High serum tumor necrosis factor-alpha levels are associated with lack of response to infliximab in fistulizing Crohn's disease.
OBJECTIVE
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.
D000209:Acute-Phase Proteins / Q000032:analysis / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use*; D003424:Crohn Disease / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005402:Fistula / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D005765:Gastrointestinal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D000209:Acute-Phase Proteins; D000911:Antibodies, Monoclonal; D016207:Cytokines; D005765:Gastrointestinal Agents; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab