Maarten Cozijnsen

126 Safety of combination therapy in IBD patients Safety in pediatric IBD Besides the potential benefits of combination therapy, the risks of additional medication should be carefully considered, especially in children who may well have many future treatment years. It is important to note that thiopurines were the traditional IMused in pediatric CD andUC, either as monotherapy or in combination with anti-TNF. Hence more data exist concerning toxicity profile of thiopurines in young IBD patients in comparison to MTX, although its use in pediatric CD has increased in recent years (Table 3). The DEVELOP registry is designed to study long-term (20 years) safety of IFX and other therapies in pediatric-onset IBD (ClinicalTrials.gov Identifier: NCT00606346). Preliminary data showed that combination therapy resulted in higher malignancy rates in patients receiving combination therapy than in those receiving anti-TNF monotherapy (0.11/100PY (4/3599PY) vs. 0/100PY (0/748PY), P<0.05).(45) Rosh et al (44) performed a post-hoc analysis on the patients included in IMAgINE 1 and its extension trial OLE, which included 192 pediatric CD patients that were treated with ADA for a total of 422 patient-years (PY). More children treated with combination therapy at baseline had serious infections but this did not reach significance (6.2 E/100PY vs. 3.5 E/100PY, P>0.05). Safety in adult IBD None of the four aforementioned adult RCTs specifically designed to compare combination therapy vs. monotherapy found increased AE rates in the combination therapy group, nor increased serious adverse events (SAEs), infections or serious infections.(11-14) On the contrary, within the SONIC trial (11), fewer SAEs occurred in the patients receiving combination therapy (27/179 (15%) vs. 39/163 (24%), P=0.04), likely due to reduced infusion reactions (9/179 (5%) vs. 27/163 (17%), P<0.001) and better disease control and thus fewer CD associated infections such as abscesses. The previouslymentioned post-hoc analysis by Jones et al (27) showed similar SAE rates across both patients groups. In a sub-group analysis, combination therapy with IFXwas associatedwith fewer infusion reactions (OR 0.43 (0.19-0.97)). Infection and serious infection rates were also similar in the aforementioned post-hoc analysis by Lichtenstein et al (25) and an additional post- hoc analysis, which utilized patient data from all industry driven IFX trials in adult IBD patients, found similar malignancy and mortality rates.(45) In contrast, Osterman et al (46) performed a post-hoc analysis on CD patients included in ADA RCTs (CLASSIC I&II, CHARM, GAIN, EXTEND, ADHERE) to assess the risk of non-melanoma skin cancer (NMSC) and other malignancies in combination and monotherapy treated patients. Of the 1594 patients treated with ADA, 694