Biological Therapies in Inflammatory Bowel Disease: Top-down or Bottom-up?

Bas Oldenburg; Daan Hommes

Disclosures

Curr Opin Gastroenterol. 2007;23(4):395-399. 

In This Article

Current Treatment of Crohn's Disease and Ulcerative Colitis and its Limitations

The ultimate goals for the management of IBD are the objective evaluation of disease activity, understanding its natural history, induction of remission, and prevention of flares, chronic steroid usage and the need for surgery. Although population-based studies found a lifetime need of steroids in less than 50% of the patients,[6,7,8] studies from referral hospitals have shown that the course of IBD frequently includes the development of severe complications despite the correct administration of conventional medical therapy.[9,10,11] In IBD corticosteroids are initially quite effective and fast acting but, with time, a considerable proportion of patients fail to respond or become steroid dependent. In these patients the cumulative probability of surgery at 1 year has been assessed to be 36% in Crohn's disease[7] and 28% in severe ulcerative colitis.[10] For Crohn's disease this translates into a need for surgery during the first 15 years after diagnosis ranging between 38 and 96%,[12] probably depending on the population-based setting, definition of disease recurrence, and different views regarding indication for introduction of immunomodulatory therapy or surgery. Relatively simple adjustments in daily life, such as cessation of smoking in Crohn's disease and optimizing standard treatment, have been reported to decrease relapse rates considerably,[13,14] but the feasibility in clinical practice is often disappointing.

Although the current clinical practice of adding more effective but toxic therapies in unresponsive patients seems justified, this has never been studied prospectively and, in particular, long-term follow-up studies on the outcome of medical treatment are lacking. Mesalamine and sulfasalazine are generally considered to be the mainstay therapy in ulcerative colitis but not to be effective for maintaining remission in Crohn's disease patients.[15,16] Corticosteroids did not show efficacy for maintenance of medically induced remission either,[17,18] but azathioprine and 6-mercaptopurine have been shown to be effective in this setting in Crohn's disease and ulcerative colitis,[15,19] and methotrexate in Crohn's disease.[20] Finally, infliximab has been found to be effective at maintaining an infliximab-induced response with fewer Crohn's disease-related hospital admissions and operations if taken as a scheduled treatment.[21] In most guidelines and consensus articles, infliximab is considered the last medical resort before handing over the patient to the surgeon in the case of luminal disease.

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