High serum tumor necrosis factor-alpha levels are associated with lack of response to infliximab

[Dave Watson]

OBJECTIVES: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor-alpha (anti-TNF-alpha), has been effective in the treatment of patients with active Crohn's disease and with fistulas. We investigated the effect of infliximab on circulating cytokines and acute phase proteins in patients with fistulas to determine the clinical response to anti-TNF-alpha.

METHODS: A total of 36 patients with fistulizing Crohn's disease were selected for study. Serum from patients was drawn before the infusion on day 0 and at wk 2, 4, 6, 8, and 10 after completion of treatment. Circulating concentrations of TNF-alpha, interleukin-1beta (IL-1beta), and IL-6 were measured by ELISA. The functional activity of circulating TNF-alpha was assessed by the WEHI 164 TNF-alpha bioassay. Acute phase proteins were also determined.

RESULTS: Elevated TNF-alpha, IL-1beta, IL-6, and acute phase proteins were observed in patients with Crohn's disease. Of the patients with fistulas, 22 (61.1%) responded to treatment. Before receiving infliximab, higher levels of serum TNF-alpha were found in patients who did not respond to infliximab compared with those who did (median interquartile range 26, 0-245 pg/ml; n = 14 vs 0, 0-22 pg/ml, n = 22). Patients showed no change in circulating levels of TNF-alpha during the course of the study.

CONCLUSIONS: This treatment produces a clinical improvement in about two-thirds of CD patients with fistulas. The circulating levels of TNF-alpha are associated with the response to infliximab and could help to identify patients who would benefit from anti-TNF-alpha treatment.

Source: http://www.ncbi.nlm.nih.gov/pubmed/12358255

I know this is an old study but very timely at the moment.

I stated in several posts that Crohn's is all about TNF. But, if that's the case, then why don't a subset of CD sufferers respond to anti-TNF drugs? David, the moderator, mentioned this in a recent post.

The answer could be incredibly simple. What if there is too much TNF in the guts of a subset of Crohn's sufferers so the anti-TNF drugs cannot neutralize enough of it to be beneficial? The above study proved that higher levels of TNF made Infliximab less effective or ineffective.

Another factor could be the immune response to anti-TNF drugs, but I'll cover that another time.

 

[David]

When you say, Crohn's is "All about TNF" can you please elaborate what you mean by that? TNF is a cytokine, a cell-signaling molecule. Why is Crohn's all about a specific cell-signaling molecule?

 

[Dave Watson]

Will cover TNF in the articles.

When you say, Crohn's is "All about TNF" can you please elaborate what you mean by that? TNF is a cytokine, a cell-signaling molecule. Why is Crohn's all about a specific cell-signaling molecule?