Risk of Serious Bacterial Infection Associated With Tumor Necrosis Factor-Alpha Inhibitors in Children and Young Adults With Inflammatory Bowel Disease.

Background: Prior studies evaluating the relationship between tumor necrosis factor-alpha inhibitors (TNFI) and infection were conducted in adults and had conflicting findings. We sought to examine the risk of serious infection associated with TNFIs compared with nonbiologic immunomodulators in children and young adults with inflammatory bowel disease (IBD) and to compare the risk among individual TNFIs.

Methods: We conducted a cohort study using the Truven MarketScan Commercial Claims and Encounters database of patients age <30 years with a diagnosis of IBD who initiated treatment with a TNFI or immunomodulator (thiopurines or methotrexate) between 2009 and 2013. The outcome of interest was serious infection, defined as a nongastrointestinal bacterial infection requiring hospitalization. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for serious infection associated with TNFIs compared with immunomodulators.

Results: We identified 10,838 children and young adults with IBD; 236 and 192 cases of serious infection were observed in 4502 TNFI initiators (5.25/100 person-years) and 6336 immunomodulator initiators (3.59/100 person-years), respectively. Compared with immunomodulators, TNFIs were associated with a higher risk of serious infection (HR, 1.36; 95% CI, 1.08-1.72). Among TNFI users, certolizumab showed a 3.38-fold (95% CI, 2.25-5.09) increased risk vs infliximab, and subcutaneously administered TNFIs also exhibited a higher risk (HR, 1.34; 95% CI, 1.18-1.53) than intravenous TNFIs.

Conclusions: TNFIs pose a higher risk of serious infection compared with immunomodulators in children and young adults with IBD, and this risk differs among individual TNFIs and routes of administration.