Maarten Cozijnsen

18 treatment with anti-TNF antibodies. 11,12,32 These trials further demonstrate that anti-TNF antibodies are able to maintain remission up to 1 year in approximately 45% to 83% of patients. The variation in these remission rates largely depends on patient or treatment factors, as will be discussed further below. Anti-TNF antibodies are also effective in closing perianal fistulas in children with CD: After 2 to 4 months of treatment, approximately 64% show complete fistula closure (range 54% to 100% 33–35 ) and after 1 year of treatment 40% to 68% show complete closure. 12,35 In Chapter 5 we describe a nationwide, observational cohort study into the real-world effectiveness of ADA treatment for children and adolescents with CD who had previously failed IFX treatment. However, a head-to-head comparison of the efficacy of anti-TNF therapy to that of the alternative therapies in use—exclusive enteral nutrition (EEN) or corticosteroids for remission induction and thiopurines or MTX for remission maintenance – is still lacking. 8 The pivotal trials of both IFX and ADA in pediatric CD did not have a control group, and since their approval no prospective trial has been published that compares the effectiveness of anti-TNF treatment with alternative treatments. Thus, there is currently no reliable way to compare their effectiveness. In the international multicenter RCT we set up, described in Chapter 3 of this thesis, we aim to compare the efficacy and safety of remission induction with IFX, prednisolone or EEN in newly diagnosed pediatric CD patients. Optimizing treatment effectiveness Patient characteristics impacting effectiveness Patient characteristics can have a high impact on drug effectiveness. In the phase 3 ADA trial, IFX experienced patients were only half as likely to achieve disease remission during follow-up than IFX naïve patients. 12 Secondly, the authors reported that younger age and shorter disease duration were associated with higher remission rates, a finding confirmed by several observational trials. 33,36–38 The third factor influencing remission rates in this trial was baseline C-reactive protein (CRP). 12 Patients with a lower CRP were more likely to achieve remission during follow-up. However, this finding conflicts with literature in adult CD patients, where several trials found high baseline CRP to be associated with higher remission rates. 39–41 Combination therapy and therapeutic drug monitoring Besides patient characteristics, some treatment options are known to impact treatment effectiveness and allow further treatment optimization. Currently there are two methods being used to improve the effectiveness of anti-TNF antibodies: combination therapy with an immunomodulator and monitoring of therapeutic drug levels. Chapter 6 is a review in which we compare the benefits and risks of combining anti-TNF treatment with immunomodulator therapy based on published evidence. In short, although evidence of