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a Division of Rheumatology, Saint Louis University Health Sciences Center, Missouri
Akgun Ince, Internal Medicine/Rheumatology, Saint Louis University School of Medicine, 1402 So. Grand Blvd., Doisy Hall-213, St. Louis, MO 63104 E-mail: incea{at}slu.edu.
Decision Editor: John E. Morley, MB, BCh
OSTEOARTHRITIS (OA) is the most common form of arthritis and is the second most common cause of long-term disability (1). Using 1990 data, 21 million individuals have signs and symptoms of OA (2). Prevalence of arthritis and prevalence of activity limitation among patients is expected to escalate at least 50% by the year 2020, largely as a result of the aging of the US population and, to a lesser degree, changes in gender and race distribution. In 1992, the total annual cost of musculoskeletal disorders (the most common being OA) in the United States was $149.4 billion, which equaled 2.5% of that year's gross national product (3).
OA is first manifested by irregularities in the cartilage, followed by eburnation or ulceration of the cartilage surface, and finally by cartilage loss. Degradation of cartilage is probably initiated by mechanical stress leading to altered chondrocyte mechanism (4). Pain is the most important symptom that brings the patient to the doctor. Treatment is primarily aimed to control the symptoms because there are no disease-modifying drugs. Functional status and health-related quality of life in OA patients might be compromised because of decreased physical functioning, increased psychological distress, decreased social functioning, increased health care utilization, and increased work disability. The main measure of treatment efficacy is pain relief, but improvement in functions and quality of life should also be taken into consideration (5). In this issue of the Journal, Lisse and colleagues (6) report that, compared with a placebo, both celecoxib (a selective COX-2 inhibitor) and naproxen significantly improved functional status and health-related quality of life in elderly patients. Overall, naproxen had a higher incidence of gastrointestinal (GI)-related side effects, but, statistically, withdrawal due to adverse events between treatments and the placebo group was not significantly different (6).
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used therapeutic agents today, with an estimated 17 million individuals using them daily (7). The number of prescriptions written for elderly patients is roughly 3.6 times the number written for younger patients (8). This widespread use created a significantly larger problem: the adverse effect of NSAIDs. The risk factors for an NSAID-induced ulcer or its complications are well defined (9)(10)(11)(12). Patients who are older than 60 years of age with a history of peptic ulcer disease, a history of cardiovascular disease, or a more serious underlying illness or debility, and patients concomitantly taking NSAIDs and glucocorticoids, taking more than one NSAID at the same time, or who are chronically treated with NSAIDs are all at a greater risk. Discovery of more than one isoform of cyclooxygenase (COX) in 1990 led to the development of selective COX-2 inhibitors (13). COX-1 is expressed normally in the gastrointestinal tract, the kidneys, and platelets, and plays a major role in their normal function. COX-2 is expressed primarily in response to inflammation throughout the body and to some degree normally in the kidneys and other sites in the body (14).
Currently, there are two COX-2 specific inhibitors available in the United States. Celecoxib has been approved for treatment of OA and rheumatoid arthritis, and rofecoxib has been approved for OA and acute pain indication. Published data show that both rofecoxib and celecoxib are as effective as ibuprofen (2400 mg/24 h), diclofenac sodium (150 mg/24 h), and naproxen (1000 mg/24 h), and that GI adverse effects and the gastroduodenal ulcer rate was lower than with traditional COX-1 NSAID treatment (15)(16)(17)(18)(19)(20)(21)(22). Most of the safety data obtained included endoscopic trials. Large, longer-term prospective complication trials that would give better insight to safety of COX-2 NSAIDs are expected to be published in the very near future.
Risk stratification is crucial in cost benefit issues in clinical practice as regards NSAIDs use. In a low-risk patient, the incidence of ulcer complications related to NSAID use is only 0.4%. On the other hand, the propensity for ulcer complication in high-risk patients, such as a patient aged 75 years or older with a history of an ulcer and gastrointestinal tract bleeding, is about 5% for developing a complicated ulcer while taking NSAIDs (23). Peterson and Cryer (24), by assuming a 50% risk reduction for a complicated ulcer when using COX-2–specific inhibitors, calculated the cost to be $400,000 for 500 patients to prevent one complicated ulcer among low-risk patients. Using the same cost numbers, preventing one ulcer complication in high-risk patients, as described above, would be about $30,000.
Bakowsky and Hanly (25) showed that 15% of the patients with NSAID-induced toxic effects were using more than one NSAID. There are at least 20 COX-1 NSAIDs and three NSAIDs, as well as aspirin available over the counter; this emphasizes the importance of preventing polypharmacy with various NSAIDs.
In dehydrated individuals or in patients with congestive heart failure, COX-2 activity is upregulated to help maximize renal vascular blood flow (26). Moreover, it must be clear that COX-2–specific agents are not "super aspirins" and cannot be substituted for aspirin as a means of decreasing cardiovascular events (24).
As with most new therapies, there is much enthusiasm and interest in the new COX-2 NSAIDs. However, simple things, such as good history taking, preventing polypharmacy, and risk stratification, are more important than specific therapeutic interventions. COX-2 inhibitors are expensive, and the paper by Lisse and colleagues (6) supports the use of celecoxib only in patients at risk for gastrointestinal complications. Physicians need to be very mindful of the other complications of COX-2 inhibitors, which may occur with more frequency in older persons.
Received September 6, 2000
Accepted September 8, 2000
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  J. E. Morley and J. H. Flaherty Editorial It's Never Too Late: Health Promotion and Illness Prevention in Older Persons J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2002; 57(6): M338 - 342. [Full Text]
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J. E. Morley Editorial: Drugs, Aging, and the Future J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2002; 57(1): M2 - 6. [Full Text] [PDF]
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