IFX antibodies negatively impact drug efficacy

Jun 21, 2016 - E-Mentoring in IBD | Volume 9 • 2016

Issue 12

Clinical Statement

Incorporating antibody to infliximab (ATI) results into the clinical decision making process remains confusing.

Editor’s Bottom Line

  • An infliximab (IFX) concentration of >3ug/mL and an ATI concentration of <3U/mL are associated with remission
  • ATI positivity increases the likelihood of active disease, even in low concentrations and in the presence of adequate IFX trough levels

Editorial Note

Extrapolation of these result to the levels of IFX and ATI obtained in Canada needs to be interpreted with caution. In general, the presence of ATI’s should increase your vigilance to an impending loss of response and lead you to seriously consider dose optimization (increased drug, combination therapy) and/or switching the biologic to another mechanism of action.

Reference

Vande Casteele N, Khanna R, Levesque BG, et al. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn’s disease. Gut. 2015 Oct;64(10):1539–45. https://www.ncbi.nlm.nih.gov/pubmed/25336114

Synopsis

Serum samples were collected from patients with Crohn’s disease who participated in 1 of 4 parent studies investigating IFX for maintenance. Trough serum samples were collected to determine IFX1, ATI1 and C-reactive protein2 (CRP) concentrations. CRP <5mg/L defined remission.

A total of 483 patients provided 1487 trough serum samples. The median CRP concentration was 3.6 mg/L. Of these:

  • 7% were negative for both IFX and ATI
  • 70% were IFX positive and ATI negative
  • 16% were IFX negative but ATI positive
  • 7% were IFX positive and ATI positive

An IFX concentration of >3ug/mL (78% specificity, 53% sensitivity) and an ATI concentration of <3U/mL (87% specificity, 38% sensitivity) were associated with remission. In the two groups that were ATI positive (see above bold italic) the likelihood of active disease was significantly increased. This implies that ATI adversely influences the efficacy of IFX, even in low concentrations and in the presence of adequate IFX trough levels.

1 Homogenous mobility shift assay, Prometheus Laboratories: LLOQ=0.98 µg/l

2 VPLEX Kit, Meso Scale Discovery: LLOQ=0.7 µg/l

Details

Study Design: Observational cohort study
Funding: Research Foundation, Belgium; Prometheus Laboratories, San Diego, CA
Allocation: n/a
Setting: Samples obtained from 4 parent clinical studies conducted at multiple centres in North America and Europe
Level of Evidence: 1b (Oxford Levels of Evidence)

The summary and conclusion in this issue of E-mentoring in IBD pertains to the manuscript(s) being reviewed, and should be considered in the context of what is already known surrounding the topic and incorporated into practice as deemed appropriate by the individual learner.