Selective cyclooxygenase-2 inhibitors for the treatment of arthritis

The purpose of this paper is to review the rationale for a new class of non steroidal anti-inflammatory drugs (NSAIDs) known as selective cyclooxygenas e (COX)-2 inhibitors and to present preliminary clinical data on 2 COX-2 in hibitors that are approved for use in the United States. The primary mechan ism of NSAIDs in the treatment of inflammation is the inhibition of COX, wh ich exists in 2 forms. COX-1 appears to regulate many normal physiologic fu nctions, and COX-2 mediates the inflammatory response. Theoretically, an NS AID that inhibits COX-2 selectively should decrease inflammation but not in fluence normal physiologic functions and thus should cause fewer gastrointe stinal side effects. Preliminary data suggest that celecoxib, a highly sele ctive COX-2 inhibitor, is superior to placebo and similar to traditional NS AIDs in the short-term treatment of pain due to osteoarthritis, although it has been associated with adverse effects such as headache, change in bowel habits, abdominal discomfort, and dizziness. Celecoxib also has been shown to be as effective as traditional NSAIDs in the treatment of rheumatoid ar thritis, but it may cause fewer adverse effects, including endoscopically d ocumented ulcers. Celecoxib is metabolized in the liver by the cytochrome P -450 isozyme CYP2C9, and thus serious drug interactions are possible. In th e treatment of osteoarthritis, rofecoxib has been shown to be as effective as traditional NSAIDs and may cause fewer endoscopically documented ulcers, but its complete adverse-effect profile is not known. Until the selective COX-2 inhibitors are widely used and more clinical as well as pharmacoecono mic studies are published, the exact role of COX-2 therapy cannot be determ ined.