High RA Disease Activity Is Tied to Greater Risk of Infection

BOSTON – Increased rheumatoid arthritis disease activity is associated with a greater risk of developing infections, judging from the analysis of data from a large rheumatology database, Dr. Daniel E. Furst said at the annual meeting of the American College of Rheumatology.

In clinical trials and in clinical practice, infectious adverse events are common among patients with rheumatoid arthritis (RA), and the frequency may vary according to factors that include disease activity and drug therapies, said Dr. Furst, who is Carl M. Pearson Professor of Medicine and director of arthritis clinical research at the University of California, Los Angeles.

To investigate the relationship between infections and disease activity after adjustment for the effects of drug therapy, analyses on infection rates were done for RA patients from the Consortium of Rheumatology Researchers of North America (CORRONA) database who were on stable doses of disease-modifying antirheumatic drugs, biologic agents, or corticosteroids, according to Dr. Furst.

Two composite measures of disease activity were used in the analysis: the Clinical Disease Activity Index (CDAI) among the entire cohort of 3,782 patients, and the Disease Activity Score (DAS) 28 among the subset of 2,081 patients who also had erythrocyte sedimentation rate (ESR) values available within 2 weeks of the study visit.

The CDAI is a validated measure that is calculated as the sum of the swollen joint count, tender joint count, patient global assessment on a 10-cm visual analog scale (VAS), and evaluator global assessment also on a 10-cm VAS.

Initial analysis considered the influence of age, sex, education, race, body mass index, disease duration, insurance, work status, smoking history, and RA drug therapies.

Covariates that were found to be significantly associated with disease activity or infection then were analyzed using a generalized estimating equation for Poisson regression multivariate model with infection as the dependent variable, and incident rate ratios (IRR) were calculated.

A total of 1,160 infections were seen among the entire cohort during 3,653 patient-years. The IRR was found to be significant for disease activity on both CDAI and DAS28.

Age, female sex, and work status-disabled also were significant, though less so, on at least one measure. An IRR of 1.04 for CDAI represents a 4% increase in risk per 5-unit increase in CDAI score, Dr. Furst explained.

No other significant associations were seen, including current use of tumor necrosis factor blockers, disease-modifying antirheumatic drug, or corticosteroids.

“In this cohort of RA patients from the CORRONA database who were on stable background medications, increased disease activity was associated with a higher probability of developing infection,” Dr. Furst wrote in a poster session. Other factors, such as age and sex, also may affect the incidence, although further investigation is needed to clarify this.

Higher disease activity might be associated with an increased risk of infection because of subtle dysfunction of the immune system, particularly the innate immune system, though this remains speculative at the moment, Dr. Furst said in an interview. “There is increasing information that there is a connection between the innate and adaptive immune systems in RA and it is the innate immune system that responds initially to infection.

“The study suggests rheumatologists should be aggressive about controlling RA and that, contrary to previous dogma, aggressive treatment actually may decrease infections despite the broader use of therapies that theoretically could worsen infections because of their immunosuppressive effects,” he said. “This will require careful follow-up and management and a balancing act between the side effects of drugs and their positive effects.”

Dr. Furst said he has received research grants and consulting fees from numerous pharmaceutical firms.

'Contrary to previous dogma, aggressive treatment actually may decrease infections.' DR. FURST

BOSTON – Increased rheumatoid arthritis disease activity is associated with a greater risk of developing infections, judging from the analysis of data from a large rheumatology database, Dr. Daniel E. Furst said at the annual meeting of the American College of Rheumatology.

In clinical trials and in clinical practice, infectious adverse events are common among patients with rheumatoid arthritis (RA), and the frequency may vary according to factors that include disease activity and drug therapies, said Dr. Furst, who is Carl M. Pearson Professor of Medicine and director of arthritis clinical research at the University of California, Los Angeles.

To investigate the relationship between infections and disease activity after adjustment for the effects of drug therapy, analyses on infection rates were done for RA patients from the Consortium of Rheumatology Researchers of North America (CORRONA) database who were on stable doses of disease-modifying antirheumatic drugs, biologic agents, or corticosteroids, according to Dr. Furst.

Two composite measures of disease activity were used in the analysis: the Clinical Disease Activity Index (CDAI) among the entire cohort of 3,782 patients, and the Disease Activity Score (DAS) 28 among the subset of 2,081 patients who also had erythrocyte sedimentation rate (ESR) values available within 2 weeks of the study visit.

The CDAI is a validated measure that is calculated as the sum of the swollen joint count, tender joint count, patient global assessment on a 10-cm visual analog scale (VAS), and evaluator global assessment also on a 10-cm VAS.

Initial analysis considered the influence of age, sex, education, race, body mass index, disease duration, insurance, work status, smoking history, and RA drug therapies.

Covariates that were found to be significantly associated with disease activity or infection then were analyzed using a generalized estimating equation for Poisson regression multivariate model with infection as the dependent variable, and incident rate ratios (IRR) were calculated.

A total of 1,160 infections were seen among the entire cohort during 3,653 patient-years. The IRR was found to be significant for disease activity on both CDAI and DAS28.

Age, female sex, and work status-disabled also were significant, though less so, on at least one measure. An IRR of 1.04 for CDAI represents a 4% increase in risk per 5-unit increase in CDAI score, Dr. Furst explained.

No other significant associations were seen, including current use of tumor necrosis factor blockers, disease-modifying antirheumatic drug, or corticosteroids.

“In this cohort of RA patients from the CORRONA database who were on stable background medications, increased disease activity was associated with a higher probability of developing infection,” Dr. Furst wrote in a poster session. Other factors, such as age and sex, also may affect the incidence, although further investigation is needed to clarify this.

Higher disease activity might be associated with an increased risk of infection because of subtle dysfunction of the immune system, particularly the innate immune system, though this remains speculative at the moment, Dr. Furst said in an interview. “There is increasing information that there is a connection between the innate and adaptive immune systems in RA and it is the innate immune system that responds initially to infection.

“The study suggests rheumatologists should be aggressive about controlling RA and that, contrary to previous dogma, aggressive treatment actually may decrease infections despite the broader use of therapies that theoretically could worsen infections because of their immunosuppressive effects,” he said. “This will require careful follow-up and management and a balancing act between the side effects of drugs and their positive effects.”

Dr. Furst said he has received research grants and consulting fees from numerous pharmaceutical firms.

'Contrary to previous dogma, aggressive treatment actually may decrease infections.' DR. FURST

BOSTON – Increased rheumatoid arthritis disease activity is associated with a greater risk of developing infections, judging from the analysis of data from a large rheumatology database, Dr. Daniel E. Furst said at the annual meeting of the American College of Rheumatology.

In clinical trials and in clinical practice, infectious adverse events are common among patients with rheumatoid arthritis (RA), and the frequency may vary according to factors that include disease activity and drug therapies, said Dr. Furst, who is Carl M. Pearson Professor of Medicine and director of arthritis clinical research at the University of California, Los Angeles.

To investigate the relationship between infections and disease activity after adjustment for the effects of drug therapy, analyses on infection rates were done for RA patients from the Consortium of Rheumatology Researchers of North America (CORRONA) database who were on stable doses of disease-modifying antirheumatic drugs, biologic agents, or corticosteroids, according to Dr. Furst.

Two composite measures of disease activity were used in the analysis: the Clinical Disease Activity Index (CDAI) among the entire cohort of 3,782 patients, and the Disease Activity Score (DAS) 28 among the subset of 2,081 patients who also had erythrocyte sedimentation rate (ESR) values available within 2 weeks of the study visit.

The CDAI is a validated measure that is calculated as the sum of the swollen joint count, tender joint count, patient global assessment on a 10-cm visual analog scale (VAS), and evaluator global assessment also on a 10-cm VAS.

Initial analysis considered the influence of age, sex, education, race, body mass index, disease duration, insurance, work status, smoking history, and RA drug therapies.

Covariates that were found to be significantly associated with disease activity or infection then were analyzed using a generalized estimating equation for Poisson regression multivariate model with infection as the dependent variable, and incident rate ratios (IRR) were calculated.

A total of 1,160 infections were seen among the entire cohort during 3,653 patient-years. The IRR was found to be significant for disease activity on both CDAI and DAS28.

Age, female sex, and work status-disabled also were significant, though less so, on at least one measure. An IRR of 1.04 for CDAI represents a 4% increase in risk per 5-unit increase in CDAI score, Dr. Furst explained.

No other significant associations were seen, including current use of tumor necrosis factor blockers, disease-modifying antirheumatic drug, or corticosteroids.

“In this cohort of RA patients from the CORRONA database who were on stable background medications, increased disease activity was associated with a higher probability of developing infection,” Dr. Furst wrote in a poster session. Other factors, such as age and sex, also may affect the incidence, although further investigation is needed to clarify this.

Higher disease activity might be associated with an increased risk of infection because of subtle dysfunction of the immune system, particularly the innate immune system, though this remains speculative at the moment, Dr. Furst said in an interview. “There is increasing information that there is a connection between the innate and adaptive immune systems in RA and it is the innate immune system that responds initially to infection.

“The study suggests rheumatologists should be aggressive about controlling RA and that, contrary to previous dogma, aggressive treatment actually may decrease infections despite the broader use of therapies that theoretically could worsen infections because of their immunosuppressive effects,” he said. “This will require careful follow-up and management and a balancing act between the side effects of drugs and their positive effects.”

Dr. Furst said he has received research grants and consulting fees from numerous pharmaceutical firms.

'Contrary to previous dogma, aggressive treatment actually may decrease infections.' DR. FURST