What does COX stand for? Cyclo-oxygenase, an endogenously produced chemical.
We have two receptors in our bodies, Cox-1 and Cox-2.
When cyclo-oxygenase goes to a Cox-1 receptor, it causes a muco-protective coating in the GI tract. This is a good thing.
When the Cox-2 receptor is stimulated, it causes inflammation of joints. This is a bad thing.
So, ideally what you want to do is block Cox-2.
Let’s go back for a moment and review the NSAID properties: Analgesic, antipyretic, anti-inflammatory. NSAID’s could also be called COX-1 and COX-2 inhibitors because they block both the cox-1 and cox-2 receptors. If cox-2 is blocked, this is good for RA. But if you block cox-1, you have a higher risk of ulcers because you don’t have that muco-protective coating. NSAID’s are the number one reason for ulcers because they block cox-1.
The manufacturers came out with cox-2-specific inhibitors so that cox-1 wouldn’t be inhibited and the risk of ulcers would be less. Unfortunately, they are not much better than the non-specific ones.
Stats: 1 in 6 patients (17%) on an NSAID were developing ulcers with NSAID’s. That same group of patients that were later put on cox-2-specific inhibitors. The incidence of ulcers went down to 13% (instead of 17%). It was statistically significant, but obviously not a big change.
So cox-2 inhibitors, such as celocoxib (Celebrex), aren’t necessarily safe, there’s no generic available, so it’s expensive, so when will you use it? If you have a patient with a history of ulcers, you’d go with this. Also, RA drug therapy is hit or miss, so if the others don’t work, maybe this one will work.
Cox-2’s have come under a lot of scrutiny. One of which is the Vioxx litigation. Vioxx is a cox-2 inhibitor. It shows a higher risk of heart attacks in patients prone to heart attacks. The media had a lot to play on this one. We had a lot of patients on this drug and it was helpful for them but it was pulled from the market. Yes, there was a higher risk of heart attacks for people who already had a high risk for a heart attack, but not for the ones with a low-risk, so those people are left without a drug therapy. Who should be doing the analysis whether a drug is safe or not? The physicians, not the media. There is talk that when the lawsuits are over in a year or two that the drug will come back, if it goes out of the lime light.