Rheumatoid arthritis is a chronic, systemic, autoimmune disease that preferentially attacks the joints but also attacks many internal organs. It affects approximately two million Americans.
Recent therapeutic developments in the last 20 years have allowed rheumatologists to achieve remission in many if not most patients with this disease.
Rheumatoid arthritis patients are at increased risk of infection. This increased risk is partly due to the disease itself. And some of the increased risk is obviously due to the immunosuppressive medications, some patients may be receiving.
The most recent therapeutic agents used in the treatment of rheumatoid arthritis are biologic therapies. And the most commonly used biologic therapies are what are called tumor necrosis factor inhibitors (TNF). Tumor necrosis factor plays an important role in the control of infection. In particular, TNF release from immune cells, called macrophages, is critical for proper defense against infecting agents such as bacteria. TNF also is important in regards to regulation of white blood cell movement within the blood stream and other areas.
On the flip side, drugs that block tumor necrosis factor can also have beneficial effects that must be weighed against their potential ill effects on infection defense. In short, they reduce the immune abnormalities that are part of rheumatoid arthritis, the disease.
A recent report (Anti-TNF Therapy is Associated with an Increased Risk of Serious Infections in Patients with Rheumatoid Arthritis Especially in the First 6 Months of Treatment: Updated Results from the British Society for Rheumatology Biologics Register with Special Emphasis on Risks in the Elderly" Galloway JB, et al Rheumatology. 2010;51(1):124-131.) highlighted the difficulties associated with estimation of infection risk in rheumatoid arthritis patients treated with TNF inhibitors.
According to the authors of the above paper, there have been several attempts in clinical trials to try and quantify the increased risk of infection in patients who are taking anti-TNF drugs. However, because of multiple reasons, including patient population size, study design, as well as the "artificial environment" associated with clinical trials, quantifying infection risk has been difficult. Also, since many patients with rheumatoid arthritis are taking steroids, which also increase infection risk, this has been another confounding factor.
Large observational studies looking at multiple clinical trials have shown that there appears to be an increased risk of certain infections in rheumatoid arthritis patients treated with anti-TNF drugs. The organisms that seem to pop up with the most frequency are Listeria, Salmonella, and Mycobacterium tuberculosis.
The number reported by the British Registry in the recent study is a 20 per cent overall increase. What is really startling though is the fact that the risk for serious infections was increased by 80 percent during the first six months of therapy.
Why such a high number early on? The authors offer a few possible explanations. The first is that patients who are really susceptible to infection may get infections early on and be taken off their TNF inhibitor medicines. That leaves a relatively healthy number of patients left to assess.
There may also be adjustments in the immune system that might, over time, compensate for the lack of TNF.
Finally, as patients become better controlled with their disease, they require less in the way of steroids, therefore reducing infection risk.
Finally... and this is an important, if not obvious point. There also appears to be an increased risk of infection with increasing age. This is not a surprise, given that older patients have other disease conditions and are on multiple medications.
While this article hasn't mentioned all the risks associated with TNF inhibitors, I have tried to at least present the latest information in regards to the most common one, which is infection.
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