Medical Therapy for Crohn’s Disease: Top-Down or Step-Up?

Abstract

The emergency of effective biological therapy in the treatment of Crohn's disease (CD) has led to a clinical debate about 'step-up versus top-down strategy'. Step-up refers to the classic therapeutic approach, namely progressive intensification of treatment as disease severity increases. Top-down refers to the early introduction, in all CD patients, of intensive therapies, including biological agents and immunosuppressive drugs, with the aim of avoiding complications and improving quality of life, starting from the assumption that these drugs may interfere with the natural history of the disease. Very recently the Belgian IBD research group together with the Gut Club of North Holland designed 'the Step Up versus Top Down Trial'. Combination of infliximab with immunosuppressives at onset was better than the current standard approach in terms of both induction and maintenance of remission. However, several observations still limit the use of infliximab as first-line treatment in adult CD patients. In particular, the epidemiological observation that over 50% of CD patients have a mild disease over time and will never require aggressive therapies is against the indiscriminate use of top-down strategy. Lack of markers able to identify high-risk patients, discussions about long-term safety and the high costs of infliximab are further factors supporting a more careful approach to the management of CD.