Guidelines on the use of etanercept for juvenile idiopathic arthritis in Japan

Etanercept is a dimeric fusion protein consisting of the extracellular domain of human tumor necrosis factor receptor II (TNFR II, molecular weight 75 kDa) coupled to the Fc region of human immunoglobulin (IgG1). It is produced by recombinant DNA technology by first introducing the gene into Chinese hamster ovarian cells and then purifying the protein from the culture supernatant. The mechanism of action of etanercept consists of binding to serum TNF-α and lymphotoxin (LT)-α (TNF-β), which prevents TNF-α and LT-α from binding to the TNF-α receptor on the plasma membrane of the target cell. Etanercept is currently approved for treating adult rheumatoid arthritis (RA) in more than 70 countries worldwide. In Japan, it was approved for this target group in January 2005. The USA and Europe were the first to approve entanercept for use in treating juvenile idiopathic arthritis (JIA), initially for the treatment of active polyarticular JIA in patients not responding to disease-modifying antirheumatic drugs (USA in May 1999, followed by the EU in February 2000). Thereafter, the drug received approval for the treatment of JIA in many other countries. In Japan, children who have been diagnosed and treated according to Yokota et al. (Mod Rheumatol 17:353–363, 2007), but who have responded poorly to treatment must move onto the next stage of treatment. Such treatments include biological drugs, which, however, should be used with strict adhesion to the indications and exclusion criteria and should be used, for the time being, only by physicians trained on how to use them. In Japan, etanercept was approved in July 2009 for use in children. Although this drug has brought about a revolutionary advance in the treatment of JIA, it is our task to maximize its therapeutic effects and minimize its toxic effects. The guidelines presented here define the indications, exclusion criteria, usage, and evaluation criteria of etanercept for the treatment of polyarticular JIA.