Maarten Cozijnsen

108 This issue has not been studied previously in pediatric CD patients, only in adult IBD patients. Ho et al studied CD patients and found a trend for lower remission rates and higher failure rates in infliximab non-responders compared to initial responders (percentages and significance not clarified).(16) Garcia-Bosch et al studied ulcerative colitis (UC) patients and found a difference in response rates after 12 weeks of treatment between infliximab prior non responders (2/6, 33%) and initial responders (25/33, 76%, p=0.01).(17) Both studies affirm the difference in efficacy found in our study. Efficacy in patients with vs without ATI We found a trend for higher remission rates and lower failure rates in patients with ATI than in those without. A possible explanation for this efficacy difference is this: Patients initially responding to the first anti-TNF agent that are confronted with loss of response resulting from anti-drug antibodies, evade the causative factor for loss of response and regain response by switching to another anti-TNF agent. On the contrary, patients without anti-drug antibodies at the time of anti-TNF treatment failure, fail for another yet unknown reason, which makes regaining response more challenging. Failure due to ATI therefore seems more favorable, since a response can be more easily regained. This issue has not been studied previously in pediatric CD patients, only in adult IBD patients. In the GAIN trial no difference was seen in remission rates at 4 weeks between CD patients with and without ATI prior to adalimumab (11/50 (22%) vs 19/88 (22%)).(11) West et al reported no relationship between the presence of ATI and response to adalimumab in CD patients, but serum ATI levels were higher in adalimumab non responders than in responders, suggesting a negative influence of high ATI concentrations on adalimumab response.(18) Afif et al found a trend for increased response in ATI positive UC patients versus ATI negative patients (5/8 (63%) vs 1/4 (20%), P≈0.5).(19) Strengths and limitations This study is the first nationwide study in pediatric CD patients evaluating adalimumab therapy in clinical practice and is strengthened by its population based design. Because of its observational character it reflects daily practice and its nationwide approach provides the inclusion of a broad spectrum of patients. However, the retrospective design has several limitations. First, the presented data might not be complete. Although participating centers were asked to identify all eligible patients, some may have been missed. When selectively more or less severely diseased patients were missed, the reported efficacy might differ from the efficacy in the total population. Some non-serious adverse events may also have been missed, such as minor infections treated in primary care practice.