PHILADELPHIA -- Two new studies failed to find a solid link between anti-tumor necrosis factor (anti-TNF) therapy and infections among rheumatoid arthritis patients.
Even though anti-TNF therapy is designed to interfere with immune response and so theoretically exposes a patient to a greater infection risk, two researchers told attendees at the American College of Rheumatology meeting here that they were unable to find such a relationship when they observed the overall infection landscape.
However, a third study that looked specifically at infections within joints, did note an increased risk of infection with anti-TNF therapy.
In the first study, Jeffrey Curtis, MD, MPH, of the University of Alabama at Birmingham, and colleagues were unable to distinguish differences in the incidence of infections among patients receiving anti-TNF therapy and those receiving treatment with more traditional disease modifying anti-rheumatic drugs (DMARDS).
"The infection-related safety profiles of the various biologic agents appear to be similar," Curtis said. "We found no significant increase in the adjusted risk for hospitalized or outpatient infections associated with anti-TNF therapy or other biologics compared with methotrexate and other nonbiologic disease modifying anti-rheumatic drugs."
Curtis and colleagues identified 18,305 rheumatoid arthritis patients from the Consortium of Rheumatology Researchers of North America (CORRONA). Among those patients were 586 cases in which patients needed to be hospitalized for infections while on treatment, and 21,258 outpatient infections.
"The most important risk factors for serious infections were not biologic medications, as some might have expected, but instead were age, medical conditions such as emphysema, and rheumatoid arthritis-specific factors such as disease duration," Curtis said.
In a second study, Eduardo Bonilla Trejos, MD, of the Pittsburgh Veterans Affairs Hospital, and colleagues found that use of steroids as opposed to anti-TNF agents were more likely to be associated with serious infections -- defined by all three of the studies as an infection requiring hospitalization.
Bonilla Trejos and colleagues used hospital codes to identify 3,457 cases of serious infection in rheumatoid arthritis patients between 2000 and 2007.
They determined that the risk of infection increased when steroids were added to treatment. In combination with an anti-TNF drug, the adjusted odds ratio was 3.42 (95% CI 2.44 to 4.81) compared with 3.06 with an anti-TNF alone.
The risk of adding a steroid to a DMARD varied depending on which of two DMARDs were prescribed and whether the patient was given a high- or low-dose steroid, but in all instances, the odds were greater with the steroid.
The highest odds of serious infection were seen with a combination of anti-TNF, a DMARD, and a steroid, they said, and warned that that combination should be used with caution.
"Although drugs such as corticosteroids or TNF-inhibitors may increase the risk of infection," Bonilla Trejos said, "they are often necessary to control rheumatoid arthritis. The important message is that if a patient with rheumatoid arthritis requires a combination of a TNF-inhibitor, disease modifying anti-rheumatic drugs, and corticosteroids to manage their disease, both patients and their rheumatologists should be particularly vigilant to the possibility of infection, especially in the presence of other comorbid conditions and/or anemia."
"Being treated with steroids, above and beyond being treated with anti-TNF agents or nonbiologic disease modifying anti-rheumatic drugs, was another part of the immunosuppressive regimen that led to the increased risk of infection," said Allan Gelber, MD, of Johns Hopkins University, who was not directly involved with the studies.
In the third study, Deborah Symmons, MD, and colleagues at the University of Manchester in Manchester, England, found that treatment with anti-TNF agents appeared to increase the risk that rheumatoid arthritis patients would experience septic arthritis -- infections of the joints.
In reviewing data from the British Society for Rheumatology Biologics Register, they found that there was a twofold risk of developing septic arthritis if a patient was taking anti-TNF drugs, compared with controls.
Symmons said her research team attempted to adjust for other factors -- including that patients on anti-TNF medication tended to have more severe rheumatoid arthritis. "However, that still left us with a residual additional risk associated with anti-TNF agents."
Gelber said the challenge in interpreting the British data on septic arthritis is in trying to adjust for disease severity in the individual patients. "That adjustment process in any observational study cannot be perfect," he said. "The answer has to be in the mind of the doctor or patient to what extent, if there is one, is the infection due to the drug or the person. We continue to grapple with that."
Primary source: Arthritis & Rheumatism