Has the time come for a systematic top-down approach in Crohn's disease?

Risk stratification and choosing the best treatment for individual patients—ie, personalised medicine—is a major unmet need in inflammatory bowel disease (IBD). Although several studies have suggested that clinical outcomes can be improved with the use of early advanced therapy, 1 Colombel JF Panaccione R Bossuyt P et al. Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial. Lancet. 2017; 390: 2779-2789 Summary Full Text Full Text PDF PubMed Scopus (602) Google Scholar , 2 D'Haens G Baert F van Assche G et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet. 2008; 371: 660-667 Summary Full Text Full Text PDF PubMed Scopus (1142) Google Scholar , 3 Khanna R Bressler B Levesque BG et al. Early combined immunosuppression for the management of Crohn's disease (REACT): a cluster randomised controlled trial. Lancet. 2015; 386: 1825-1834 Summary Full Text Full Text PDF PubMed Scopus (341) Google Scholar accurately identifying which patients could benefit from early intervention remains a key point. Implementing a strategy using the most effective drugs for all patients would potentially lead to overtreatment of some patients with milder disease, with subsequent extraneous costs for health-care systems and unnecessary risks of adverse events. 4 Kirchgesner J Lemaitre M Carrat F et al. Risk of serious and opportunistic infections associated with treatment of inflammatory bowel diseases. Gastroenterology. 2018; 155: 337-346 Summary Full Text Full Text PDF PubMed Scopus (391) Google Scholar , 5 Lemaitre M Kirchgesner J Rudnichi A et al. Association between use of thiopurines or tumor necrosis factor antagonists alone or in combination and risk of lymphoma in patients with inflammatory bowel disease. JAMA. 2017; 318: 1679-1686 Crossref PubMed Scopus (407) Google Scholar Identifying biomarkers to predict disease course and therapeutic response in IBD is now critical. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trialTop-down treatment with combination infliximab plus immunomodulator achieved substantially better outcomes at 1 year than accelerated step-up treatment. The biomarker did not show clinical utility. Top-down treatment should be considered standard of care for patients with newly diagnosed active Crohn's disease. Full-Text PDF Open Access