Maarten Cozijnsen

107 Chapter 5 Adalimumab therapy in children with infliximab-refractory CD Discussion In this nationwide, observational study, adalimumab therapy induced remission in two thirds of the infliximab refractory patients, of whom 50% maintained remission up to 2 years. Adalimumab failure occurred in 24% within 1 year and in 42% within 2 years. Only 1 serious adverse event occurred. The remission rates correspond well with those in previously published retrospective studies by Russell et al and Rosh et al(13, 14), but less with those in the prospective study by Hyams et al(12). The latter authors reported lower remission rates during follow-up than the authors of the retrospective studies did. This discrepancy might be the result of a difference in denominator, as Hyams et al divided the number of patient in remission by the number of included patients, whereas the retrospective studies, including the current study, divided it by the number of patients still receiving therapy. Combining the retrospective data, adalimumab induced remission in 61 to 64% of the infliximab refractory patients within a median of 2.4 to 3.3 months, and after 12 months of treatment 41 to 53% of the patients still receiving adalimumab, were in remission. Secondly, the adalimumab failure rate in our cohort corresponds well with that in the retrospective studies, and also with that in the prospective study. Overall, adalimumab failure occurred in 15 to 28% of the infliximab refractory patients within the first year and in 20 to 42% within 2 years. Lastly, the incidence of serious adverse events (SAE) within our cohort (1 SAE within 66 PY, 1.5 SAE/100PY) was lower than that within previously published studies. Within the study of Russell et al four SAE were reported within 72.5 PY (5.5 SAE/100PY) and in the prospective study 63 SAE developed within 152 PY (41 SAE/100PY). The higher incidence in the prospective study, may be the result of the use of more extensive criteria for SAE and more stringent monitoring. Efficacy in infliximab non-responders vs loss of responders Within our cohort, we have demonstrated that a small group of patients who had not responded to infliximab (n=3), had higher risk for adalimumab failure than those who had lost response to infliximab. Some patients do not respond well to anti-TNF therapy, while other patients do, which may be the result of a difference in underlying disease mechanism. Different disease mechanisms may require different treatment strategies.