Maarten Cozijnsen

61 Chapter 3 TISKids: an international multicenter RCT Table 1. Study endpoints Time (weeks) Primary endpoint Remission 1 without need for additional CD-related therapy or surgery 52 Secondary efficacy endpoints Remission 1 and response 2 10, 52 Endoscopic disease activity (presence of ulcers, SES-CD) 10, optionally 52 Fecal calprotectin 10, 52 Height and BMI Z-scores, bone age and pubertal development 52 Quality of life (IMPACT-III) 14, 52 Cumulative therapy use and therapy failure 52 Secondary safety endpoints Adverse events and complications 52 Long-term endpoints Remission 1 without need for additional CD-related therapy or surgery 104, 156, 208, 260 Remission 1 and response 2 104, 156, 208, 260 Fecal calprotectin 104, 156, 208, 260 Number of flares 104, 156, 208, 260 Quality of life (IMPACT-III) 260 Cumulative therapy use and therapy failure 260 Adverse events and complications 260 Sub analyses Comparing efficacy and safety of prednisolone plus AZA with EEN plus AZA Correlations between wPCDAI, fecal calprotectin and endoscopic disease severity (SES-CD) Additional objectives Comparing cost-effectiveness of top-down with step-up Identifying predictive biomarkers for treatment response Assessing the pharmacokinetic and pharmacodynamic properties of IFX in children 1 Remission = wPCDAI<12.5; 2 Response = wPCDAI decrease>17.5; wPCDAI = weighted Pediatric Crohn’s Disease Activity Index (25); SES-CD = Simplified Endoscopic activity Score for Crohn’s Disease (27); IMPACT-III (28, 29); IFX = infliximab; EEN = Exclusive Enteral Nutrition; AZA = azathioprine Health-care costs, response prediction, and evaluation of the kinetic and dynamic properties of IFX Three additional objectives are set. First additional objective is to compare the health-care related cost of both treatment strategies. This is an important outcome, because of the large difference in costs between biologic and non-biologic drugs. The recent introduction of an IFX biosimilar to the market has strongly reduced the costs of IFX therapy, while the costs of