First-line therapy in adult Crohn's disease: who should receive anti-TNF agents?

Therapy for Crohn's disease has traditionally been based on a step-up approach, with treatment with the powerful TNF antagonists reserved as a last resort before surgery. In this Review, the authors discuss the use of anti-TNF agents as first-line therapy to achieve disease modification and the challenges in selecting appropriate patients for this approach. Therapy for Crohn's disease has long been based on a step-up approach, with monoclonal antibodies against TNF as a final option before surgery. Despite the introduction of these monoclonal antibodies, no major changes have occurred in the natural history of Crohn's disease, with half of all patients still requiring intestinal resection at 10 years. Labelling for anti-TNF agents does not take into account prognostic factors. In this Review, we propose that treatment of Crohn's disease be based on the following three disease stages: mild, moderate and severe. In patients with Crohn's disease who have complicated disease or bowel damage, and with poor prognostic factors and/or severe disease, anti-TNF treatment should be considered as first-line therapy. For patients living in areas of high risk of developing tuberculosis, as well as for patients with mild-to-moderate Crohn's disease without poor prognostic factors and with uncomplicated disease, steroids and thiopurine should be the first-line therapy. By treating patients with Crohn's disease in accordance with these disease stages, we might be able to alter disease course and reduce overtreatment. Upcoming disease-modification trials are expected to provide information to guide decision-making, ultimately changing the course of disease and improving patient quality of life.