Maarten Cozijnsen

115 Chapter 6 Benefits and risks of combination therapy in children with IBD Introduction Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD), which present before the age of 20 years in 25-30% of CD and in 20% of UC patients. (1) In comparison to adult-onset disease, chronic inflammation in childhood onset CD leads often to impairment of linear growth and pubertal development, whereas childhood onset UC is more often extensive and therefore more often associated with acute severe exacerbations.(1, 2) First-line treatment of pediatric CD traditionally consists of exclusive enteral nutrition or corticosteroids to induce remission and immunomodulators (IM), i.e. thiopurines or methotrexate (MTX), to maintain remission – neither thiopurines nor MTX are labelled for the use in pediatric IBD.(3) In pediatric UC, based on disease severity, initial treatment consists of 5-aminosalicylic acid (5-ASA) or corticosteroids followed by 5-ASA maintenance therapy, optionally combined with thiopurines.(4) When these therapies fail, anti-tumor necrosis factor (TNF) antibody therapy is often indicated. Anti-TNF antibody therapy can induce and maintain remission in both pediatric and adult IBD patients.(5-7) It has become increasingly important in young patients, given the necessity to heal their intestine in a timely fashion so that normal growth can be restored, while growth potential remains. Indeed, the recent ESPGHAN-ECCO guideline on the management of pediatric CD proposes using anti-TNF in high-risk patients from disease onset, such as those with severely impaired growth. Though very efficacious, approximately 10-20% of anti-TNF treated patients annually lose response to anti-TNF therapies.(8-10) This may partly be explained by neutralizing anti-drug antibodies, but in remaining cases its reason is unknown. (8) Researchers hypothesized that combined treatment with an anti-TNF antibody and an IM will increase the efficacy of therapy and reduce the risk of loss of response. (11-14) Particularly in young patients maintaining therapy response is important given their long lives ahead. Pediatric gastroenterologists are required to weigh the potential benefits against the risk of combination therapy. In case evidence in pediatric IBD is limited, data from adult IBD studies should be extrapolated. This article reviews the literature to date comparing the efficacy and/or safety of combination therapy (anti-TNF with IM therapy) with anti-TNF monotherapy for the treatment of pediatric and adult IBD patients.