ACR Annual Meeting 2012

WASHINGTON – A new model for estimating 10-year cardiovascular disease risk in patients with rheumatoid arthritis that draws on a combination of demographic factors, cardiovascular risk factors, and RA-related factors appears to more accurately predict risk than do currently available models.

The new model was developed based on findings from the prospective longitudinal CARRE study, Dr. Alper M. van Sijl reported at the annual meeting of the American College of Rheumatology.

In that study of 353 RA patients, 58 cardiovascular events occurred over 2,361 patient years of follow-up. The cardiovascular disease incidence was 16.4%, but existing, commonly used risk prediction models, including the Reynolds Risk Score, the Systemic Coronary Risk Evaluation (SCORE), and the Framingham Risk Score, underestimated the risk. At baseline, the SCORE and Framingham models, for example, estimated the incidence at 5.9% and 13%, respectively, said Dr. van Sijl of Jan van Breemen Research Institute, Reade, Amsterdam.

Using CARRE study information, including cardiovascular risk factors, RA-related factors, and surrogate markers of cardiovascular disease collected at baseline, predictive models using a number of variables alone or in combinations were tested. The new model for predicting risk in RA patients without prior cardiovascular disease that emerged included age, gender, use of statins and prednisone, body-mass index, diastolic blood pressure, low-density lipoprotein cholesterol, total cholesterol to high-density lipoprotein cholesterol ratio, C-reactive protein, Health Assessment Questionnaire scores, and erythrocyte sedimentation rate.

Using receiver operating curves analyses, the new model predicted cardiovascular disease incidence better than the other methods (area under the curve [AUC] 0.801 vs. 0.712), he said, noting that at a cutoff value of 10, the model had 85% sensitivity.

The findings are important because RA is associated with an increased risk of incident cardiovascular disease, which, according to the CARRE findings, has failed to decline significantly since 2000 despite the advent of effective anti-inflammatory therapies and the increased use of cardioprotective therapies. The risk is only partly explained by cardiovascular risk factors.

Additional external validation studies are needed to confirm these findings before the model can be implemented, and studies should also consider whether modification of existing risk models is necessary to improve the cardiovascular risk assessment of RA patients, he concluded.

Dr. van Sijl reported having no disclosures.

WASHINGTON – A new model for estimating 10-year cardiovascular disease risk in patients with rheumatoid arthritis that draws on a combination of demographic factors, cardiovascular risk factors, and RA-related factors appears to more accurately predict risk than do currently available models.

The new model was developed based on findings from the prospective longitudinal CARRE study, Dr. Alper M. van Sijl reported at the annual meeting of the American College of Rheumatology.

In that study of 353 RA patients, 58 cardiovascular events occurred over 2,361 patient years of follow-up. The cardiovascular disease incidence was 16.4%, but existing, commonly used risk prediction models, including the Reynolds Risk Score, the Systemic Coronary Risk Evaluation (SCORE), and the Framingham Risk Score, underestimated the risk. At baseline, the SCORE and Framingham models, for example, estimated the incidence at 5.9% and 13%, respectively, said Dr. van Sijl of Jan van Breemen Research Institute, Reade, Amsterdam.

Using CARRE study information, including cardiovascular risk factors, RA-related factors, and surrogate markers of cardiovascular disease collected at baseline, predictive models using a number of variables alone or in combinations were tested. The new model for predicting risk in RA patients without prior cardiovascular disease that emerged included age, gender, use of statins and prednisone, body-mass index, diastolic blood pressure, low-density lipoprotein cholesterol, total cholesterol to high-density lipoprotein cholesterol ratio, C-reactive protein, Health Assessment Questionnaire scores, and erythrocyte sedimentation rate.

Using receiver operating curves analyses, the new model predicted cardiovascular disease incidence better than the other methods (area under the curve [AUC] 0.801 vs. 0.712), he said, noting that at a cutoff value of 10, the model had 85% sensitivity.

The findings are important because RA is associated with an increased risk of incident cardiovascular disease, which, according to the CARRE findings, has failed to decline significantly since 2000 despite the advent of effective anti-inflammatory therapies and the increased use of cardioprotective therapies. The risk is only partly explained by cardiovascular risk factors.

Additional external validation studies are needed to confirm these findings before the model can be implemented, and studies should also consider whether modification of existing risk models is necessary to improve the cardiovascular risk assessment of RA patients, he concluded.

Dr. van Sijl reported having no disclosures.

WASHINGTON – A new model for estimating 10-year cardiovascular disease risk in patients with rheumatoid arthritis that draws on a combination of demographic factors, cardiovascular risk factors, and RA-related factors appears to more accurately predict risk than do currently available models.

The new model was developed based on findings from the prospective longitudinal CARRE study, Dr. Alper M. van Sijl reported at the annual meeting of the American College of Rheumatology.

In that study of 353 RA patients, 58 cardiovascular events occurred over 2,361 patient years of follow-up. The cardiovascular disease incidence was 16.4%, but existing, commonly used risk prediction models, including the Reynolds Risk Score, the Systemic Coronary Risk Evaluation (SCORE), and the Framingham Risk Score, underestimated the risk. At baseline, the SCORE and Framingham models, for example, estimated the incidence at 5.9% and 13%, respectively, said Dr. van Sijl of Jan van Breemen Research Institute, Reade, Amsterdam.

Using CARRE study information, including cardiovascular risk factors, RA-related factors, and surrogate markers of cardiovascular disease collected at baseline, predictive models using a number of variables alone or in combinations were tested. The new model for predicting risk in RA patients without prior cardiovascular disease that emerged included age, gender, use of statins and prednisone, body-mass index, diastolic blood pressure, low-density lipoprotein cholesterol, total cholesterol to high-density lipoprotein cholesterol ratio, C-reactive protein, Health Assessment Questionnaire scores, and erythrocyte sedimentation rate.

Using receiver operating curves analyses, the new model predicted cardiovascular disease incidence better than the other methods (area under the curve [AUC] 0.801 vs. 0.712), he said, noting that at a cutoff value of 10, the model had 85% sensitivity.

The findings are important because RA is associated with an increased risk of incident cardiovascular disease, which, according to the CARRE findings, has failed to decline significantly since 2000 despite the advent of effective anti-inflammatory therapies and the increased use of cardioprotective therapies. The risk is only partly explained by cardiovascular risk factors.

Additional external validation studies are needed to confirm these findings before the model can be implemented, and studies should also consider whether modification of existing risk models is necessary to improve the cardiovascular risk assessment of RA patients, he concluded.

Dr. van Sijl reported having no disclosures.

WASHINGTON – The presence of the antisynthetase antibody Jo-1, as well as Mi-2 autoantibodies, strongly predicted improvement in rituximab-treated myositis patients.

On the other hand, global damage is a poor indicator of good response to rituximab in multivariate analysis, meaning that further research into these biomarkers – especially Jo-1 – could have a major impact on treatment in this population, reported Dr. Rohit Aggarwal at the annual meeting of the American College of Rheumatology.

Denise Napoli/IMNG Medical Media

Dr. Aggarwal of the myositis center of the University of Pittsburgh and his colleagues looked at data from the RIM study (Rituximab in Myositis), which evaluated 200 myositis patients treated with the B-cell depleting agent, 83% of whom met the "definition of improvement" (DOI).

The DOI included a 20% or greater improvement in three of six measures: manual muscle testing, muscle enzymes, health assessment questionnaire, patient/parent global assessment, physician global disease activity assessment, and extramuscular disease activity, with not more than 25% worsening of greater than two measures.

These improvements also had to be noted at two consecutive visits to count as meeting the DOI.

Overall, 76 of the 200 myositis patients were more specifically classified as having adult polymyositis; 76 had adult dermatomyositis; and the remaining 48 patients had juvenile dermatomyositis.

In univariate analysis, several factors were associated with more rapid achievement of the DOI. These included lower baseline muscle damage, a higher white blood cell count, lower global damage, and the absence of muscle atrophy.

However, "the primary and strongest predictor of improvement on univariate analysis was autoantibodies," said Dr. Aggarwal – specifically, Jo-1 and Mi-2 – but also other myositis-associated antibodies, including SRP.

Dr. Aggarwal then conducted a multivariate analysis looking only at those variables with P value less than .1 in univariate assessment.

This time, the only significant predictors of improvement were the presence of the antisynthetase autoantibody Jo-1, but only in adults (hazard ratio, 3.08; 95% confidence interval, 1.80-5.28) as well as Mi-2, but only in juvenile and adult dermatomyositis – not adult polymyositis (HR 2.49; 95% CI, 1.42-4.41).

Other antibodies, including those to the signal recognition particle, did not confer a significantly increased association with improvement.

On the other hand, having less global damage at baseline was associated with improvement at 8 weeks, but the effect was washed out by week 20.

"Our findings regarding anti–Jo-1 are even more interesting when these results are coupled with other data that were presented in a concurrent session yesterday," said Dr. Aggarwal, citing a study he also led looking at the relation between anti–Jo-1 serum levels and the six improvement measures assessed in the DOI.

In that study, "After start of the treatment [with rituximab], autoantibody levels in Jo-1 subjects decreased by approximately nine units per week," he wrote.

"Anti–Jo-1 levels longitudinally correlated with all core set measures [of improvement] univariately and after adjusting for IgG levels."

He added, "These data suggest that anti–Jo-1 is also a disease biomarker."

"Further study of B-cell depletion in autoantibody positive, low-damage and juvenile dermatomyositis is warranted."

The RIM study was funded by Genentech, maker of rituximab; several investigators reported relationships to Genentech as well as other pharmaceutical companies.

WASHINGTON – The presence of the antisynthetase antibody Jo-1, as well as Mi-2 autoantibodies, strongly predicted improvement in rituximab-treated myositis patients.

On the other hand, global damage is a poor indicator of good response to rituximab in multivariate analysis, meaning that further research into these biomarkers – especially Jo-1 – could have a major impact on treatment in this population, reported Dr. Rohit Aggarwal at the annual meeting of the American College of Rheumatology.

Denise Napoli/IMNG Medical Media

Dr. Aggarwal of the myositis center of the University of Pittsburgh and his colleagues looked at data from the RIM study (Rituximab in Myositis), which evaluated 200 myositis patients treated with the B-cell depleting agent, 83% of whom met the "definition of improvement" (DOI).

The DOI included a 20% or greater improvement in three of six measures: manual muscle testing, muscle enzymes, health assessment questionnaire, patient/parent global assessment, physician global disease activity assessment, and extramuscular disease activity, with not more than 25% worsening of greater than two measures.

These improvements also had to be noted at two consecutive visits to count as meeting the DOI.

Overall, 76 of the 200 myositis patients were more specifically classified as having adult polymyositis; 76 had adult dermatomyositis; and the remaining 48 patients had juvenile dermatomyositis.

In univariate analysis, several factors were associated with more rapid achievement of the DOI. These included lower baseline muscle damage, a higher white blood cell count, lower global damage, and the absence of muscle atrophy.

However, "the primary and strongest predictor of improvement on univariate analysis was autoantibodies," said Dr. Aggarwal – specifically, Jo-1 and Mi-2 – but also other myositis-associated antibodies, including SRP.

Dr. Aggarwal then conducted a multivariate analysis looking only at those variables with P value less than .1 in univariate assessment.

This time, the only significant predictors of improvement were the presence of the antisynthetase autoantibody Jo-1, but only in adults (hazard ratio, 3.08; 95% confidence interval, 1.80-5.28) as well as Mi-2, but only in juvenile and adult dermatomyositis – not adult polymyositis (HR 2.49; 95% CI, 1.42-4.41).

Other antibodies, including those to the signal recognition particle, did not confer a significantly increased association with improvement.

On the other hand, having less global damage at baseline was associated with improvement at 8 weeks, but the effect was washed out by week 20.

"Our findings regarding anti–Jo-1 are even more interesting when these results are coupled with other data that were presented in a concurrent session yesterday," said Dr. Aggarwal, citing a study he also led looking at the relation between anti–Jo-1 serum levels and the six improvement measures assessed in the DOI.

In that study, "After start of the treatment [with rituximab], autoantibody levels in Jo-1 subjects decreased by approximately nine units per week," he wrote.

"Anti–Jo-1 levels longitudinally correlated with all core set measures [of improvement] univariately and after adjusting for IgG levels."

He added, "These data suggest that anti–Jo-1 is also a disease biomarker."

"Further study of B-cell depletion in autoantibody positive, low-damage and juvenile dermatomyositis is warranted."

The RIM study was funded by Genentech, maker of rituximab; several investigators reported relationships to Genentech as well as other pharmaceutical companies.

WASHINGTON – The presence of the antisynthetase antibody Jo-1, as well as Mi-2 autoantibodies, strongly predicted improvement in rituximab-treated myositis patients.

On the other hand, global damage is a poor indicator of good response to rituximab in multivariate analysis, meaning that further research into these biomarkers – especially Jo-1 – could have a major impact on treatment in this population, reported Dr. Rohit Aggarwal at the annual meeting of the American College of Rheumatology.

Denise Napoli/IMNG Medical Media

Dr. Aggarwal of the myositis center of the University of Pittsburgh and his colleagues looked at data from the RIM study (Rituximab in Myositis), which evaluated 200 myositis patients treated with the B-cell depleting agent, 83% of whom met the "definition of improvement" (DOI).

The DOI included a 20% or greater improvement in three of six measures: manual muscle testing, muscle enzymes, health assessment questionnaire, patient/parent global assessment, physician global disease activity assessment, and extramuscular disease activity, with not more than 25% worsening of greater than two measures.

These improvements also had to be noted at two consecutive visits to count as meeting the DOI.

Overall, 76 of the 200 myositis patients were more specifically classified as having adult polymyositis; 76 had adult dermatomyositis; and the remaining 48 patients had juvenile dermatomyositis.

In univariate analysis, several factors were associated with more rapid achievement of the DOI. These included lower baseline muscle damage, a higher white blood cell count, lower global damage, and the absence of muscle atrophy.

However, "the primary and strongest predictor of improvement on univariate analysis was autoantibodies," said Dr. Aggarwal – specifically, Jo-1 and Mi-2 – but also other myositis-associated antibodies, including SRP.

Dr. Aggarwal then conducted a multivariate analysis looking only at those variables with P value less than .1 in univariate assessment.

This time, the only significant predictors of improvement were the presence of the antisynthetase autoantibody Jo-1, but only in adults (hazard ratio, 3.08; 95% confidence interval, 1.80-5.28) as well as Mi-2, but only in juvenile and adult dermatomyositis – not adult polymyositis (HR 2.49; 95% CI, 1.42-4.41).

Other antibodies, including those to the signal recognition particle, did not confer a significantly increased association with improvement.

On the other hand, having less global damage at baseline was associated with improvement at 8 weeks, but the effect was washed out by week 20.

"Our findings regarding anti–Jo-1 are even more interesting when these results are coupled with other data that were presented in a concurrent session yesterday," said Dr. Aggarwal, citing a study he also led looking at the relation between anti–Jo-1 serum levels and the six improvement measures assessed in the DOI.

In that study, "After start of the treatment [with rituximab], autoantibody levels in Jo-1 subjects decreased by approximately nine units per week," he wrote.

"Anti–Jo-1 levels longitudinally correlated with all core set measures [of improvement] univariately and after adjusting for IgG levels."

He added, "These data suggest that anti–Jo-1 is also a disease biomarker."

"Further study of B-cell depletion in autoantibody positive, low-damage and juvenile dermatomyositis is warranted."

The RIM study was funded by Genentech, maker of rituximab; several investigators reported relationships to Genentech as well as other pharmaceutical companies.

WASHINGTON – Rheumatoid arthritis–related autoantibodies are associated with subclinical and clinical atherosclerosis, according to findings from a prospective population-based study.

The results suggest that autoimmune factors play a role in the pathogenesis of atherosclerosis and cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients, as well as in individuals without RA, Dr. Darcy S. Majka said at the annual meeting of the American College of Rheumatology.

Although the association between RA and CVD is well established, the exact mechanism is unknown.

"RA-related autoantibodies have been identified in individuals years before they develop RA, but most individuals with positive RA-related circulating autoantibodies do not develop clinical RA," said Dr. Majka of Northwestern University, Chicago.

In addition, preliminary data on stored serum samples from individuals without connective tissue disease demonstrated that circulating antiphospholipid antibodies measured in African Americans and whites were associated with subclinical atherosclerosis, she noted.

"This led us to develop the following conceptual model: We know that RA-related autoantibodies can produce inflammation and in some cases lead to possible progression to RA. In addition, the increased progression of subclinical atherosclerosis and cardiovascular events in RA is hypothesized to be mediated by the inflammation of clinically active RA. But we hypothesized that RA-related autoantibodies might be independently associated with subclinical atherosclerosis ... and this might potentially lead to progression to clinical cardiovascular events," she said, in describing the Multi-Ethnic Study of Atherosclerosis (MESA).

Indeed, in 6,557 middle-aged to elderly white, African American, Hispanic, and Chinese middle-aged to elderly adults who have been followed since 2000 as part of MESA, rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP-2) were associated with coronary artery calcium (CAC), a surrogate measure of subclinical atherosclerosis, in both white and African American women. The associations remained after investigators adjusted for traditional risk factors, including age, smoking status, blood pressure, body mass index, high-density lipoprotein cholesterol level, low-density lipoprotein cholesterol level, diabetes mellitus, aspirin use, and cholesterol and blood pressure medication use, she said.

A CAC level of at least 300 was present in 12.2% of participants at baseline, and after 7.1 years of follow-up, 3.0% experienced hard coronary heart disease (CHD) end points, including myocardial infarction, resuscitated cardiac arrest, and CHD death, and 4.8% experienced hard cardiovascular disease end points, including myocardial infarction, cardiac arrest, CHD death, stroke, and stroke death.

Rheumatoid factor (RF) IgM, RF IgA, and anti-CCP-2 were positive in 15.9%, 8.7%, and 2.0% of the MESA participants, respectively. In addition, 4.0% were positive for both RF IgM and RF IgA, and 20.6% were positive for one RF isotype.

The associations between baseline RF/anti-CCP and CAC were assessed and stratified based on race and sex, with adjustment for traditional cardiovascular risk factors.

Among the 1,323 white women in the study, those with RF IgA positivity, either RF IgM or RF IgA positivity, and/or anti-CCP-2 had an increased likelihood of having a CAC level greater than 300 (adjusted odds ratios of 2.3, 1.7, and 0.9 respectively, vs. a CAC of 0). Among 1,000 African American women in the study, those with RF IgA positivity or both RF IgM and RF IgA positivity had an increased likelihood of a CAC level between 100 and 300 (adjusted odds ratios, 2.2 and 2.7, respectively), and those with anti-CCP-2 had an increased likelihood of a CAC level greater than 300 (adjusted odds ratio, 4.0).

In addition, strong associations between RA-related autoantibodies and clinical cardiovascular disease events were seen in African American women in the study. For example, those with RF IgA positivity, either RF IgM or RF IgA positivity, or both RF isotypes were at increased risk of CHD hard end points (adjusted hazard ratios of 5, 2.5, and 4.5, respectively), Also, those with RF IgM positivity were at increased risk for CVD hard end points (adjusted hazard ratio, 2.1). Dr. Majka said.

No clear associations were seen between RA-related autoantibodies and CAC or CHD and CVD hard events in Hispanic and Chinese participants.

"RA-related autoantibodies appear to be independent risk factors for subclinical atherosclerosis and subsequent clinical CVD events," Dr. Majka concluded.

She reported having no relevant financial disclosures.

WASHINGTON – Rheumatoid arthritis–related autoantibodies are associated with subclinical and clinical atherosclerosis, according to findings from a prospective population-based study.

The results suggest that autoimmune factors play a role in the pathogenesis of atherosclerosis and cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients, as well as in individuals without RA, Dr. Darcy S. Majka said at the annual meeting of the American College of Rheumatology.

Although the association between RA and CVD is well established, the exact mechanism is unknown.

"RA-related autoantibodies have been identified in individuals years before they develop RA, but most individuals with positive RA-related circulating autoantibodies do not develop clinical RA," said Dr. Majka of Northwestern University, Chicago.

In addition, preliminary data on stored serum samples from individuals without connective tissue disease demonstrated that circulating antiphospholipid antibodies measured in African Americans and whites were associated with subclinical atherosclerosis, she noted.

"This led us to develop the following conceptual model: We know that RA-related autoantibodies can produce inflammation and in some cases lead to possible progression to RA. In addition, the increased progression of subclinical atherosclerosis and cardiovascular events in RA is hypothesized to be mediated by the inflammation of clinically active RA. But we hypothesized that RA-related autoantibodies might be independently associated with subclinical atherosclerosis ... and this might potentially lead to progression to clinical cardiovascular events," she said, in describing the Multi-Ethnic Study of Atherosclerosis (MESA).

Indeed, in 6,557 middle-aged to elderly white, African American, Hispanic, and Chinese middle-aged to elderly adults who have been followed since 2000 as part of MESA, rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP-2) were associated with coronary artery calcium (CAC), a surrogate measure of subclinical atherosclerosis, in both white and African American women. The associations remained after investigators adjusted for traditional risk factors, including age, smoking status, blood pressure, body mass index, high-density lipoprotein cholesterol level, low-density lipoprotein cholesterol level, diabetes mellitus, aspirin use, and cholesterol and blood pressure medication use, she said.

A CAC level of at least 300 was present in 12.2% of participants at baseline, and after 7.1 years of follow-up, 3.0% experienced hard coronary heart disease (CHD) end points, including myocardial infarction, resuscitated cardiac arrest, and CHD death, and 4.8% experienced hard cardiovascular disease end points, including myocardial infarction, cardiac arrest, CHD death, stroke, and stroke death.

Rheumatoid factor (RF) IgM, RF IgA, and anti-CCP-2 were positive in 15.9%, 8.7%, and 2.0% of the MESA participants, respectively. In addition, 4.0% were positive for both RF IgM and RF IgA, and 20.6% were positive for one RF isotype.

The associations between baseline RF/anti-CCP and CAC were assessed and stratified based on race and sex, with adjustment for traditional cardiovascular risk factors.

Among the 1,323 white women in the study, those with RF IgA positivity, either RF IgM or RF IgA positivity, and/or anti-CCP-2 had an increased likelihood of having a CAC level greater than 300 (adjusted odds ratios of 2.3, 1.7, and 0.9 respectively, vs. a CAC of 0). Among 1,000 African American women in the study, those with RF IgA positivity or both RF IgM and RF IgA positivity had an increased likelihood of a CAC level between 100 and 300 (adjusted odds ratios, 2.2 and 2.7, respectively), and those with anti-CCP-2 had an increased likelihood of a CAC level greater than 300 (adjusted odds ratio, 4.0).

In addition, strong associations between RA-related autoantibodies and clinical cardiovascular disease events were seen in African American women in the study. For example, those with RF IgA positivity, either RF IgM or RF IgA positivity, or both RF isotypes were at increased risk of CHD hard end points (adjusted hazard ratios of 5, 2.5, and 4.5, respectively), Also, those with RF IgM positivity were at increased risk for CVD hard end points (adjusted hazard ratio, 2.1). Dr. Majka said.

No clear associations were seen between RA-related autoantibodies and CAC or CHD and CVD hard events in Hispanic and Chinese participants.

"RA-related autoantibodies appear to be independent risk factors for subclinical atherosclerosis and subsequent clinical CVD events," Dr. Majka concluded.

She reported having no relevant financial disclosures.

WASHINGTON – Rheumatoid arthritis–related autoantibodies are associated with subclinical and clinical atherosclerosis, according to findings from a prospective population-based study.

The results suggest that autoimmune factors play a role in the pathogenesis of atherosclerosis and cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients, as well as in individuals without RA, Dr. Darcy S. Majka said at the annual meeting of the American College of Rheumatology.

Although the association between RA and CVD is well established, the exact mechanism is unknown.

"RA-related autoantibodies have been identified in individuals years before they develop RA, but most individuals with positive RA-related circulating autoantibodies do not develop clinical RA," said Dr. Majka of Northwestern University, Chicago.

In addition, preliminary data on stored serum samples from individuals without connective tissue disease demonstrated that circulating antiphospholipid antibodies measured in African Americans and whites were associated with subclinical atherosclerosis, she noted.

"This led us to develop the following conceptual model: We know that RA-related autoantibodies can produce inflammation and in some cases lead to possible progression to RA. In addition, the increased progression of subclinical atherosclerosis and cardiovascular events in RA is hypothesized to be mediated by the inflammation of clinically active RA. But we hypothesized that RA-related autoantibodies might be independently associated with subclinical atherosclerosis ... and this might potentially lead to progression to clinical cardiovascular events," she said, in describing the Multi-Ethnic Study of Atherosclerosis (MESA).

Indeed, in 6,557 middle-aged to elderly white, African American, Hispanic, and Chinese middle-aged to elderly adults who have been followed since 2000 as part of MESA, rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP-2) were associated with coronary artery calcium (CAC), a surrogate measure of subclinical atherosclerosis, in both white and African American women. The associations remained after investigators adjusted for traditional risk factors, including age, smoking status, blood pressure, body mass index, high-density lipoprotein cholesterol level, low-density lipoprotein cholesterol level, diabetes mellitus, aspirin use, and cholesterol and blood pressure medication use, she said.

A CAC level of at least 300 was present in 12.2% of participants at baseline, and after 7.1 years of follow-up, 3.0% experienced hard coronary heart disease (CHD) end points, including myocardial infarction, resuscitated cardiac arrest, and CHD death, and 4.8% experienced hard cardiovascular disease end points, including myocardial infarction, cardiac arrest, CHD death, stroke, and stroke death.

Rheumatoid factor (RF) IgM, RF IgA, and anti-CCP-2 were positive in 15.9%, 8.7%, and 2.0% of the MESA participants, respectively. In addition, 4.0% were positive for both RF IgM and RF IgA, and 20.6% were positive for one RF isotype.

The associations between baseline RF/anti-CCP and CAC were assessed and stratified based on race and sex, with adjustment for traditional cardiovascular risk factors.

Among the 1,323 white women in the study, those with RF IgA positivity, either RF IgM or RF IgA positivity, and/or anti-CCP-2 had an increased likelihood of having a CAC level greater than 300 (adjusted odds ratios of 2.3, 1.7, and 0.9 respectively, vs. a CAC of 0). Among 1,000 African American women in the study, those with RF IgA positivity or both RF IgM and RF IgA positivity had an increased likelihood of a CAC level between 100 and 300 (adjusted odds ratios, 2.2 and 2.7, respectively), and those with anti-CCP-2 had an increased likelihood of a CAC level greater than 300 (adjusted odds ratio, 4.0).

In addition, strong associations between RA-related autoantibodies and clinical cardiovascular disease events were seen in African American women in the study. For example, those with RF IgA positivity, either RF IgM or RF IgA positivity, or both RF isotypes were at increased risk of CHD hard end points (adjusted hazard ratios of 5, 2.5, and 4.5, respectively), Also, those with RF IgM positivity were at increased risk for CVD hard end points (adjusted hazard ratio, 2.1). Dr. Majka said.

No clear associations were seen between RA-related autoantibodies and CAC or CHD and CVD hard events in Hispanic and Chinese participants.

"RA-related autoantibodies appear to be independent risk factors for subclinical atherosclerosis and subsequent clinical CVD events," Dr. Majka concluded.

She reported having no relevant financial disclosures.

WASHINGTON – Younger age, lower baseline pain, and shorter time to remission were significant predictors of sustained remission for early rheumatoid arthritis patients, based on data from more than 1,000 patients older than 16 years.

The prevalence of and predictive factors for sustained remission in early rheumatoid arthritis (RA) is not well understood, "particularly in the context of new stringent definitions," said Dr. Vivian P. Bykerk, who is on the staff of the Inflammatory Arthritis Center of the Hospital for Special Surgery in New York.

Dr. Bykerk and her colleagues reviewed data from the Canadian Early Arthritis Cohort (CATCH) study. Their selected study population included 1,244 adults with probable or confirmed RA. The average age of the patients was 54 years, 83% were white, and 73% were women. The researchers presented the data at the annual American College of Rheumatology meeting.

Remission was defined using the Simple Disease Activity Index (SDAI) and the ACR/EULAR clinical practice and clinical trial definitions. The remission definition using SDAI was a score of 3.3 or less. The ACR/EULAR clinical practice remission definition included a tender joint count, swollen joint count, and patient global assessment scores of 1 or less; the clinical trial definition added a CRP level of 1 mg/dL or less to the clinical practice definition.

Overall, 40% of the patients achieved SDAI remission, 42% achieved ACR/EULAR clinical practice remission, and 35% achieved ACR/EULAR clinical trial remission. The median time to remission based on the three definitions was 10 months, 8 months, and 9 months, respectively.

Of the patients who achieved SDAI, ACR/EULAR clinical practice, and ACR/EULAR clinical trial remission, 56%, 59%, and 54%, respectively, achieved sustained remission (defined as remission lasting at least 12 months).

The average duration of symptoms was 6 months. Patients were either treatment naïve or in the early stages of treatment. In the first 3 months, 44% of the patients received combination therapy, 32% received methotrexate monotherapy, 30% received oral corticosteroids, and 2% received biologics.

The average SDAI score at baseline was 29, and the baseline number of tender and swollen joints was approximately 8. Patients were evaluated every 3 months for the first year, followed by evaluations every 6 months.

After researchers adjusted for confounding variables, they determined that younger age, lower baseline pain score, and shorter time to remission were significantly associated with sustained remission. The effect of shorter time to remission on sustained remission supports striving for early remission in early RA patients, Dr. Bykerk noted.

Variables that were not associated with sustained remission included smoking status, symptom duration, tender or swollen joint counts, morning stiffness, and initial treatment with oral corticosteroids or biologics.

Methotrexate monotherapy was associated with lower sustained remission, and the data could not prove an association between combination disease-modifying antirheumatic drugs (DMARD) therapy and sustained remission, said Dr. Bykerk.

In addition, laboratory values for erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and anticitrullinated protein antibodies (ACPA) were not associated with sustained remission, she said.

The study findings were limited by several factors including a lack of data on medication changes and the limited follow-up times of 3- and 6-month intervals, Dr. Bykerk said. But the results are strengthened by the use of a real-world observational cohort and suggest that more work is needed to determine the best patient-specific treatment strategies, she said.

Dr. Bykerk disclosed financial relationships with multiple companies including Abbott, Amgen, Pfizer, and Roche.

WASHINGTON – Younger age, lower baseline pain, and shorter time to remission were significant predictors of sustained remission for early rheumatoid arthritis patients, based on data from more than 1,000 patients older than 16 years.

The prevalence of and predictive factors for sustained remission in early rheumatoid arthritis (RA) is not well understood, "particularly in the context of new stringent definitions," said Dr. Vivian P. Bykerk, who is on the staff of the Inflammatory Arthritis Center of the Hospital for Special Surgery in New York.

Dr. Bykerk and her colleagues reviewed data from the Canadian Early Arthritis Cohort (CATCH) study. Their selected study population included 1,244 adults with probable or confirmed RA. The average age of the patients was 54 years, 83% were white, and 73% were women. The researchers presented the data at the annual American College of Rheumatology meeting.

Remission was defined using the Simple Disease Activity Index (SDAI) and the ACR/EULAR clinical practice and clinical trial definitions. The remission definition using SDAI was a score of 3.3 or less. The ACR/EULAR clinical practice remission definition included a tender joint count, swollen joint count, and patient global assessment scores of 1 or less; the clinical trial definition added a CRP level of 1 mg/dL or less to the clinical practice definition.

Overall, 40% of the patients achieved SDAI remission, 42% achieved ACR/EULAR clinical practice remission, and 35% achieved ACR/EULAR clinical trial remission. The median time to remission based on the three definitions was 10 months, 8 months, and 9 months, respectively.

Of the patients who achieved SDAI, ACR/EULAR clinical practice, and ACR/EULAR clinical trial remission, 56%, 59%, and 54%, respectively, achieved sustained remission (defined as remission lasting at least 12 months).

The average duration of symptoms was 6 months. Patients were either treatment naïve or in the early stages of treatment. In the first 3 months, 44% of the patients received combination therapy, 32% received methotrexate monotherapy, 30% received oral corticosteroids, and 2% received biologics.

The average SDAI score at baseline was 29, and the baseline number of tender and swollen joints was approximately 8. Patients were evaluated every 3 months for the first year, followed by evaluations every 6 months.

After researchers adjusted for confounding variables, they determined that younger age, lower baseline pain score, and shorter time to remission were significantly associated with sustained remission. The effect of shorter time to remission on sustained remission supports striving for early remission in early RA patients, Dr. Bykerk noted.

Variables that were not associated with sustained remission included smoking status, symptom duration, tender or swollen joint counts, morning stiffness, and initial treatment with oral corticosteroids or biologics.

Methotrexate monotherapy was associated with lower sustained remission, and the data could not prove an association between combination disease-modifying antirheumatic drugs (DMARD) therapy and sustained remission, said Dr. Bykerk.

In addition, laboratory values for erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and anticitrullinated protein antibodies (ACPA) were not associated with sustained remission, she said.

The study findings were limited by several factors including a lack of data on medication changes and the limited follow-up times of 3- and 6-month intervals, Dr. Bykerk said. But the results are strengthened by the use of a real-world observational cohort and suggest that more work is needed to determine the best patient-specific treatment strategies, she said.

Dr. Bykerk disclosed financial relationships with multiple companies including Abbott, Amgen, Pfizer, and Roche.

WASHINGTON – Younger age, lower baseline pain, and shorter time to remission were significant predictors of sustained remission for early rheumatoid arthritis patients, based on data from more than 1,000 patients older than 16 years.

The prevalence of and predictive factors for sustained remission in early rheumatoid arthritis (RA) is not well understood, "particularly in the context of new stringent definitions," said Dr. Vivian P. Bykerk, who is on the staff of the Inflammatory Arthritis Center of the Hospital for Special Surgery in New York.

Dr. Bykerk and her colleagues reviewed data from the Canadian Early Arthritis Cohort (CATCH) study. Their selected study population included 1,244 adults with probable or confirmed RA. The average age of the patients was 54 years, 83% were white, and 73% were women. The researchers presented the data at the annual American College of Rheumatology meeting.

Remission was defined using the Simple Disease Activity Index (SDAI) and the ACR/EULAR clinical practice and clinical trial definitions. The remission definition using SDAI was a score of 3.3 or less. The ACR/EULAR clinical practice remission definition included a tender joint count, swollen joint count, and patient global assessment scores of 1 or less; the clinical trial definition added a CRP level of 1 mg/dL or less to the clinical practice definition.

Overall, 40% of the patients achieved SDAI remission, 42% achieved ACR/EULAR clinical practice remission, and 35% achieved ACR/EULAR clinical trial remission. The median time to remission based on the three definitions was 10 months, 8 months, and 9 months, respectively.

Of the patients who achieved SDAI, ACR/EULAR clinical practice, and ACR/EULAR clinical trial remission, 56%, 59%, and 54%, respectively, achieved sustained remission (defined as remission lasting at least 12 months).

The average duration of symptoms was 6 months. Patients were either treatment naïve or in the early stages of treatment. In the first 3 months, 44% of the patients received combination therapy, 32% received methotrexate monotherapy, 30% received oral corticosteroids, and 2% received biologics.

The average SDAI score at baseline was 29, and the baseline number of tender and swollen joints was approximately 8. Patients were evaluated every 3 months for the first year, followed by evaluations every 6 months.

After researchers adjusted for confounding variables, they determined that younger age, lower baseline pain score, and shorter time to remission were significantly associated with sustained remission. The effect of shorter time to remission on sustained remission supports striving for early remission in early RA patients, Dr. Bykerk noted.

Variables that were not associated with sustained remission included smoking status, symptom duration, tender or swollen joint counts, morning stiffness, and initial treatment with oral corticosteroids or biologics.

Methotrexate monotherapy was associated with lower sustained remission, and the data could not prove an association between combination disease-modifying antirheumatic drugs (DMARD) therapy and sustained remission, said Dr. Bykerk.

In addition, laboratory values for erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and anticitrullinated protein antibodies (ACPA) were not associated with sustained remission, she said.

The study findings were limited by several factors including a lack of data on medication changes and the limited follow-up times of 3- and 6-month intervals, Dr. Bykerk said. But the results are strengthened by the use of a real-world observational cohort and suggest that more work is needed to determine the best patient-specific treatment strategies, she said.

Dr. Bykerk disclosed financial relationships with multiple companies including Abbott, Amgen, Pfizer, and Roche.

WASHINGTON – Opportunistic infections in children with juvenile idiopathic arthritis are rare, but they occur at a significantly higher rate in JIA patients than in unaffected children, according to findings from an analysis of national Medicaid claims data.

However, the association between these infections and the use of immunosuppressive treatments for JIA appears weak.

The findings, based on data from 2000 through 2005, show that 42 infections occurred in 8,503 children with JIA, and 584 infections occurred in 360,362 non-JIA comparators, for incidence rates of 300 and 125 per 100,000 person years, respectively, and an incident rate ratio (IRR) of 2.4, Dr. Timothy Beukelman reported at the annual meeting of the American College of Rheumatology.

After excluding herpes zoster, which was by far the most common infection among those with JIA, the rate of opportunistic infections was fourfold higher in the JIA cohort compared with the non-JIA cohort.

The infections that occurred at a higher rate in the JIA cohort were Coccidioides (3 infections, for an incidence rate of 21 per 100,000 and an IRR of 101.0), Salmonella (5 infections, for an incidence rate of 35 per 100,000 and an IRR of 3.8), and herpes zoster infections (32 infections for an incidence rate of 225 per 100,000 and an IRR of 2.1), said Dr. Beukelman of the University of Alabama at Birmingham.

One infection each with Nocardia, nontuberculosis mycobateria, Toxoplasma, and Pneumocystis occurred, for an incidence rate of 7 per 100,000 for each of these infections. Incidence rate ratios were not calculated.

No infections with Aspergillus, Blastomyces, Histoplasma, Cryptococcus, Legionella, Listeria, John Cunningham virus, or tuberculosis were identified in the JIA cohort.

These findings differ from those in adults with rheumatoid arthritis (RA).

"We know that adults with RA who are treated with certain biologics have an increased incidence of some opportunistic infections, in particular tuberculosis, endemic mycoses, Listeria, and Legionella," Dr. Beukelman said.

Among the children with JIA, 1,392 used tumor necrosis factor (TNF) inhibitors, and 3,491 used methotrexate during follow-up. An analysis of the association between these treatments and herpes zoster infection found only weak associations with respect to current use of methotrexate (IRR, 1.4 vs. no current methotrexate or TNF inhibitor use), TNF inhibitors (IRR, 2.2 vs. current methotrexate use without current TNF inhibitor use), or glucocorticoids (IRR, 1.8 vs. no current glucocorticoid use), Dr. Beukelman said.

With respect to the Coccidioides infections, the rate was unexpectedly high in the JIA cohort, but two of the patients had no current exposure to TNF inhibitors, methotrexate, or glucocorticoids, and one had exposure only to methotrexate at the time of the infection. None had been treated by TNF inhibitors at any time during the study.

The findings are the first from a controlled trial to address and characterize the incidence of opportunistic infections in JIA patients, Dr. Beukelman said, noting that very little is known about the incidence of opportunistic infections in children with JIA.

Prior studies have, however, demonstrated a twofold increase in the rate of hospitalized infections associated with JIA vs. without JIA in the absence of immunosuppressive infection, so it appears that the JIA disease process itself may predispose to serious bacterial infections.

"We wondered if there might be a similar situation with opportunistic infections," he said.

The findings of the current study suggest that is, indeed, the case.

JIA in this study was based on physician diagnosis codes and dispensed medication. The comparator cohort was composed of children diagnosed with attention deficit hyperactivity disorder. The cohorts had 14,370 and 490,939 person-years of follow-up, respectively.

All subjects had a 3-month baseline period prior to study follow-up during which they were assessed for prevalent opportunistic infections and medication exposures. Infections were identified using physician diagnosis or hospital discharge codes, with the exception of mycoses, tuberculosis, and herpes zoster, which also required evidence of treatment with specific antimicrobials.

"Future studies of the association between opportunistic infections and JIA medications must consider there’s likely an increased rate of opportunistic infections associated with JIA itself, and not just with the medications we use to treat it," Dr. Beukelman said.

This study was supported by the Agency for Healthcare Research and Quality. Dr. Beukelman disclosed that he has received a research grant from Pfizer, and consulting fees and/or other remuneration from Novartis Pharmaceutical Corporation, and Genentech and Biogen IDEC Inc.

WASHINGTON – Opportunistic infections in children with juvenile idiopathic arthritis are rare, but they occur at a significantly higher rate in JIA patients than in unaffected children, according to findings from an analysis of national Medicaid claims data.

However, the association between these infections and the use of immunosuppressive treatments for JIA appears weak.

The findings, based on data from 2000 through 2005, show that 42 infections occurred in 8,503 children with JIA, and 584 infections occurred in 360,362 non-JIA comparators, for incidence rates of 300 and 125 per 100,000 person years, respectively, and an incident rate ratio (IRR) of 2.4, Dr. Timothy Beukelman reported at the annual meeting of the American College of Rheumatology.

After excluding herpes zoster, which was by far the most common infection among those with JIA, the rate of opportunistic infections was fourfold higher in the JIA cohort compared with the non-JIA cohort.

The infections that occurred at a higher rate in the JIA cohort were Coccidioides (3 infections, for an incidence rate of 21 per 100,000 and an IRR of 101.0), Salmonella (5 infections, for an incidence rate of 35 per 100,000 and an IRR of 3.8), and herpes zoster infections (32 infections for an incidence rate of 225 per 100,000 and an IRR of 2.1), said Dr. Beukelman of the University of Alabama at Birmingham.

One infection each with Nocardia, nontuberculosis mycobateria, Toxoplasma, and Pneumocystis occurred, for an incidence rate of 7 per 100,000 for each of these infections. Incidence rate ratios were not calculated.

No infections with Aspergillus, Blastomyces, Histoplasma, Cryptococcus, Legionella, Listeria, John Cunningham virus, or tuberculosis were identified in the JIA cohort.

These findings differ from those in adults with rheumatoid arthritis (RA).

"We know that adults with RA who are treated with certain biologics have an increased incidence of some opportunistic infections, in particular tuberculosis, endemic mycoses, Listeria, and Legionella," Dr. Beukelman said.

Among the children with JIA, 1,392 used tumor necrosis factor (TNF) inhibitors, and 3,491 used methotrexate during follow-up. An analysis of the association between these treatments and herpes zoster infection found only weak associations with respect to current use of methotrexate (IRR, 1.4 vs. no current methotrexate or TNF inhibitor use), TNF inhibitors (IRR, 2.2 vs. current methotrexate use without current TNF inhibitor use), or glucocorticoids (IRR, 1.8 vs. no current glucocorticoid use), Dr. Beukelman said.

With respect to the Coccidioides infections, the rate was unexpectedly high in the JIA cohort, but two of the patients had no current exposure to TNF inhibitors, methotrexate, or glucocorticoids, and one had exposure only to methotrexate at the time of the infection. None had been treated by TNF inhibitors at any time during the study.

The findings are the first from a controlled trial to address and characterize the incidence of opportunistic infections in JIA patients, Dr. Beukelman said, noting that very little is known about the incidence of opportunistic infections in children with JIA.

Prior studies have, however, demonstrated a twofold increase in the rate of hospitalized infections associated with JIA vs. without JIA in the absence of immunosuppressive infection, so it appears that the JIA disease process itself may predispose to serious bacterial infections.

"We wondered if there might be a similar situation with opportunistic infections," he said.

The findings of the current study suggest that is, indeed, the case.

JIA in this study was based on physician diagnosis codes and dispensed medication. The comparator cohort was composed of children diagnosed with attention deficit hyperactivity disorder. The cohorts had 14,370 and 490,939 person-years of follow-up, respectively.

All subjects had a 3-month baseline period prior to study follow-up during which they were assessed for prevalent opportunistic infections and medication exposures. Infections were identified using physician diagnosis or hospital discharge codes, with the exception of mycoses, tuberculosis, and herpes zoster, which also required evidence of treatment with specific antimicrobials.

"Future studies of the association between opportunistic infections and JIA medications must consider there’s likely an increased rate of opportunistic infections associated with JIA itself, and not just with the medications we use to treat it," Dr. Beukelman said.

This study was supported by the Agency for Healthcare Research and Quality. Dr. Beukelman disclosed that he has received a research grant from Pfizer, and consulting fees and/or other remuneration from Novartis Pharmaceutical Corporation, and Genentech and Biogen IDEC Inc.

WASHINGTON – Opportunistic infections in children with juvenile idiopathic arthritis are rare, but they occur at a significantly higher rate in JIA patients than in unaffected children, according to findings from an analysis of national Medicaid claims data.

However, the association between these infections and the use of immunosuppressive treatments for JIA appears weak.

The findings, based on data from 2000 through 2005, show that 42 infections occurred in 8,503 children with JIA, and 584 infections occurred in 360,362 non-JIA comparators, for incidence rates of 300 and 125 per 100,000 person years, respectively, and an incident rate ratio (IRR) of 2.4, Dr. Timothy Beukelman reported at the annual meeting of the American College of Rheumatology.

After excluding herpes zoster, which was by far the most common infection among those with JIA, the rate of opportunistic infections was fourfold higher in the JIA cohort compared with the non-JIA cohort.

The infections that occurred at a higher rate in the JIA cohort were Coccidioides (3 infections, for an incidence rate of 21 per 100,000 and an IRR of 101.0), Salmonella (5 infections, for an incidence rate of 35 per 100,000 and an IRR of 3.8), and herpes zoster infections (32 infections for an incidence rate of 225 per 100,000 and an IRR of 2.1), said Dr. Beukelman of the University of Alabama at Birmingham.

One infection each with Nocardia, nontuberculosis mycobateria, Toxoplasma, and Pneumocystis occurred, for an incidence rate of 7 per 100,000 for each of these infections. Incidence rate ratios were not calculated.

No infections with Aspergillus, Blastomyces, Histoplasma, Cryptococcus, Legionella, Listeria, John Cunningham virus, or tuberculosis were identified in the JIA cohort.

These findings differ from those in adults with rheumatoid arthritis (RA).

"We know that adults with RA who are treated with certain biologics have an increased incidence of some opportunistic infections, in particular tuberculosis, endemic mycoses, Listeria, and Legionella," Dr. Beukelman said.

Among the children with JIA, 1,392 used tumor necrosis factor (TNF) inhibitors, and 3,491 used methotrexate during follow-up. An analysis of the association between these treatments and herpes zoster infection found only weak associations with respect to current use of methotrexate (IRR, 1.4 vs. no current methotrexate or TNF inhibitor use), TNF inhibitors (IRR, 2.2 vs. current methotrexate use without current TNF inhibitor use), or glucocorticoids (IRR, 1.8 vs. no current glucocorticoid use), Dr. Beukelman said.

With respect to the Coccidioides infections, the rate was unexpectedly high in the JIA cohort, but two of the patients had no current exposure to TNF inhibitors, methotrexate, or glucocorticoids, and one had exposure only to methotrexate at the time of the infection. None had been treated by TNF inhibitors at any time during the study.

The findings are the first from a controlled trial to address and characterize the incidence of opportunistic infections in JIA patients, Dr. Beukelman said, noting that very little is known about the incidence of opportunistic infections in children with JIA.

Prior studies have, however, demonstrated a twofold increase in the rate of hospitalized infections associated with JIA vs. without JIA in the absence of immunosuppressive infection, so it appears that the JIA disease process itself may predispose to serious bacterial infections.

"We wondered if there might be a similar situation with opportunistic infections," he said.

The findings of the current study suggest that is, indeed, the case.

JIA in this study was based on physician diagnosis codes and dispensed medication. The comparator cohort was composed of children diagnosed with attention deficit hyperactivity disorder. The cohorts had 14,370 and 490,939 person-years of follow-up, respectively.

All subjects had a 3-month baseline period prior to study follow-up during which they were assessed for prevalent opportunistic infections and medication exposures. Infections were identified using physician diagnosis or hospital discharge codes, with the exception of mycoses, tuberculosis, and herpes zoster, which also required evidence of treatment with specific antimicrobials.

"Future studies of the association between opportunistic infections and JIA medications must consider there’s likely an increased rate of opportunistic infections associated with JIA itself, and not just with the medications we use to treat it," Dr. Beukelman said.

This study was supported by the Agency for Healthcare Research and Quality. Dr. Beukelman disclosed that he has received a research grant from Pfizer, and consulting fees and/or other remuneration from Novartis Pharmaceutical Corporation, and Genentech and Biogen IDEC Inc.

WASHINGTON – Aggressive treatment during the so-called window of opportunity in rheumatoid arthritis can significantly alter disease outcomes.

That was the conclusion of Dr. Vivian Bykerk in a presentation on Tuesday, Nov. 13, at the annual meeting of the American College of Rheumatology.

The window of opportunity is not a new concept, according to Dr. Bykerk, who is with the Inflammatory Arthritis Center at the Hospital for Special Surgery in New York.

Denise Napoli/IMNG Medical Media

"It’s 10 years old," she said, pointing to a 2003 editorial stating that "similar to a primary cancer, early arthritis is less entrenched, has a smaller load of disease cells, and is more responsive to treatment" (Arthritis Rheum. 2003;48:1771-4).

However, it’s unclear exactly what disease state corresponds to this window, said Dr. Bykerk. "Is it during the period of arthralgia or pre-RA? Is it okay to be in a period of early inflammatory arthritis, or can we still win when arthritis is becoming persistent and starting to become destructive, just becoming classifiable?"

One of the most important landmarks in early disease is when "soft tissue damage can begin to occur that is irreversible," she said. "That can start within a year."

Then again, "immune modulator changes occur well before the onset of synovitis," she said, citing a 2004 study showing C-reactive protein levels already elevated in time periods up to 15 years prior to presentation with swollen joints (Arthritis Rheum. 2004;50:2423-7).

At least one study offers compelling evidence for the window being within at least 12 weeks of symptom presentation, said Dr. Bykerk.

Indeed, in a 2010 study, "it’s clear that patients who are treated within 12 weeks of symptom onset have less radiographic damage than patients treated after 12 weeks" (Arthritis Rheum. 2010; 62:3537-46).

And while that study was not a randomized controlled trial, "nonetheless, in the same cohort, patients who are seen earlier have a higher probability of DMARD [disease-modifying antirheumatic drug]-free remission, upwards of 35%, whereas the patients who were seen after 1 year have less than a 12% chance of DMARD-free remission if you follow them out for 7-8 years," she said.

In any case, it is combination therapy that seems to confer the most benefit in this window.

For example, Dr. Bykerk called attention to data showing that in RA of less than 4 months’ duration, treatment with methotrexate plus etanercept was associated with no radiographic progression of disease in 80% of patients after 1 year of treatment (Ann. Rheum. Dis. 2012;71:989-92).

"When combined therapy is used in very early patients, there are significantly more patients who meet these higher criteria outcomes than the patients who [begin treatment later in the course of their RA], but you don’t see that with methotrexate [monotherapy]," she said.

Findings from the TEAR (Treatment of Early Aggressive Rheumatoid Arthritis) study also support aggressive, early combination therapy. One group of patients that was randomized to initial methotrexate plus etanercept and another to initial methotrexate plus sulfasalazine plus hydroxychloroquine outperformed patients treated with methotrexate monotherapy at 24 weeks on the DAS28-ESR (Disease Activity Score in 28 joints using the erythrocyte sedimentation rate).

On the other hand, "Does it matter if you miss the window of opportunity? Can patients ‘catch up’ in terms of achieving our high-level goals of remission?" asked Dr. Bykerk.

Indeed, in the TEAR study, initial-monotherapy subjects who switched to a step-up combination therapy arm after the first 24 weeks ultimately had a DAS28-ESR clinical response "that was not different from that of subjects who initially received combination therapy, regardless of the treatment arm" by 102 weeks, according to the authors of that study.

In conclusion, "Future studies need to look at the impact of treatment much, much closer to the onset of disease, so that we can better understand: When does the window open? When does the window close? And what time frame does it truly extend to?" said Dr. Bykerk.

"But is all lost if the window isn’t met? I think not."

Dr. Bykerk disclosed relationships with several pharmaceutical companies, including the makers of biologic and nonbiologic disease-modifying antirheumatic drugs.

WASHINGTON – Aggressive treatment during the so-called window of opportunity in rheumatoid arthritis can significantly alter disease outcomes.

That was the conclusion of Dr. Vivian Bykerk in a presentation on Tuesday, Nov. 13, at the annual meeting of the American College of Rheumatology.

The window of opportunity is not a new concept, according to Dr. Bykerk, who is with the Inflammatory Arthritis Center at the Hospital for Special Surgery in New York.

Denise Napoli/IMNG Medical Media

"It’s 10 years old," she said, pointing to a 2003 editorial stating that "similar to a primary cancer, early arthritis is less entrenched, has a smaller load of disease cells, and is more responsive to treatment" (Arthritis Rheum. 2003;48:1771-4).

However, it’s unclear exactly what disease state corresponds to this window, said Dr. Bykerk. "Is it during the period of arthralgia or pre-RA? Is it okay to be in a period of early inflammatory arthritis, or can we still win when arthritis is becoming persistent and starting to become destructive, just becoming classifiable?"

One of the most important landmarks in early disease is when "soft tissue damage can begin to occur that is irreversible," she said. "That can start within a year."

Then again, "immune modulator changes occur well before the onset of synovitis," she said, citing a 2004 study showing C-reactive protein levels already elevated in time periods up to 15 years prior to presentation with swollen joints (Arthritis Rheum. 2004;50:2423-7).

At least one study offers compelling evidence for the window being within at least 12 weeks of symptom presentation, said Dr. Bykerk.

Indeed, in a 2010 study, "it’s clear that patients who are treated within 12 weeks of symptom onset have less radiographic damage than patients treated after 12 weeks" (Arthritis Rheum. 2010; 62:3537-46).

And while that study was not a randomized controlled trial, "nonetheless, in the same cohort, patients who are seen earlier have a higher probability of DMARD [disease-modifying antirheumatic drug]-free remission, upwards of 35%, whereas the patients who were seen after 1 year have less than a 12% chance of DMARD-free remission if you follow them out for 7-8 years," she said.

In any case, it is combination therapy that seems to confer the most benefit in this window.

For example, Dr. Bykerk called attention to data showing that in RA of less than 4 months’ duration, treatment with methotrexate plus etanercept was associated with no radiographic progression of disease in 80% of patients after 1 year of treatment (Ann. Rheum. Dis. 2012;71:989-92).

"When combined therapy is used in very early patients, there are significantly more patients who meet these higher criteria outcomes than the patients who [begin treatment later in the course of their RA], but you don’t see that with methotrexate [monotherapy]," she said.

Findings from the TEAR (Treatment of Early Aggressive Rheumatoid Arthritis) study also support aggressive, early combination therapy. One group of patients that was randomized to initial methotrexate plus etanercept and another to initial methotrexate plus sulfasalazine plus hydroxychloroquine outperformed patients treated with methotrexate monotherapy at 24 weeks on the DAS28-ESR (Disease Activity Score in 28 joints using the erythrocyte sedimentation rate).

On the other hand, "Does it matter if you miss the window of opportunity? Can patients ‘catch up’ in terms of achieving our high-level goals of remission?" asked Dr. Bykerk.

Indeed, in the TEAR study, initial-monotherapy subjects who switched to a step-up combination therapy arm after the first 24 weeks ultimately had a DAS28-ESR clinical response "that was not different from that of subjects who initially received combination therapy, regardless of the treatment arm" by 102 weeks, according to the authors of that study.

In conclusion, "Future studies need to look at the impact of treatment much, much closer to the onset of disease, so that we can better understand: When does the window open? When does the window close? And what time frame does it truly extend to?" said Dr. Bykerk.

"But is all lost if the window isn’t met? I think not."

Dr. Bykerk disclosed relationships with several pharmaceutical companies, including the makers of biologic and nonbiologic disease-modifying antirheumatic drugs.

WASHINGTON – Aggressive treatment during the so-called window of opportunity in rheumatoid arthritis can significantly alter disease outcomes.

That was the conclusion of Dr. Vivian Bykerk in a presentation on Tuesday, Nov. 13, at the annual meeting of the American College of Rheumatology.

The window of opportunity is not a new concept, according to Dr. Bykerk, who is with the Inflammatory Arthritis Center at the Hospital for Special Surgery in New York.

Denise Napoli/IMNG Medical Media

"It’s 10 years old," she said, pointing to a 2003 editorial stating that "similar to a primary cancer, early arthritis is less entrenched, has a smaller load of disease cells, and is more responsive to treatment" (Arthritis Rheum. 2003;48:1771-4).

However, it’s unclear exactly what disease state corresponds to this window, said Dr. Bykerk. "Is it during the period of arthralgia or pre-RA? Is it okay to be in a period of early inflammatory arthritis, or can we still win when arthritis is becoming persistent and starting to become destructive, just becoming classifiable?"

One of the most important landmarks in early disease is when "soft tissue damage can begin to occur that is irreversible," she said. "That can start within a year."

Then again, "immune modulator changes occur well before the onset of synovitis," she said, citing a 2004 study showing C-reactive protein levels already elevated in time periods up to 15 years prior to presentation with swollen joints (Arthritis Rheum. 2004;50:2423-7).

At least one study offers compelling evidence for the window being within at least 12 weeks of symptom presentation, said Dr. Bykerk.

Indeed, in a 2010 study, "it’s clear that patients who are treated within 12 weeks of symptom onset have less radiographic damage than patients treated after 12 weeks" (Arthritis Rheum. 2010; 62:3537-46).

And while that study was not a randomized controlled trial, "nonetheless, in the same cohort, patients who are seen earlier have a higher probability of DMARD [disease-modifying antirheumatic drug]-free remission, upwards of 35%, whereas the patients who were seen after 1 year have less than a 12% chance of DMARD-free remission if you follow them out for 7-8 years," she said.

In any case, it is combination therapy that seems to confer the most benefit in this window.

For example, Dr. Bykerk called attention to data showing that in RA of less than 4 months’ duration, treatment with methotrexate plus etanercept was associated with no radiographic progression of disease in 80% of patients after 1 year of treatment (Ann. Rheum. Dis. 2012;71:989-92).

"When combined therapy is used in very early patients, there are significantly more patients who meet these higher criteria outcomes than the patients who [begin treatment later in the course of their RA], but you don’t see that with methotrexate [monotherapy]," she said.

Findings from the TEAR (Treatment of Early Aggressive Rheumatoid Arthritis) study also support aggressive, early combination therapy. One group of patients that was randomized to initial methotrexate plus etanercept and another to initial methotrexate plus sulfasalazine plus hydroxychloroquine outperformed patients treated with methotrexate monotherapy at 24 weeks on the DAS28-ESR (Disease Activity Score in 28 joints using the erythrocyte sedimentation rate).

On the other hand, "Does it matter if you miss the window of opportunity? Can patients ‘catch up’ in terms of achieving our high-level goals of remission?" asked Dr. Bykerk.

Indeed, in the TEAR study, initial-monotherapy subjects who switched to a step-up combination therapy arm after the first 24 weeks ultimately had a DAS28-ESR clinical response "that was not different from that of subjects who initially received combination therapy, regardless of the treatment arm" by 102 weeks, according to the authors of that study.

In conclusion, "Future studies need to look at the impact of treatment much, much closer to the onset of disease, so that we can better understand: When does the window open? When does the window close? And what time frame does it truly extend to?" said Dr. Bykerk.

"But is all lost if the window isn’t met? I think not."

Dr. Bykerk disclosed relationships with several pharmaceutical companies, including the makers of biologic and nonbiologic disease-modifying antirheumatic drugs.

WASHINGTON – Subcutaneous nodules in patients with rheumatoid arthritis signal a significantly increased risk of cardiovascular disease, based on findings from the CORRONA database.

Although subcutaneous nodules are associated with more severe rheumatoid arthritis (RA), and RA is known to be associated with an increased risk of cardiovascular disease, the findings are the first to demonstrate a link between these "conspicuous, accessible, and assessable clinical markers" and cardiovascular morbidity in RA, Dr. Prashant Kaushik reported at the annual meeting of the American College of Rheumatology.

In 23,327 RA patients included in the CORRONA (Consortium of Rheumatology Researchers of North America) database who were evaluated at 182,201 individual visits between October 2001 and September 2011, the presence of subcutaneous nodules was found to confer a 44% increase in the risk of cardiovascular disease (hazard ratio, 1.44). The association remained significant after the investigators adjusted for age, sex, age of onset of RA, presence of diabetes mellitus, hypertension, smoking, alcohol consumption, and the use of a lipid-lowering agent (adjusted hazard ratio, 1.25), said Dr. Kaushik, who is rheumatology section chief at the Stratton VA Medical Center, Albany, N.Y.

Additionally, an age-sex interaction was found for women, who had a steeper increase in risk with age, compared with men. The hazard ratios per year of age for men and women were 1.01 and 1.03, but the hazard ratio for women vs. men at age 40 was 0.39, and at age 70 was 0.59, he noted.

Patients included in the CORRONA database had an average follow-up of 3 years and 70,455 patient-years. Nearly a third had subcutaneous nodules, and 795 had a cardiovascular event including a myocardial infarction, stroke or transient ischemic attack, heart failure, and/or cardiovascular death.

While the precise mechanism of the biologic association still needs to be ascertained, these findings indicate that subcutaneous nodules, which are the most common extra-articular manifestation of RA, should serve as a red flag for clinicians, Dr. Kaushik said.

"Subcutaneous nodules may be thought of as a clinical indicator of cardiovascular disease in RA," he concluded.

Dr. Kaushik reported having no relevant financial disclosures.

WASHINGTON – Subcutaneous nodules in patients with rheumatoid arthritis signal a significantly increased risk of cardiovascular disease, based on findings from the CORRONA database.

Although subcutaneous nodules are associated with more severe rheumatoid arthritis (RA), and RA is known to be associated with an increased risk of cardiovascular disease, the findings are the first to demonstrate a link between these "conspicuous, accessible, and assessable clinical markers" and cardiovascular morbidity in RA, Dr. Prashant Kaushik reported at the annual meeting of the American College of Rheumatology.

In 23,327 RA patients included in the CORRONA (Consortium of Rheumatology Researchers of North America) database who were evaluated at 182,201 individual visits between October 2001 and September 2011, the presence of subcutaneous nodules was found to confer a 44% increase in the risk of cardiovascular disease (hazard ratio, 1.44). The association remained significant after the investigators adjusted for age, sex, age of onset of RA, presence of diabetes mellitus, hypertension, smoking, alcohol consumption, and the use of a lipid-lowering agent (adjusted hazard ratio, 1.25), said Dr. Kaushik, who is rheumatology section chief at the Stratton VA Medical Center, Albany, N.Y.

Additionally, an age-sex interaction was found for women, who had a steeper increase in risk with age, compared with men. The hazard ratios per year of age for men and women were 1.01 and 1.03, but the hazard ratio for women vs. men at age 40 was 0.39, and at age 70 was 0.59, he noted.

Patients included in the CORRONA database had an average follow-up of 3 years and 70,455 patient-years. Nearly a third had subcutaneous nodules, and 795 had a cardiovascular event including a myocardial infarction, stroke or transient ischemic attack, heart failure, and/or cardiovascular death.

While the precise mechanism of the biologic association still needs to be ascertained, these findings indicate that subcutaneous nodules, which are the most common extra-articular manifestation of RA, should serve as a red flag for clinicians, Dr. Kaushik said.

"Subcutaneous nodules may be thought of as a clinical indicator of cardiovascular disease in RA," he concluded.

Dr. Kaushik reported having no relevant financial disclosures.

WASHINGTON – Subcutaneous nodules in patients with rheumatoid arthritis signal a significantly increased risk of cardiovascular disease, based on findings from the CORRONA database.

Although subcutaneous nodules are associated with more severe rheumatoid arthritis (RA), and RA is known to be associated with an increased risk of cardiovascular disease, the findings are the first to demonstrate a link between these "conspicuous, accessible, and assessable clinical markers" and cardiovascular morbidity in RA, Dr. Prashant Kaushik reported at the annual meeting of the American College of Rheumatology.

In 23,327 RA patients included in the CORRONA (Consortium of Rheumatology Researchers of North America) database who were evaluated at 182,201 individual visits between October 2001 and September 2011, the presence of subcutaneous nodules was found to confer a 44% increase in the risk of cardiovascular disease (hazard ratio, 1.44). The association remained significant after the investigators adjusted for age, sex, age of onset of RA, presence of diabetes mellitus, hypertension, smoking, alcohol consumption, and the use of a lipid-lowering agent (adjusted hazard ratio, 1.25), said Dr. Kaushik, who is rheumatology section chief at the Stratton VA Medical Center, Albany, N.Y.

Additionally, an age-sex interaction was found for women, who had a steeper increase in risk with age, compared with men. The hazard ratios per year of age for men and women were 1.01 and 1.03, but the hazard ratio for women vs. men at age 40 was 0.39, and at age 70 was 0.59, he noted.

Patients included in the CORRONA database had an average follow-up of 3 years and 70,455 patient-years. Nearly a third had subcutaneous nodules, and 795 had a cardiovascular event including a myocardial infarction, stroke or transient ischemic attack, heart failure, and/or cardiovascular death.

While the precise mechanism of the biologic association still needs to be ascertained, these findings indicate that subcutaneous nodules, which are the most common extra-articular manifestation of RA, should serve as a red flag for clinicians, Dr. Kaushik said.

"Subcutaneous nodules may be thought of as a clinical indicator of cardiovascular disease in RA," he concluded.

Dr. Kaushik reported having no relevant financial disclosures.

WASHINGTON – The advent of effective anti-inflammatory therapies and the increased use of cardioprotective therapies in recent years have failed to reduce the risk of incident cardiovascular disease in patients with rheumatoid arthritis, according to findings from the prospective longitudinal CARRE study.

During the 10-year Dutch study, 58 cardiovascular events occurred in 353 patients with more than 2,361 patient-years of follow-up, for an incidence rate of 25.3/1,000 patient-years. This did not differ significantly from the incidence rate of 22.8/1,000 patient-years between 3 years and 10 years of follow-up, Dr. Alper M. van Sijl reported at the annual meeting of the American College of Rheumatology.

Nonetheless, the findings do suggest that improving disease activity and inflammatory markers over time might mitigate cardiovascular risk, said Dr. van Sijl of the Jan van Breemen Research Institute, Reade, Amsterdam.

Patients with RA have a twofold increase in the risk of mortality compared with the general population, and this is largely attributable to cardiovascular disease, he said, noting that it has been unclear what role cardiovascular risk factors vs. the underlying inflammatory processes of RA play in this.

"Most research only accounts for cardiovascular risk factors at baseline, and does not look at longitudinal data," he said.

To evaluate whether the increased use of anti-inflammatory and cardioprotective medications has reduced the risk, Dr. van Sijl and his colleagues compared changes in cardiovascular risk factors, RA-related factors, and medication use over time based on whether study participants did or did not develop cardiovascular disease during follow-up. The investigators found that general cardiovascular risk increased over time, as did the use of antihypertensives, statins, and tumor necrosis factor inhibitors, while RA-related factors improved significantly over time.

For example, with respect to cardiovascular disease risk, changes in markers such as intima-media thickness and cardiovascular risk score were seen. Intima-media thickness increased by 0.030 mm between baseline and 3-year follow-up, and decreased by 0.006 mm between 3 and 10 years. Ten-year CV risk (SCORE) increased by 0.5 points between baseline and 3-year follow-up, and by 4.4 points between 3 and 10 years. Antihypertensive use increased by 4% and 11% during the same periods (from 24% at baseline), respectively; statin use increased by 3% and 5% (from 9% at baseline) during the same periods; and use of biologic agents increased 9% and 14% (from 2% at baseline).

As for RA-related factors, improvements were seen in erythrocyte sedimentation rate in those who did not develop cardiovascular disease, while the rate increased in those who did develop cardiovascular disease. Similarly, disease activity scores (DAS28) improved in both groups between baseline and 3 years, then increased between the assessment done at 3 and that done at 10 years in those who developed cardiovascular disease, while they continued to decrease in those who did not.

The use of biologics increased significantly more over time in those without cardiovascular disease, compared with those with cardiovascular disease (to about 35% vs. 15%).

Generalized estimating equation analysis demonstrated a positive association between the use of tumor necrosis factor inhibitors and a reduction in incident cardiovascular disease, Dr. van Sijl said.

The findings suggest that more aggressive cardioprotective and anti-inflammatory treatment might mitigate the burden of cardiovascular disease in patients with RA, he said.

CARRE study participants were enrolled beginning in 2000. All fulfilled ACR 1987 criteria for RA, and had a mean disease duration of 7 years. Most were women in their 60s with high levels of disease activity, Dr. van Sijl said.

"In summary, the risk of incident cardiovascular disease persists in RA despite incremental use of cardioprotective medication and/or TNF blocking agents. At baseline, cardiovascular risk factors such as blood pressure and renal function were more associated with incident cardiovascular disease than RA-related factors, and changes in RA-related factors during follow-up were associated with an increased risk of incident cardiovascular disease," he said. Although traditional cardiovascular risk factors remain relevant in the risk of cardiovascular disease in RA patients, improving disease activity and inflammatory markers over time might positively influence this risk, he added.

Dr. van Sijl reported having no disclosures.

WASHINGTON – The advent of effective anti-inflammatory therapies and the increased use of cardioprotective therapies in recent years have failed to reduce the risk of incident cardiovascular disease in patients with rheumatoid arthritis, according to findings from the prospective longitudinal CARRE study.

During the 10-year Dutch study, 58 cardiovascular events occurred in 353 patients with more than 2,361 patient-years of follow-up, for an incidence rate of 25.3/1,000 patient-years. This did not differ significantly from the incidence rate of 22.8/1,000 patient-years between 3 years and 10 years of follow-up, Dr. Alper M. van Sijl reported at the annual meeting of the American College of Rheumatology.

Nonetheless, the findings do suggest that improving disease activity and inflammatory markers over time might mitigate cardiovascular risk, said Dr. van Sijl of the Jan van Breemen Research Institute, Reade, Amsterdam.

Patients with RA have a twofold increase in the risk of mortality compared with the general population, and this is largely attributable to cardiovascular disease, he said, noting that it has been unclear what role cardiovascular risk factors vs. the underlying inflammatory processes of RA play in this.

"Most research only accounts for cardiovascular risk factors at baseline, and does not look at longitudinal data," he said.

To evaluate whether the increased use of anti-inflammatory and cardioprotective medications has reduced the risk, Dr. van Sijl and his colleagues compared changes in cardiovascular risk factors, RA-related factors, and medication use over time based on whether study participants did or did not develop cardiovascular disease during follow-up. The investigators found that general cardiovascular risk increased over time, as did the use of antihypertensives, statins, and tumor necrosis factor inhibitors, while RA-related factors improved significantly over time.

For example, with respect to cardiovascular disease risk, changes in markers such as intima-media thickness and cardiovascular risk score were seen. Intima-media thickness increased by 0.030 mm between baseline and 3-year follow-up, and decreased by 0.006 mm between 3 and 10 years. Ten-year CV risk (SCORE) increased by 0.5 points between baseline and 3-year follow-up, and by 4.4 points between 3 and 10 years. Antihypertensive use increased by 4% and 11% during the same periods (from 24% at baseline), respectively; statin use increased by 3% and 5% (from 9% at baseline) during the same periods; and use of biologic agents increased 9% and 14% (from 2% at baseline).

As for RA-related factors, improvements were seen in erythrocyte sedimentation rate in those who did not develop cardiovascular disease, while the rate increased in those who did develop cardiovascular disease. Similarly, disease activity scores (DAS28) improved in both groups between baseline and 3 years, then increased between the assessment done at 3 and that done at 10 years in those who developed cardiovascular disease, while they continued to decrease in those who did not.

The use of biologics increased significantly more over time in those without cardiovascular disease, compared with those with cardiovascular disease (to about 35% vs. 15%).

Generalized estimating equation analysis demonstrated a positive association between the use of tumor necrosis factor inhibitors and a reduction in incident cardiovascular disease, Dr. van Sijl said.

The findings suggest that more aggressive cardioprotective and anti-inflammatory treatment might mitigate the burden of cardiovascular disease in patients with RA, he said.

CARRE study participants were enrolled beginning in 2000. All fulfilled ACR 1987 criteria for RA, and had a mean disease duration of 7 years. Most were women in their 60s with high levels of disease activity, Dr. van Sijl said.

"In summary, the risk of incident cardiovascular disease persists in RA despite incremental use of cardioprotective medication and/or TNF blocking agents. At baseline, cardiovascular risk factors such as blood pressure and renal function were more associated with incident cardiovascular disease than RA-related factors, and changes in RA-related factors during follow-up were associated with an increased risk of incident cardiovascular disease," he said. Although traditional cardiovascular risk factors remain relevant in the risk of cardiovascular disease in RA patients, improving disease activity and inflammatory markers over time might positively influence this risk, he added.

Dr. van Sijl reported having no disclosures.

WASHINGTON – The advent of effective anti-inflammatory therapies and the increased use of cardioprotective therapies in recent years have failed to reduce the risk of incident cardiovascular disease in patients with rheumatoid arthritis, according to findings from the prospective longitudinal CARRE study.

During the 10-year Dutch study, 58 cardiovascular events occurred in 353 patients with more than 2,361 patient-years of follow-up, for an incidence rate of 25.3/1,000 patient-years. This did not differ significantly from the incidence rate of 22.8/1,000 patient-years between 3 years and 10 years of follow-up, Dr. Alper M. van Sijl reported at the annual meeting of the American College of Rheumatology.

Nonetheless, the findings do suggest that improving disease activity and inflammatory markers over time might mitigate cardiovascular risk, said Dr. van Sijl of the Jan van Breemen Research Institute, Reade, Amsterdam.

Patients with RA have a twofold increase in the risk of mortality compared with the general population, and this is largely attributable to cardiovascular disease, he said, noting that it has been unclear what role cardiovascular risk factors vs. the underlying inflammatory processes of RA play in this.

"Most research only accounts for cardiovascular risk factors at baseline, and does not look at longitudinal data," he said.

To evaluate whether the increased use of anti-inflammatory and cardioprotective medications has reduced the risk, Dr. van Sijl and his colleagues compared changes in cardiovascular risk factors, RA-related factors, and medication use over time based on whether study participants did or did not develop cardiovascular disease during follow-up. The investigators found that general cardiovascular risk increased over time, as did the use of antihypertensives, statins, and tumor necrosis factor inhibitors, while RA-related factors improved significantly over time.

For example, with respect to cardiovascular disease risk, changes in markers such as intima-media thickness and cardiovascular risk score were seen. Intima-media thickness increased by 0.030 mm between baseline and 3-year follow-up, and decreased by 0.006 mm between 3 and 10 years. Ten-year CV risk (SCORE) increased by 0.5 points between baseline and 3-year follow-up, and by 4.4 points between 3 and 10 years. Antihypertensive use increased by 4% and 11% during the same periods (from 24% at baseline), respectively; statin use increased by 3% and 5% (from 9% at baseline) during the same periods; and use of biologic agents increased 9% and 14% (from 2% at baseline).

As for RA-related factors, improvements were seen in erythrocyte sedimentation rate in those who did not develop cardiovascular disease, while the rate increased in those who did develop cardiovascular disease. Similarly, disease activity scores (DAS28) improved in both groups between baseline and 3 years, then increased between the assessment done at 3 and that done at 10 years in those who developed cardiovascular disease, while they continued to decrease in those who did not.

The use of biologics increased significantly more over time in those without cardiovascular disease, compared with those with cardiovascular disease (to about 35% vs. 15%).

Generalized estimating equation analysis demonstrated a positive association between the use of tumor necrosis factor inhibitors and a reduction in incident cardiovascular disease, Dr. van Sijl said.

The findings suggest that more aggressive cardioprotective and anti-inflammatory treatment might mitigate the burden of cardiovascular disease in patients with RA, he said.

CARRE study participants were enrolled beginning in 2000. All fulfilled ACR 1987 criteria for RA, and had a mean disease duration of 7 years. Most were women in their 60s with high levels of disease activity, Dr. van Sijl said.

"In summary, the risk of incident cardiovascular disease persists in RA despite incremental use of cardioprotective medication and/or TNF blocking agents. At baseline, cardiovascular risk factors such as blood pressure and renal function were more associated with incident cardiovascular disease than RA-related factors, and changes in RA-related factors during follow-up were associated with an increased risk of incident cardiovascular disease," he said. Although traditional cardiovascular risk factors remain relevant in the risk of cardiovascular disease in RA patients, improving disease activity and inflammatory markers over time might positively influence this risk, he added.

Dr. van Sijl reported having no disclosures.

WASHINGTON – Tocilizumab for the treatment of systemic juvenile idiopathic arthritis was associated with significant catch-up growth at 2-year follow-up in the vast majority of children who participated in the pivotal phase III TENDER study.

Treatment with the interleukin-6 (IL-6) receptor inhibitor, which is marketed as Actemra, also significantly increased insulinlike growth factor-1 (IGF-1) levels and osteocalcin/C-telopeptide of type 1 collagen (OC/CTX-1) ratios, suggesting that the therapy has beneficial effects on growth hormone axis and bone metabolism, reported Dr. Fabrizio De Benedetti, speaking at the annual meeting of the American College of Rheumatology.

The findings are important because systemic juvenile idiopathic arthritis (sJIA) has a significant impact on the growing skeleton and is associated with impaired linear growth and systemic osteoporosis, he explained.

Height measurements at baseline in 112 children aged 2-17 years who were enrolled in the study showed profound growth failure, with most having height velocity well below normal for age and gender. However, during treatment, most patients had above normal height velocities: 85% of girls and 73% of boys experienced catch-up growth, said Dr. De Benedetti of Ospedale Pediatrico Bambino Gesu, Rome.

In 86 children from the study who were below Tanner stage 4 development at baseline, the 0.61 mean improvement in height standard deviation score at 2-year follow-up was statistically significant, and although mean corticosteroid dose was higher in the first year of treatment (0.13 mg/kg per day vs. 0.05 mg/kg per day), mean height velocities were comparable in both years, at 5.8 cm and 6.3 cm, respectively, he noted.

IGF-1 standard deviation score increased from a mean of –1.1 at baseline to 0.0 at 2 years, and OC/CTX-1 ratio increased significantly, suggesting an increase in osteoblast activity relative to osteoclast activity.

Improvements in the Juvenile Arthritis Disease Activity Score–71 (JADAS-71) during the first year correlated with increases in height velocities during that year, as did younger age at baseline.

Tocilizumab, which was approved by the U.S. Food and Drugs Administration in 2010 for the treatment of rheumatoid arthritis, received an expanded approval for the treatment of sJIA in April 2011, based on 12-week results from the randomized, placebo-controlled TENDER study. Treatment was shown in that phase, as well as in an open-label long-term extension phase, to be safe and effective for the management of sJIA. Two-year findings of the study, which included children with active refractory disease, were reported at the 2011 annual meeting of the American College of Rheumatology.

Data collection will continue through 5 years of follow-up, allowing a more comprehensive analysis of growth outcomes, said Dr. De Benedetti, the lead investigator for the TENDER study.

Dr. De Benedetti disclosed that he has received research grants and/or consulting fees from Abbott, BMS, Novartis, NovImmune, Pfizer, Roche Pharmaceuticals, and Sobi. The TENDER study was sponsored by Roche, the maker of tocilizumab.

WASHINGTON – Tocilizumab for the treatment of systemic juvenile idiopathic arthritis was associated with significant catch-up growth at 2-year follow-up in the vast majority of children who participated in the pivotal phase III TENDER study.

Treatment with the interleukin-6 (IL-6) receptor inhibitor, which is marketed as Actemra, also significantly increased insulinlike growth factor-1 (IGF-1) levels and osteocalcin/C-telopeptide of type 1 collagen (OC/CTX-1) ratios, suggesting that the therapy has beneficial effects on growth hormone axis and bone metabolism, reported Dr. Fabrizio De Benedetti, speaking at the annual meeting of the American College of Rheumatology.

The findings are important because systemic juvenile idiopathic arthritis (sJIA) has a significant impact on the growing skeleton and is associated with impaired linear growth and systemic osteoporosis, he explained.

Height measurements at baseline in 112 children aged 2-17 years who were enrolled in the study showed profound growth failure, with most having height velocity well below normal for age and gender. However, during treatment, most patients had above normal height velocities: 85% of girls and 73% of boys experienced catch-up growth, said Dr. De Benedetti of Ospedale Pediatrico Bambino Gesu, Rome.

In 86 children from the study who were below Tanner stage 4 development at baseline, the 0.61 mean improvement in height standard deviation score at 2-year follow-up was statistically significant, and although mean corticosteroid dose was higher in the first year of treatment (0.13 mg/kg per day vs. 0.05 mg/kg per day), mean height velocities were comparable in both years, at 5.8 cm and 6.3 cm, respectively, he noted.

IGF-1 standard deviation score increased from a mean of –1.1 at baseline to 0.0 at 2 years, and OC/CTX-1 ratio increased significantly, suggesting an increase in osteoblast activity relative to osteoclast activity.

Improvements in the Juvenile Arthritis Disease Activity Score–71 (JADAS-71) during the first year correlated with increases in height velocities during that year, as did younger age at baseline.

Tocilizumab, which was approved by the U.S. Food and Drugs Administration in 2010 for the treatment of rheumatoid arthritis, received an expanded approval for the treatment of sJIA in April 2011, based on 12-week results from the randomized, placebo-controlled TENDER study. Treatment was shown in that phase, as well as in an open-label long-term extension phase, to be safe and effective for the management of sJIA. Two-year findings of the study, which included children with active refractory disease, were reported at the 2011 annual meeting of the American College of Rheumatology.

Data collection will continue through 5 years of follow-up, allowing a more comprehensive analysis of growth outcomes, said Dr. De Benedetti, the lead investigator for the TENDER study.

Dr. De Benedetti disclosed that he has received research grants and/or consulting fees from Abbott, BMS, Novartis, NovImmune, Pfizer, Roche Pharmaceuticals, and Sobi. The TENDER study was sponsored by Roche, the maker of tocilizumab.

WASHINGTON – Tocilizumab for the treatment of systemic juvenile idiopathic arthritis was associated with significant catch-up growth at 2-year follow-up in the vast majority of children who participated in the pivotal phase III TENDER study.

Treatment with the interleukin-6 (IL-6) receptor inhibitor, which is marketed as Actemra, also significantly increased insulinlike growth factor-1 (IGF-1) levels and osteocalcin/C-telopeptide of type 1 collagen (OC/CTX-1) ratios, suggesting that the therapy has beneficial effects on growth hormone axis and bone metabolism, reported Dr. Fabrizio De Benedetti, speaking at the annual meeting of the American College of Rheumatology.

The findings are important because systemic juvenile idiopathic arthritis (sJIA) has a significant impact on the growing skeleton and is associated with impaired linear growth and systemic osteoporosis, he explained.

Height measurements at baseline in 112 children aged 2-17 years who were enrolled in the study showed profound growth failure, with most having height velocity well below normal for age and gender. However, during treatment, most patients had above normal height velocities: 85% of girls and 73% of boys experienced catch-up growth, said Dr. De Benedetti of Ospedale Pediatrico Bambino Gesu, Rome.

In 86 children from the study who were below Tanner stage 4 development at baseline, the 0.61 mean improvement in height standard deviation score at 2-year follow-up was statistically significant, and although mean corticosteroid dose was higher in the first year of treatment (0.13 mg/kg per day vs. 0.05 mg/kg per day), mean height velocities were comparable in both years, at 5.8 cm and 6.3 cm, respectively, he noted.

IGF-1 standard deviation score increased from a mean of –1.1 at baseline to 0.0 at 2 years, and OC/CTX-1 ratio increased significantly, suggesting an increase in osteoblast activity relative to osteoclast activity.

Improvements in the Juvenile Arthritis Disease Activity Score–71 (JADAS-71) during the first year correlated with increases in height velocities during that year, as did younger age at baseline.

Tocilizumab, which was approved by the U.S. Food and Drugs Administration in 2010 for the treatment of rheumatoid arthritis, received an expanded approval for the treatment of sJIA in April 2011, based on 12-week results from the randomized, placebo-controlled TENDER study. Treatment was shown in that phase, as well as in an open-label long-term extension phase, to be safe and effective for the management of sJIA. Two-year findings of the study, which included children with active refractory disease, were reported at the 2011 annual meeting of the American College of Rheumatology.

Data collection will continue through 5 years of follow-up, allowing a more comprehensive analysis of growth outcomes, said Dr. De Benedetti, the lead investigator for the TENDER study.

Dr. De Benedetti disclosed that he has received research grants and/or consulting fees from Abbott, BMS, Novartis, NovImmune, Pfizer, Roche Pharmaceuticals, and Sobi. The TENDER study was sponsored by Roche, the maker of tocilizumab.