Biological Therapies for Inflammatory Bowel Diseases

Crohn's disease and ulcerative colitis are chronic disabling inflammatory bowel diseases (IBDs). Although the causes of IBD are unknown, defects in innate and adaptive immune pathways have been identified and biological therapies that target key molecules have been designed. Infliximab, a chimeric immunoglobulin (Ig)G1 monoclonal antibody to tumor necrosis factor, dramatically improved treatment of patients with Crohn's disease and ulcerative colitis. Infliximab has achieved treatment goals such as mucosal healing and decreasing the need for hospitalizations and surgeries. Although several anti–tumor necrosis factor therapies have been developed, there is a great need for drugs that target other pathways. Natalizumab, an antibody against the integrin α4 subunit, blocks leukocyte adhesion and has reached the clinic in the United States but has not been approved in the European Union; other anti-adhesion molecules currently are under development. Additional approaches under clinical development include therapeutics that target cytokines, such as interleukin-12/23, as well as those that block T-cell signaling. The use of recombinant human proteins, including immunoregulatory cytokines and growth factors, has not been successful so far. The efficacy of each therapy must be shown in carefully designed clinical programs. Biological therapies carry a definite safety risk, so their place in treatment algorithms must be defined carefully.

Abbreviations used in this paper: ACCENT, A Crohn's disease Clinical trial Evaluating infliximab in a New long-term Treatment regimen, ACT, The Active Ulcerative Colitis trials, CDAI, Crohn's Disease Activity Index, CHARM, Crohn's trial of the Fully Human Antibody Adalimumab for Remission Maintenance, CLASSIC, Clinical Assessment of Adallmumab Safety and Efficacy Studied as an Induction Therapy In Crohn's disease, CRP, C-reactive protein, ENACT, Evaluation of Natalizumab As Continuous Therapy trial, GAIN, Gauging Adalimumab Effectiveness in Infliximab Nonresponders, IFN, Interferon, IL, Interleukin, PML, progressive multifocal leukoencephalopathy, PRECISE, Pegylated Antibody Fragment Evaluation In Crohn's disease: Safety and Efficacy, Th, T-helper, TNF, tumor necrosis factor