Biologic-Associated Infections in Pediatric Rheumatology

During the past 15 years, biologics for juvenile idiopathic arthritis (JIA) therapy has led to new options. However, despite the high effectiveness and safety profile of these agents, infections are of great concern. The risk for bacterial infections, which appears to be increased in JIA patients as a result of the disease itself, seems to be increased further by antirheumatic treatment. Combining data from several sources, infection rates appear to be comparable for abatacept (1.33/100 person-years (PY); 95 % confidence interval (CI)=0.50-2.48), adalimumab (1.42/100 PY; 1.01-1.99), and etanercept (1.28/100 PY; 1.06-1.55); higher with golimumab (3.03/100 PY; 1.26-7.29) and infliximab (3.42/100 PY; 1.71-6.84); and even higher with tocilizumab (8.62/100 PY; 6.69-11.10). The rate of serious infection was lowest with methotrexate (0.67/100 PY; 0.48-0.93). In patient cohorts treated with methotrexate without a biologic as a comparator, risk ratios for serious infections were significantly increased for all biologics, except abatacept, because of insignificant patient numbers. Opportunistic infections, including tuberculosis, were very rare. Herpes zoster was the only specific infection occurring frequently throughout the studies. Thus, the safety profiles of approved biologics are highly acceptable. Although this conclusion is based on limited experience and is not easily expanded to the interleukin (IL)-1 inhibitor canakinumab or the T cell activation inhibitor abatacept, both these agents have demonstrated an excellent safety profile so far.