Maarten Cozijnsen

35 Chapter 2 Development and validation of the MINI-index Introduction It is widely accepted that treating Crohn’s disease (CD) to the target of mucosal healing (MH), may be associated with improved long-term outcomes and may reduce the risk of bowel damage 1–3 . The visualized degree of mucosal inflammation is quantified by endoscopic scores, such as the simple endoscopic score for Crohn’s disease (SESCD) 4,5 ; it scores each bowel segment for ulcerations, affected surface area and luminal narrowing. However, the use of endoscopic evaluation as a target to treatment has several limitations given its invasiveness, cost and potential risks, including the requirement of anesthesia 6 . Therefore, non-invasive measures of MH are desirable for tight monitoring of CD patients. Clinical disease activity indices correlate poorly with endoscopic disease activity in CD 4,7–10 . In children, the reported correlation of the pediatric Crohn’s disease activity index (PCDAI) and the weighted PCDAI (wPCDAI) with the SESCD, whilst higher than reported for the adult clinical disease activity index (CDAI), still does not surpass 0.3–0.45 9,11 . In every day practice, physicians regularly use serum markers, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), to monitor disease activity given their correlation with mucosal disease activity (SESCD or CDEIS) that ranged between 0.12 and 0.54 in different studies 4,6,9,12–14 . While the specificity of both markers is high they lack sensitivity and approximately half of patients with normal serum markers may still have significant mucosal inflammation 15 . Fecal calprotectin (FC) is increasingly used as a superior measure of mucosal inflammation with correlation coefficients ranging from 0.45 to 0.76 6,16–18 . However, its large inter-patient variability prevents determining a clear cutoff value to reflect MH 1,15 . In addition, FC proportionally reflects histological rather than macroscopic inflammation and thus intermediate values (e.g. 100-300) do not necessarily reflect macroscopic mucosal inflammation 19 . We hypothesized that a combination of clinical symptoms with serum and fecal inflammatory markers can reflect mucosal inflammation if weighted mathematically on a large cohort of patients 9 . We thus aimed to develop a novel, Mucosal-Inflammation Non-Invasive (MINI) index that correlates with SESCD, and accurately discriminates MH from mucosal inflammation in children with CD.