Maarten Cozijnsen

122 Efficacy of combination vs. monotherapy in UC patients Pediatric UC patients Thus far, the evidence available within pediatric UC is too limited to conclude whether or not combination therapy is more effective than anti-TNF monotherapy. Two studies compared their efficacy in treatment of pediatric UC, but both may suffer from confounding- by-indication bias (Table 2). In the T72 trial by Hyams et al (7), 60 pediatric UC patients with moderate-to-severe disease were treated with IFX and the responders at week 8 (44/60) were randomized to receive IFX either every 8 or 12 weeks. At baseline, 32 patients received concomitant IM therapy while 28 did not. In a post-hoc analysis, no differences in outcomes were observed between the groups (response week 8: 23/32 (72%) vs. 21/28 (75%), P≈0.8; remission week 8: 13/32 (41%) vs. 11/28 (39%), P≈0.9; mucosal healing week 8: 21/32 (67%) vs. 20/28 (71%); P≈0.6; remission week 54: 5/11 (46%) vs. 3/10 (30%), P≈0.5). In an earlier analysis from the North American pediatric IBD registry, Hyams et al (39) studied 52 pediatric UC patients that had started IFX before the age of 18, of whom 32 (63%) used concomitant IMs at the start of IFX. Although not significant, a clear clinical trend for lower colectomy rate was noted in the combination group at 3 months (13% vs. 38%), at 6 months (25% vs. 38%), at 12 months (26% vs. 50%), and at 24 months (47% vs. 78%). Adult UC patients One RCT in adult UC patients was specifically designed to compare combination vs. monotherapy. In the UC-SUCCESS trial, Panaccione et al (12) randomized 239 adult UC patient with moderate-to-severe disease, naïve to anti-TNF therapy, to receive either AZA plus placebo, IFX plus placebo, or a combination of both drugs. At 16 weeks, more patients treated with combination therapy were in remission (31/78 (40%)) than those treated with IFX (17/77 (22%), P=0.017) or AZA (18/76 (24%), but no significant differences were noted in mucosal healing rates (49/78 (63%) vs. 52/77 (55%), P=0.30). Interestingly, IFX alone was not better than AZA. Fewer patients developed ATIs in the combination therapy group than in the IFX monotherapy group (1/31 (3%) vs. 7/37 (19%), P≈0.045); IFX drug levels were not reported. Like in SONIC, a fixed IFX dosing schedule was used. Lichtenstein et al (25) performed a post-hoc analysis of UC patients included in the IFX trials ACT 1&2(484 received IFX, of whom 227 (47%) received concomitant IM). No differences in clinical response or remission rates were found between patients with and without IM. However, concomitant IMs did reduce the occurrence of ATIs (ACT I: 1/59 (2%) vs. 8/53 (15%), P≈0.01; ACT II: 1/43 (2%) vs. 12/53 (23%), P≈0.005), but IFX levels did not differ, except in ACT II at 30 weeks (higher IFX levels in the combination therapy group).