Crohn's targeted therapy: myth or real goal?

Abstract

The broad spectrum of chronic inflammatory bowel diseases encompasses the two main entities Crohn's disease (CD) and ulcerative colitis (UC). Rapid action and long-term duration is the superordinate goal in most therapeutic approaches facing chronic inflammation including inflammatory bowel diseases (IBD) for induction and maintenance of remission. The availability of antibodies targeting TNF-alpha or alpha 4 integrin has recently offered new opportunities apart from classical remedies for the treatment of CD, a major challenge for future therapeutic concepts. Classical way of treating CD is an escalation scheme ("step-up") whereas the novel and still controverse approach ("top-down") favors a biological as initial drug. Today, four biologicals have proven efficacy and safety in CD treatment strategies and have received approval by FDA and, with the exception of natalizumab and certolizumab, by EMEA. Infliximab was the first TNF-alpha blocker and extended the care in CD. Adalimumab and certolizumab pegol followed as humanized second generation TNF-alpha blockers. Another targeted therapy option is natalizumab, an alpha 4 integrin monoclonal antibody, which blocks the migration of leukocytes into inflamed gut tissue. Nevertheless, a considerable number of patients remain refractory, lose response or render intolerant to these biologicals. An overall long lasting remission of less than 30% with scheduled administration of TNF-alpha blockers in patients with steroid dependent or refractory CD seems to be lifelike and alternative therapeutic options are warranted. Broad acting antimetabolites come into focus again and recent data provide substantial evidence for the efficacy and safety of cyclophosphamide pulse therapy in ileocolonic, refractory CD. This therapeutic option should be kept in mind as a reasonable agent to target the inflammatory process in severely disabled patients. Hence, targeted therapy in CD seems to be still a myth at present owing to the complex nature of disease.