Mild to moderate Crohn's disease: still room for step-up therapies?

Step-up therapy in Crohn's disease refers to the classic therapeutic approach resulting in progressive increase of therapies with the increasing severity of the disease. This approach has been recently challenged by the top-down strategy, where biologicals together with thiopurines were used as first-line therapy. Several arguments exist against the top-down therapy. The current ECCO recommendation is in favor of the step-up therapy. ECCO recommended budesonide 9 mg daily as the preferred treatment in mild to moderate Crohn's disease patients. The benefit of mesalazine in small bowel disease is limited and should be considered clinically no more effective than placebo. Antibiotics cannot be recommended unless septic complications are suspected. No treatment is an option for some patients with mild symptoms. Budesonide is preferred to prednisone for mild active Crohn's disease because it is associated with fewer side effects. Active mild colonic disease may be treated with sulfasalazine and when needed with systemic corticosteroids as well. Topical treatment should be considered for distal disease. The national cooperative Crohn's disease study and the European co-operative Crohn's disease study established corticosteroids as an effective therapy for inducing remission in Crohn's disease. Remission is achieved in 60-83% of the patients. A Cochrane review of the efficacy of azathioprine and 6-mercaptopurine for inducing remission in active Crohn's disease showed a benefit for thiopurine therapy compared with placebo. Methotrexate is another effective medication that has been confirmed in a systematic review. Once remission has been achieved with systemic corticosteroids, maintenance with azathioprine should be considered. For patients with extensive colitis, long-term treatment with mesalazine is an option as this may reduce the risk of colon cancer, although this is still unproved in Crohn's disease. In conclusion, the natural course of most patients with Crohn's disease is relatively mild and there is a room for step-up therapy. The efficacy of most medications is similar to the efficacy of infliximab but with less adverse effects. Infliximab should be reserved only for patients where other therapies failed.