BACKGROUND: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. METHODS: This double-blind trial evaluated the safety and efficacy of a human monoclonal antibody against interleukin-12 (anti-interleukin-12) in 79 patients with active Crohn’s disease. Patients were randomly assigned to receive seven weekly subcutaneous injections of 1 mg or 3 mg of anti-interleukin-12 per kilogram of body weight or placebo, with 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 primar y end point, and the rates of clinical response (defined by a reduction in the s core for the Crohn’s Disease Activity Index [AI] of at least 100 points) and re mission (defined by a CDAI score of 150 or less) were secondary end points. RESU LTS: Seven weeks of uninterrupted treatment with 3 mg of anti interleukin-12 p er kilogram resulted in higher response rates than did placebo administration (7 5 percent vs. 25 percent, P=0.03). At 18 weeks of follow up, the difference in response rates was no longer significant (69 percent vs. 25 percent, P=0.08). Di fferences in remission rates between the group given 3 mg of anti in terleukin -12 per kilogram and the placebo group in Cohort 2 were not significant at eith er the end of treatment or the end of follow up (38 percent and 0 percent, resp ectively, at both times; P=0.07). There were no significant differences in respo nse rates among the groups in Cohort 1. The rates of adverse events among patien ts receiving anti interleukin-12 were similar to those among patients given pl acebo, except for a higher rate of local reactions at injection sites in the for mer group. Decreases in the secretion of interleukin-12, interferon γ, and tu mor necrosis factor α.by mononuclear cells of the colonic lamina propria accomp anied clinical improvement in patients receiving anti interleukin-12. CONCLUSI ONS:Treatment with a monoclonal antibody against interleukin-12 may induce cli nical responses and remissions in patients with active Crohn’s disease. This tr eatment is associated with decreases in Th1 mediated inflammatory cytokines at the site of disease. BACKGROUND: 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. METHODS: This double-blind trial evaluated the safety and efficacy of a human monoclonal antibody against interleukin-12 (anti-interleukin-12) in 79 patients with active Crohn’s disease. Patients were randomly assigned to receive seven weekly subcutaneous injections of 1 mg or 3 mg of anti-interleukin-12 per kilogram of body weight or placebo, with 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 primar y end point, and the rates of clinical response (defined by a reduction in the s core for the Crohn’s Disease Activity Index [AI] of at least 100 points) and re mission (defined by a CDAI score of 150 or less) were secondary end points. RESU LTS: Seven weeks of uninterrupted treatment wi th 3 mg of anti interleukin-12 p er kilogram resulted in higher response rates than did placebo administration (7 5 percent vs. 25 percent, P = 0.03). At 18 weeks of follow up, the difference in response rates was no longer significant (69 percent vs. 25 percent, P = 0.08). Di fferences in remission rates between the group given 3 mg of anti in terleukin -12 per kilogram and the placebo group in Cohort 2 were not significant at eith er the end of treatment or the end of follow up (38 percent and 0 percent, resp ectively, at both times; P = 0.07). There were no significant differences in respo nse rates among the groups in Cohort 1. The rates of adverse events among patien ts receiving anti interleukin-12 were similar to those among patients given pl acebo, except for a higher rate of local reactions at injection sites in the for mer group. Decreases in the secretion of interleukin-12, interferon γ, and tu mor necrosis factor α.by mononuclear cells of the colonic lamina propria accompied clinical improvement in patients receiving anti interleukin-12. CONCLUSI ONS: Treatment with a monoclonal antibody against interleukin-12 may induce cli nical responses and remissions in patients with active Crohn’s disease. This tr eatment is associated with decreasing in Th1 mediated inflammatory cytokines at the site of disease.