Maarten Cozijnsen

15 Chapter 1 General introduction This is especially true for patients that are not effectively treated with—i.e. do not respond to or quickly relapse under—the conventional non-biologic treatment options (prednisolone or EEN, combined with AZA or MTX). However, it remains difficult to predict responsiveness to these therapeutic options, so further research is needed to assess the benefits (and risks) of starting anti-TNF antibodies as first-line treatment option. Patients at greater risk of disease complication, such as strictures and fistulas, would benefit most from an early initiation with anti-TNF antibodies. For this purpose, the current guidelines lists the following seven factors as potentially predictive of poor outcome – mostly based on clinical experience: 8 • deep colonic ulcerations on endoscopy • persistent severe disease despite adequate induction therapy • extensive (pan-enteric) disease • marked growth retardation N−2.5 (minus 2.5) height Z scores), • severe osteoporosis • stricturing and penetrating disease (B2 and/or B3 disease behavior at onset • severe perianal disease Recently, new results of the RISK study were published ( Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease ). 16 This prospective inception cohort followed 913 pediatric CD patients from disease onset up to 3 years after. Baseline predictive factors for stricturing or penetrating disease at 3 years, were older age, African-American race, isolated ileal disease, and ASCA and CBir1 serum-positivity. However, their combined sensitivity and specificity were low (66% [95% CI 51%–82%] and 63% [55%–71%]). The authors state that the accuracy was low because of the low prevalence of complications within those 3 years in their cohort. Due to the low accuracy, the significance of these predictive factors in clinical decision making is limited. Thus, it remains difficult to accurately determine patients at high risk of complications. Starting with anti-TNF treatment after patients lose response to other treatment options - the so-called step-up treatment strategy – has several disadvantages. Although prednisolone and EEN both induce clinical remission effectively (in ~ 80% of patients), prednisolone has considerable side effects, and EEN necessitates a complete refrain from normal food for a long period of time which is unpleasant and hard to comply with. Furthermore, prednisolone rarely induces endoscopic remission. 8,17,18 Once in clinical remission, approximately 60% of patients maintain remission during the first year of AZA treatment. 19–22 One registry showed that 54% (55/102) of pediatric patients with CD had received either an additional corticosteroid course or had started infliximab (IFX) within the first year after diagnosis. 23