Gettysburg Medical News
The Clinical View
by P.E. Hoffsten, MD
7, February 2007

UPDATE ON ARTHRITIS MEDICINES

            Of all the various maladies that come with age, arthritis symptoms are almost universal.  Of all the symptoms that individuals develop, arthritis problems are the one that patients most like to have effective treatment for.  Heart disease, high blood pressure, or high cholesterol are responsible for many more deaths than is arthritis but they don’t cause symptoms that bother people the way arthritis does.   Thus finding a medication to effectively treat arthritis has been a high priority of the pharmaceutical industry for many years. 

            Perhaps the first arthritis medicine ever developed came from the bark of a tree and was known at the time of the Greeks.  Eventually, the active ingredient of the bark of that tree was called colchicine and it is still intermittently used for individuals who have gout causing their arthritis.  But colchicine has many side effects including abdominal cramping and diarrhea.  Around the turn of the century 107 years ago, aspirin was found to be an effective arthritis medicine and until 1948 was a backbone of treatment for arthritic conditions.  In doses that were effective to treat arthritis (sometimes 20 tablets per day), aspirin caused ulcers, ringing in the ears, and fluid retention. 

            In the late 1940’s, cortisone was developed for commercial use and was like a miracle drug.  Individuals who had rheumatoid arthritis could have their disease remarkably well controlled for the first time.  Unfortunately, cortisol proved to be highly dangerous for long-term use having many side effects.  Today, we use cortisol in short bursts for several weeks but it is rare to use this medication on a long-term basis for arthritis. 

            Cortisol was one member of a family of drugs called steroids.  In 1965, a new drug called indomethacin was introduced to the public and was the first “non-steroidal anti-inflammatory drug”.   The abbreviation for this became NSAID.  Since the introduction of indomethacin, there have been more than 30 competing products introduced.  Each of them has more or less success with different individual patients.  Some work for one patient and not others and vice versa.  Of the first products that were introduced in late 1960’s and early 1970’s, ibuprofen (Motrin, Advil, Nuprin) and naproxen (Naprosyn, Aleve) still have wide use today. 

            But then the story gets complicated.  In 1969, Dr. John Vane, working in England discovered the enzyme called cyclooxygenase which aspirin and all the NSAID’s inhibit.  By the 1980’s, it was found that there were two different kinds of cyclooxygenase which for the sake of brevity were referred to as COX-1 and COX-2.  It turns out that the COX-1 enzymes in our bodies are a so-called constitutive enzyme that serves many important functions including blood pressure, protection of our stomachs and water balance.  If COX-1 is inhibited, there is a tendency to have gastric ulcers, high blood pressure, and fluid retention.  It was found that there was a second enzyme called COX-2 which was involved in inflammation.  It didn’t take scientists long to figure out that if they could inhibit the COX-2 enzyme and not the COX-1 enzyme, the body could do its normal job but not get inflamed. 

            Thus, was born the push to find “selective” COX-2 inhibitors that did not inhibit the COX-1 enzyme.  The first products of this sort were called Vioxx, Celebrex, and Bextra.  They came out with great fanfare, outrageous prices and inflated claims of success.  These three products did seem to have a lesser incidence of gastric ulcers.  Vioxx especially seemed to be a very effective drug but as fate would have it, the “soup hit the fan” in 2004 when it was published that patients taking Vioxx had an increased incidence of heart attacks as compared to other NSAID’s.  Merck Company stock dropped from $44.00 a share to $33.00 a share in 3 days because Vioxx was a 6 billion dollar drug that was suddenly removed from the market. 

            What wasn’t known then, was what the relative incidence of heart attacks was with all of the other NSAID’s.  It turns out that poor Vioxx was not the only offender in this area.  Other drugs still on the market have every bit the risk that Vioxx ever had including diclofenac (Voltaren) and meloxicam (Mobic).   Drugs that have proved to be very safe in regard to not causing heart attacks include naproxen and ibuprofen. 

But now comes the most difficult part of all.  How does one balance the quality of life vs the quantity of life.  If there is a particular NSAID that works for a particular patient remarkably well but that NSAID has a slightly increased risk of some side effect, who should make the choice on whether that patient wants to take that risk for the relief of pain that they get.  As it stands today, Vioxx and Bextra were both taken off the market voluntarily by the companies that made them but the litigation in regard to Vioxx is still in monetary amounts too big for anyone but trail lawyers to contemplate.  Too this time, there is still no “black box warning” in regard to the other NSAID’s.  One must remember that while naproxen and ibuprofen seem to be safe for the heart, they are still not safe for tummies that develop gastric ulcers or for individuals who have high blood pressure, or for individuals who tend to fluid retention.  If a person is taking a drug called furosemide (Lasix) the use of an NSAID will completely neutralize the diuretic effect of furosemide (Lasix).

            In summary, this topic has no fewer than 5,000 articles written about it in the past three years.  The best care for the individual patient comes with consultation with your health care provider at your local clinics.  There the relative risks and benefits from any individual drug can be determined and discussed.  Unfortunately, the use of the right drug is still a trial and error consideration.  Health care providers are continually trying to balance the safety versus the effectiveness of medications.