Rheumatoid Arthritis

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 – Men with rheumatoid arthritis who have depression or depressive symptoms were significantly more likely to die compared with RA patients who were not depressed, according to data from a longitudinal cohort study of 530 patients. The findings were presented at the annual meeting of the American College of Rheumatology.

The deleterious effect of depression on early mortality also was seen in women with RA, but to a lesser extent.

"Depression is often underdiagnosed in RA," but the risk of mortality associated with depression in RA has not been well studied, said Patricia Katz, Ph.D., of the University of California, San Francisco.

Dr. Katz and colleagues conducted annual telephone surveys of 530 adults with RA over a 7-year period, with an average of 5 years’ follow-up. The average age of the patients was 60 years, 84% were women, the average disease duration was 19 years, and 46% reported at least one cardiovascular risk factor. Depression was defined as a score of 5 or higher on the 15-item Geriatric Depression Scale (GDS).

"Even though depression is very common in RA, it is not normal."

A total of 63 patients (12%) died during the study period. The risk of death in depressed men and women with RA was approximately three times that of RA patients who were not depressed (hazard ratio 3.5), according to the results of a bivariate analysis.

"People who were depressed at their last interview were more likely to die," Dr. Katz said. In a multivariate analysis, depression remained a significant predictor of mortality.

In particular, men with RA who met criteria for depression had the highest risk of mortality.

"Overall, men were two and half times more likely to die than women," Dr. Katz said, but men with depression had a risk that was six times higher than women with no depression (who served as a reference group), she added. Women with depression had a risk of death of two and half times that of women with no depression.

In addition, a change in depressive symptoms that did not meet the criteria for depression (defined as a worsening of GDS scores by at least 2 points) was associated with an approximately twofold increased risk of death in depressed women compared to women with no depression. Men with an increase in depressive symptom scores had an increase in risk five times that of women with no depression.

"Both depression and an increase in depressive symptoms are significant risk factors for all-cause mortality in RA," Dr. Katz noted.

"I think it is important to recognize that depression is a treatable condition," said Dr. Katz. "Even though depression is very common in RA, it is not normal. It needs to be treated, and to be treated it needs to be recognized," she said.

"This is the clinical challenge; there needs to be some sort of regular monitoring to recognize these changes early, so intervention can happen at an appropriate time," she added.

The study was funded in part by the National Institute for Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health. Dr. Katz had no financial conflicts to disclose.

WASHINGTON – Men with rheumatoid arthritis who have depression or depressive symptoms were significantly more likely to die compared with RA patients who were not depressed, according to data from a longitudinal cohort study of 530 patients. The findings were presented at the annual meeting of the American College of Rheumatology.

The deleterious effect of depression on early mortality also was seen in women with RA, but to a lesser extent.

"Depression is often underdiagnosed in RA," but the risk of mortality associated with depression in RA has not been well studied, said Patricia Katz, Ph.D., of the University of California, San Francisco.

Dr. Katz and colleagues conducted annual telephone surveys of 530 adults with RA over a 7-year period, with an average of 5 years’ follow-up. The average age of the patients was 60 years, 84% were women, the average disease duration was 19 years, and 46% reported at least one cardiovascular risk factor. Depression was defined as a score of 5 or higher on the 15-item Geriatric Depression Scale (GDS).

"Even though depression is very common in RA, it is not normal."

A total of 63 patients (12%) died during the study period. The risk of death in depressed men and women with RA was approximately three times that of RA patients who were not depressed (hazard ratio 3.5), according to the results of a bivariate analysis.

"People who were depressed at their last interview were more likely to die," Dr. Katz said. In a multivariate analysis, depression remained a significant predictor of mortality.

In particular, men with RA who met criteria for depression had the highest risk of mortality.

"Overall, men were two and half times more likely to die than women," Dr. Katz said, but men with depression had a risk that was six times higher than women with no depression (who served as a reference group), she added. Women with depression had a risk of death of two and half times that of women with no depression.

In addition, a change in depressive symptoms that did not meet the criteria for depression (defined as a worsening of GDS scores by at least 2 points) was associated with an approximately twofold increased risk of death in depressed women compared to women with no depression. Men with an increase in depressive symptom scores had an increase in risk five times that of women with no depression.

"Both depression and an increase in depressive symptoms are significant risk factors for all-cause mortality in RA," Dr. Katz noted.

"I think it is important to recognize that depression is a treatable condition," said Dr. Katz. "Even though depression is very common in RA, it is not normal. It needs to be treated, and to be treated it needs to be recognized," she said.

"This is the clinical challenge; there needs to be some sort of regular monitoring to recognize these changes early, so intervention can happen at an appropriate time," she added.

The study was funded in part by the National Institute for Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health. Dr. Katz had no financial conflicts to disclose.

WASHINGTON – Men with rheumatoid arthritis who have depression or depressive symptoms were significantly more likely to die compared with RA patients who were not depressed, according to data from a longitudinal cohort study of 530 patients. The findings were presented at the annual meeting of the American College of Rheumatology.

The deleterious effect of depression on early mortality also was seen in women with RA, but to a lesser extent.

"Depression is often underdiagnosed in RA," but the risk of mortality associated with depression in RA has not been well studied, said Patricia Katz, Ph.D., of the University of California, San Francisco.

Dr. Katz and colleagues conducted annual telephone surveys of 530 adults with RA over a 7-year period, with an average of 5 years’ follow-up. The average age of the patients was 60 years, 84% were women, the average disease duration was 19 years, and 46% reported at least one cardiovascular risk factor. Depression was defined as a score of 5 or higher on the 15-item Geriatric Depression Scale (GDS).

"Even though depression is very common in RA, it is not normal."

A total of 63 patients (12%) died during the study period. The risk of death in depressed men and women with RA was approximately three times that of RA patients who were not depressed (hazard ratio 3.5), according to the results of a bivariate analysis.

"People who were depressed at their last interview were more likely to die," Dr. Katz said. In a multivariate analysis, depression remained a significant predictor of mortality.

In particular, men with RA who met criteria for depression had the highest risk of mortality.

"Overall, men were two and half times more likely to die than women," Dr. Katz said, but men with depression had a risk that was six times higher than women with no depression (who served as a reference group), she added. Women with depression had a risk of death of two and half times that of women with no depression.

In addition, a change in depressive symptoms that did not meet the criteria for depression (defined as a worsening of GDS scores by at least 2 points) was associated with an approximately twofold increased risk of death in depressed women compared to women with no depression. Men with an increase in depressive symptom scores had an increase in risk five times that of women with no depression.

"Both depression and an increase in depressive symptoms are significant risk factors for all-cause mortality in RA," Dr. Katz noted.

"I think it is important to recognize that depression is a treatable condition," said Dr. Katz. "Even though depression is very common in RA, it is not normal. It needs to be treated, and to be treated it needs to be recognized," she said.

"This is the clinical challenge; there needs to be some sort of regular monitoring to recognize these changes early, so intervention can happen at an appropriate time," she added.

The study was funded in part by the National Institute for Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health. Dr. Katz had no financial conflicts to disclose.

WASHINGTON – Anti–tumor necrosis factor therapy does not increase the risk of lymphoma in patients with rheumatoid arthritis.

That’s the conclusion of a study presented in a plenary session here by Dr. Kimme L. Hyrich on Monday, Nov. 12, at the annual meeting of the American College of Rheumatology.

"The challenge in studying whether therapies for rheumatoid arthritis (RA) patients can increase the risk of lymphoma is the knowledge that the disease itself has been associated with this outcome," said Dr. Hyrich.

"It’s possible that with immunosuppression, we may see an increased risk of lymphoma, but equally, if we can control the disease activity that has been associated with this outcome, it’s possible that we actually can see a decrease in lymphoma risk over time."

Dr. Hyrich, of the arthritis research UK epidemiology unit at the University of Manchester (England), and colleagues looked at patients from the British Society for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA), a prospective registry of RA patients taking biologic drugs, recruited between 2001 and 2009.

The treatment group comprised 11,987 patients who started therapy with an anti–tumor necrosis factor (TNF) including infliximab, etanercept, or adalimumab; they were compared to 3,465 patients who were treated solely with nonbiologic disease modifying antirheumatic drugs (DMARDs).

Incident cancers were detected either by flagging in a national cancer database (95% of cancers were identified by this method, according to Dr. Hyrich) in one of six monthly patient and physician questionnaires, or in annual physician questionnaires thereafter.

Subjects were followed until Sept. 30, 2010, or their first lymphoma, or death, whichever came first.

The cutoff date of the study was 2010 because there can be up to a 2-year lag between incident cancer and reporting of those data in the registry, due to rigorous confirmatory processes, said Dr. Hyrich.

The investigators found 84 incident lymphomas over the study period: 20 in the nonbiologic DMARD patients and 64 in the anti-TNF cohort, for a rate of 152 per 100,000 person years versus 96 per 100,000 person-years, respectively.

The tally included five cases of Hodgkin’s lymphomas in the nonbiologic DMARD group and nine in the anti-TNF patients. Among the non-Hodgkin’s lymphoma cases, diffuse large B cell lymphomas accounted for the greatest proportion of cancers.

After adjustment for baseline age, gender, disease activity score, health assessment questionnaire results, disease duration, smoking, and current or previous cyclophosphamide use, the hazard ratio for all lymphomas for anti-TNF users was calculated to be a nonsignificant 1.13 (95% confidence interval, 0.55-2.31).

Similarly, looking at non-Hodgkin’s lymphoma only, Dr. Hyrich determined an adjusted hazard ratio among the anti-TNF patients of 1.26, also nonsignificant (95% CI, 0.58-2.72).

In her presentation, Dr. Hyrich commented that the study was unable to assess risk associated with a particular anti-TNF agent, given that the majority of patients in this real-world cohort had a history of treatment with multiple drugs in the class; indeed, 15% of the cohort had a history of treatment with three or more anti-TNF agents.

"How do you attribute risk in a situation where patients have been exposed to all of these agents?" she said.

"I think further analysis of these cohorts is needed to know whether any exposure to anti-TNFs, or any particular order of anti-TNFs, or any particular duration of anti-TNFs" increases risk.

The researchers stated that they had no disclosures relative to this presentation.

WASHINGTON – Anti–tumor necrosis factor therapy does not increase the risk of lymphoma in patients with rheumatoid arthritis.

That’s the conclusion of a study presented in a plenary session here by Dr. Kimme L. Hyrich on Monday, Nov. 12, at the annual meeting of the American College of Rheumatology.

"The challenge in studying whether therapies for rheumatoid arthritis (RA) patients can increase the risk of lymphoma is the knowledge that the disease itself has been associated with this outcome," said Dr. Hyrich.

"It’s possible that with immunosuppression, we may see an increased risk of lymphoma, but equally, if we can control the disease activity that has been associated with this outcome, it’s possible that we actually can see a decrease in lymphoma risk over time."

Dr. Hyrich, of the arthritis research UK epidemiology unit at the University of Manchester (England), and colleagues looked at patients from the British Society for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA), a prospective registry of RA patients taking biologic drugs, recruited between 2001 and 2009.

The treatment group comprised 11,987 patients who started therapy with an anti–tumor necrosis factor (TNF) including infliximab, etanercept, or adalimumab; they were compared to 3,465 patients who were treated solely with nonbiologic disease modifying antirheumatic drugs (DMARDs).

Incident cancers were detected either by flagging in a national cancer database (95% of cancers were identified by this method, according to Dr. Hyrich) in one of six monthly patient and physician questionnaires, or in annual physician questionnaires thereafter.

Subjects were followed until Sept. 30, 2010, or their first lymphoma, or death, whichever came first.

The cutoff date of the study was 2010 because there can be up to a 2-year lag between incident cancer and reporting of those data in the registry, due to rigorous confirmatory processes, said Dr. Hyrich.

The investigators found 84 incident lymphomas over the study period: 20 in the nonbiologic DMARD patients and 64 in the anti-TNF cohort, for a rate of 152 per 100,000 person years versus 96 per 100,000 person-years, respectively.

The tally included five cases of Hodgkin’s lymphomas in the nonbiologic DMARD group and nine in the anti-TNF patients. Among the non-Hodgkin’s lymphoma cases, diffuse large B cell lymphomas accounted for the greatest proportion of cancers.

After adjustment for baseline age, gender, disease activity score, health assessment questionnaire results, disease duration, smoking, and current or previous cyclophosphamide use, the hazard ratio for all lymphomas for anti-TNF users was calculated to be a nonsignificant 1.13 (95% confidence interval, 0.55-2.31).

Similarly, looking at non-Hodgkin’s lymphoma only, Dr. Hyrich determined an adjusted hazard ratio among the anti-TNF patients of 1.26, also nonsignificant (95% CI, 0.58-2.72).

In her presentation, Dr. Hyrich commented that the study was unable to assess risk associated with a particular anti-TNF agent, given that the majority of patients in this real-world cohort had a history of treatment with multiple drugs in the class; indeed, 15% of the cohort had a history of treatment with three or more anti-TNF agents.

"How do you attribute risk in a situation where patients have been exposed to all of these agents?" she said.

"I think further analysis of these cohorts is needed to know whether any exposure to anti-TNFs, or any particular order of anti-TNFs, or any particular duration of anti-TNFs" increases risk.

The researchers stated that they had no disclosures relative to this presentation.

WASHINGTON – Anti–tumor necrosis factor therapy does not increase the risk of lymphoma in patients with rheumatoid arthritis.

That’s the conclusion of a study presented in a plenary session here by Dr. Kimme L. Hyrich on Monday, Nov. 12, at the annual meeting of the American College of Rheumatology.

"The challenge in studying whether therapies for rheumatoid arthritis (RA) patients can increase the risk of lymphoma is the knowledge that the disease itself has been associated with this outcome," said Dr. Hyrich.

"It’s possible that with immunosuppression, we may see an increased risk of lymphoma, but equally, if we can control the disease activity that has been associated with this outcome, it’s possible that we actually can see a decrease in lymphoma risk over time."

Dr. Hyrich, of the arthritis research UK epidemiology unit at the University of Manchester (England), and colleagues looked at patients from the British Society for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA), a prospective registry of RA patients taking biologic drugs, recruited between 2001 and 2009.

The treatment group comprised 11,987 patients who started therapy with an anti–tumor necrosis factor (TNF) including infliximab, etanercept, or adalimumab; they were compared to 3,465 patients who were treated solely with nonbiologic disease modifying antirheumatic drugs (DMARDs).

Incident cancers were detected either by flagging in a national cancer database (95% of cancers were identified by this method, according to Dr. Hyrich) in one of six monthly patient and physician questionnaires, or in annual physician questionnaires thereafter.

Subjects were followed until Sept. 30, 2010, or their first lymphoma, or death, whichever came first.

The cutoff date of the study was 2010 because there can be up to a 2-year lag between incident cancer and reporting of those data in the registry, due to rigorous confirmatory processes, said Dr. Hyrich.

The investigators found 84 incident lymphomas over the study period: 20 in the nonbiologic DMARD patients and 64 in the anti-TNF cohort, for a rate of 152 per 100,000 person years versus 96 per 100,000 person-years, respectively.

The tally included five cases of Hodgkin’s lymphomas in the nonbiologic DMARD group and nine in the anti-TNF patients. Among the non-Hodgkin’s lymphoma cases, diffuse large B cell lymphomas accounted for the greatest proportion of cancers.

After adjustment for baseline age, gender, disease activity score, health assessment questionnaire results, disease duration, smoking, and current or previous cyclophosphamide use, the hazard ratio for all lymphomas for anti-TNF users was calculated to be a nonsignificant 1.13 (95% confidence interval, 0.55-2.31).

Similarly, looking at non-Hodgkin’s lymphoma only, Dr. Hyrich determined an adjusted hazard ratio among the anti-TNF patients of 1.26, also nonsignificant (95% CI, 0.58-2.72).

In her presentation, Dr. Hyrich commented that the study was unable to assess risk associated with a particular anti-TNF agent, given that the majority of patients in this real-world cohort had a history of treatment with multiple drugs in the class; indeed, 15% of the cohort had a history of treatment with three or more anti-TNF agents.

"How do you attribute risk in a situation where patients have been exposed to all of these agents?" she said.

"I think further analysis of these cohorts is needed to know whether any exposure to anti-TNFs, or any particular order of anti-TNFs, or any particular duration of anti-TNFs" increases risk.

The researchers stated that they had no disclosures relative to this presentation.

WASHINGTON – Biologics use by rheumatoid arthritis patients was associated with a 25% reduction in the risk of premature death, compared with patients without exposure to biologics, based on data from a population-based study of more than 4,000 patients. The findings were presented at the annual meeting of the American College of Rheumatology.

Rheumatoid arthritis (RA) is associated with a twofold increase in premature mortality risk, primarily caused by cardiovascular disease, said Dr. Diane Lacaille of the Arthritis Research Centre of Canada, in Vancouver. Previous research suggests that the increased risk is linked to inflammation that affects other organs beyond the RA-affected joints, she said. Biologic agents have shown effectiveness in controlling the inflammation associated with joint damage in RA, but the drugs’ impact on reducing early mortality has not been well studied, Dr. Lacaille said.

Dr. Lacaille and her colleagues reviewed data from the Canadian Ministry of Health to identify all RA cases that used a biologic agent (anti–tumor necrosis factor (anti-TNF), rituximab, anakinra, or abatacept) during follow-up. The study population included 2,156 patients who used biologics and 2,156 controls matched for age, sex, and calendar year. The average age of the patients was 56 years, and 75% were women. The researchers obtained data on all health services used by the study participants – including medications, lab tests, and hospitalizations – between January 1996 and March 2006, with follow-up to March 2010.

"Exposure to biologics was associated with a reduced risk of death, with a hazard ratio of 0.26 [(95% confidence interval, 0.18-0.36), P less than or equal to .0001)], which means that the risk of death in the biologics users was a quarter that of the nonbiologic users," Dr. Lacaille said. Approximately 90% of the biologics users were using anti-TNF therapy, but the findings were consistent for all biologics in a multivariate analysis, she noted.

Overall, 573 deaths were noted during the study period, including 247 in the biologics group and 326 in the control group. The use of three previous disease-modifying antirheumatic drugs or a change in DMARD did not affect the results, Dr. Lacaille noted.

"I think it wouldn’t be accurate from an epidemiological point of view to say that biologics lead to a 75% reduction" in the risk of premature death, she said.

"But we can be confident that there was an association with a reduction in the reduced risk of death," she added.

The study was limited by the lack of randomization, which may have led to some selection bias, said Dr. Lacaille. But given the increased risk of early mortality associated with RA, the data have "important implications for health policy makers, health care providers, and people with RA," she said.

Approximately 28% of the patients had used more than one biologic, but the number or course of prior biologics had no apparent impact on the risk of death, she added.

Dr. Lacaille had no financial conflicts to disclose.

WASHINGTON – Biologics use by rheumatoid arthritis patients was associated with a 25% reduction in the risk of premature death, compared with patients without exposure to biologics, based on data from a population-based study of more than 4,000 patients. The findings were presented at the annual meeting of the American College of Rheumatology.

Rheumatoid arthritis (RA) is associated with a twofold increase in premature mortality risk, primarily caused by cardiovascular disease, said Dr. Diane Lacaille of the Arthritis Research Centre of Canada, in Vancouver. Previous research suggests that the increased risk is linked to inflammation that affects other organs beyond the RA-affected joints, she said. Biologic agents have shown effectiveness in controlling the inflammation associated with joint damage in RA, but the drugs’ impact on reducing early mortality has not been well studied, Dr. Lacaille said.

Dr. Lacaille and her colleagues reviewed data from the Canadian Ministry of Health to identify all RA cases that used a biologic agent (anti–tumor necrosis factor (anti-TNF), rituximab, anakinra, or abatacept) during follow-up. The study population included 2,156 patients who used biologics and 2,156 controls matched for age, sex, and calendar year. The average age of the patients was 56 years, and 75% were women. The researchers obtained data on all health services used by the study participants – including medications, lab tests, and hospitalizations – between January 1996 and March 2006, with follow-up to March 2010.

"Exposure to biologics was associated with a reduced risk of death, with a hazard ratio of 0.26 [(95% confidence interval, 0.18-0.36), P less than or equal to .0001)], which means that the risk of death in the biologics users was a quarter that of the nonbiologic users," Dr. Lacaille said. Approximately 90% of the biologics users were using anti-TNF therapy, but the findings were consistent for all biologics in a multivariate analysis, she noted.

Overall, 573 deaths were noted during the study period, including 247 in the biologics group and 326 in the control group. The use of three previous disease-modifying antirheumatic drugs or a change in DMARD did not affect the results, Dr. Lacaille noted.

"I think it wouldn’t be accurate from an epidemiological point of view to say that biologics lead to a 75% reduction" in the risk of premature death, she said.

"But we can be confident that there was an association with a reduction in the reduced risk of death," she added.

The study was limited by the lack of randomization, which may have led to some selection bias, said Dr. Lacaille. But given the increased risk of early mortality associated with RA, the data have "important implications for health policy makers, health care providers, and people with RA," she said.

Approximately 28% of the patients had used more than one biologic, but the number or course of prior biologics had no apparent impact on the risk of death, she added.

Dr. Lacaille had no financial conflicts to disclose.

WASHINGTON – Biologics use by rheumatoid arthritis patients was associated with a 25% reduction in the risk of premature death, compared with patients without exposure to biologics, based on data from a population-based study of more than 4,000 patients. The findings were presented at the annual meeting of the American College of Rheumatology.

Rheumatoid arthritis (RA) is associated with a twofold increase in premature mortality risk, primarily caused by cardiovascular disease, said Dr. Diane Lacaille of the Arthritis Research Centre of Canada, in Vancouver. Previous research suggests that the increased risk is linked to inflammation that affects other organs beyond the RA-affected joints, she said. Biologic agents have shown effectiveness in controlling the inflammation associated with joint damage in RA, but the drugs’ impact on reducing early mortality has not been well studied, Dr. Lacaille said.

Dr. Lacaille and her colleagues reviewed data from the Canadian Ministry of Health to identify all RA cases that used a biologic agent (anti–tumor necrosis factor (anti-TNF), rituximab, anakinra, or abatacept) during follow-up. The study population included 2,156 patients who used biologics and 2,156 controls matched for age, sex, and calendar year. The average age of the patients was 56 years, and 75% were women. The researchers obtained data on all health services used by the study participants – including medications, lab tests, and hospitalizations – between January 1996 and March 2006, with follow-up to March 2010.

"Exposure to biologics was associated with a reduced risk of death, with a hazard ratio of 0.26 [(95% confidence interval, 0.18-0.36), P less than or equal to .0001)], which means that the risk of death in the biologics users was a quarter that of the nonbiologic users," Dr. Lacaille said. Approximately 90% of the biologics users were using anti-TNF therapy, but the findings were consistent for all biologics in a multivariate analysis, she noted.

Overall, 573 deaths were noted during the study period, including 247 in the biologics group and 326 in the control group. The use of three previous disease-modifying antirheumatic drugs or a change in DMARD did not affect the results, Dr. Lacaille noted.

"I think it wouldn’t be accurate from an epidemiological point of view to say that biologics lead to a 75% reduction" in the risk of premature death, she said.

"But we can be confident that there was an association with a reduction in the reduced risk of death," she added.

The study was limited by the lack of randomization, which may have led to some selection bias, said Dr. Lacaille. But given the increased risk of early mortality associated with RA, the data have "important implications for health policy makers, health care providers, and people with RA," she said.

Approximately 28% of the patients had used more than one biologic, but the number or course of prior biologics had no apparent impact on the risk of death, she added.

Dr. Lacaille had no financial conflicts to disclose.

WASHINGTON – More than one-third of U.S. rheumatoid arthritis patients report using alternative medicine, such as fish oil and glucosamine, at some time after their diagnosis.

However, only 10% of these patients stick with these complementary and alternative (CAM) therapies long term, Dr. Peri H. Pepmueller reported in a poster presentation at the annual meeting of the American College of Rheumatology.

This finding means that rheumatologists "need to ask" about the use of these alternative medicines, Dr. Pepmueller said in an interview.

"I think we can counsel patients that if they want to take them, [they should] take them in addition to the prescription medications," she said.

Dr. Pepmueller of St. Louis University and her colleagues looked at data from the CORRONA (Consortium of Rheumatology Researchers of North America) registry, a multicenter, longitudinal prospective database in the United States with more than 30,000 patients.

The researchers assessed reported CAM use, including the use of fish oil and glucosamine/chondroitin supplements. They also assessed the use of borage seed oil, evening primrose oil, and flax seed oil, the presumed effect of which is to decrease inflammation, Dr. Pepmueller said.

"The oils ... have been shown in many studies to have an anti-inflammatory effect on a variety of chronic conditions in which inflammation is thought to play a role," she said.

In total, 11,970 patients were included in the final analysis. All had at least 2 years of follow-up and at least three visits.

The researchers defined the use of CAM as the use of any of the above-listed therapies within 2 years of their first recorded visit. "Long-term" therapy was defined as the use of the same therapy at either three consecutive visits or all visits in 1 year.

They found that 35.2% of patients reported using one of the complementary therapies looked at, but only 10.8% reported long-term use.

Fish oil was the most commonly reported supplement, used by 27.3% of the cohort.

The next most common supplement was glucosamine/chondroitin, used by a reported 13.6% of the cohort, followed by flax seed oil (3.3%), evening primrose oil (2.1%), and borage seed oil (1.4%).

Dr. Pepmueller then analyzed which, if any, demographic and disease factors predicted complementary alternative medicine use.

Of current smokers, the odds that they would ever use CAM were 0.70 (95% confidence interval, 0.62-0.79; P less than .0001) and the odds of long term CAM use was .71 (95% CI, 0.57-0.87; P less than .05), based on findings of the multivariate analysis.

Patients with education levels of high school or less were also less likely to try complementary medicines, with an OR of 0.69 ( 95% CI, 0.63-0.75; P less than .0001), versus patients with any college-level education.

Geographically, patients in the Western United States were more likely to try complementary medicine alternatives, compared with Midwestern patients (OR, 1.49; 95% CI, 1.29-1.72; P less than .0001), while patients in the Northeastern United States were even less likely than their Midwestern counterparts to try these alternatives (OR, 0.83; 95% CI, 0.74-0.93; P less than .0001 for both values).

On the other hand, while disease duration and severity were not significant predictors of complementary medicine use in a multivariate analysis, unadjusted models showed that a longer duration and a greater number of swollen and tender joints, as well as patient- and physician-assessed disease severity, were all associated with decreased use of complementary medicine.

Dr. Pepmueller also pointed to articles detailing some of the risks involved with alternative medicines, including reports of increased levels of low-density lipoprotein cholesterol levels with fish oil consumption (Rheum. Dis. Clin. North Am. 2011;37:77-84).

Medication interactions are also possible. For example, there have been reports of fish oil potentiating the effects of coumadin.

Dr. Pepmueller stated that she had no relevant financial disclosures; a coinvestigator reported funding from Axio Research.

WASHINGTON – More than one-third of U.S. rheumatoid arthritis patients report using alternative medicine, such as fish oil and glucosamine, at some time after their diagnosis.

However, only 10% of these patients stick with these complementary and alternative (CAM) therapies long term, Dr. Peri H. Pepmueller reported in a poster presentation at the annual meeting of the American College of Rheumatology.

This finding means that rheumatologists "need to ask" about the use of these alternative medicines, Dr. Pepmueller said in an interview.

"I think we can counsel patients that if they want to take them, [they should] take them in addition to the prescription medications," she said.

Dr. Pepmueller of St. Louis University and her colleagues looked at data from the CORRONA (Consortium of Rheumatology Researchers of North America) registry, a multicenter, longitudinal prospective database in the United States with more than 30,000 patients.

The researchers assessed reported CAM use, including the use of fish oil and glucosamine/chondroitin supplements. They also assessed the use of borage seed oil, evening primrose oil, and flax seed oil, the presumed effect of which is to decrease inflammation, Dr. Pepmueller said.

"The oils ... have been shown in many studies to have an anti-inflammatory effect on a variety of chronic conditions in which inflammation is thought to play a role," she said.

In total, 11,970 patients were included in the final analysis. All had at least 2 years of follow-up and at least three visits.

The researchers defined the use of CAM as the use of any of the above-listed therapies within 2 years of their first recorded visit. "Long-term" therapy was defined as the use of the same therapy at either three consecutive visits or all visits in 1 year.

They found that 35.2% of patients reported using one of the complementary therapies looked at, but only 10.8% reported long-term use.

Fish oil was the most commonly reported supplement, used by 27.3% of the cohort.

The next most common supplement was glucosamine/chondroitin, used by a reported 13.6% of the cohort, followed by flax seed oil (3.3%), evening primrose oil (2.1%), and borage seed oil (1.4%).

Dr. Pepmueller then analyzed which, if any, demographic and disease factors predicted complementary alternative medicine use.

Of current smokers, the odds that they would ever use CAM were 0.70 (95% confidence interval, 0.62-0.79; P less than .0001) and the odds of long term CAM use was .71 (95% CI, 0.57-0.87; P less than .05), based on findings of the multivariate analysis.

Patients with education levels of high school or less were also less likely to try complementary medicines, with an OR of 0.69 ( 95% CI, 0.63-0.75; P less than .0001), versus patients with any college-level education.

Geographically, patients in the Western United States were more likely to try complementary medicine alternatives, compared with Midwestern patients (OR, 1.49; 95% CI, 1.29-1.72; P less than .0001), while patients in the Northeastern United States were even less likely than their Midwestern counterparts to try these alternatives (OR, 0.83; 95% CI, 0.74-0.93; P less than .0001 for both values).

On the other hand, while disease duration and severity were not significant predictors of complementary medicine use in a multivariate analysis, unadjusted models showed that a longer duration and a greater number of swollen and tender joints, as well as patient- and physician-assessed disease severity, were all associated with decreased use of complementary medicine.

Dr. Pepmueller also pointed to articles detailing some of the risks involved with alternative medicines, including reports of increased levels of low-density lipoprotein cholesterol levels with fish oil consumption (Rheum. Dis. Clin. North Am. 2011;37:77-84).

Medication interactions are also possible. For example, there have been reports of fish oil potentiating the effects of coumadin.

Dr. Pepmueller stated that she had no relevant financial disclosures; a coinvestigator reported funding from Axio Research.

WASHINGTON – More than one-third of U.S. rheumatoid arthritis patients report using alternative medicine, such as fish oil and glucosamine, at some time after their diagnosis.

However, only 10% of these patients stick with these complementary and alternative (CAM) therapies long term, Dr. Peri H. Pepmueller reported in a poster presentation at the annual meeting of the American College of Rheumatology.

This finding means that rheumatologists "need to ask" about the use of these alternative medicines, Dr. Pepmueller said in an interview.

"I think we can counsel patients that if they want to take them, [they should] take them in addition to the prescription medications," she said.

Dr. Pepmueller of St. Louis University and her colleagues looked at data from the CORRONA (Consortium of Rheumatology Researchers of North America) registry, a multicenter, longitudinal prospective database in the United States with more than 30,000 patients.

The researchers assessed reported CAM use, including the use of fish oil and glucosamine/chondroitin supplements. They also assessed the use of borage seed oil, evening primrose oil, and flax seed oil, the presumed effect of which is to decrease inflammation, Dr. Pepmueller said.

"The oils ... have been shown in many studies to have an anti-inflammatory effect on a variety of chronic conditions in which inflammation is thought to play a role," she said.

In total, 11,970 patients were included in the final analysis. All had at least 2 years of follow-up and at least three visits.

The researchers defined the use of CAM as the use of any of the above-listed therapies within 2 years of their first recorded visit. "Long-term" therapy was defined as the use of the same therapy at either three consecutive visits or all visits in 1 year.

They found that 35.2% of patients reported using one of the complementary therapies looked at, but only 10.8% reported long-term use.

Fish oil was the most commonly reported supplement, used by 27.3% of the cohort.

The next most common supplement was glucosamine/chondroitin, used by a reported 13.6% of the cohort, followed by flax seed oil (3.3%), evening primrose oil (2.1%), and borage seed oil (1.4%).

Dr. Pepmueller then analyzed which, if any, demographic and disease factors predicted complementary alternative medicine use.

Of current smokers, the odds that they would ever use CAM were 0.70 (95% confidence interval, 0.62-0.79; P less than .0001) and the odds of long term CAM use was .71 (95% CI, 0.57-0.87; P less than .05), based on findings of the multivariate analysis.

Patients with education levels of high school or less were also less likely to try complementary medicines, with an OR of 0.69 ( 95% CI, 0.63-0.75; P less than .0001), versus patients with any college-level education.

Geographically, patients in the Western United States were more likely to try complementary medicine alternatives, compared with Midwestern patients (OR, 1.49; 95% CI, 1.29-1.72; P less than .0001), while patients in the Northeastern United States were even less likely than their Midwestern counterparts to try these alternatives (OR, 0.83; 95% CI, 0.74-0.93; P less than .0001 for both values).

On the other hand, while disease duration and severity were not significant predictors of complementary medicine use in a multivariate analysis, unadjusted models showed that a longer duration and a greater number of swollen and tender joints, as well as patient- and physician-assessed disease severity, were all associated with decreased use of complementary medicine.

Dr. Pepmueller also pointed to articles detailing some of the risks involved with alternative medicines, including reports of increased levels of low-density lipoprotein cholesterol levels with fish oil consumption (Rheum. Dis. Clin. North Am. 2011;37:77-84).

Medication interactions are also possible. For example, there have been reports of fish oil potentiating the effects of coumadin.

Dr. Pepmueller stated that she had no relevant financial disclosures; a coinvestigator reported funding from Axio Research.

WASHINGTON – Use of adalimumab in combination with another drug, usually methotrexate, seems to boost treatment response to such an extent that patients with rheumatoid arthritis can sometimes be tapered off one or both drugs over the subsequent 2 years.

Those are the findings of three separate posters that were based on data from the CORRONA (Consortium of Rheumatology Researchers of North America) registry – a multicenter, longitudinal, prospective database in the United States with more than 30,000 patients.

The studies were presented on Nov. 11 at the annual meeting of the American College of Rheumatology.

In the first study, led by Dr. Daniel E. Furst, Carl M. Pearson Professor of Medicine at the University of California, Los Angeles, the researchers looked at RA patients enrolled in CORRONA between March 2002 and September 2011 who initiated adalimumab treatment and had at least one follow-up visit on record.

The researchers assessed 417 patients with 2 years of follow-up, a mean age of 54.2 years, and a mean disease duration of 10.1 years; most (79.3%) were female.

Overall, 67% of patients were treated concurrently with methotrexate upon adalimumab initiation, but at 2 years, the odds ratio for concomitant methotrexate was 0.68 (95% confidence interval, 0.48-0.95; P = .05).

Patients with two or more comorbidities, including hypertension, cancer, chronic obstructive pulmonary disease, and diabetes, were even less likely to continue to need to take methotrexate (OR, 0.48; 95% CI, 0.29-0.80; P = .01).

"This suggests the clinical efficacy of adalimumab in RA disease control across a medically diverse patient population," noted Dr. Furst.

In a second, independent study from CORRONA, Dr. Allan Gibofsky, professor of medicine and public health at Cornell University and professor of law at Fordham University, both in New York, looked at 1,639 patients who initiated adalimumab therapy over the same time period and who had at least one follow-up visit on record.

Dr. Gibofsky found that 1,003 of these patients eventually discontinued adalimumab after a median of 632 days, according to a Kaplan-Meier estimate; 1,358 experienced some form of treatment change (including discontinuation, but also dosing/frequency changes or addition of another disease-modifying antirheumatic drug).

In this analysis, while use of a prior biologic was highly predictive of regimen change (hazard ratio, 1.532; CI, 1.259-1.864; P less than .0001), use of methotrexate at adalimumab initiation was associated with a significantly decreased likelihood of adalimumab treatment change (HR, 0.88; CI, 0.835-0.919; P less than .0001).

Finally, a third CORRONA-based study presented at the meeting confirmed that combination therapy with methotrexate and tumor necrosis factor–inhibitors like adalimumab is increasing.

Dr. Deborah Wenkert of Amgen Inc., based in Thousand Oaks, Calif., and her colleagues looked at the prevalence of combination therapy over two time periods: 2002-2004 and 2007-2009.

She found that the mean clinical disease activity index (CDAI) at initiation of combination therapy was significantly lower during the later time period, versus the earlier, and that "among all RA patients with 2 years of follow-up, a higher percentage of patients initiated combination therapy in 2007-2009 than 2002-2004 in each maximum CDAI category."

The trend could reflect "stricter definition and implementation of aggressive treatment goals in the later time periods," Dr. Wenkert added.

All investigators disclosed multiple relationships to pharmaceutical makers, including the makers of adalimumab.

WASHINGTON – Use of adalimumab in combination with another drug, usually methotrexate, seems to boost treatment response to such an extent that patients with rheumatoid arthritis can sometimes be tapered off one or both drugs over the subsequent 2 years.

Those are the findings of three separate posters that were based on data from the CORRONA (Consortium of Rheumatology Researchers of North America) registry – a multicenter, longitudinal, prospective database in the United States with more than 30,000 patients.

The studies were presented on Nov. 11 at the annual meeting of the American College of Rheumatology.

In the first study, led by Dr. Daniel E. Furst, Carl M. Pearson Professor of Medicine at the University of California, Los Angeles, the researchers looked at RA patients enrolled in CORRONA between March 2002 and September 2011 who initiated adalimumab treatment and had at least one follow-up visit on record.

The researchers assessed 417 patients with 2 years of follow-up, a mean age of 54.2 years, and a mean disease duration of 10.1 years; most (79.3%) were female.

Overall, 67% of patients were treated concurrently with methotrexate upon adalimumab initiation, but at 2 years, the odds ratio for concomitant methotrexate was 0.68 (95% confidence interval, 0.48-0.95; P = .05).

Patients with two or more comorbidities, including hypertension, cancer, chronic obstructive pulmonary disease, and diabetes, were even less likely to continue to need to take methotrexate (OR, 0.48; 95% CI, 0.29-0.80; P = .01).

"This suggests the clinical efficacy of adalimumab in RA disease control across a medically diverse patient population," noted Dr. Furst.

In a second, independent study from CORRONA, Dr. Allan Gibofsky, professor of medicine and public health at Cornell University and professor of law at Fordham University, both in New York, looked at 1,639 patients who initiated adalimumab therapy over the same time period and who had at least one follow-up visit on record.

Dr. Gibofsky found that 1,003 of these patients eventually discontinued adalimumab after a median of 632 days, according to a Kaplan-Meier estimate; 1,358 experienced some form of treatment change (including discontinuation, but also dosing/frequency changes or addition of another disease-modifying antirheumatic drug).

In this analysis, while use of a prior biologic was highly predictive of regimen change (hazard ratio, 1.532; CI, 1.259-1.864; P less than .0001), use of methotrexate at adalimumab initiation was associated with a significantly decreased likelihood of adalimumab treatment change (HR, 0.88; CI, 0.835-0.919; P less than .0001).

Finally, a third CORRONA-based study presented at the meeting confirmed that combination therapy with methotrexate and tumor necrosis factor–inhibitors like adalimumab is increasing.

Dr. Deborah Wenkert of Amgen Inc., based in Thousand Oaks, Calif., and her colleagues looked at the prevalence of combination therapy over two time periods: 2002-2004 and 2007-2009.

She found that the mean clinical disease activity index (CDAI) at initiation of combination therapy was significantly lower during the later time period, versus the earlier, and that "among all RA patients with 2 years of follow-up, a higher percentage of patients initiated combination therapy in 2007-2009 than 2002-2004 in each maximum CDAI category."

The trend could reflect "stricter definition and implementation of aggressive treatment goals in the later time periods," Dr. Wenkert added.

All investigators disclosed multiple relationships to pharmaceutical makers, including the makers of adalimumab.

WASHINGTON – Use of adalimumab in combination with another drug, usually methotrexate, seems to boost treatment response to such an extent that patients with rheumatoid arthritis can sometimes be tapered off one or both drugs over the subsequent 2 years.

Those are the findings of three separate posters that were based on data from the CORRONA (Consortium of Rheumatology Researchers of North America) registry – a multicenter, longitudinal, prospective database in the United States with more than 30,000 patients.

The studies were presented on Nov. 11 at the annual meeting of the American College of Rheumatology.

In the first study, led by Dr. Daniel E. Furst, Carl M. Pearson Professor of Medicine at the University of California, Los Angeles, the researchers looked at RA patients enrolled in CORRONA between March 2002 and September 2011 who initiated adalimumab treatment and had at least one follow-up visit on record.

The researchers assessed 417 patients with 2 years of follow-up, a mean age of 54.2 years, and a mean disease duration of 10.1 years; most (79.3%) were female.

Overall, 67% of patients were treated concurrently with methotrexate upon adalimumab initiation, but at 2 years, the odds ratio for concomitant methotrexate was 0.68 (95% confidence interval, 0.48-0.95; P = .05).

Patients with two or more comorbidities, including hypertension, cancer, chronic obstructive pulmonary disease, and diabetes, were even less likely to continue to need to take methotrexate (OR, 0.48; 95% CI, 0.29-0.80; P = .01).

"This suggests the clinical efficacy of adalimumab in RA disease control across a medically diverse patient population," noted Dr. Furst.

In a second, independent study from CORRONA, Dr. Allan Gibofsky, professor of medicine and public health at Cornell University and professor of law at Fordham University, both in New York, looked at 1,639 patients who initiated adalimumab therapy over the same time period and who had at least one follow-up visit on record.

Dr. Gibofsky found that 1,003 of these patients eventually discontinued adalimumab after a median of 632 days, according to a Kaplan-Meier estimate; 1,358 experienced some form of treatment change (including discontinuation, but also dosing/frequency changes or addition of another disease-modifying antirheumatic drug).

In this analysis, while use of a prior biologic was highly predictive of regimen change (hazard ratio, 1.532; CI, 1.259-1.864; P less than .0001), use of methotrexate at adalimumab initiation was associated with a significantly decreased likelihood of adalimumab treatment change (HR, 0.88; CI, 0.835-0.919; P less than .0001).

Finally, a third CORRONA-based study presented at the meeting confirmed that combination therapy with methotrexate and tumor necrosis factor–inhibitors like adalimumab is increasing.

Dr. Deborah Wenkert of Amgen Inc., based in Thousand Oaks, Calif., and her colleagues looked at the prevalence of combination therapy over two time periods: 2002-2004 and 2007-2009.

She found that the mean clinical disease activity index (CDAI) at initiation of combination therapy was significantly lower during the later time period, versus the earlier, and that "among all RA patients with 2 years of follow-up, a higher percentage of patients initiated combination therapy in 2007-2009 than 2002-2004 in each maximum CDAI category."

The trend could reflect "stricter definition and implementation of aggressive treatment goals in the later time periods," Dr. Wenkert added.

All investigators disclosed multiple relationships to pharmaceutical makers, including the makers of adalimumab.

WASHINGTON – Ulcers of the lower leg and foot occurred at an incidence of 1% per year among people with rheumatoid arthritis, with the rate having doubled over the last few years, according to findings from a retrospective assessment of a population-based incidence cohort in Olmstead County, Minn.

The study cohort all met the 1987 American College of Rheumatology criteria for rheumatoid arthritis (RA) in 1980-2007. The cohort included 813 people with RA, said Dr. Adlene Jebakumar during her presentation at the annual meeting of the American College of Rheumatology. Of these, 66% were positive for rheumatoid factor, 53% had erosive joint disease, and 33% had rheumatoid nodules, all markers of severe disease.

During 9,771 total person-years of follow-up, there were 171 episodes of leg and/or foot ulcers in 125 of these people. These cases did not include ulcers resulting from animal bites, surgery, burns, biopsy, cellulitis, ingrown toenails, toenail removal, abrasion, foreign body, or herpes zoster.

Patients’ mean age at first ulcer onset was 73.5 years, and 74% were female.

The area between the ankle and knee was the most common location for ulcers (58 ulcers, 34%), followed by the tips of the toes (46 ulcers, 27%).

The major etiology was pressure (62 ulcers, 36%) or trauma (49 ulcers, 27%). Another 22 ulcers (13%) were ischemic, and 2 (1%) were vasculitic, reported Dr. Jebakumar of the division of rheumatology at the Mayo Clinic in Rochester, Minn.

The incidence of lower leg and foot ulcers was higher among patients diagnosed with RA in 1995-2007, compared with those diagnosed in 1980-1994 (hazard ratio, 2.03; P less than .001). The median time for the lower leg and foot ulcers to heal was 30 days. Ten (6%) of 171 episodes led to amputation. Lower leg and foot ulcers in RA were associated with increased mortality (HR, 2.42; P less than .001), adjusted for age, sex, and calendar year.

The risk factors for lower extremity ulcers in RA were age (HR, 1.90/10-year increase; P less than .001); current smoking (HR, 1.51; P = .048); diabetes mellitus (HR, 1.65; P =.015); coronary heart disease or heart failure (HR, 1.56; P less than .035); presence of rheumatoid nodules (HR, 1.64; P = .010); ESR of 60 mm/hr or greater on three occasions (HR, 1.78; P = .022); venous thromboembolism (HR, 2.08; P = .014); and severe extra-articular manifestations (HR, 1.67; P = .048). The patients on corticosteroid therapy accounted for 79 (46%) of 171 ulcer episodes.

Dr. Eric L. Matteson said in an interview that the incidence of leg and foot ulcers in RA patients should not come as a surprise. "Leg ulcers are a real big problem in RA because these patients have increased cardiovascular disease and peripheral artery disease. Lots of ulcers are due to poor circulation. And long-term high-dose steroids sometimes used to treat RA patients may contribute to that."

The situation is made worse in elderly patients who become sedentary in response to lower-extremity RA-related pain, he added.

"The best prevention of lower extremity ulcers is to have RA under control," said Dr. Matteson, chair of the department of rheumatology at the Mayo Clinic. And treat ulcers early in their course, when they are small, he noted, adding that patients need to be told to seek care early rather than wait until the ulcers have become large and harder to heal.

Another important aspect of prevention is harder to do than it sounds: "Keep patients active," Dr. Matteson advised.

Dr. Jebakumar and Dr. Matteson reported having no relevant financial conflicts of interest

WASHINGTON – Ulcers of the lower leg and foot occurred at an incidence of 1% per year among people with rheumatoid arthritis, with the rate having doubled over the last few years, according to findings from a retrospective assessment of a population-based incidence cohort in Olmstead County, Minn.

The study cohort all met the 1987 American College of Rheumatology criteria for rheumatoid arthritis (RA) in 1980-2007. The cohort included 813 people with RA, said Dr. Adlene Jebakumar during her presentation at the annual meeting of the American College of Rheumatology. Of these, 66% were positive for rheumatoid factor, 53% had erosive joint disease, and 33% had rheumatoid nodules, all markers of severe disease.

During 9,771 total person-years of follow-up, there were 171 episodes of leg and/or foot ulcers in 125 of these people. These cases did not include ulcers resulting from animal bites, surgery, burns, biopsy, cellulitis, ingrown toenails, toenail removal, abrasion, foreign body, or herpes zoster.

Patients’ mean age at first ulcer onset was 73.5 years, and 74% were female.

The area between the ankle and knee was the most common location for ulcers (58 ulcers, 34%), followed by the tips of the toes (46 ulcers, 27%).

The major etiology was pressure (62 ulcers, 36%) or trauma (49 ulcers, 27%). Another 22 ulcers (13%) were ischemic, and 2 (1%) were vasculitic, reported Dr. Jebakumar of the division of rheumatology at the Mayo Clinic in Rochester, Minn.

The incidence of lower leg and foot ulcers was higher among patients diagnosed with RA in 1995-2007, compared with those diagnosed in 1980-1994 (hazard ratio, 2.03; P less than .001). The median time for the lower leg and foot ulcers to heal was 30 days. Ten (6%) of 171 episodes led to amputation. Lower leg and foot ulcers in RA were associated with increased mortality (HR, 2.42; P less than .001), adjusted for age, sex, and calendar year.

The risk factors for lower extremity ulcers in RA were age (HR, 1.90/10-year increase; P less than .001); current smoking (HR, 1.51; P = .048); diabetes mellitus (HR, 1.65; P =.015); coronary heart disease or heart failure (HR, 1.56; P less than .035); presence of rheumatoid nodules (HR, 1.64; P = .010); ESR of 60 mm/hr or greater on three occasions (HR, 1.78; P = .022); venous thromboembolism (HR, 2.08; P = .014); and severe extra-articular manifestations (HR, 1.67; P = .048). The patients on corticosteroid therapy accounted for 79 (46%) of 171 ulcer episodes.

Dr. Eric L. Matteson said in an interview that the incidence of leg and foot ulcers in RA patients should not come as a surprise. "Leg ulcers are a real big problem in RA because these patients have increased cardiovascular disease and peripheral artery disease. Lots of ulcers are due to poor circulation. And long-term high-dose steroids sometimes used to treat RA patients may contribute to that."

The situation is made worse in elderly patients who become sedentary in response to lower-extremity RA-related pain, he added.

"The best prevention of lower extremity ulcers is to have RA under control," said Dr. Matteson, chair of the department of rheumatology at the Mayo Clinic. And treat ulcers early in their course, when they are small, he noted, adding that patients need to be told to seek care early rather than wait until the ulcers have become large and harder to heal.

Another important aspect of prevention is harder to do than it sounds: "Keep patients active," Dr. Matteson advised.

Dr. Jebakumar and Dr. Matteson reported having no relevant financial conflicts of interest

WASHINGTON – Ulcers of the lower leg and foot occurred at an incidence of 1% per year among people with rheumatoid arthritis, with the rate having doubled over the last few years, according to findings from a retrospective assessment of a population-based incidence cohort in Olmstead County, Minn.

The study cohort all met the 1987 American College of Rheumatology criteria for rheumatoid arthritis (RA) in 1980-2007. The cohort included 813 people with RA, said Dr. Adlene Jebakumar during her presentation at the annual meeting of the American College of Rheumatology. Of these, 66% were positive for rheumatoid factor, 53% had erosive joint disease, and 33% had rheumatoid nodules, all markers of severe disease.

During 9,771 total person-years of follow-up, there were 171 episodes of leg and/or foot ulcers in 125 of these people. These cases did not include ulcers resulting from animal bites, surgery, burns, biopsy, cellulitis, ingrown toenails, toenail removal, abrasion, foreign body, or herpes zoster.

Patients’ mean age at first ulcer onset was 73.5 years, and 74% were female.

The area between the ankle and knee was the most common location for ulcers (58 ulcers, 34%), followed by the tips of the toes (46 ulcers, 27%).

The major etiology was pressure (62 ulcers, 36%) or trauma (49 ulcers, 27%). Another 22 ulcers (13%) were ischemic, and 2 (1%) were vasculitic, reported Dr. Jebakumar of the division of rheumatology at the Mayo Clinic in Rochester, Minn.

The incidence of lower leg and foot ulcers was higher among patients diagnosed with RA in 1995-2007, compared with those diagnosed in 1980-1994 (hazard ratio, 2.03; P less than .001). The median time for the lower leg and foot ulcers to heal was 30 days. Ten (6%) of 171 episodes led to amputation. Lower leg and foot ulcers in RA were associated with increased mortality (HR, 2.42; P less than .001), adjusted for age, sex, and calendar year.

The risk factors for lower extremity ulcers in RA were age (HR, 1.90/10-year increase; P less than .001); current smoking (HR, 1.51; P = .048); diabetes mellitus (HR, 1.65; P =.015); coronary heart disease or heart failure (HR, 1.56; P less than .035); presence of rheumatoid nodules (HR, 1.64; P = .010); ESR of 60 mm/hr or greater on three occasions (HR, 1.78; P = .022); venous thromboembolism (HR, 2.08; P = .014); and severe extra-articular manifestations (HR, 1.67; P = .048). The patients on corticosteroid therapy accounted for 79 (46%) of 171 ulcer episodes.

Dr. Eric L. Matteson said in an interview that the incidence of leg and foot ulcers in RA patients should not come as a surprise. "Leg ulcers are a real big problem in RA because these patients have increased cardiovascular disease and peripheral artery disease. Lots of ulcers are due to poor circulation. And long-term high-dose steroids sometimes used to treat RA patients may contribute to that."

The situation is made worse in elderly patients who become sedentary in response to lower-extremity RA-related pain, he added.

"The best prevention of lower extremity ulcers is to have RA under control," said Dr. Matteson, chair of the department of rheumatology at the Mayo Clinic. And treat ulcers early in their course, when they are small, he noted, adding that patients need to be told to seek care early rather than wait until the ulcers have become large and harder to heal.

Another important aspect of prevention is harder to do than it sounds: "Keep patients active," Dr. Matteson advised.

Dr. Jebakumar and Dr. Matteson reported having no relevant financial conflicts of interest

The new oral janus kinase inhibitor approved on Nov. 6 by the Food and Drug Administration is likely to be embraced by those rheumatoid arthritis patients who have found infection and infusions of biologics to be needling.

The Janus kinase inhibitor (JAK) tofacitinib, a drug that has the promise to change the treatment experience for some patients with rheumatoid arthritis (RA), has been approved to treat adults with moderately to severely active disease who have not responded adequately to or cannot tolerate methotrexate.

Tofacitinib is a small-molecule inhibitor of the JAK pathway of inflammatory cytokines that play a role in the pathogenesis of RA, and is the first drug in this class of oral drugs to be approved for RA.

Dr. Eric L. Matteson said in an interview that he plans to offer this drug to patients with active disease. While some patients may embrace the idea of taking a pill, those who do not mind the needles because of their convenience and efficiency may opt to stay on their injected therapy. Of the nine biologic agents on the market currently for RA, four are infused and the others either are taken as subcutaneous injections or self-administered subcutaneously via a prefilled syringe. One of the four infused drugs is available as a prefilled self-administered syringe as well, with another biologic maker about to launch such a product.

Dr. Larry Greenbaum, a rheumatologist in Greenwood, Ind., recalled that before the introduction of biologics, "I thought patients would never accept parenteral medications, but almost all of them do accept these medications when they see how well they work. A pill will certainly be more welcome than an injection for most patients. But the Enbrel SureClick and the Humira Pen are very easy to use, so I don’t think patients are going to be breaking down the doors demanding this medication just so they don’t have to give themselves an injection!"

When asked where the new JAK inhibitor would fit into his own therapeutic lineup, Dr. Greenbaum noted that "the number of biologic medications is increasing all the time, and my conservative approach is usually to park the new medication at the bottom of the treatment algorithm until I have some compelling reason to use it sooner. No matter how good this medication is, it will have some very stiff competition from the available biologic drugs that work well and have long clinical track records."

In contrast, Dr. Karmela K. Chan, a rheumatologist in Pawtucket, R.I., said, "I definitely have patients who are completely opposed to any kind of injection, and, given a choice, they would rather take an oral drug. Several patients have asked me about switching from their injectable drug to an oral drug that they\'d already heard of.

"I don’t think I will switch most patients over. If something works, I tend not to want to mess with it. For new patients, I suspect my pitch will still be for the anti-TNF agent. I feel it is prudent to use agents that have been around longer. Another question will be how much more comfortable we are with how much information we have about potential adverse effects. However, I will most likely also present the option of the oral drug."

And then there is cost.

The JAK inhibitor will be expensive, just as the currently available biologic agents are. Pfizer has said that the recommended regimen of one 5-mg tablet twice a day will be priced at $2,000 a month, according to Dr. Matteson, chair of rheumatology and professor of medicine at the Mayo Clinic Medical School in Rochester, Minn. He noted that Pfizer is already offering a program to help patients cover their share of the copayment for the new drug.

Dr. Chan said that "without a doubt the cost will be an issue for patients. Cost of drug, side effect potential, efficaciousness, and convenience all factor into patients’ decisions.

"Also, yes, in our practice, I have been told multiple times that I could make more money if I put more people on infusions. We can buy and bill so we make more money that way, plus we make money off just the service of the infusion. But I think this issue of making money from infusions will perhaps not pass muster too much longer for the following reasons: Ethical physicians won’t infuse just to infuse (one would hope), and I think in the coming years fewer insurers will allow buy and bill. On top of that, I am not sure if Medicare reimbursement rates for the infusion service will change."

Dr. Matteson noted that the drug, to be marketed as Xeljanz, has shown efficacy compared with placebo in a number of studies considered by the Food and Drug Administration (FDA). The drug inhibits the protein kinase, which is important in cell-to-cell interaction and may be how the drug acts to decrease inflammation.

Only time will tell whether that decrease in inflammation will translate into reduced joint damage in RA patients or even into decreased risk for extra-articular manifestations of the disease, including cardiovascular disease, lung disease, and eye disease.

Treatment with anti–tumor necrosis factor (anti-TNF) drugs has been shown to lower the risk for cardiovascular disease associated with RA. But it took 5 years of post-marketing surveillance before rheumatologists began to recognize that benefit. Any similar effect with the JAK inhibitor may take just as long to become apparent, said Dr. Matteson.

In order to detect any effects, the FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) that addresses the serious risks associated with treatment, and a requirement that the manufacturer, Pfizer, conduct a post-marketing study, according to the FDA’s statement announcing the approval.

Dr. Matteson noted that safety and efficacy trials of the drugs showed that two common side effects were headaches and diarrhea, severe enough to cause the patient to discontinue the drug.

Approval was based on the results of seven studies, which found that patients with moderately to severely active RA had improvements in clinical response and physical functioning, when compared with those on placebo. Tofacitinib was associated with an increased risk of serious infections, including opportunistic infections; tuberculosis; cancers; and lymphoma, which are described in the boxed warning in the drug’s label, the FDA said.

Treatment was also associated with increases in cholesterol and liver enzymes, and decreased blood counts. The REMS consists of a Medication Guide that includes information for patients about the drug’s safety and a communication plan that will educate health care providers about the serious risks associated with the treatment.

The post-marketing study will compare two doses of tofacitinib with another approved treatment for RA.

At a meeting in May, the FDA’s Arthritis Advisory Committee voted 8 to 2 to recommend approval of tofacitinib for patients with RA, although panel members had lingering safety concerns.

Another JAK inhibitor, ruxolitinib (Jakafi), was approved to treat myelofibrosis in 2011.

The new oral janus kinase inhibitor approved on Nov. 6 by the Food and Drug Administration is likely to be embraced by those rheumatoid arthritis patients who have found infection and infusions of biologics to be needling.

The Janus kinase inhibitor (JAK) tofacitinib, a drug that has the promise to change the treatment experience for some patients with rheumatoid arthritis (RA), has been approved to treat adults with moderately to severely active disease who have not responded adequately to or cannot tolerate methotrexate.

Tofacitinib is a small-molecule inhibitor of the JAK pathway of inflammatory cytokines that play a role in the pathogenesis of RA, and is the first drug in this class of oral drugs to be approved for RA.

Dr. Eric L. Matteson said in an interview that he plans to offer this drug to patients with active disease. While some patients may embrace the idea of taking a pill, those who do not mind the needles because of their convenience and efficiency may opt to stay on their injected therapy. Of the nine biologic agents on the market currently for RA, four are infused and the others either are taken as subcutaneous injections or self-administered subcutaneously via a prefilled syringe. One of the four infused drugs is available as a prefilled self-administered syringe as well, with another biologic maker about to launch such a product.

Dr. Larry Greenbaum, a rheumatologist in Greenwood, Ind., recalled that before the introduction of biologics, "I thought patients would never accept parenteral medications, but almost all of them do accept these medications when they see how well they work. A pill will certainly be more welcome than an injection for most patients. But the Enbrel SureClick and the Humira Pen are very easy to use, so I don’t think patients are going to be breaking down the doors demanding this medication just so they don’t have to give themselves an injection!"

When asked where the new JAK inhibitor would fit into his own therapeutic lineup, Dr. Greenbaum noted that "the number of biologic medications is increasing all the time, and my conservative approach is usually to park the new medication at the bottom of the treatment algorithm until I have some compelling reason to use it sooner. No matter how good this medication is, it will have some very stiff competition from the available biologic drugs that work well and have long clinical track records."

In contrast, Dr. Karmela K. Chan, a rheumatologist in Pawtucket, R.I., said, "I definitely have patients who are completely opposed to any kind of injection, and, given a choice, they would rather take an oral drug. Several patients have asked me about switching from their injectable drug to an oral drug that they\'d already heard of.

"I don’t think I will switch most patients over. If something works, I tend not to want to mess with it. For new patients, I suspect my pitch will still be for the anti-TNF agent. I feel it is prudent to use agents that have been around longer. Another question will be how much more comfortable we are with how much information we have about potential adverse effects. However, I will most likely also present the option of the oral drug."

And then there is cost.

The JAK inhibitor will be expensive, just as the currently available biologic agents are. Pfizer has said that the recommended regimen of one 5-mg tablet twice a day will be priced at $2,000 a month, according to Dr. Matteson, chair of rheumatology and professor of medicine at the Mayo Clinic Medical School in Rochester, Minn. He noted that Pfizer is already offering a program to help patients cover their share of the copayment for the new drug.

Dr. Chan said that "without a doubt the cost will be an issue for patients. Cost of drug, side effect potential, efficaciousness, and convenience all factor into patients’ decisions.

"Also, yes, in our practice, I have been told multiple times that I could make more money if I put more people on infusions. We can buy and bill so we make more money that way, plus we make money off just the service of the infusion. But I think this issue of making money from infusions will perhaps not pass muster too much longer for the following reasons: Ethical physicians won’t infuse just to infuse (one would hope), and I think in the coming years fewer insurers will allow buy and bill. On top of that, I am not sure if Medicare reimbursement rates for the infusion service will change."

Dr. Matteson noted that the drug, to be marketed as Xeljanz, has shown efficacy compared with placebo in a number of studies considered by the Food and Drug Administration (FDA). The drug inhibits the protein kinase, which is important in cell-to-cell interaction and may be how the drug acts to decrease inflammation.

Only time will tell whether that decrease in inflammation will translate into reduced joint damage in RA patients or even into decreased risk for extra-articular manifestations of the disease, including cardiovascular disease, lung disease, and eye disease.

Treatment with anti–tumor necrosis factor (anti-TNF) drugs has been shown to lower the risk for cardiovascular disease associated with RA. But it took 5 years of post-marketing surveillance before rheumatologists began to recognize that benefit. Any similar effect with the JAK inhibitor may take just as long to become apparent, said Dr. Matteson.

In order to detect any effects, the FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) that addresses the serious risks associated with treatment, and a requirement that the manufacturer, Pfizer, conduct a post-marketing study, according to the FDA’s statement announcing the approval.

Dr. Matteson noted that safety and efficacy trials of the drugs showed that two common side effects were headaches and diarrhea, severe enough to cause the patient to discontinue the drug.

Approval was based on the results of seven studies, which found that patients with moderately to severely active RA had improvements in clinical response and physical functioning, when compared with those on placebo. Tofacitinib was associated with an increased risk of serious infections, including opportunistic infections; tuberculosis; cancers; and lymphoma, which are described in the boxed warning in the drug’s label, the FDA said.

Treatment was also associated with increases in cholesterol and liver enzymes, and decreased blood counts. The REMS consists of a Medication Guide that includes information for patients about the drug’s safety and a communication plan that will educate health care providers about the serious risks associated with the treatment.

The post-marketing study will compare two doses of tofacitinib with another approved treatment for RA.

At a meeting in May, the FDA’s Arthritis Advisory Committee voted 8 to 2 to recommend approval of tofacitinib for patients with RA, although panel members had lingering safety concerns.

Another JAK inhibitor, ruxolitinib (Jakafi), was approved to treat myelofibrosis in 2011.

The new oral janus kinase inhibitor approved on Nov. 6 by the Food and Drug Administration is likely to be embraced by those rheumatoid arthritis patients who have found infection and infusions of biologics to be needling.

The Janus kinase inhibitor (JAK) tofacitinib, a drug that has the promise to change the treatment experience for some patients with rheumatoid arthritis (RA), has been approved to treat adults with moderately to severely active disease who have not responded adequately to or cannot tolerate methotrexate.

Tofacitinib is a small-molecule inhibitor of the JAK pathway of inflammatory cytokines that play a role in the pathogenesis of RA, and is the first drug in this class of oral drugs to be approved for RA.

Dr. Eric L. Matteson said in an interview that he plans to offer this drug to patients with active disease. While some patients may embrace the idea of taking a pill, those who do not mind the needles because of their convenience and efficiency may opt to stay on their injected therapy. Of the nine biologic agents on the market currently for RA, four are infused and the others either are taken as subcutaneous injections or self-administered subcutaneously via a prefilled syringe. One of the four infused drugs is available as a prefilled self-administered syringe as well, with another biologic maker about to launch such a product.

Dr. Larry Greenbaum, a rheumatologist in Greenwood, Ind., recalled that before the introduction of biologics, "I thought patients would never accept parenteral medications, but almost all of them do accept these medications when they see how well they work. A pill will certainly be more welcome than an injection for most patients. But the Enbrel SureClick and the Humira Pen are very easy to use, so I don’t think patients are going to be breaking down the doors demanding this medication just so they don’t have to give themselves an injection!"

When asked where the new JAK inhibitor would fit into his own therapeutic lineup, Dr. Greenbaum noted that "the number of biologic medications is increasing all the time, and my conservative approach is usually to park the new medication at the bottom of the treatment algorithm until I have some compelling reason to use it sooner. No matter how good this medication is, it will have some very stiff competition from the available biologic drugs that work well and have long clinical track records."

In contrast, Dr. Karmela K. Chan, a rheumatologist in Pawtucket, R.I., said, "I definitely have patients who are completely opposed to any kind of injection, and, given a choice, they would rather take an oral drug. Several patients have asked me about switching from their injectable drug to an oral drug that they\'d already heard of.

"I don’t think I will switch most patients over. If something works, I tend not to want to mess with it. For new patients, I suspect my pitch will still be for the anti-TNF agent. I feel it is prudent to use agents that have been around longer. Another question will be how much more comfortable we are with how much information we have about potential adverse effects. However, I will most likely also present the option of the oral drug."

And then there is cost.

The JAK inhibitor will be expensive, just as the currently available biologic agents are. Pfizer has said that the recommended regimen of one 5-mg tablet twice a day will be priced at $2,000 a month, according to Dr. Matteson, chair of rheumatology and professor of medicine at the Mayo Clinic Medical School in Rochester, Minn. He noted that Pfizer is already offering a program to help patients cover their share of the copayment for the new drug.

Dr. Chan said that "without a doubt the cost will be an issue for patients. Cost of drug, side effect potential, efficaciousness, and convenience all factor into patients’ decisions.

"Also, yes, in our practice, I have been told multiple times that I could make more money if I put more people on infusions. We can buy and bill so we make more money that way, plus we make money off just the service of the infusion. But I think this issue of making money from infusions will perhaps not pass muster too much longer for the following reasons: Ethical physicians won’t infuse just to infuse (one would hope), and I think in the coming years fewer insurers will allow buy and bill. On top of that, I am not sure if Medicare reimbursement rates for the infusion service will change."

Dr. Matteson noted that the drug, to be marketed as Xeljanz, has shown efficacy compared with placebo in a number of studies considered by the Food and Drug Administration (FDA). The drug inhibits the protein kinase, which is important in cell-to-cell interaction and may be how the drug acts to decrease inflammation.

Only time will tell whether that decrease in inflammation will translate into reduced joint damage in RA patients or even into decreased risk for extra-articular manifestations of the disease, including cardiovascular disease, lung disease, and eye disease.

Treatment with anti–tumor necrosis factor (anti-TNF) drugs has been shown to lower the risk for cardiovascular disease associated with RA. But it took 5 years of post-marketing surveillance before rheumatologists began to recognize that benefit. Any similar effect with the JAK inhibitor may take just as long to become apparent, said Dr. Matteson.

In order to detect any effects, the FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) that addresses the serious risks associated with treatment, and a requirement that the manufacturer, Pfizer, conduct a post-marketing study, according to the FDA’s statement announcing the approval.

Dr. Matteson noted that safety and efficacy trials of the drugs showed that two common side effects were headaches and diarrhea, severe enough to cause the patient to discontinue the drug.

Approval was based on the results of seven studies, which found that patients with moderately to severely active RA had improvements in clinical response and physical functioning, when compared with those on placebo. Tofacitinib was associated with an increased risk of serious infections, including opportunistic infections; tuberculosis; cancers; and lymphoma, which are described in the boxed warning in the drug’s label, the FDA said.

Treatment was also associated with increases in cholesterol and liver enzymes, and decreased blood counts. The REMS consists of a Medication Guide that includes information for patients about the drug’s safety and a communication plan that will educate health care providers about the serious risks associated with the treatment.

The post-marketing study will compare two doses of tofacitinib with another approved treatment for RA.

At a meeting in May, the FDA’s Arthritis Advisory Committee voted 8 to 2 to recommend approval of tofacitinib for patients with RA, although panel members had lingering safety concerns.

Another JAK inhibitor, ruxolitinib (Jakafi), was approved to treat myelofibrosis in 2011.