title: Anti-interleukin-12 antibody for active Crohn's disease.
abstract: 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 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.
  
  
  RESULTS
  Seven 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-gamma, and tumor necrosis factor alpha by mononuclear cells of the colonic lamina propria accompanied clinical improvement in patients receiving anti-interleukin-12.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md 20892, USA. pmannon@niaid.nih.gov
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mannon
authors.forename: Ivan J
authors.initials: IJ
authors.lastname: Fuss
authors.forename: Lloyd
authors.initials: L
authors.lastname: Mayer
authors.forename: Charles O
authors.initials: CO
authors.lastname: Elson
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.forename: Daniel
authors.initials: D
authors.lastname: Present
authors.forename: Ben
authors.initials: B
authors.lastname: Dolin
authors.forename: Nancy
authors.initials: N
authors.lastname: Goodman
authors.forename: Catherine
authors.initials: C
authors.lastname: Groden
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hornung
authors.forename: Martha
authors.initials: M
authors.lastname: Quezado
authors.forename: Zhiqiong
authors.initials: Z
authors.lastname: Yang
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
authors.forename: Jochen
authors.initials: J
authors.lastname: Salfeld
authors.forename: Geertruida M
authors.initials: GM
authors.lastname: Veldman
authors.forename: Ullrich
authors.initials: U
authors.lastname: Schwertschlag
authors.forename: Warren
authors.initials: W
authors.lastname: Strober
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D003106:Colon / Q000276:immunology; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012074:Remission Induction
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D018664:Interleukin-12