Mannon PJ et al. (2004) Anti-interleukin-12 antibody for active Crohn's disease. N Engl J Med 351: 2069–2079

Interleukin-12 is implicated in the pathogenesis of several autoimmune disorders. A recent phase II study has investigated the use of a human monoclonal antibody against this cytokine in the treatment of Crohn's disease.

A total of 79 patients with active Crohn's disease were randomized to receive seven weekly subcutaneous injections of anti-interleukin-12 antibody at two different doses (1 mg or 3 mg per kg body weight), or placebo. Approximately half of the patients received uninterrupted treatment, whereas the remainder had a 4-week interval after the first injection, to allow assessment of a single dose of the antibody.

At the end of treatment, 75% of patients who had received uninterrupted 3 mg/kg doses of the antibody showed a clinical response, compared with only 25% of those in the placebo group (P = 0.03). The corresponding remission rates were 38% and 0% (P = 0.07). The clinical response was sustained in the treatment group during the following 18 weeks, although the difference from placebo was no longer significant at the end of this period (69% vs 25%, P = 0.08). None of the other treatment groups showed significant responses to therapy. Patients receiving antibody treatment showed decreased secretion of other TH1-mediated inflammatory cytokines by mononuclear cells of the colonic lamina propria.

This early data suggests that anti-interleukin-12 therapy may have been associated with clinical improvement in patients with active Crohn's disease, and the authors add that this effect was related to a decrease in Th1-mediated inflammation.