Early Crohn disease: a proposed definition for use in disease-modification trials

Crohn disease is a chronic condition characterised by intestinal inflammation and progressive bowel damage associated with impaired functioning. In rheumatoid arthritis, which shares some common aetiological pathways and treatments with Crohn disease, treatment goals no longer include symptom control alone, but also alteration of the biological processes underlying synovial inflammation and progressive structural destruction, thereby preventing structural joint damage and functional decline.1 Analogous disease-modifying treatment goals for Crohn disease are currently being conceptualised and may include prevention of structural bowel damage (stricture, fistula, abscess) and impaired gastrointestinal physiology (ie, maintaining normal gastrointestinal physiology).2 3 In order to achieve disease modification, an effective intervention must occur at the right time, that is, before the development of bowel damage and impaired functioning. While it has been said in this context ‘the earlier, the better’, there is no formal definition of early Crohn disease.4 This article will review the rationale for defining early Crohn disease and the rationale for specifically targeting early Crohn disease from both immunopathological and clinical points of view, using rheumatoid arthritis (another chronic, progressive, destructive disease), as an example. We will then propose a definition of early Crohn disease and briefly discuss its potential application in future clinical trials. Studies from referral centres have demonstrated that the clinical features of Crohn disease change over time with a decreasing frequency of inflammatory (non-stricturing non-penetrating) disease behaviour and an increasing frequency of stricturing and/or penetrating disease behaviour (disease progression).5 6 Population-based studies have demonstrated that more than 50% of adult patients with Crohn disease develop stricturing or penetrating intestinal complications within 20 years of diagnosis7 and similarly these complications occur in more than 50% of children after a median follow-up of 84 months.8 The development of these complications is associated with a need for surgical resection. …