New Arthritis Drug Guidelines... Do They Help... Or Do They Hurt?

Non-steroidal anti-inflammatory drugs (NSAIDS) have been the mainstay of arthritis treatment for more than 50 years. Over this time multiple drugs have reached the market and have been used by millions of people. In most cases, the safety profile has been one that has been predictable. In a few unusual cases, safety has been problematic leading to the withdrawal from the market of at least three drugs- Oraflex, Vioxx, and Bextra.

NSAIDS provide both analgesic (pain-relieving) as well as anti-inflammatory effects in arthritis.

Their action is dependent upon their effect in blocking the cyclooxygenase pathway. Cyclooxygenase is an enzyme that is responsible for the production of inflammation producing enzymes called prostaglandins. There are at least two cyclooxygenase pathways. Pathway one- termed COX-1 is the pathway blocked by most NSAIDS. These include drugs such as ibuprofen (Motrin), naproxyn (Naprosyn), piroxicam (Feldene), sulindac (Clinoril), oxaprocin (Daypro), nabumetone (Relafen), etodolac (Lodine), ketoprofen (Orudis), and meloxicam (Mobic).

COX-2 is the other pathway blocked by drugs like Celebrex.

Because these drugs are prescribed so widely by many different types of physicians including family practitioners, internists, orthopedic surgeons, as well as by rheumatologists, the extent to which serious side-effect issues have been addressed is unknown. The American College of Rheumatology recently released their recommendations in a paper published in the August 15th issue of Arthritis Care & Research (Arthritis Care and Research. 2008; 59: 1058-1073).

The authors recognized the fact that these drugs are often prescribed for patients with cardiovascular risk factors such as hypertension and hypercholesterolemia, as well as kidney dysfunction. What this means is that each patient needs to be evaluated as an individual. If the patient is on anti-cholesterol medicine or ACE inhibitors for hypertension, or aspirin for heart protection, these factors must be considered before prescribing NSAIDS.

Patients must be counseled in regards to potential toxicities and drug interactions. If the patient agrees that they want to take an NSAID, the drug needs to be monitored. Also, if the patient fails one NSAID, they may respond to another. Low doses are safer than high doses.

Monitoring of complete blood count as well as liver and kidney function should be done routinely.

If a patient is taking aspirin for heart protection, NSAIDS should be taken cautiously and with stomach protection if possible.

Unfortunately, there is a problem in that patients who need to be on heart-protective aspirin and who desperately need an NSAID for their arthritis are subject to a double whammy. The combination of low dose aspirin plus an NSAID increases the risk of gastrointestinal complications such as ulcer. At the same time NSAIDS themselves increase the risk for cardiovascular events such as stokes and heart attacks.

Also, it has been shown that the combination of ibuprofen plus aspirin actually reduces the cardiac protection of aspirin and the drug, naproxyn, if used intermittently also increases cardiovascular risk.

All NSAIDS increase the risk of kidney damage.

Many NSAIDS, particularly diclofenac (Voltaren) increase the risk of liver damage and need to be monitored closely and avoided in patients with pre-existing liver damage.

Patients on anticoagulant therapy should avoid drugs in the COX-1 class. Even COX-2 drugs may be problematic and should be evaluated carefully.

What's a mother to do?

NSAIDS are potentially dangerous drugs that should be used by physicians who are experienced with this class of medications. Patients should realize the potential dangers and discuss them frankly with their physician.