Low-Dose Aspirin Fails to Prevent RA
Reported April 08, 2010
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.
Nor was there a significant risk reduction for seropositive rheumatoid arthritis (RR 1, 95% CI 0.61 to 1.63, P=0.99) or seronegative disease (RR 0.62, 95% CI 0.33 to 1.15, P=0.13), the researchers reported in the April Arthritis Care & Research.
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-?B 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-?B 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.
Source : MEDPAGE TODAY