Maarten Cozijnsen

14 CD treatment and endoscopic remission Immunosuppressive treatment is required for inducing andmaintaining disease remission and preventing development of disease complications. It focuses on relieving symptoms, restoring longitudinal growth and pubertal development. Furthermore, it focuses on suppressing the inflammatory immune response leading to macroscopically detectable repair of the mucosal surface, also known as endoscopic remission. 8 Acquiring endoscopic remission is important since it predicts a favorable disease outcome, and reduces the need for steroids, the risk of complications, of hospitalization and the need for surgery. 9 Endoscopic remission can be assessed with ileocolonoscopy. However, frequent assessment of endoscopic remission with endoscopy has several limitations given its invasiveness, cost and potential risks, including the requirement of anaesthesia. 10 Therefore, non-invasive measures of endoscopic remission are desirable for tight monitoring of CD patients. In Chapter 2 we describe the mucosal- inflammation non-invasive (MINI) index we developed and validated. This non-invasive index identifies children with endoscopic remission with high sensitivity and specificity. Pediatric CD guidelines instruct physicians, in most cases, to start treatment with EEN or prednisolone to induce disease remission, and at the same time start with a thiopurine, such as azathioprine (AZA), or methotrexate (MTX) to maintain remission. 8 Patients refractory to these treatments can step up to anti-tumor necrosis factor alfa (anti-TNF) antibody treatment. Additionally the guideline suggests starting with anti-TNF treatment as initial treatment in patients with high risk for poor outcome and in patients with active perianal fistulizing disease. 8 Anti-TNF treatment has shown to be very effective in inducing and maintaining remission in therapy refractory pediatric CD patients. 11,12 It not only induces remission of clinical symptoms, but also heals the mucosa, restores mucosal tissue integrity, denoted as endoscopic remission. 13 Since the market approval of the first anti-TNF 14 treatment – infliximab (IFX) – researchers have searched for ways to optimize anti-TNF antibody usage, to increase response rates and to prolong the duration of disease remission. Based on research findings, the use of anti-TNF treatment in managing pediatric CD has significantly evolved over time. Step-up versus top-down treatment strategy Both IFX and adalimumab (ADA) are approved for a restricted population of pediatric CD patients, namely the therapy refractory patients with moderately-to-severely active disease. Yet, their benefit seems higher when given earlier in the course of disease. 15 If more effective treatment is given early, it may prevent disease complication. It may therefore be more beneficial to start anti-TNF antibodies right after diagnosis rather than delay the initiation.