Clinical perspectives in Crohn's disease. Turning traditional treatment strategies on their heads: current evidence for "step-up" versus "top-down".

Abstract

The current Crohn's disease treatment algorithm involves a "step-up" approach in which conventional medications such as corticosteroids are given first and anti-tumor necrosis factor-a (TNF-a) agents are reserved for refractory cases. Although this approach may seem to be cost-efficient, recent studies have shown that "top-down" therapy using anti-TNF-a agents in newly diagnosed patients improves long-term rates of mucosal healing, a therapeutic endpoint that correlates with reduced hospitalizations and surgeries, thereby reducing overall costs and enhancing patients' quality of life. Another reason the step-up approach has been favored over the top-down is concern about side effects; however, a multivariate logistic regression analysis of patients treated with or without infliximab showed no differences in mortality, serious infections, or malignancies between the 2 groups. Moreover, newer anti-TNF-a agents, such as adalimumab and certolizumab pegol, have the potential to reduce the risk of immunogenicity and the associated infusion reactions and loss of response, as well as reducing autoimmunity associated with infliximab therapy. The potential advantages of "reversing" our current therapeutic pyramid/algorithm for the treatment of Crohn's disease include early disease stabilization and disease modification, minimization of complications such as strictures and fistulae that lead to the need for surgery, reduction of postoperative recurrence, and avoidance of the ubiquitous complications of corticosteroid therapy.