Tumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

Am J Gastroenterol. 2008 Apr;103(4):944-8. doi: 10.1111/j.1572-0241.2007.01638.x. Epub 2007 Nov 19.


Objectives: To investigate if the combined assessment of anti-infliximab antibodies (Ab) and the degree of TNF-alpha binding capacity (TNF-alpha-BC) afforded by infliximab may predict the response to infliximab treatment in patients with Crohn's disease (CD).

Methods: Three groups of CD patients, in total 33 patients, treated with infliximab were retrospectively selected: (a) patients with a maintained response throughout treatment; (b) patients with good initial response, but subsequent loss of response; and (c) patients with inadequate response to the first two or three doses. Blood samples were analyzed for TNF-alpha-BC and Ab using fluid-phase radioimmunoassay (RIA).

Results: At 8 wk after last infliximab infusion, TNF-alpha-BC was significantly higher (P = 0.002) in patients maintaining response (median [interquartile range] 2.9 [0.9-4.3] microg/mL), as compared to patients losing response (0.0 [0-0.1] microg/mL). Conversely, Ab levels were significantly lower (P < 0.0001) in patients maintaining response (1.3 [0-6]% bound tracer/total tracer), as compared to patients losing response (19 [14-27]%). Ab were not present and TNF-alpha-BC was high (30 [20-32]) in patients with no primary response.

Conclusions: While secondary loss of response to infliximab is associated with high levels of Ab and low levels of TNF-alpha-BC, primary response failure may be seen in the presence of high effective levels of TNF-alpha-BC afforded by infliximab. The results suggest that combined assessment of anti-infliximab Ab and serum TNF-alpha-BC may pave the way for a more rational use of infliximab in patients with CD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / therapeutic use*
  • Crohn Disease / drug therapy*
  • Female
  • Humans
  • Infliximab
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Radioimmunoassay / methods
  • Retrospective Studies
  • Statistics, Nonparametric
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood*


  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha
  • Infliximab