The use of low-dose aspirin did not reduce women's risk of developing rheumatoid arthritis, despite biologic plausibility that the drug could do so, researchers said.
After an average of 10 years of follow-up, the relative risk of definite rheumatoid arthritis among women who had taken 100 mg aspirin every other day was a nonsignificant 0.83 (95% CI 0.56 to 1.21, P=0.33), according to Nancy A. Shadick, MD, and colleagues from Harvard Medical School in Boston.
Clinical manifestations of rheumatoid arthritis are preceded, often for years, by serologic markers and asymptomatic synovitis. Detection of these prodromal abnormalities theoretically could allow for preventive intervention with anti-inflammatory agents such as aspirin.
Studies have shown beneficial effects for multiple diseases including cardiovascular disease and colon cancer, but aspirin has not previously been considered for potential preventive effects against rheumatoid arthritis.
"Evaluating whether a commonly used prophylactic medication such as aspirin can reduce the incidence of [rheumatoid arthritis] is an important public health question," asserted Shadick and colleagues.
To address this question, they turned to the Women's Health Study, which took place between 1992 and 2004, analyzing data from 39,144 women without prevalent rheumatoid arthritis at baseline.
Women in that study, whose mean age was 54.6 years at entry, were randomized to receive low-dose aspirin or placebo and followed yearly.
At study completion, 1,110 participants self-reported having rheumatoid arthritis and were mailed a connective tissue disease screening questionnaire.
Those who reported having at least three symptoms such as morning stiffness, arthritis of the hand joints, or rheumatoid factor positivity had their medical records reviewed for confirmation as definite rheumatoid arthritis according to American College of Rheumatology (ACR) criteria.
Definite rheumatoid arthritis was diagnosed in 106 women, which represented an annual incidence rate of 27.1 cases per 100,000 person-years.
A total of 60% were seropositive and 40% were seronegative.
Not only was the relative risk nonsignificant for definite, seropositive, and seronegative arthritis, but there also was no risk reduction on secondary endpoints such as all self-reported rheumatoid arthritis, or joint symptoms but in too few joints to meet the ACR criteria (inflammatory polyarthritis).
In discussing their findings, the researchers wrote, "We were interested in examining the role of aspirin in preventing the development of [rheumatoid arthritis] because several plausible mechanisms exist."
For instance, aspirin influences cyclo-oxygenase (COX) activity and thereby targets inflammation, and also inhibits interleukin-4 and NF-κB gene expression in non-COX-dependent pathways.
COX-2 mediates the production of prostaglandins, so the use of aspirin also might modulate prostaglandin-driven estrogen biosynthesis.
Moreover, inhibition of COX-2 restores apoptosis and prevents angiogenesis, which could delay the onset of synovitis.
An additional reason why aspirin might be effective in reducing the risk of arthritis is its antioxidant capacity, inhibiting cytokine-dependent induction of NOS2 gene expression via NF-κB activation.
As to why no protective effect was seen, the investigators pointed to the study's limited power to detect moderate reductions in risk and the possibility that higher doses of aspirin might provide more anti-inflammatory, antioxidant, and COX-2 inhibitory effects.
However, they also noted that higher doses also might mask symptoms of arthritis and delay diagnosis.
A limitation of the study, according to the researchers, was the fact that subjects who participate in research trials typically are healthier than the general population.
They concluded that despite the lack of benefit seen in this study, investigations that include greater numbers of patients with rheumatoid arthritis or use higher doses might show significant benefits.
"Given the frequency of aspirin use in the general population, this question deserves further study," they said.
http://www.medpagetoday.com/Rheumatology/Arthritis/19451
I"m shaking my head in wonder and asking myself what yahoo was silly enough to think for even a moment that aspirin prevented RA.
True, but there's a difference between Cox-1 and Cox-2.
Prostaglandins whose synthesis involves the cyclooxygenase-I enzyme, or COX-1, are responsible for maintenance and protection of the gastrointestinal tract, while prostaglandins whose synthesis involves the cyclooxygenase-II enzyme, or COX-2, are responsible for inflammation and pain.
The existing non-steroidal anti-inflammatory drugs (NSAIDs) differ in their relative specificities for COX-2 and COX-1; while aspirin is equipotent at inhibiting COX-2 and COX-1 enzymes in vitro and ibuprofen demonstrates a sevenfold greater inhibition of COX-2, other NSAIDs appear to have partial COX-2 specificity, particularly meloxicam (Mobic). Studies of meloxicam 7.5 mg per day for 23 days find a level of gastric injury similar to that of a placebo, and for meloxicam 15 mg per day a level of injury lower than that of other NSAIDs; however, in clinical practice meloxicam can still cause some ulcer complications.
A search for COX-2-specific inhibitors resulted in promising candidates such as valdecoxib, celecoxib, and rofecoxib (marketed under the brand names Bextra, and Vioxx respectively). Valdecoxib and rofecoxib are about 300 times more potent at inhibiting COX-2, than COX-1, suggesting the possibility of relief from pain and inflammation, without gastrointestinal irritation, and promising to be a boon for those who had experienced such adverse effects previously or had comorbidities that could lead to such complications. Celecoxib is approximately 30 times more potent at inhibiting COX-2 than COX-1.
True, but there's a difference between Cox-1 and Cox-2.
Your assertion "I guess, if this is really true, everyone should try Celebrex before using Relafen, Lodine, etc., etc." doesn't really make sense.