Maarten Cozijnsen

103 Chapter 5 Adalimumab therapy in children with infliximab-refractory CD Table 2. Response to adalimumab Follow-up (months) 0 1 4 8 12 24 36 48 Remission 3 (6) 11 (21) 18 (38) 20(57) 16 (53) 9 (47) 4 (67) 1 (100) Response but no remission - 20 (38) 8 (17) 6(17) 4 (13) 4 (21) 1 (17) - No response - 17 (32) 7 (15) 3 (9) 2 (7) 1 (5) - - Loss of response - - 7 (15) 6(17) 8 (27) 5 (26) - - Missing evaluation - 5 (9) 7 (15) - - - 1 (17) - Number of patients on adalimumab treatment 53 53 47 35 30 19 6 1 No more follow-up - 0 0 7 11 20 29 34 Adalimumab failure - 0 6 11 12 14 18 18 Table displaying the response to adalimumab during follow-up, The results are presented as number (%=N/total of patients on continued therapy). Adalimumab treatment failed or discontinuedwithin amedian of 5.3months (IQR 2.9-18.0), the 4 non-responders discontinuedwithin amedian of 3.2months (IQR 1.4-4.0), the 11 patientswho lost response failed within a median of 7.5months (IQR 3.5-18.4), the 3 patients with adverse effects within amedian of 16months (1.5, 16.1 and 19.6). Adalimumab failure over time is displayed using a cumulative hazard curve in Figure 2: 24% failed within 12 months and 42% within 24 months. Twelve patients were evaluated for ATA formation at least once during follow-up. In 4 patients ATA were present, 3 patients suffered loss of response and the last suffered adverse effects (fatigue after injections, hair loss, pain and redness at the injection site). Sub analyses Adalimumab was less effective in patients that had not responded to infliximab than in those who had lost response to infliximab. Only one of the three patients with non-response to infliximab reached remission during follow-up versus 24 out of 34 patients who had lost response to infliximab (1/3 (33%) vs 24/34 (71%), P=0.24). Furthermore, two of the former patients developed adalimumab failure (non-response and loss of response) compared to 8 of the latter patients (2/3 (67%) vs 8/34 (24%), P=0.17; HR 18.8, CI 1.1-304) (Figure 3). ATI presence had been studied in 38 of 53 patient (72%) and found present in 21. We detected a trend towards a higher remission rate in patients with ATI than in those without ATI at the time of infliximab failure (17/21 (81%) vs 9/17 (53%), P=0.09) and a trend towards a lower failure rate (4/21 (19%) vs 7/17 (41%), P=0.13; HR 0.37, CI 0.11-1.23) (Figure 4). Furthermore, none of the former patients suffered non response to adalimumab compared to 4 of the latter patients (24%). At 12 and 24 months, 14% and 22% of the former patients had failed adalimumab versus 40% and 55% of the latter patients.