New insights into the biological therapy of Crohn's disease

Conventional treatment of Crohn's disease (CD) has resulted in only a limited therapeutic benefit. Advancing knowledge of CD pathogenesis and recent advances in biotechnology have led to the development of biological agents that selectively target individual inflammatory pathways. Such agents may be divided in anti-TNF-alpha strategies, lymphocyte trafficking inhibitors, anti-inflammatory cytokines and pro-inflammatory cytokine inhibitors. Based on the early success of infliximab, humanised anti-TNF-a antibodies (CDP-571, CDP-870, adalimumab), soluble TNF-alpha receptors (etanercept, onercept), mitogen-activated protein kinase (MAPK) inhibitors and NF-kappa B inhibitors have been developed. To block lymphocyte migration, anti-integrin antibodies (natalizumab, MLN-02), antisense intercellular adhesion molecule-1, antinectin antibodies and chemotactic factors inhibitors have been engineered. Anti-inflammatory cytokines (IL-10, IL-11) have been tested with limited results in Crohn's disease, but further improvement in delivery of these molecules has been achieved. Pro-inflammatory cytokine inhibitors, such as anti-IL-6 and anti-IL-12, have been shown to be effective in clinical trials; and new antibodies, as well as genetic manipulation, have been developed. The aim of this review is to provide an insight into the biological therapies already applied in human studies, and to the new patents potentially applicable in the forthcoming years.