Biologics, novel therapeutic alternatives in inflammatory bowel disease

Abstract

Biologics refer to novel exogenous protein-based molecules designed to recognize and bind specific antigens, including monoclonal antibodies or derivatives of monoclonal antibodies, in order to treat disease. In inflammatory bowel disease (IBD) biologics are largely directed at cytokines and receptors involved in T-cell activation as well as selective adhesion molecule blockers. Particularly, the success of the intravenously administered chimeric anti-tumour necrosis factor alpha (TNF-α) IgG₁ antibody, infliximab, has set new treatment standards for IBD and substantially aided to drag Crohn’s disease (CD) and ulcerative colitis (UC) out of the attic into the spotlight of internal medicine. Infliximab has demonstrated efficacy in the induction and maintenance of remission in luminal and fistulizing CD both in adults and children, and patients with moderate to severe UC. Adalimumab, a fully human monoclonal antibody anti-TNF-α, has proved to be effective and safe in patients with CD after subcutaneous administration, both naive and refractory to infliximab. Certolizumab pegol, a subcutaneous pegylated anti-TNF-α Fab fragment, and natalizumab, a monoclonal 4-integrin antibody, suggested efficacy for luminal CD. Some evidence supports the theory that biologics not only control symptoms of CD but also may potentially alter the natural course of disease. However, economic costs and the risks of severe opportunistic infections associated with biologic therapy have still not settled the appropriate role for these agents in the clinical care of patients with IBD.