| hat if joint pain and stiffness are inevitable if you | | | | the ongoing assessment of the safety of a product |
| don't take the medication, yet heart problems could | | | | once it is in widespread use." |
| occur if you do? Health officials say that, as with any | | | | Others Weigh In |
| drug, only you and your doctor can determine the | | | | The concerns with the safety of so many pain |
| level of risk that is acceptable with medications | | | | relievers used to treat arthritis underscores the |
| currently available to treat arthritis. | | | | importance of arthritis as a major health care issue in |
| The unsettling news in late 2004 that the popular | | | | the United States. Arthritis experts, patient advocacy |
| anti-inflammatory arthritis drugs Vioxx (rofecoxib), | | | | groups, and other health organizations also are |
| Celebrex (celecoxib), and Bextra (valdecoxib) could | | | | weighing in on the uncertainty of NSAIDs, and are |
| cause a heart attack or stroke or aggravate high | | | | recognizing the need for developing new and safer |
| blood pressure has left some patients wondering | | | | medications. |
| whether they should keep taking them. | | | | The American College of Rheumatology is advising |
| Data from clinical trials showed that | | | | physicians to follow current treatment guidelines and |
| cyclooxygenase-2 selective agents, better known as | | | | manufacturers' dosage recommendations for NSAIDs. |
| COX-2 inhibitors, may be associated with an | | | | Treatment guidelines exist to help doctors choose |
| increased risk of serious cardiovascular problems, | | | | the best options for their patients, based on current |
| especially when used in high doses or for long periods | | | | scientific studies. |
| in patients with existing cardiovascular disease, or in | | | | The Arthritis Foundation said in a statement that the |
| very high-risk situations, such as immediately after | | | | findings about the drugs should not have any |
| heart surgery. COX-2 inhibitors are the newest | | | | immediate impact on the clinical use of them. |
| subset of non-steroidal anti-inflammatory drugs | | | | "Non-steroidal anti-inflammatory drugs continue to |
| (NSAIDs). COX-2 inhibitors were developed | | | | play an important role in the management of arthritis |
| specifically to decrease the well-recognized gastric | | | | pain," says John H. Klippel, M.D., president and CEO of |
| side effects and intolerance associated with the use | | | | the Arthritis Foundation. "Patients who derive benefit |
| of some NSAIDs. | | | | from these drugs should remain on their treatment |
| Traditional NSAIDs, such as aspirin or ibuprofen, act | | | | regimen, and discuss concerns with their physicians," |
| by blocking the production of a family of chemicals | | | | he says. |
| known as prostaglandins, which are not only | | | | But Charles A. Birbara, M.D., a rheumatologist and |
| important in the development of inflammation, but | | | | associate professor of medicine at the University of |
| also play an important role in maintaining the integrity | | | | Massachusetts Medical School in Worcester, Mass., |
| of the stomach lining. At least two enzymes are | | | | says that he has prescribed COX inhibitors cautiously |
| involved in this inflammation, namely | | | | in older people or those with cardiovascular or renal |
| cyclooxygenase-1 (COX-1) and cyclooxygenase-2 | | | | disease ever since early clinical studies discovered a |
| (COX-2). Traditional NSAIDs inhibit both COX-1 and | | | | possible risk in this patient population. |
| COX-2. Unfortunately, this non-selective inhibition of | | | | "I'm not always willing to take a risk with my |
| both COX enzymes also inhibits those prostaglandins | | | | patients, because we clearly don't have a complete |
| involved in some of the important "housekeeping" | | | | understanding of all the potential clinical issues |
| functions of the body, such as helping blood to clot | | | | associated with use of these drugs," he says. Even |
| and protecting the stomach from ulceration. | | | | before the controversy, Birbara notes that the |
| It is this non-selective inhibition of both enzymes by | | | | long-term effects of COX-2 agents were unknown. |
| aspirin and other non-selective NSAIDs that increases | | | | Besides, he says, there are other treatment options |
| the risk of stomach ulcers and consequent bleeding. | | | | available that are equally effective. |
| In theory, the newer COX-2 selective inhibitors only | | | | "There are so many wonderful things happening with |
| inhibit the enzyme involved in inflammation, leaving | | | | respect to current therapies of arthritis," he says. |
| the other functions alone. | | | | "Clearly, we are so much better able to control |
| But Sandra Kweder, M.D., deputy director of the | | | | inflammatory arthritis with new biologic agents." |
| Food and Drug Administration's Office of New Drugs, | | | | Birbara adds that so many people whose lives were |
| says that new studies have had a surprising twist. | | | | diminished by joint disease can now look forward to |
| "The downside of the COX-2 selective inhibitors is | | | | an unrestricted lifestyle, which was "not even |
| that they appear to be associated--particularly when | | | | imaginable just a few short years ago." |
| used for many consecutive months to years--with an | | | | Richard Shirley, 64, an avid birdwatcher from |
| increased risk of cardiovascular problems," she says. | | | | Wrentham, Mass., battled rheumatoid arthritis in |
| Moreover, COX-2 inhibitors, like other NSAIDs, don't | | | | nearly every joint in his body for more than 25 years |
| influence the course of the disease--which doctors | | | | before he saw Birbara. He couldn't button his shirt |
| say is a common misconception among | | | | cuffs, walk frontward down a flight of stairs, or get |
| patients--because these drugs only provide for | | | | in and out of a car without a struggle. At times, his |
| symptom relief. | | | | hands were so swollen he couldn't grasp small |
| Coincidentally, preliminary results from a three-year | | | | objects or make a closed fist. Shirley had his wedding |
| trial on the non-selective NSAID Aleve (naproxen) | | | | ring resized so it would fit. |
| also suggested that long-term use may be associated | | | | "Richard had seen a number of physicians and had |
| with an increased risk for cardiovascular problems. | | | | been on many medications to treat his disease," |
| Since the results of studies on both non-selective and | | | | Birbara says. "However, the aggressive nature of his |
| selective NSAIDs are preliminary and conflict with | | | | arthritis was not very responsive to standard |
| data from earlier studies of the same drugs, the FDA | | | | medications." According to Birbara, X-rays of Shirley |
| issued a public health advisory in December 2004 | | | | also showed evidence of joint destruction. |
| concerning use of all NSAIDs, pending further review | | | | "Doctor Birbara has a zero tolerance for hot and |
| of data that continue to be collected. The agency | | | | inflamed joints," Shirley says, "because that's when |
| has recommended, among other things, that | | | | the damage is done." Shirley also believes, from his |
| physicians limit the use of COX-2 inhibitors until | | | | own experience, that each person needs to work |
| further review. | | | | with his or her physician to find the appropriate |
| "Monitoring the drug safety of marketed products | | | | medicine. For him, a new biologic product made the |
| requires close collaboration between our clinical | | | | difference. |
| reviewers and drug safety staff to evaluate and | | | | Finding the right treatments for those at greatest |
| respond to adverse events identified in ongoing clinical | | | | risk for the potential complications of arthritis and |
| trials or reported to us by physicians and their | | | | other rheumatic conditions, Birbara says, hopefully will |
| patients," says Kweder. "The most recent actions | | | | lessen the burden of this disease, not only in the |
| concerning [NSAIDs] illustrate the vital importance of | | | | United States, but for the entire world. |