Do top arthritis drugs deliver?

Americans spend $6 billion a year on the arthritis painkillers Vioxx and Celebrex, which are said to be as good as over-the-counter drugs -- but easier on the stomach.

But the two have not lived up to their hype, according to published research and interviews with arthritis doctors and drug specialists.

Vioxx, which may be better for the stomach, appears to have a far worse side effect than over-the-counter drugs: an increased risk of heart attack. For reasons doctors don’t yet understand, Celebrex does not seem to be linked to heart problems, but there’s conflicting evidence on whether it is easier on the stomach.

“There is no proof that these COX-2 drugs are better for arthritis pain than traditional ibuprofen, and there is also no proof, except for a certain subset of patients, that these drugs are safer,” said Dr. Neil Minkoff, medical director of pharmacy at Harvard Pilgrim HealthCare, which insures 800,000 people in Massachusetts, New Hampshire and Maine.

Back in the late 1990s, when the hype over Vioxx and Celebrex began, the excitement seemed well-founded. Researchers had long known that prostaglandins, natural chemicals that are made in cells under the direction of enzymes called cyclooxygenases, were the root cause of pain and inflammation. But then they discovered two types of cyclooxygenases, COX-1 and COX-2.

COX-1 releases “good” prostaglandins that protect the stomach. COX-2 releases “bad” prostaglandins that further drive inflammation. The new drugs -- Vioxx and Celebrex and their lesser-known cousins Bextra and Mobic -- were hailed for their ability to block only COX-2 and leave the good prostaglandins intact, something that traditional over-the-counter anti-inflammatory drugs such as ibuprofen could not do.

Eager to get the painkilling benefits without such stomach-killing side effects as bleeding ulcers, doctors and patients flocked to these COX-2 inhibitors to help dampen the pain of arthritis, migraines, acute pain and menstrual cramps.

Then the bad news began trickling in. The COX-2 inhibitors actually “don’t eliminate gastrointestinal side effects, they just reduce them somewhat, and even that is more problematic than first thought,” said Dr. Jerry Avorn, chief of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital in Boston.

In September 2000, a study of 8,000 patients showed that people taking Celebrex had fewer ulcer complications than those taking over-the-counter medications. But the study, published in the Journal of the American Medical Assn., focused on only six months of drug use, “the most appropriate” time frame, said Dr. Gail Cawkwell, worldwide medical team leader for Pfizer, which sells Celebrex.

When a later analysis by the U.S. Food and Drug Administration looked at 12 months of data, this apparent advantage disappeared.

In November 2000, a study found that 50 milligrams a day of Vioxx -- a high dose -- reduced the risk of serious stomach problems, compared with prescription-strength naproxen (Aleve). But the study, published in the New England Journal of Medicine, also showed that the risk of heart attack was two to four times higher for patients on Vioxx.

Since then, most -- but not all -- studies have shown a link between Vioxx and heart disease. This spring, researchers from Brigham and Women’s Hospital, writing in the journal Circulation, concluded that compared with high doses of Celebrex, high doses of Vioxx were linked to a 70% increase in heart attack risk in the first 90 days of use.

So where does this leave us? Use over-the-counter medications if they work for you. If they don’t, talk with your doctor.