Biologic agents have been designed with the help of immunological studies to 
target particular areas of the immune system which are thought to play a role in 
the pathogenesis of disease. Etanercept is a soluble anti-tumor necrosis factor 
alpha (TNF-alpha) agent licensed for the treatment of active poly-articular 
juvenile idiopathic arthritis (JIA) in children aged 4 to 17 years who have 
failed to respond to methotrexate alone, or who have been intolerant of 
methotrexate. The safety and efficacy of etanercept in this patient group has 
been established by one randomized controlled trial and several longitudinal 
studies. This, together with the fact that until recently etanercept was the 
only anti-TNF licensed in JIA, has made it the most common first choice biologic 
for many clinicians. However, there are still many unanswered questions about 
etanercept, including its efficacy and safety in different subtypes of JIA, in 
children under 4 years of age and in those with uveitis. There are still 
concerns about the long term safety of TNF antagonists in the pediatric age 
group and unanswered questions about increased risks of malignancy and 
infection. Although adult studies are useful to improve understanding of these 
risks, they are not a substitute for good quality pediatric research and 
follow-up studies. Adult trials often include greater numbers of patients. 
However, they evaluate a different population and drug behavior may vary in 
children due to differences in metabolism, growth and impact on a developing 
immune system. In addition, rheumatoid arthritis is a different disease than 
JIA. Clinicians need to carefully weigh up the risk benefit ratio of anti-TNF 
use in children with JIA and push for robust clinical trials to address the 
questions that remain unanswered. This article summarizes the evidence available 
for use of etanercept in children with JIA and highlights aspects of treatment 
in need of further research.