Increasing disease activity in rheumatoid arthritis is associated with a higher risk for both outpatient infections and more serious infections requiring hospitalization in patients receiving stable therapy.
Moreover, this finding was true even among patients with mild disease activity, according to Dr. Karen Au of the division of rheumatology at the University of California, Los Angeles.
In a study published in the May issue of Annals of the Rheumatic Diseases, Dr. Au and her colleagues looked at 6,246 patients with RA who were listed on the CORRONA (Consortium of Rheumatology Researchers of North America) registry, which includes data contributed by 80 academic and private practices across the United States.
The patients’ mean age was 60 years; 75% were women. CDAI (Clinical Disease Activity Index) scores were available for 6,020 patients. DAS28 (disease activity score based on a 28-joint count) was calculated throughout the study period for 3,666 patients (Ann. Rheum. Dis. 2011;70:785-91).
"To minimize confounding related to recent changes in disease-modifying medications on the rate of infections, we limited the study to RA patients on stable therapy" (defined as no change in the dose of either methotrexate, TNF (tumor necrosis factor) inhibitor, corticosteroid, or any other disease-modifying anti-rheumatic drug over three consecutive visits spanning at least 6 months), according to the researchers.
Overall, 2,282 infections were reported during the study period, from March 2002 to December 2007; 1,382 patients had one or more outpatient infections and 50 patients had serious infections that required hospitalization.
Most of the infections tallied (2,223 of the total 2,282) were of an outpatient nature.
When outpatient infections alone were considered, researchers found that for all patients with CDAI scores less than 10 of a possible 76 (corresponding to the mildest class of disease), there was a 14% increase in outpatient infections for each 5-point increase in score, after the researchers controlled for covariates including body mass index, smoking, disease duration, therapy, and coexisting cardiovascular disease (incidence rate ratio, 1.14; P = .003).
And although no further linear relationship was noted, patients with moderate (CDAI scores of 10-22) and high (CDAI scores greater than 22) disease activity had increased infections, compared with patients with mild disease activity, although only the moderate category was statistically significant (IRR for moderate activity, compared with low activity, 1.19; 95% confidence interval, 1.06-1.34; IRR for high activity, 1.07; 95% CI 0.90-1.27).
Among patients for whom DAS28 data were available, there was a 4% increase in outpatient infections for each 0.6-point increase in the score, which persisted throughout the entire DAS28 spectrum (IRR, 1.04; P = .03).
A history of infections increased the likelihood of having an outpatient infection (IRR, 2.84-3.15; P less than .001), as did use of methotrexate, use of TNF inhibitors, and poorer functional class.
Although infections requiring hospitalization were much less frequent among the study participants, the authors were able to identify that for every 0.6-point increase in the DAS28, there was a corresponding significant 25% increase in the rate of infections that required hospitalization.
On the CDAI scale, there was no significant trend between an increasing score and inpatient infections on multivariate analysis, likely because of the small number of inpatient infections observed, according to the authors.
Prednisone use of 7.5 mg daily or more was also independently associated with infections that required hospitalization, as was a history of infection, they noted.
Previous studies have shown that RA patients have a twofold increased risk of developing infections, compared with patients who do not have RA, and they are also at higher risk of serious infections requiring hospitalization, the researchers said.
Indeed, they added, the "continued increased mortality observed in RA patients compared with the general population can be explained partly by a higher susceptibility to infections."
However, until now, the "independent contribution of RA disease activity and associated systemic inflammation is unclear."
The strength of this study, they pointed out, lies in the size and quality of the prospectively collected clinical data in the CORRONA database.
Several of the authors reported contracts and professional affiliations with the CORRONA database. Several also reported financial relationships with multiple pharmaceutical companies, including Amgen, Centocor, Pfizer, Roche/Genentech, and UCB.