New Drugs for Crohn's Disease

A range of new and developing treatments for Crohn's disease are targeting not only on the autoimmune response associated with the condition, but also aiming to reinforce the intestinal barrier. These treatments and their methods of action are discussed in a New Drug Class paper in this week's edition of The Lancet, authored by professor Jean-Frederic Colombel, Hopital Claude Huriez, Centre Hospitalier Universitaire de Lille, France, and colleagues.

Crohn's disease is characterized by areas of inflammation of the gastrointestinal tract with areas of normal lining between, in a symptom known as skip lesions. The main gastrointestinal symptoms are abdominal pain, diarrhea (which may be bloody, though this may not be visible to the naked eye), constipation, vomiting, weight loss or weight gain.

Currently, antagonists of tumor necrosis factor are the standard drug choice for treating Crohn's disease. However, while these have contributed in a big way to treatment of Crohn's disease, some patients lose their response or become intolerant. Thus, new drugs are needed.

The T-cells of the immune system are pivotal in the immune response in inflammatory bowel disease (IBD). As such, various new drugs such as visilizumab, daclizumab and basiliximab have been developed which blockade particular T-cells. Other drugs such as tocilizumab and fontolizumab work by preventing the formation of the T-cells in the first place, or by preventing their activation. T-cells can also be "reset," as shown by patients with Crohn's disease receiving bone-marrow transplants for unrelated disorders who had extended remission of their Crohn's disease.

Further strategies include controlling regulatory T-cell modulation and blocking the action of the cytokine pathway in the immune system, and also enhancing the repair processes of the lining of the intestine rather than interfering in the course of the disease. Growth factors have also emerged as a new drug class. Finally, induction of oral tolerance -- a long-recognized method of inducing immune tolerance by feeding protein, has been used to prevent or treat many T-cell-mediated disorders. The merits of all these drugs and strategies are discussed at length in the paper.

The authors conclude, "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."

Source: Lancet