Maarten Cozijnsen

116 Efficacy of combination vs. monotherapy in CD patients Pediatric CD patients In pediatric CD patients, only one RCT was specifically designed to compare the efficacy of combination therapy with that of anti-TNF monotherapy (Table 1). The RCT by Kierkus et al (15) included 99 pediatric CD patients who were treated with IFX induction therapy. At week 10, responders were – in non-blinded fashion – randomized to receive either continued combination therapy through week 54 or combination therapy until week 26 and then IFX monotherapy until week 54. At 54 weeks, loss of response rates, defined by increase in Pediatric Crohn’s Disease Activity Index, were similar in both groups (2/45 (4%) vs. 2/39 (5%), P≈0.9), similar proportions of patients required an increase or change of therapy (13/45 (29%) vs. 11/39 (28%), P≈0.9), and equal proportions of patients had increased SES CD scores compared to baseline (13/45 (29%) vs. 11/39 (28%), P≈0.9). Additionally, one post-hoc analysis of a prospective trial and seven retrospective studies compared the efficacy of combination vs. monotherapy in children with CD. Hyams et al (16) performed a post-hoc analysis of the patients included in the RCT IMAgINE 1, which assessed the safety and efficacy of adalimumab in treating children with moderate-to- severe CD. Of the 188 patients treated with ADA, 117 (62%) used concomitant IM at baseline. Similar remission rates were observed at week 26 in patients with and without concomitant IMs (42/117 (35.9%) vs. 21/71 (29.6%), P≈0.4). ADA clearance and the occurrence of anti-drug antibodies were similar in both groups (clearance: 12.4±5.74 mL/h vs 15.2±7.88 mL/h; ATI occurrence: 2/117 (1.7%) vs 4/71 (5.6%), P≈0.2).(17) Five retrospective pediatric cohort studies, totaling 512 patients, showed no difference in remission or loss of response rates between those treated with combination therapy or monotherapy.(18-22) However, Russell et al (23), in a cohort of 70 CD patients treated with ADA, found a higher remission rate in patients receiving combination therapy (ADA+IM) than in those receiving monotherapy (34/46 (74%) vs. 9/24 (37%), P=0.003).Furthermore, Church et al(24), among a cohort of 195 children with CD treated with IFX, found an increased duration of response in those treated with combination vs. monotherapy (Hazard ratio: 0.25 (CI 0.08- 0.76)), both in IMnaïve and experienced patients – loss of response was defined in this study as complete loss of responsiveness to IFX infusions, rather than simply a need to increase dose or shorten interval in order tomaintain response. It should be emphasized that these retrospective cohorts studies, as well as the aforementioned post-hoc analysis are severely biased due to “confounding-by-indication”, i.e. patients with more severe disease may have been more likely to have received IM therapy, and thus even if combination therapy was more effective, it just leveraged the outcome to those of the milder patients on monotherapy.