Rheumatoid Arthritis Watch

Statins May Lower Risk for Rheumatoid Arthritis

Can statins decrease the risk of developing rheumatoid arthritis? Researchers from Tel Aviv, Israel, demonstrated an association between persistent statin therapy and reduced risk of developing rheumatoid arthritis (RA) in a restrospective cohort study of more than 200,000 patients that was published online on PLoS Medicine in September 2010.

Gabriel Chodick, MD, and colleagues examined almost 2 million medical records from Maccabi Health Services, Israel’s universal health maintenance organization. To account for a “healthy-user bias,” which is the tendency of healthier patients to be more likely to persist with preventive treatments, the researchers enrolled adults with osteoarthritis, in addition to adults with RA, who were started on statin therapy between 1998 and 2007.

Adjusted hazard ratios (HRs) were then calculated to see if persistent statin therapy influenced the risk of developing RA. In patients who received persistent therapy with a high-dose, highly potent statin, the risk of developing RA was significantly lower than in patients who did not receive persistent therapy or in patients who received a lower-dose or less potent statin. This decreased risk was seen more in a younger patient population as well.

The reasons researchers theorize for statins’ protective properties against RA include their modulation of signaling pathways involved in inflammation as well as their bone-specific antiresorptive effects, which may be responsible for improving disease activity. Nevertheless, no definitive conclusion about statins’ ability to modify the risks for RA can be made until randomized, controlled trials are conducted.

Does Therapeutic Drug Monitoring Have a Role in RA?

As the treatment paradigm for RA shifts from traditional step-up regimens to more aggressive “hit hard and early” strategies, the need for therapeutic drug monitoring (TDM) becomes an increasingly important issue, writes Alfons A. den Broeder and colleagues in an editorial in the October 2010 issue of Rheumatology. Because of the new trend in treating RA early with high-dose biologics, many patients are experiencing unnecessary side effects that could be minimized if doses were de-escalated to the lowest dose required for symptomatic improvement.

Data from a cohort of RA patients treated with infliximab showed that in 37% of patients with low disease activity, low or no infliximab was present in the serum, while another 30% of these patients had high to very high infliximab trough levels (>5 mg/ ml). These findings suggest that some patients might have improved without medication, while others would have responded to a lower dose than what was given.

The authors believe that TDM can be beneficial in determining the proper dose of biologics in RA patients, particularly measuring trough levels of these drugs. However, no test characteristics have been established, such as cut-off thresholds, sensitivity, and specificity. “Future research should aim at providing answers to these important questions,” the authors write.

Rheumatoid Arthritis May Protect Against Alzheimer’s Disease

It has always been thought that nonsteroidal anti-inflammatory drugs (NSAIDs) were responsible for the decreased incidence of Alzheimer’s disease (AD) seen in patients with RA. Now the results of a new study, published in the Journal of Alzheimer’s Disease, suggests that rather than NSAIDs, the pathology unique to RA may be responsible for preventing Alzheimer’s disease later in life.

Tim D. Boyd, PhD, and colleagues from University of Southern Florida in Tampa have published results from an experiment conducted in mice, studying the effects on neurologic disability of exogenous administration of granulocyte-macrophage colony-stimulating factor (GM-CSF)—a growth factor seen in excess in patients with RA and also a treatment option marketed as Leukine used in cancer chemotherapy patients to prevent neutropenic fever.

Scientists used transgenic AD mice that had buildup of cerebral amyloid plaques, which are peptide formations in the brain associated with AD pathophysiology in mice and in humans. The mice were then infused with 3 different growth factors. The researchers found that while 2 of the growth factors had no effect on the amyloid plaques, GM-CSF demonstrated pronounced decreases in amyloid deposition, suggesting the role GM-CSF may have in decreasing and even preventing plaque formation.

Huntington Potter, PhD, an author of the study, believes that the neuroprotective effects GM-CSF may have on patients warrant a human trial. “Our study, along with the drug’s track record for safety, suggests Leukine should be tested in humans as a potential treatment for Alzheimer’s disease,” he said.