operating characteristic curve [AUC] 0.75 [0.53-0.97], p = 0.035; HMSA, AUC 0.74 [0.53-0.95], p = 0.042). All responders exhibited an IFX increase ≥2.6 μg/mL (sensitivity 100%, specificity 50%). Anti-IFX Abs detected by HMSA in 13 patients (32%) were often non-functional and became undetectable during IFX intensification. However, even functional anti-IFX Abs detected by RGA in six patients (15%) became undetectable.

Conclusion: Increase in IFX levels following treatment intensification was associated with improved clinical outcomes, indicating insufficient drug levels in a subgroup of patients. Anti-IFX Abs may become undetectable during treatment intensification, suggesting lowered production or the formation of immune complexes.

Trial registration: NCT00851565.

Keywords: IBD; antibodies against IFX; dose intensification; dose optimization; infliximab; loss of response; therapeutic drug monitoring.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies / blood*
  • Crohn Disease / blood
  • Crohn Disease / drug therapy*
  • Crohn Disease / immunology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Monitoring
  • Female
  • Gastrointestinal Agents / blood
  • Gastrointestinal Agents / immunology
  • Gastrointestinal Agents / pharmacokinetics*
  • Gastrointestinal Agents / therapeutic use
  • Humans
  • Infliximab / blood
  • Infliximab / immunology
  • Infliximab / pharmacokinetics*
  • Infliximab / therapeutic use
  • Linear Models
  • Male
  • Prospective Studies
  • ROC Curve
  • Treatment Failure
  • Young Adult


  • Antibodies
  • Gastrointestinal Agents
  • Infliximab

Associated data