A New Drug Class article released on July 4, 2008 in The Lancet seeks to highlight a new group of drugs intended to treat Crohn’s disease. Most current drugs seek to control the autoimmune response via the tumor necrosis factor alpha (TNF-alpha), but many new classes attempt to control other aspects of the immune response or even to reinforce the intestinal barrier itself.

Crohn’s Disease (CD) is a gastrointestinal disorder which is indicated by chronic inflammation of the wall of the digestive tract. Usually, regions of inflammation are separated by regions of normal lining, called skip lesions. The disease involves constant cycles of flare-ups and remission throughout the life of the patient, and is an inflammatory bowel disease (IBD), similar to ulcerative colitis. The primary gastrointestinal symptoms are abdominal pain, blood in the stool, diarrhea,constipation, vomiting, weight loss, or weight gain.

Presently, the standard drug treatment of Crohn’s disease attempt to inhibit tumor necrosis factor alpha, which would normally amplify the immune response. However, some novel therapies instead target other biochemical factors that initiate or participate in the immune response, often by controlling T-cells, an instrumental part of the immune response. Drugs such as visilizumab, daclizumab and basiliximab blockade specific T-cells from responding, and tocilizumab and fontolizumab actually prevent the formation or activation of T-cells. In another experimental therapeutic technique, T-cells are “reset” through bone-marrow transplants, which can bring extended remission.

In addition to modulation of T-cell response, other approaches are being explored A new class of drugs hopes to modulate T-cell response while additionally attempting to reinforce the intestinal barrier by encouraging the repair processes in the intestinal lining. Additionally, a tolerance against the instigators of the immune response can be built orally by ingesting protein extracts, thus reducing the overall immune response in inflammatory bowel diseases.

The authors, including Professor Jean-Frederic Colombel, Hopital Claude Huriez, Centre Hospitalier Universitaire de Lille, France, and colleagues, discuss the mechanisms and merits of all of these strategies. They conclude with a statement of hope for future therapies for this disease: “As a result of decades of intensive research, treatment for inflammatory bowel disease is undergoing a transition from the era of TNF antagonists to an era of new biological agents, including those that are able to stimulate the innate immune system. In parallel, clinicians are working on new strategies aimed at modification of the natural history of Crohn’s disease, including an early aggressive therapeutic approach.”

Crohn’s disease: beyond antagonists of tumour necrosis factor
Laurent Peyrin-Biroulet, Pierre Desreumaux, William J Sandborn, Jean-Frederic Colombel
Lancet 2008; 372: 67-81
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Written by Anna Sophia McKenney