What is the optimal therapy for Crohn’s disease: step-up or top-down?

Abstract

Crohn’s disease (CD) is an idiopathic chronic inflammatory disorder of the digestive tract, which is incurable. Present therapeutic guidelines follow a sequential step-up approach that focuses on treating acute disease or ‘inducing clinical remission’ and subsequently aims to ‘maintain clinical response’. In view of the chronic relapsing–remitting disabling disease course, new treatment approaches have been sought with the ultimate end point of disease course modification and mucosal healing. A recent preliminary study from D’Haens et al. has provided evidence suggesting that reversing the treatment paradigm from a ‘step-up’ to a ‘top-down’ approach may positively alter the natural course of this illness. Their findings indicate that early use of biologic therapy, in combination with immunomodulators, resulted in remission occuring more rapidly than the conventional ‘step-up’ treatment, with a longer time period to relapse, a decreased need for treatment with corticosteroids, a faster reduction in clinical symptoms, rapid decline in biochemical inflammatory markers (C-reactive protein) and improved endoscopic mucosal healing. These results, supported by previous studies on infliximab use, may hold a promising outcome of fewer stricturing complications, hospitalizations and surgeries for patients with CD. However, we need to better define the timing and candidates for the ‘top-down’ approach as we are still uncertain about the safety data and the long-term benefits if biologic agents are given as routine maintenance treatment, since most of the trials in CD have been short term, and approximately 30% of patients might have been overtreated. Future clinical trials will be crucial in answering these questions.

Keywords::

• anti-TNF-α agent
• corticosteroid
• Crohn’s disease
• immunomodulator
• step-up
• top-down

Financial & competing interests disclosure

Gary R Lichtenstein has acted as a consultant for Abbott Corporation, Axcan Corporation, Bristol-Myers Squibb Corporation, Centocor, Inc., Elan, Proctor and Gamble, Prometheus Laboratories, Inc., Protein Design Labs, Protomed Scientific, Salix Pharmaceuticals, Schering-Plough Corporation, Serono, Shire Pharmaceuticals, Smith Kline Beecham Corporation, Synta Pharmaceuticals, UCB and Wyeth. He has also conducted research for Abbott Corporation, Bristol-Myers Squibb Corporation, Centocor, Inc., Intesco Corporation, Millenium Pharmaceuticals, Protein Design Labs, Protomed Scientific, Salix Pharmaceuticals and Shire Pharmaceuticals. Gary R Lichtenstein is a member of the Speakers Bureau for Axcan Corporation, Centocor, Inc., Proctor and Gamble, Salix Pharmaceuticals, Schering-Plough Corporation and Shire Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.