Maarten Cozijnsen

117 Chapter 6 Benefits and risks of combination therapy in children with IBD Up to date, the evidence available within pediatric CD is too limited to conclude whether or not combination therapy is more effective than anti-TNF monotherapy. Although the only RCT did not find a significant difference in efficacy, a clinically significant difference may well exist smaller than the RCT could detect. Moreover, it only compared remission maintenance rates between combination vs. monotherapy treated patients and not remission induction rates. Since the evidence in children is limited, extrapolation from adult literature should be considered. Adult CD patients In adult CD patients, three RCTs were specifically designed to compare the efficacy of combination therapy with that of anti-TNF monotherapy. Van Assche et al (14)randomized 80 CD patients with mild or no disease activity after 6 months combination therapy to either continue combination therapy or to switch to IFX monotherapy. After 104 weeks of follow-up, similar clinical relapse rates were seen in both groups (24/40 (60%) vs. 22/40 (55%), P=0.65). Furthermore, no difference was seen in their mucosal healing rates at week 104 (16/25 (64%) vs. 14/23 (61%); P≈0.8). However, higher median IFX trough levels were found in patients continuing IM therapy (median IFX trough 2.87 µg/mL (1.42–4.80) vs. 1.65 µg/mL (0.54–3.53), P=0.0001) and ATIs were detected in a non-significantly lower proportion of patients (2/40 (5%) vs. 5/40 (12.5%), P=0.43). The placebo-controlled SONIC trial (11) compared the effectiveness and safety of IFX plus placebo, AZA plus placebo and combination therapy with both drugs in 508 adult CD patients with moderate-to-severe disease, naïve to both AZA and IFX. After 26 weeks of therapy, more patients treated with combination therapy (96/169 (57%)) were in corticosteroid-free remission than those treated with IFX (75/169 (44%), P=0.02) or AZA (51/170 (30%)). Furthermore, a trend for increasedmucosal healing rates among patients with ulcers present at baseline, was seen in the combination therapy group (47/107 (44%)) compared to the IFX monotherapy group (28/93 (30%), P=0.06). Higher IFX trough levels and less often antibodies-to-IFX (ATIs) were found in the patients receiving combination therapy vs. those receiving monotherapy (median IFX trough: 3.5 vs. 1.6 µg/ml, P<0.001; ATI week 30: 1/116 (0.9%) vs. 15/103 (14.6%), P<0.001). The COMMIT trial by Feagan et al (13) compared the efficacy and safety of combined treatment with IFX and MTX, with that of IFX and placebo for both the induction and maintenance of remission in adult CD patients. A total of 126 anti-TNF naïve CD patients who had initiated prednisone therapy for active symptoms were included (tapering of prednisone therapy started 7 days after randomization). At 14 weeks and at 50 weeks, no differences were seen in prednisone-free remission rates between the two treatment arms (week 14: 48/63 (76%) vs. 49/63 (78%), P=0.83; week 50: 27/48 (56%) vs. 28/49 (57%); P=0.86). However, again, fewer patients developed ATIs and a trend for higher IFX trough levels was seen in the combination group (ATI: 4% vs. 20%, P=0.01; median IFX trough: 6.4 vs. 3.8 µg/ml, P=0.08).