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Anti–Interleukin-12 Antibody for Active Crohn's Disease

Anti–Interleukin-12 Antibody for Active Crohn's Disease BackgroundCrohn'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.MethodsThis 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 primary end point, and 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) were secondary end points.ResultsSeven weeks of uninterrupted treatment with 3 mg of anti–interleukin-12 per kilogram resulted in higher response rates than did placebo administration (75 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). 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 (38 percent and 0 percent, respectively, at both times; P=0.07). 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-γ, and tumor necrosis factor α by mononuclear cells of the colonic lamina propria accompanied clinical improvement in patients receiving anti–interleukin-12.ConclusionsTreatment 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The New England Journal of Medicine The New England Journal of Medicine

Anti–Interleukin-12 Antibody for Active Crohn's Disease

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References (20)

Publisher
The New England Journal of Medicine
Copyright
Copyright © 2004 Massachusetts Medical Society. All rights reserved.
ISSN
0028-4793
eISSN
1533-4406
DOI
10.1056/NEJMoa033402
pmid
15537905
Publisher site
See Article on Publisher Site

Abstract

BackgroundCrohn'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.MethodsThis 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 primary end point, and 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) were secondary end points.ResultsSeven weeks of uninterrupted treatment with 3 mg of anti–interleukin-12 per kilogram resulted in higher response rates than did placebo administration (75 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). 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 (38 percent and 0 percent, respectively, at both times; P=0.07). 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-γ, and tumor necrosis factor α by mononuclear cells of the colonic lamina propria accompanied clinical improvement in patients receiving anti–interleukin-12.ConclusionsTreatment 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.

Journal

The New England Journal of Medicine – The New England Journal of Medicine

Published: Nov 11, 2004

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