Lessons to Learn from Crohn's Disease Clinical Trials: Implications for Ulcerative Colitis

Aranzazu      Jauregui-Amezaga; Elena      Ricart; Julian      Panes

Abstract

The perception that Crohn's disease is a more severe process than ulcerative colitis, led to the initial development of a majority drugs, and testing of treatment strategies, in the former. In the absence of similar studies in ulcerative colitis, information of Crohn's disease studies may help the clinician in decision making in UC. Studies on aminosalicylates show that drugs with a topical effect which are not effective in Crohn's disease may still have efficacy in ulcerative colitis, and this should be considered in future drug development. The best efficacy of corticorteroids is achieved with high doses of 1 mg/kg/day, and reaching remission may be delayed by several weeks, although nonresponse in the initial days should lead to treatment escalation, in particular in severe patients. Thiopurines have a steroidsparing effect, and the duration of treatment should be at least 4 years; caution should be exerted in using these drugs in EBV negative young patients and in the older population for the risk of lymphoma. Anti-TNF monoclonal antibody therapy is optimized by use of induction followed by scheduled maintenance as opposed to episodic treatment, resulting in higher sustained response rates and lower immunogenicity. Associations of non-biological immunosuppressants with anti- TNF antibodies can further increase therapeutic efficacy maintaining a safe profile. Patients under combined therapy with sustained clinical and biological remission and mucosal healing may be candidates to stop anti-TNF treatment. The majority of these recommendations need to be specifically studied in patients with ulcerative colitis before generalization in clinical practice.

Keywords: Inflammatory bowel disease, Crohn's disease, Ulcerative colitis, Treatment, Corticosteroids, Azathioprine, Inflixamab, Adalimumab, Mesalazine, Methotrexate, Stopping immunosuppressant therapy, ACCENT 1 trial, GETAID trial, ACT 1, ACT 2