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.