Review article: altering the natural history of Crohn's disease – evidence for and against current therapies

BACKGROUND: The natural course of Crohn's disease is characterized by flare-ups altered with periods of remission. The majority of Crohn's disease patients need surgery within 10 years of diagnosis. Major advances in treatment options over the past years have made our treatment goals more ambitious and modification of the natural course has become the ultimate endpoint. AIM: To review the evidence of existing therapies for Crohn's disease for changing the natural history. METHODS: A Medline search was undertaken by using 'natural history', 'Crohn's disease', 'therapy' (corticosteroids, azathioprine, methotrexate, infliximab and enteral feeding), 'surgery', 'hospitalizations' and 'mucosal healing'. RESULTS: Corticosteroids do not alter the disease course and maintenance therapy with corticosteroids should be avoided given their side effects. The immunomodulators azathioprine and methotrexate heal the mucosa but their onset of action is slow. Infliximab therapy introduces rapid mucosal healing and is associated with decreased hospitalizations and surgical interventions. Despite the fact that immunomodulators and infliximab are effective in maintaining clinical and endoscopic remission, there is little hard evidence at present that these therapies alter the natural history of the disease. The main reason being the fact that these therapies have so far been used only in refractory patients and that early initiation in the right patient is crucial in order to change the disease course. CONCLUSION: Prospective studies should validate predictors of complicated disease and randomized studies in high-risk groups should be performed to answer if early introduction of immunomodulators or biological therapies slows down disease progression and alters natural history.