BERLIN—The world of arthritis research is drawing a clearer picture of the kind of patient who might develop infections, a significant recent step forward in understanding the link between infection and rheumatoid arthritis (RA), one expert reported at the European League Against Rheumatism (EULAR) 2012 Annual European Congress of Rheumatology, held June 6–9.
“I think what’s more interesting is not whether there’s an increased risk of infection with people with arthritis,” said Alan Silman, MD, professor and medical director at Arthritis Research UK in Chesterfield, U.K. “I think what is developing is an understanding of whether we can identify which patients we need to worry about. And, if we know which patients we need to worry about, that is going to help us interpret the information about the potential level of risk from anti-TNFs [tumor necrosis factor inhibitors] and other biologics.”
In another talk during the session, Lars Klareskog, MD, professor and chair of the department of rheumatology at the Karolinska Hospital in Stockholm, Sweden, talked about the importance of taking nuanced action to prevent comorbidities associated with RA.
Earlier research, Dr. Silman said, has suggested strongly that environmental factors play a role in the development of RA. For someone with a monozygotic twin with RA, the chance of having RA is just 15%. Declines in the incidence of RA suggest that there is an environmental factor at work in the development of RA—and that factor might very well be infection.
But what is the infectious agent? Researchers haven’t made much progress there, Dr. Silman said.
“Even today, despite 40 years of study, I don’t think we’re anywhere nearer identifying what that infectious agent might be,” he said.
With the abundance of published research, Dr. Silman offered guideposts for interpreting it all.
“It’s actually quite important when you come to this literature to have, in your own mind, some questions that you need to address as you read those publications,” he said.
Such questions include asking about the nature of the organism and the infection to determine whether it’s biologically plausible that it might be involved in RA development. Physicians should also pay attention to the attack rate, noting that most people show some signs of exposure to Epstein-Barr virus, but few people have RA.
He also cautioned against the notion of the “uniqueness” of an infecting agent.
“The likelihood that rheumatoid arthritis is going to be caused by a single infectious organism is very, very distant and, therefore, … attempting to use epidemiological methods, for example, to find the single organism that causes arthritis, is likely to come up with a blank,” Dr. Silman said.
Progress in Determining Risk
The most progress has been made in determining which patients might be at the greatest risk, with much attention given to biologics.
A study of almost 12,000 patients using data largely from Medicare and Medicaid found that the rate of serious infections for anti-TNF agents was incrementally increased by a fixed absolute difference, regardless of age, comorbidities, and other factors that contribute to infections. Higher rates of infection were seen for new infliximab users compared to new etanercept and adalimumab users.1
The more serious the disease, the greater the risk of infection, as well, Dr. Silman said. One study found that the Disease Activity Score (DAS) bore a relationship to the infection risk.2
In a patient with a high DAS, not only do physicians need to think about suppressing the disease activity, but they also need to consider that these patients are at the highest risk of developing a serious infection, Dr. Silman said. In his talk, Dr. Klareskog said it’s important not to lump together comorbidities into one bundle, but to distinguish between those that run parallel to RA, those that seem to be causes of RA, and those that are consequences of RA treatment.
Each category, and each type of comorbidity, calls for individualized action.
“They can be of many different kinds, and I think that we should keep them apart because there are different consequences and different measures that we could take,” he said.
Dr. Klareskog talked about the progress of identifying early lung abnormalities in patients who later develop RA—although it is not known yet how these abnormalities and RA are linked.3
“This is a disease that may be parallel,” he said. “It may also be causative to RA.” More attention needs to be paid to what happens in the lungs in the early stages of RA, he said.
Connecting Pain and Inflammation
Dr. Klareskog also drew attention to the emerging understanding of the separation between pain and inflammation. Reducing inflammation frequently does not lessen a patient’s pain.
“It’s not enough to take away the inflammation—you have to continue with pain treatments,” he said. “And that may be one of the major reasons why patients who get…treatment for inflammation actually don’t go back to work and still have decreased quality of life.”
One recent study found that anti-TNFs have distinct effects on pain and inflammation, acting to reduce pain rapidly. Researchers suggest that neutralizing TNF-α affects nocireceptive brain activity in arthritis, before it achieves antiinflammatory effects in the joints, which might explain its earlier-than-expected effects.4
Dr. Klareskog issued a special warning that rheumatologists need to take early action against cardiovascular risk in RA patients. A recent meta-analysis found that there is a 1.5- to 2-fold increase in cardiovascular disease risk for patients with RA.5
Even with the plethora of new therapies, there has not been much improvement in this risk, he said.
“This is still a problem that is very important for all of us,” Dr. Klareskog said. “The major message when we’re talking about comorbidity is that we have a fantastic opportunity here to do something.”
Thomas Collins is a freelance medical writer based in Florida.
References
- Curtis J, Xie F, Chen L, et al. Use of a disease risk score to compare serious infections associated with anti-TNF therapy among high versus lower risk rheumatoid arthritis patients. Arthritis Care Res (Hoboken). 2012 May 3. [Epub ahead of print]
- Emery P, Gallo G, Morgan CL, Currie CJ, Poole CD, and Nab H. Evaluation of the association between disease activity and risk of serious infections in subjects with rheumatoid arthritis when treated with etanercept or disease-modifying antirheumatic drugs. Arthritis Rheum. 2011;63:S163.
- Demoruelle MK, Weisman MH, Simonian PL, et al. Brief report: Airways abnormalities and rheumatoid arthritis-related autoantibodies in subjects without arthritis: Early injury or initiating site of autoimmunity? Arthritis Rheum. 2012:64;1756-1764.
- Hess A, Axmann R, Rech J, et al. Blockade of TNF-α rapidly inhibits pain responses in the central nervous system. Proc Natl Acad Sci USA. 2011;108:3731-3736.
- Avina-Zubieta JA, Thomas J, Sadatsafavi M, Lehman AJ, Lacaille D. Risk of incident cardiovascular events in patients with rheumatoid arthritis: A meta-analysis of observational studies. Ann Rheum Dis. 2012 Mar 16. [Epub ahead of print]
