Serious Adverse Events Associated with Anti-Tumor Necrosis Factor Alpha Agents in Pediatric-Onset Inflammatory Bowel Disease and Juvenile Idiopathic Arthritis in A Real-Life Setting

Objectives Anti-tumor necrosis factor alpha (anti-TNF-α) agents are generally well tolerated, yet they can be associated with serious adverse events (SAEs) in a minority of patients. We examined the incidence of SAEs in a pediatric referral center for chronic rheumatologic and gastroenterological inflammatory disorders. Methods Retrospective analysis of SAEs occurring during treatment with anti-TNF-α agents in patients with juvenile idiopathic arthritis (JIA) ( n = 78) or pediatric-onset inflammatory bowel disease (IBD) ( n = 105) seen at the Institute for Maternal and Child Health IRCCS “Burlo Garofolo” in Trieste, Italy, between June 2001 and February 2016. Only SAEs grade 3–5 according to the Common Terminology Criteria for Adverse Events version 4.03 and/or requiring definitive therapy discontinuation were reported. Results Total anti-TNF-α exposure was 390.5 patient-years (PYs). The overall incidence rate of SAEs for etanercept was 4.14/100 PYs. Four patients developed uveitis, two had anxiety disorders, one had a serious zoster infection, and one developed TNF-α antagonist–induced lupus-like syndrome (TAILS). The overall incidence rate of SAEs for infliximab was 22.49/100 PYs. The most common SAEs were anaphylactoid reactions ( n = 18), followed by infectious events ( n = 9) and TAILS ( n = 3). The overall incidence rate of SAEs for adalimumab was 4.71/100 PYs (two infectious SAEs). No malignancies or deaths were observed. A greater incidence rate of infectious SAEs was observed in IBD patients receiving infliximab compared to JIA patients receiving etanercept (8.11 vs 0.52 per 100 PYs). Conclusions Anti-TNF-α therapy was generally well tolerated. SAEs leading to anti-TNF-α discontinuation were rare and non-fatal. Infliximab was associated with the highest incidence of SAEs. Infectious SAEs were more frequently observed in IBD patients treated with infliximab than in JIA patients receiving etanercept.