Clinical applications of biologic treatment strategies in Crohn's disease therapy

Although sulfasalazine and other 5-aminosalicylates are the standard treatment for patients with mild-to-moderate Crohn's disease, their ability to maintain long-term remission is debatable. Many patients with moderate-to-severe Crohn's disease benefit from glucocorticoids, though these agents do not induce long-term remission and confer significant adverse effects. Immunomodulators such as azathioprine and 6-mercaptopurine are often used in patients with steroid-dependent disease. More recently, biologic agents targeting the proinflammatory cytokine tumor necrosis factor-alfa (TNF-α) have been developed and approved by the US Food and Drug Administration, providing additional treatment options. The monoclonal antibody infliximab was the first biologic approved for Crohn's disease; a second anti-TNF-α antibody, adalimumab, was approved in February 2007. Both biologics have been approved for the treatment of patients with moderately to severely active Crohn's disease that does not respond to conventional therapies. Other biologies currently under study for treatment of Crohn's disease include certolizumab pegol and natalizumab. Although these agents have demonstrated significant efficacy, they are also associated with safety issues that clinicians must consider when deciding whether to start patients on one of them.