An historical overview of the treatment of Crohn's disease: why do we need biological therapies?

Crohn's disease is a disabling inflammatory bowel disease that may involve any part of the gastrointestinal tract. The disease decreases quality of life and leads to complications including stenoses, abscesses, and fistulae necessitating repeated surgeries and bowel resections. Until the late 1990s, standard therapies included mainly glucocorticosteroids, 5-aminosalicylic acid (5-ASA), antibiotics, and to a lesser extent, immunosuppression with azathioprine (AZA)/6-mercaptopurine (6-MP) or methotrexate. These therapies, especially glucocorticosteroids, mainly controlled symptoms without modifying the long-term disease course. Glucocorticosteroids also do not induce sustained mucosal healing. The lack of healing capacity mirrors the absent long-term efficacy of these drugs. Moreover, long-term use of glucocorticosteroids is associated with serious and sometimes irreversible side effects. AZA/6-MP are effective disease-modifying therapies that have been used in patients who are refractory to or relapse after steroids. Unfortunately, these agents have yet to have an established optimal benefit due to variations in genetically determined metabolism. With the advent of biologicals, new treatment aims have been advanced, including induction of remission with bowel healing both short term and long term, as well as reduction in the rate of complications, surgeries, and mortality.