Safety of anti-inflammatory treatment--new ways of thinking.

The development of osteoarthritis may be accompanied by increased production of leukotrienes (LTs) and prostaglandins (PGs) from arachidonic acid. These products contribute to joint damage, pain and inflammation. Cyclooxygenase (COX)-1 and COX-2 are responsible for the production of PGs. Inhibition of these enzymes by non-steroidal anti-inflammatory drugs and selective COX-2 inhibitors reduces the levels of PGs, resulting in a reduction in pain and inflammation. However, this inhibition can cause alternative processing of arachidonic acid via the 5-lipoxygenase (5-LOX) pathway, resulting in increased production of proinflammatory and gastrotoxic LTs. Licofelone is a competitive inhibitor of 5-LOX, COX-1 and COX-2 that is currently being developed for the treatment of osteoarthritis. Licofelone decreases the production of both LTs and PGs, and thereby reduces inflammation and pain with low gastrotoxicity. Unlike selective COX-2 inhibitors, coadministration of licofelone and aspirin does not appear to be associated with an increase in gastrointestinal adverse events, at least under experimental conditions. Furthermore, there is evidence from animal models to suggest that licofelone may stop disease progression.