Clinical role, optimal timing and frequency of serum infliximab and anti-infliximab antibody level measurements in patients with inflammatory bowel disease

PLoS One. 2017 Mar 31;12(3):e0172916. doi: 10.1371/journal.pone.0172916. eCollection 2017.

Abstract

Background: Serum infliximab (IFX) and antibody-to-infliximab (ATI) levels are objective parameters, that may have a great role in the therapeutic decisions during maintenance biological therapy.

Research design and methods: 48 inflammatory bowel disease patients receiving maintenance IFX therapy were prospectively enrolled and divided into adequate (complete remission N = 20) and inadequate responder (partial response, loss of response, dose escalation; N = 28) groups. Blood samples were collected just before (trough level, TL) and two (W2aTL) and six weeks (W6aTL) after the administration of IFX.

Results: Single measurement of ATI titer was insufficient for predicting therapeutic response due to transient expression of ATI, however, using the three points' measurements, significant difference has been detected between the adequate and inadequate responder group (5.0% vs 35.7%; p = 0.016). The mean value of TL was significantly higher in the adequate responder group (3.11±1.64 vs.1.19±1.11; p<0.001) without further difference on the second and sixth week. Sensitivity and specificity for predicting the therapeutic response were 85.0% and 71.4% based on the cut-off value of TL 2.0 μg/ml.

Conclusion: Simultaneous measurement of serum IFX level prior to administration of regular IFX infusion and ATI titers significantly increase the diagnostic accuracy for the therapeutic decision in patients uncertainly responding to the therapy. The measurement of W2aTL and W6aTL levels did not result in further improvement in the prediction of therapeutic response.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal / blood*
  • Female
  • Humans
  • Inflammatory Bowel Diseases / blood*
  • Inflammatory Bowel Diseases / immunology
  • Infliximab / blood*
  • Infliximab / immunology
  • Logistic Models
  • Male
  • ROC Curve
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Infliximab

Grants and funding

This work was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00632/14/5), the ÚNKP-ÚNKP-16-4 New National Excellence Program of the Ministry of Human Capacities and by the research grant of the National Research, Development and Innovation Office (K119809).