Crohn's disease is associated with excess cytokine activity mediated by type 1 helper T (Th1) cells.
Interleukin-12 is a key cytokine that initiates Th1-mediated inflammatory responses.
Dr Mannon and Dr Fuss lead fellow researchers from America in a double-blind trial that evaluated the safety and efficacy of a human monoclonal antibody against interleukin-12 (anti–interleukin-12).
The researchers included a total of 79 patients with active Crohn's disease in the study.
Researchers randomly assigned participants to receive seven weekly subcutaneous injections of 1 mg or 3 mg of anti–interleukin-12 per kilogram of body weight or placebo.
The researchers allowed either a four-week interval between the first and second injection (Cohort 1) or no interruption between the two injections (Cohort 2).
Safety was the primary end point.
The researchers used the rates of clinical response (defined by a reduction in the score for the Crohn's Disease Activity Index [CDAI] of at least 100 points) and remission (defined by a CDAI score of 150 or less) as secondary end points.
The researchers found that 7 weeks of uninterrupted treatment with 3 mg of anti–interleukin-12 per kilogram resulted in higher response rates than did placebo administration.
However, at 18 weeks of follow-up, the difference in response rates was no longer significant.
| Decreases in the secretion of interleukin-12 and tumour necrosis factor accompanied clinical improvement in patients receiving anti–interleukin-12|
|The New England Journal of Medicine|
The research team found that the differences in remission rates between the group given 3 mg of anti–interleukin-12 per kilogram and the placebo group in Cohort 2 were not significant at either the end of treatment or the end of follow-up.
In addition, there were no significant differences in response rates among the groups in Cohort 1.
The rates of adverse events among patients receiving anti–interleukin-12 were similar to those among patients given placebo, except for a higher rate of local reactions at injection sites in the former group.
Decreases in the secretion of interleukin-12, interferon-, and tumor necrosis factor by mononuclear cells of the colonic lamina propria accompanied clinical improvement in patients receiving anti–interleukin-12.
Dr Mannon, speaking on behalf of the researchers concluded, "Treatment with a monoclonal antibody against interleukin-12 may induce clinical responses and remissions in patients with active Crohn's disease."
"This treatment is associated with decreases in Th1-mediated inflammatory cytokines at the site of disease."