Risks of serious infection or lymphoma with anti-tumor necrosisfactor therapy for pediatric inflammatory bowel disease: A systematic review

Background & Aims: Many physicians hesitate to recommend anti-tumor necrosis factor (TNF) therapy for pediatric patients with inflammatory bowel disease (IBD) because of concerns about risk of infection and cancer. We performed a systematic review to quantify the incidence of serious infection, lymphoma, and death among pediatric patients with IBD who received anti-TNF therapy. These values were compared with those expected from other treatments, from adults with IBD, and from the general pediatric population. Methods: We searched MEDLINE, EMBASE, the Cochrane Collaboration, and Web of Knowledge for studies of infliximab therapy for children with ulcerative colitis or Crohn's disease, or adalimumab therapy for children with Crohn's disease. Standardized incidence ratios (SIRs) were calculated, comparing rates of infection and cancer among pediatric patients exposed to anti-TNF agents vs expected rates from pediatric patients not exposed to anti-TNF therapies or adult patients exposed to anti-TNF agents. Our analysis included 5528 patients with 9516 patient-years of follow-up evaluation (PYF). Results: The rate of serious infections among pediatric patients treated with anti-TNF agents (352/10,000 PYF) was similar to that of pediatric patients who received immunomodulator monotherapy (333/10,000 PYF; SIR, 1.06; 95% confidence interval [CI], 0.83-1.36), but significantly lower than the expected rate for pediatric patients treated with steroids (730/10,000 PYF; SIR, 0.48; 95% CI, 0.40-0.58) or adults treated with anti-TNF agents (654/10,000 PYF; SIR, 0.54; 95% CI, 0.43-0.67). Five treatment-related deaths occurred (4 from sepsis and 1 from arrhythmia). Two patients developed lymphoma (2.1/10,000 PYF). This value was similar to the expected rate of lymphoid neoplasia in the entire pediatric population (5.8/100,000 PYF; SIR, 3.5; 95% CI, 0.35-19.6), and lower than the population of pediatric patients receiving thiopurine monotherapy (4.5/10,000 PYF; SIR, 0.47; 95% CI, 0.03-6.44), and among adults treated with anti-TNF agents (6.1/10,000 PYF; SIR, 0.34; 95% CI, 0.04-1.51). Conclusions: Based on a systematic review, the risk of lymphoma was no greater among children with IBD who received anti-TNF therapy than those treated with other IBD therapies or adults treated with anti-TNF agents. The rate of serious infection was significantly lower among pediatric patients with IBD treated with anti-TNF agents than those treated with steroids, or adults with IBD who received anti-TNF therapy.