Anti-interleukin-12 safe, may effectively treat Crohn's disease

Results of a Phase II study have shown that a monoclonal antibody targeting interleukin-12 (IL-12) p40 protein is safe and may induce clinical responses and remissions in patients with active Crohn's disease.

"IL-12 is a key cytokine that initiates Th1-mediated inflammatory responses," the Anti-IL-12 Crohn's Disease Study Group notes in its report, published in the November 11th issue of The New England Journal of Medicine. IL-12 antibody treatment has also been shown effective in animal models of Crohn's disease.

Led by Dr Peter Mannon at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, the group enrolled 79 patients with scores on the Crohn's Disease Activity Index (CDAI) of 220 to 450 out of a possible 600 (with higher scores indicating more severe disease). Remission was defined as a CDAI score of 150 points or less, while clinical response was defined as a decrease of at least 100 points.

Clinical improvement was accompanied by decreases in the secretion of IL-12, interferon-gamma and tumour necrosis factor alpha by mononuclear cells of the colonic lamina propria, the authors note.

"The development of anticytokine therapies as part of the physician's armamentarium is an important staging post on the road to a cure for Crohn's disease," said Dr Fabio Cominelli, at the University of Virginia, Charlottesville in a related editorial.

He points out that the long-term safety of such drugs remains unproven. Moreover, Crohn's disease may exist in multiple phases, such that effective treatment for this inflammatory bowel disease may "involve the blockade of multiple cytokines in order to intervene in several pathways."