Rheumatoid Arthritis

WASHINGTON – The risk of infection following orthopedic surgery is increased in patients with inflammatory rheumatic disease, compared with those with degenerative disease or traumatic injury, according to findings from a review of more than 50,000 surgical procedures.

The risk is greatest in those inflammatory rheumatic disease patients treated with conventional disease-modifying anti-rheumatic drugs (cDMARDs) or tumor necrosis factor (TNF) inhibitors, especially those receiving more than one cDMARD or TNF inhibitor with a long administration interval, and when surgery takes place without discontinuation of treatment, Catrina B. Scherrer reported at the annual meeting of the American College of Rheumatology.

Of 50,359 surgical procedures performed in 37,137 patients from a hospital surgery registry, 422 resulted in surgery-related infections. Of these infections, 49 occurred in 2,472 patients with an inflammatory rheumatic disease (IRD; 2%), and 373 occurred in 47,887 patients with degenerative disease/posttraumatic injury (0.8%). The difference was statistically significant, even after adjustment for other risk factors, including age, gender, diabetes, being overweight, cardiovascular disease, smoking, and type of surgery, said Ms. Scherrer of the Schulthess Clinic, Zürich.

The lowest rates of infection occurred with hand and shoulder surgery; the highest rates occurred with elbow surgery, she noted.

In 1,329 patients in the IRD group for whom complete information about medication was available, 171 (13%) had documented use of TNF inhibitors, and 49 of these (29%) discontinued treatment more than three administration intervals before surgery. Of the remaining 122 TNF inhibitor users, the time lag was three or fewer administration intervals.

An increased infection rate was seen in those who used more than one cDMARD (odds ratio, 2.425) and more than one TNF inhibitor (OR, 2.627) prior to surgery, and the risk of infection was increased tenfold when surgery was performed within one administration interval (OR, 10.047).

Patients who had their last treatment within one administration interval before surgery included 81% of infliximab users, compared with only 33% of adalimumab users and 24% of etanercept users, Ms. Scherrer noted.

Surgery patients in this study were followed over 8 years as part of a single-center surgery registry. The findings, which are limited by the study’s retrospective design and thus require confirmation in prospective studies, are nonetheless important because patients with aggressive disease such as IRDs frequently require orthopedic surgery.

The study findings suggest that IRD patients are, in general, at high risk of postoperative infection, that special attention should be paid to patients using more than one cDMARD or TNF inhibitor with long administration intervals, and that the last intake of TNF inhibitors – particularly infliximab – should be at least more than one administration interval before planned surgery, as the risk of postoperative infection is significantly increased if surgery occurs within this period, she concluded.

Ms. Scherrer reported having no disclosures.

WASHINGTON – The risk of infection following orthopedic surgery is increased in patients with inflammatory rheumatic disease, compared with those with degenerative disease or traumatic injury, according to findings from a review of more than 50,000 surgical procedures.

The risk is greatest in those inflammatory rheumatic disease patients treated with conventional disease-modifying anti-rheumatic drugs (cDMARDs) or tumor necrosis factor (TNF) inhibitors, especially those receiving more than one cDMARD or TNF inhibitor with a long administration interval, and when surgery takes place without discontinuation of treatment, Catrina B. Scherrer reported at the annual meeting of the American College of Rheumatology.

Of 50,359 surgical procedures performed in 37,137 patients from a hospital surgery registry, 422 resulted in surgery-related infections. Of these infections, 49 occurred in 2,472 patients with an inflammatory rheumatic disease (IRD; 2%), and 373 occurred in 47,887 patients with degenerative disease/posttraumatic injury (0.8%). The difference was statistically significant, even after adjustment for other risk factors, including age, gender, diabetes, being overweight, cardiovascular disease, smoking, and type of surgery, said Ms. Scherrer of the Schulthess Clinic, Zürich.

The lowest rates of infection occurred with hand and shoulder surgery; the highest rates occurred with elbow surgery, she noted.

In 1,329 patients in the IRD group for whom complete information about medication was available, 171 (13%) had documented use of TNF inhibitors, and 49 of these (29%) discontinued treatment more than three administration intervals before surgery. Of the remaining 122 TNF inhibitor users, the time lag was three or fewer administration intervals.

An increased infection rate was seen in those who used more than one cDMARD (odds ratio, 2.425) and more than one TNF inhibitor (OR, 2.627) prior to surgery, and the risk of infection was increased tenfold when surgery was performed within one administration interval (OR, 10.047).

Patients who had their last treatment within one administration interval before surgery included 81% of infliximab users, compared with only 33% of adalimumab users and 24% of etanercept users, Ms. Scherrer noted.

Surgery patients in this study were followed over 8 years as part of a single-center surgery registry. The findings, which are limited by the study’s retrospective design and thus require confirmation in prospective studies, are nonetheless important because patients with aggressive disease such as IRDs frequently require orthopedic surgery.

The study findings suggest that IRD patients are, in general, at high risk of postoperative infection, that special attention should be paid to patients using more than one cDMARD or TNF inhibitor with long administration intervals, and that the last intake of TNF inhibitors – particularly infliximab – should be at least more than one administration interval before planned surgery, as the risk of postoperative infection is significantly increased if surgery occurs within this period, she concluded.

Ms. Scherrer reported having no disclosures.

WASHINGTON – The risk of infection following orthopedic surgery is increased in patients with inflammatory rheumatic disease, compared with those with degenerative disease or traumatic injury, according to findings from a review of more than 50,000 surgical procedures.

The risk is greatest in those inflammatory rheumatic disease patients treated with conventional disease-modifying anti-rheumatic drugs (cDMARDs) or tumor necrosis factor (TNF) inhibitors, especially those receiving more than one cDMARD or TNF inhibitor with a long administration interval, and when surgery takes place without discontinuation of treatment, Catrina B. Scherrer reported at the annual meeting of the American College of Rheumatology.

Of 50,359 surgical procedures performed in 37,137 patients from a hospital surgery registry, 422 resulted in surgery-related infections. Of these infections, 49 occurred in 2,472 patients with an inflammatory rheumatic disease (IRD; 2%), and 373 occurred in 47,887 patients with degenerative disease/posttraumatic injury (0.8%). The difference was statistically significant, even after adjustment for other risk factors, including age, gender, diabetes, being overweight, cardiovascular disease, smoking, and type of surgery, said Ms. Scherrer of the Schulthess Clinic, Zürich.

The lowest rates of infection occurred with hand and shoulder surgery; the highest rates occurred with elbow surgery, she noted.

In 1,329 patients in the IRD group for whom complete information about medication was available, 171 (13%) had documented use of TNF inhibitors, and 49 of these (29%) discontinued treatment more than three administration intervals before surgery. Of the remaining 122 TNF inhibitor users, the time lag was three or fewer administration intervals.

An increased infection rate was seen in those who used more than one cDMARD (odds ratio, 2.425) and more than one TNF inhibitor (OR, 2.627) prior to surgery, and the risk of infection was increased tenfold when surgery was performed within one administration interval (OR, 10.047).

Patients who had their last treatment within one administration interval before surgery included 81% of infliximab users, compared with only 33% of adalimumab users and 24% of etanercept users, Ms. Scherrer noted.

Surgery patients in this study were followed over 8 years as part of a single-center surgery registry. The findings, which are limited by the study’s retrospective design and thus require confirmation in prospective studies, are nonetheless important because patients with aggressive disease such as IRDs frequently require orthopedic surgery.

The study findings suggest that IRD patients are, in general, at high risk of postoperative infection, that special attention should be paid to patients using more than one cDMARD or TNF inhibitor with long administration intervals, and that the last intake of TNF inhibitors – particularly infliximab – should be at least more than one administration interval before planned surgery, as the risk of postoperative infection is significantly increased if surgery occurs within this period, she concluded.

Ms. Scherrer reported having no disclosures.

WASHINGTON – Autoantibody seronegativity may be the best predictor of which patients will achieve remission in rheumatoid arthritis, but the question of whether and when to withdraw treatment still looms.

"Drug-free remission is possible. Sustained remission is less common," Dr. Stanley Cohen said at the annual meeting of the American College of Rheumatology. "But certainly seronegativity seems to be a strong predictor of the likelihood of sustained remission."

Denise Napoli/IMNG Medical Media

First, Dr. Cohen of Metroplex Clinical Research Center, Dallas, cited several "prebiologic era" studies, including one 1996 randomized controlled trial of 285 patients who stopped nonbiological disease-modifying antirheumatic drug (DMARD) therapy after achieving the "quite stringent" 1981 ACR/ARA remission definitions for 1 year.

In that study, after the year of remission, patients were randomized to either placebo or to continue their treatment regimen: by 52 weeks, 38% of the placebo group had flared, compared with 22% of the continued therapy group (P = .002) (Lancet 1996;347:347-52).

The authors then looked at the predictors of maintaining remission.

"They determined that having rheumatoid factor activity [there were no CCP (cyclic citrullinated peptide) antibodies at that time] was a poor prognostic factor for maintaining remission," said Dr. Cohen.

"More aggressive treatment prior to remission also boded poorly for maintaining that remission," he noted.

A similar finding was seen with the Leiden Early Arthritis Clinic trial of 454 patients and the British Early Rheumatoid Arthritis Study (ERAS) of 895 patients, both reviewed in 2009.

Sustained drug-free remission was seen in 15% of the former cohort and in 9% in the latter. The absences of CCP autoantibodies and rheumatoid factor were the sole two independent predictors of remission in multivariate analysis (Arthritis Rheum. 2009;60:2262-71).

Having early disease also plays a role in the ability to withdraw treatment, Dr. Cohen said. He pointed to the COMET trial (Combination of Methotrexate and Etanercept in Active Early Rheumatoid Arthritis), which looked at etanercept plus methotrexate versus methotrexate alone in moderate-to-severe rheumatoid arthritis for a duration of 3-24 months.

"What I’m interested in is year 2," Dr. Cohen said, when 111 patients who were on methotrexate plus etanercept in year 1 stopped methotrexate (Arthritis Rheum. 2010;62:674-82).

"Compared to the group that continued etanercept plus methotrexate, the majority continued to be in DAS28 remission without methotrexate" at 2 years, he said. "So, in patients with very early disease, it looks like we can withdraw or simplify the therapy in a significant number of those patients."

Treatment withdrawal, however, also can be achieved in patients with more longstanding disease.

Dr. Cohen cited a 2003 long-term extension of a clinical registration trial in which 79 patients with very long and very severe disease (mean duration of disease, 14 years) received etanercept and methotrexate for a median of 44 months (Arthritis Rheum. 2003;48:1493-9).

Among the 36 patients assessed at 3 years, 30 (83%) were able to decrease their dosages of corticosteroids and 20 (56%) could stop corticosteroids altogether.

"This certainly follows what we see in the clinic, in that we can frequently lower our doses of corticosteroids or withdraw them," Dr. Cohen said.

"What about methotrexate?" he asked. At 3 years, the dosage of methotrexate was decreased in 41 of 66 patients (62%), and methotrexate therapy was discontinued in 19 patients (29%).

"We try to wean our therapy in the majority of these patients," said Dr. Cohen. "Some are successful, some are not."

Dr. Cohen stated that he had no disclosures related to this presentation; he previously disclosed relationships with Abbott Laboratories, Amgen, Astellas, Bristol-Myers Squibb, Janssen, Pfizer, and Roche.

WASHINGTON – Autoantibody seronegativity may be the best predictor of which patients will achieve remission in rheumatoid arthritis, but the question of whether and when to withdraw treatment still looms.

"Drug-free remission is possible. Sustained remission is less common," Dr. Stanley Cohen said at the annual meeting of the American College of Rheumatology. "But certainly seronegativity seems to be a strong predictor of the likelihood of sustained remission."

Denise Napoli/IMNG Medical Media

First, Dr. Cohen of Metroplex Clinical Research Center, Dallas, cited several "prebiologic era" studies, including one 1996 randomized controlled trial of 285 patients who stopped nonbiological disease-modifying antirheumatic drug (DMARD) therapy after achieving the "quite stringent" 1981 ACR/ARA remission definitions for 1 year.

In that study, after the year of remission, patients were randomized to either placebo or to continue their treatment regimen: by 52 weeks, 38% of the placebo group had flared, compared with 22% of the continued therapy group (P = .002) (Lancet 1996;347:347-52).

The authors then looked at the predictors of maintaining remission.

"They determined that having rheumatoid factor activity [there were no CCP (cyclic citrullinated peptide) antibodies at that time] was a poor prognostic factor for maintaining remission," said Dr. Cohen.

"More aggressive treatment prior to remission also boded poorly for maintaining that remission," he noted.

A similar finding was seen with the Leiden Early Arthritis Clinic trial of 454 patients and the British Early Rheumatoid Arthritis Study (ERAS) of 895 patients, both reviewed in 2009.

Sustained drug-free remission was seen in 15% of the former cohort and in 9% in the latter. The absences of CCP autoantibodies and rheumatoid factor were the sole two independent predictors of remission in multivariate analysis (Arthritis Rheum. 2009;60:2262-71).

Having early disease also plays a role in the ability to withdraw treatment, Dr. Cohen said. He pointed to the COMET trial (Combination of Methotrexate and Etanercept in Active Early Rheumatoid Arthritis), which looked at etanercept plus methotrexate versus methotrexate alone in moderate-to-severe rheumatoid arthritis for a duration of 3-24 months.

"What I’m interested in is year 2," Dr. Cohen said, when 111 patients who were on methotrexate plus etanercept in year 1 stopped methotrexate (Arthritis Rheum. 2010;62:674-82).

"Compared to the group that continued etanercept plus methotrexate, the majority continued to be in DAS28 remission without methotrexate" at 2 years, he said. "So, in patients with very early disease, it looks like we can withdraw or simplify the therapy in a significant number of those patients."

Treatment withdrawal, however, also can be achieved in patients with more longstanding disease.

Dr. Cohen cited a 2003 long-term extension of a clinical registration trial in which 79 patients with very long and very severe disease (mean duration of disease, 14 years) received etanercept and methotrexate for a median of 44 months (Arthritis Rheum. 2003;48:1493-9).

Among the 36 patients assessed at 3 years, 30 (83%) were able to decrease their dosages of corticosteroids and 20 (56%) could stop corticosteroids altogether.

"This certainly follows what we see in the clinic, in that we can frequently lower our doses of corticosteroids or withdraw them," Dr. Cohen said.

"What about methotrexate?" he asked. At 3 years, the dosage of methotrexate was decreased in 41 of 66 patients (62%), and methotrexate therapy was discontinued in 19 patients (29%).

"We try to wean our therapy in the majority of these patients," said Dr. Cohen. "Some are successful, some are not."

Dr. Cohen stated that he had no disclosures related to this presentation; he previously disclosed relationships with Abbott Laboratories, Amgen, Astellas, Bristol-Myers Squibb, Janssen, Pfizer, and Roche.

WASHINGTON – Autoantibody seronegativity may be the best predictor of which patients will achieve remission in rheumatoid arthritis, but the question of whether and when to withdraw treatment still looms.

"Drug-free remission is possible. Sustained remission is less common," Dr. Stanley Cohen said at the annual meeting of the American College of Rheumatology. "But certainly seronegativity seems to be a strong predictor of the likelihood of sustained remission."

Denise Napoli/IMNG Medical Media

First, Dr. Cohen of Metroplex Clinical Research Center, Dallas, cited several "prebiologic era" studies, including one 1996 randomized controlled trial of 285 patients who stopped nonbiological disease-modifying antirheumatic drug (DMARD) therapy after achieving the "quite stringent" 1981 ACR/ARA remission definitions for 1 year.

In that study, after the year of remission, patients were randomized to either placebo or to continue their treatment regimen: by 52 weeks, 38% of the placebo group had flared, compared with 22% of the continued therapy group (P = .002) (Lancet 1996;347:347-52).

The authors then looked at the predictors of maintaining remission.

"They determined that having rheumatoid factor activity [there were no CCP (cyclic citrullinated peptide) antibodies at that time] was a poor prognostic factor for maintaining remission," said Dr. Cohen.

"More aggressive treatment prior to remission also boded poorly for maintaining that remission," he noted.

A similar finding was seen with the Leiden Early Arthritis Clinic trial of 454 patients and the British Early Rheumatoid Arthritis Study (ERAS) of 895 patients, both reviewed in 2009.

Sustained drug-free remission was seen in 15% of the former cohort and in 9% in the latter. The absences of CCP autoantibodies and rheumatoid factor were the sole two independent predictors of remission in multivariate analysis (Arthritis Rheum. 2009;60:2262-71).

Having early disease also plays a role in the ability to withdraw treatment, Dr. Cohen said. He pointed to the COMET trial (Combination of Methotrexate and Etanercept in Active Early Rheumatoid Arthritis), which looked at etanercept plus methotrexate versus methotrexate alone in moderate-to-severe rheumatoid arthritis for a duration of 3-24 months.

"What I’m interested in is year 2," Dr. Cohen said, when 111 patients who were on methotrexate plus etanercept in year 1 stopped methotrexate (Arthritis Rheum. 2010;62:674-82).

"Compared to the group that continued etanercept plus methotrexate, the majority continued to be in DAS28 remission without methotrexate" at 2 years, he said. "So, in patients with very early disease, it looks like we can withdraw or simplify the therapy in a significant number of those patients."

Treatment withdrawal, however, also can be achieved in patients with more longstanding disease.

Dr. Cohen cited a 2003 long-term extension of a clinical registration trial in which 79 patients with very long and very severe disease (mean duration of disease, 14 years) received etanercept and methotrexate for a median of 44 months (Arthritis Rheum. 2003;48:1493-9).

Among the 36 patients assessed at 3 years, 30 (83%) were able to decrease their dosages of corticosteroids and 20 (56%) could stop corticosteroids altogether.

"This certainly follows what we see in the clinic, in that we can frequently lower our doses of corticosteroids or withdraw them," Dr. Cohen said.

"What about methotrexate?" he asked. At 3 years, the dosage of methotrexate was decreased in 41 of 66 patients (62%), and methotrexate therapy was discontinued in 19 patients (29%).

"We try to wean our therapy in the majority of these patients," said Dr. Cohen. "Some are successful, some are not."

Dr. Cohen stated that he had no disclosures related to this presentation; he previously disclosed relationships with Abbott Laboratories, Amgen, Astellas, Bristol-Myers Squibb, Janssen, Pfizer, and Roche.

WASHINGTON – Seropositivity for either rheumatoid factor or anti-cyclic citrullinated peptide was significantly associated with progressive joint damage in adults with established rheumatoid arthritis, based on a single-center, observational cohort study of 390 patients.

Most rheumatoid arthritis (RA) patients in clinical practice have established disease, but the predictors and proportion of disease progression in these patients has not been well studied, Dr. Siri Lillegraven of Diakonhjemmet Hospital in Oslo said at the annual meeting of the American College of Rheumatology.

Dr. Lillegraven and her colleagues reviewed data from BRASS (the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study). Joint damage was assessed using baseline and 2-year radiographic data for patients with disease duration of at least 5 years. The average age of the patients was 60 years, 84% were women, and 44% received biologic treatment in the form of disease-modifying antirheumatic drugs (DMARDs). The median disease duration was 17 years. Disease progression was defined as a change in Sharp/van der Heijde score of 1 or more units per year.

Overall, 44% of the patients showed disease progression after 2 years. A total of 68% of the patients were positive for both rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP), 16% were positive for either RF or anti-CCP, and 16% were negative for both.

Seropositivity was the only significant independent predictor of disease progression after controlling for factors including age, gender, body-mass index, smoking status, treatment, DMARD use, disease duration, and presence of subcutaneous nodules, Dr. Lillegraven said.

Patients who were seropositive for either RF or anti-CCP were five times more likely than were seronegative patients to have disease progression (odds ratio 5.0), while seropositivity for both was associated with four times greater odds for disease progression (odds ratio 4.1).

"Although the odds ratios for progressive joint damage were similar if patients were positive for one or both of RF and anti-CCP, patients who were positive for both RF and anti-CCP tended to experience more joint damage," Dr. Lillegraven said. Rapid progression of joint damage (defined as a change in van der Heijde-Sharp score of 5 or more units per year) was noted in 16% patients who were seropositive for both RF and anti-CCP, compared with 9% of those who were positive for either RF or anti-CCP, although this difference was not statistically significant.

The results were limited by the use of data from a single center and by the challenge of fully adjusting for treatment in patients with established RA, Dr. Lillegraven noted. However, the findings suggest that seropositivity could be used to inform treatment decisions for these patients, she said.

Dr. Lillegraven had no financial conflicts to disclose. Several of the study coauthors disclosed relationships with multiple pharmaceutical companies, including Amgen, Abbott, Merck, and MedImmune.

WASHINGTON – Seropositivity for either rheumatoid factor or anti-cyclic citrullinated peptide was significantly associated with progressive joint damage in adults with established rheumatoid arthritis, based on a single-center, observational cohort study of 390 patients.

Most rheumatoid arthritis (RA) patients in clinical practice have established disease, but the predictors and proportion of disease progression in these patients has not been well studied, Dr. Siri Lillegraven of Diakonhjemmet Hospital in Oslo said at the annual meeting of the American College of Rheumatology.

Dr. Lillegraven and her colleagues reviewed data from BRASS (the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study). Joint damage was assessed using baseline and 2-year radiographic data for patients with disease duration of at least 5 years. The average age of the patients was 60 years, 84% were women, and 44% received biologic treatment in the form of disease-modifying antirheumatic drugs (DMARDs). The median disease duration was 17 years. Disease progression was defined as a change in Sharp/van der Heijde score of 1 or more units per year.

Overall, 44% of the patients showed disease progression after 2 years. A total of 68% of the patients were positive for both rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP), 16% were positive for either RF or anti-CCP, and 16% were negative for both.

Seropositivity was the only significant independent predictor of disease progression after controlling for factors including age, gender, body-mass index, smoking status, treatment, DMARD use, disease duration, and presence of subcutaneous nodules, Dr. Lillegraven said.

Patients who were seropositive for either RF or anti-CCP were five times more likely than were seronegative patients to have disease progression (odds ratio 5.0), while seropositivity for both was associated with four times greater odds for disease progression (odds ratio 4.1).

"Although the odds ratios for progressive joint damage were similar if patients were positive for one or both of RF and anti-CCP, patients who were positive for both RF and anti-CCP tended to experience more joint damage," Dr. Lillegraven said. Rapid progression of joint damage (defined as a change in van der Heijde-Sharp score of 5 or more units per year) was noted in 16% patients who were seropositive for both RF and anti-CCP, compared with 9% of those who were positive for either RF or anti-CCP, although this difference was not statistically significant.

The results were limited by the use of data from a single center and by the challenge of fully adjusting for treatment in patients with established RA, Dr. Lillegraven noted. However, the findings suggest that seropositivity could be used to inform treatment decisions for these patients, she said.

Dr. Lillegraven had no financial conflicts to disclose. Several of the study coauthors disclosed relationships with multiple pharmaceutical companies, including Amgen, Abbott, Merck, and MedImmune.

WASHINGTON – Seropositivity for either rheumatoid factor or anti-cyclic citrullinated peptide was significantly associated with progressive joint damage in adults with established rheumatoid arthritis, based on a single-center, observational cohort study of 390 patients.

Most rheumatoid arthritis (RA) patients in clinical practice have established disease, but the predictors and proportion of disease progression in these patients has not been well studied, Dr. Siri Lillegraven of Diakonhjemmet Hospital in Oslo said at the annual meeting of the American College of Rheumatology.

Dr. Lillegraven and her colleagues reviewed data from BRASS (the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study). Joint damage was assessed using baseline and 2-year radiographic data for patients with disease duration of at least 5 years. The average age of the patients was 60 years, 84% were women, and 44% received biologic treatment in the form of disease-modifying antirheumatic drugs (DMARDs). The median disease duration was 17 years. Disease progression was defined as a change in Sharp/van der Heijde score of 1 or more units per year.

Overall, 44% of the patients showed disease progression after 2 years. A total of 68% of the patients were positive for both rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP), 16% were positive for either RF or anti-CCP, and 16% were negative for both.

Seropositivity was the only significant independent predictor of disease progression after controlling for factors including age, gender, body-mass index, smoking status, treatment, DMARD use, disease duration, and presence of subcutaneous nodules, Dr. Lillegraven said.

Patients who were seropositive for either RF or anti-CCP were five times more likely than were seronegative patients to have disease progression (odds ratio 5.0), while seropositivity for both was associated with four times greater odds for disease progression (odds ratio 4.1).

"Although the odds ratios for progressive joint damage were similar if patients were positive for one or both of RF and anti-CCP, patients who were positive for both RF and anti-CCP tended to experience more joint damage," Dr. Lillegraven said. Rapid progression of joint damage (defined as a change in van der Heijde-Sharp score of 5 or more units per year) was noted in 16% patients who were seropositive for both RF and anti-CCP, compared with 9% of those who were positive for either RF or anti-CCP, although this difference was not statistically significant.

The results were limited by the use of data from a single center and by the challenge of fully adjusting for treatment in patients with established RA, Dr. Lillegraven noted. However, the findings suggest that seropositivity could be used to inform treatment decisions for these patients, she said.

Dr. Lillegraven had no financial conflicts to disclose. Several of the study coauthors disclosed relationships with multiple pharmaceutical companies, including Amgen, Abbott, Merck, and MedImmune.

WASHINGTON – "Blanket" monitoring guidelines for liver toxicity in patients taking methotrexate may do more harm than good.

That’s according to Dr. Gabriela Schmajuk, who found that up to a third of patients taking the drug for rheumatoid arthritis may have the drug discontinued unnecessarily in the presence of mildly elevated liver function tests (LFTs).

"We need more research to say what the best strategies are [when it comes to] LFT monitoring, and what our response to abnormal LFTs should be," she said at the annual meeting of the American College of Rheumatology.

In a poster presented at the meeting, Dr. Schmajuk of the University of California, San Francisco, and her colleagues looked at 899 new methotrexate users (97% male, mean age 71 years) aged 65 years and older treated at the Veterans Health Administration (VHA) during 2007-2008.

The study was conducted in response to the recent measure issued by the National Quality Forum, which assesses whether rheumatoid arthritis patients prescribed methotrexate received an LFT within 120 days of their prescription claim. The measure is for public quality reporting purposes.

First, Dr. Schmajuk looked at how many patients met the National Quality Forum’s measure.

Patients all had at least a 28-day supply of methotrexate with follow-up at the VHA for 3 months after the drug was dispensed.

Patients were excluded from the study if they had any diagnosis of inflammatory bowel disease or if they sought medical care outside the VHA, and the researchers correlated the first abnormal LFT with the rate of methotrexate discontinuation.

Overall, they found that 148 patients (16.5%) did not have any LFT testing after methotrexate was initiated.

Among the patients who did have their LFTs monitored, 136 (15.1%) had any abnormality of AST or ALT, and only 49 patients (5%) had an elevation of at least 1.5 times the upper limit of normal; among these, methotrexate was discontinued in 27 patients.

However, the researchers also found that methotrexate was discontinued in 28 (32%) of 87 patients with LFT elevations less than 1.5 times the upper limit of normal.

In an e-mail interview, Dr. Schmajuk conceded that a full chart review on these patients has not yet been completed, and that "it is entirely possible that patients were discontinuing [methotrexate] for reasons not related to the LFTs."

However, "We need more research to help decide what a safe cutoff of discontinuation should be – it is possible that it is higher than previously thought."

She added: "In the future, we should be able to tailor monitoring frequency to individual patients."

A second poster, also presented at the meeting, offered a step forward toward just that.

In that study, Dr. Monica Ramirez of Brigham and Women’s Hospital, Boston, attempted to identify clinical predictors of liver enzyme elevation in methotrexate-treated rheumatoid arthritis patients.

Dr. Ramirez and her colleagues conducted detailed chart evaluations of 500 rheumatoid arthritis patients treated at a single center since 1992 who were identified as ever having received treatment with methotrexate and who had LFTs greater than two times the upper limit of normal.

Patients were excluded if they had ever been diagnosed with hepatitis or any other liver disease, or if they had any concurrent hospital or clinic visits for cardiac disease, sepsis, acute kidney disease, metastatic cancer, trauma, or surgery.

A total of 90 (18%) cases were confirmed as having LFT elevations attributed to methotrexate usage.

The authors then assessed the relationship between several known risk factors for liver toxicity to see whether any of them predicted methotrexate dose reduction or discontinuation: age, sex, obesity, hyperlipidemia, methotrexate dose (2.5-7.5 mg, 10-17.5 mg, or 20-25 mg), alcohol use, statin use, and NSAID use.

In univariate analysis, only obesity was significantly associated with a likelihood of methotrexate discontinuation or dose reduction (odds ratio, 2.89; 95% confidence interval, 1.20-7.00; P = .02). Similarly, in multivariate analysis, obesity was the lone predictor (OR, 2.60; 95% CI, 1.01-6.66; P = .05).

"This suggests a potentially heightened risk of hepatotoxicity among obese patients," the authors concluded.

Dr. Schmajuk and her fellow researchers reported no disclosures and no outside funding for their study. The authors of the second study, led by Dr. Ramirez, reported funding from the National Institutes of Health, and one of the investigators reported financial support from Amgen, Abbott, and other companies.

WASHINGTON – "Blanket" monitoring guidelines for liver toxicity in patients taking methotrexate may do more harm than good.

That’s according to Dr. Gabriela Schmajuk, who found that up to a third of patients taking the drug for rheumatoid arthritis may have the drug discontinued unnecessarily in the presence of mildly elevated liver function tests (LFTs).

"We need more research to say what the best strategies are [when it comes to] LFT monitoring, and what our response to abnormal LFTs should be," she said at the annual meeting of the American College of Rheumatology.

In a poster presented at the meeting, Dr. Schmajuk of the University of California, San Francisco, and her colleagues looked at 899 new methotrexate users (97% male, mean age 71 years) aged 65 years and older treated at the Veterans Health Administration (VHA) during 2007-2008.

The study was conducted in response to the recent measure issued by the National Quality Forum, which assesses whether rheumatoid arthritis patients prescribed methotrexate received an LFT within 120 days of their prescription claim. The measure is for public quality reporting purposes.

First, Dr. Schmajuk looked at how many patients met the National Quality Forum’s measure.

Patients all had at least a 28-day supply of methotrexate with follow-up at the VHA for 3 months after the drug was dispensed.

Patients were excluded from the study if they had any diagnosis of inflammatory bowel disease or if they sought medical care outside the VHA, and the researchers correlated the first abnormal LFT with the rate of methotrexate discontinuation.

Overall, they found that 148 patients (16.5%) did not have any LFT testing after methotrexate was initiated.

Among the patients who did have their LFTs monitored, 136 (15.1%) had any abnormality of AST or ALT, and only 49 patients (5%) had an elevation of at least 1.5 times the upper limit of normal; among these, methotrexate was discontinued in 27 patients.

However, the researchers also found that methotrexate was discontinued in 28 (32%) of 87 patients with LFT elevations less than 1.5 times the upper limit of normal.

In an e-mail interview, Dr. Schmajuk conceded that a full chart review on these patients has not yet been completed, and that "it is entirely possible that patients were discontinuing [methotrexate] for reasons not related to the LFTs."

However, "We need more research to help decide what a safe cutoff of discontinuation should be – it is possible that it is higher than previously thought."

She added: "In the future, we should be able to tailor monitoring frequency to individual patients."

A second poster, also presented at the meeting, offered a step forward toward just that.

In that study, Dr. Monica Ramirez of Brigham and Women’s Hospital, Boston, attempted to identify clinical predictors of liver enzyme elevation in methotrexate-treated rheumatoid arthritis patients.

Dr. Ramirez and her colleagues conducted detailed chart evaluations of 500 rheumatoid arthritis patients treated at a single center since 1992 who were identified as ever having received treatment with methotrexate and who had LFTs greater than two times the upper limit of normal.

Patients were excluded if they had ever been diagnosed with hepatitis or any other liver disease, or if they had any concurrent hospital or clinic visits for cardiac disease, sepsis, acute kidney disease, metastatic cancer, trauma, or surgery.

A total of 90 (18%) cases were confirmed as having LFT elevations attributed to methotrexate usage.

The authors then assessed the relationship between several known risk factors for liver toxicity to see whether any of them predicted methotrexate dose reduction or discontinuation: age, sex, obesity, hyperlipidemia, methotrexate dose (2.5-7.5 mg, 10-17.5 mg, or 20-25 mg), alcohol use, statin use, and NSAID use.

In univariate analysis, only obesity was significantly associated with a likelihood of methotrexate discontinuation or dose reduction (odds ratio, 2.89; 95% confidence interval, 1.20-7.00; P = .02). Similarly, in multivariate analysis, obesity was the lone predictor (OR, 2.60; 95% CI, 1.01-6.66; P = .05).

"This suggests a potentially heightened risk of hepatotoxicity among obese patients," the authors concluded.

Dr. Schmajuk and her fellow researchers reported no disclosures and no outside funding for their study. The authors of the second study, led by Dr. Ramirez, reported funding from the National Institutes of Health, and one of the investigators reported financial support from Amgen, Abbott, and other companies.

WASHINGTON – "Blanket" monitoring guidelines for liver toxicity in patients taking methotrexate may do more harm than good.

That’s according to Dr. Gabriela Schmajuk, who found that up to a third of patients taking the drug for rheumatoid arthritis may have the drug discontinued unnecessarily in the presence of mildly elevated liver function tests (LFTs).

"We need more research to say what the best strategies are [when it comes to] LFT monitoring, and what our response to abnormal LFTs should be," she said at the annual meeting of the American College of Rheumatology.

In a poster presented at the meeting, Dr. Schmajuk of the University of California, San Francisco, and her colleagues looked at 899 new methotrexate users (97% male, mean age 71 years) aged 65 years and older treated at the Veterans Health Administration (VHA) during 2007-2008.

The study was conducted in response to the recent measure issued by the National Quality Forum, which assesses whether rheumatoid arthritis patients prescribed methotrexate received an LFT within 120 days of their prescription claim. The measure is for public quality reporting purposes.

First, Dr. Schmajuk looked at how many patients met the National Quality Forum’s measure.

Patients all had at least a 28-day supply of methotrexate with follow-up at the VHA for 3 months after the drug was dispensed.

Patients were excluded from the study if they had any diagnosis of inflammatory bowel disease or if they sought medical care outside the VHA, and the researchers correlated the first abnormal LFT with the rate of methotrexate discontinuation.

Overall, they found that 148 patients (16.5%) did not have any LFT testing after methotrexate was initiated.

Among the patients who did have their LFTs monitored, 136 (15.1%) had any abnormality of AST or ALT, and only 49 patients (5%) had an elevation of at least 1.5 times the upper limit of normal; among these, methotrexate was discontinued in 27 patients.

However, the researchers also found that methotrexate was discontinued in 28 (32%) of 87 patients with LFT elevations less than 1.5 times the upper limit of normal.

In an e-mail interview, Dr. Schmajuk conceded that a full chart review on these patients has not yet been completed, and that "it is entirely possible that patients were discontinuing [methotrexate] for reasons not related to the LFTs."

However, "We need more research to help decide what a safe cutoff of discontinuation should be – it is possible that it is higher than previously thought."

She added: "In the future, we should be able to tailor monitoring frequency to individual patients."

A second poster, also presented at the meeting, offered a step forward toward just that.

In that study, Dr. Monica Ramirez of Brigham and Women’s Hospital, Boston, attempted to identify clinical predictors of liver enzyme elevation in methotrexate-treated rheumatoid arthritis patients.

Dr. Ramirez and her colleagues conducted detailed chart evaluations of 500 rheumatoid arthritis patients treated at a single center since 1992 who were identified as ever having received treatment with methotrexate and who had LFTs greater than two times the upper limit of normal.

Patients were excluded if they had ever been diagnosed with hepatitis or any other liver disease, or if they had any concurrent hospital or clinic visits for cardiac disease, sepsis, acute kidney disease, metastatic cancer, trauma, or surgery.

A total of 90 (18%) cases were confirmed as having LFT elevations attributed to methotrexate usage.

The authors then assessed the relationship between several known risk factors for liver toxicity to see whether any of them predicted methotrexate dose reduction or discontinuation: age, sex, obesity, hyperlipidemia, methotrexate dose (2.5-7.5 mg, 10-17.5 mg, or 20-25 mg), alcohol use, statin use, and NSAID use.

In univariate analysis, only obesity was significantly associated with a likelihood of methotrexate discontinuation or dose reduction (odds ratio, 2.89; 95% confidence interval, 1.20-7.00; P = .02). Similarly, in multivariate analysis, obesity was the lone predictor (OR, 2.60; 95% CI, 1.01-6.66; P = .05).

"This suggests a potentially heightened risk of hepatotoxicity among obese patients," the authors concluded.

Dr. Schmajuk and her fellow researchers reported no disclosures and no outside funding for their study. The authors of the second study, led by Dr. Ramirez, reported funding from the National Institutes of Health, and one of the investigators reported financial support from Amgen, Abbott, and other companies.

WASHINGTON – Exposure to anti-tumor necrosis factor therapy does not appear to be associated with a greater short-term risk of ischemic stroke in patients with rheumatoid arthritis when compared with exposure to nonbiologic disease-modifying antirheumatic drug therapy, according to findings from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis.

Of 130 verified incident ischemic cerebrovascular accidents that occurred among participants in that large prospective cohort study of RA patients, 109 occurred in 11,642 patients treated with anti–tumor necrosis factor drugs (anti-TNFs) for an incidence rate of 178/100,000 person-years, and 21 occurred in 3,271 patients in a comparator group of biologic-naive patients who had been treated with only nonbiologic disease-modifying antirheumatic drugs (nbDMARDs) for an incident rate of 175/100,000 person-years, Dr. Audrey S. Low reported at the annual meeting of the American College of Rheumatology.

The incident rates did not differ significantly, and no association was seen between ever exposure to anti-TNF drugs and ischemic stroke risk after adjustment for confounders using a propensity score based on age, sex, ethnicity, body mass index, disease activity score, disease duration, Health Assessment Questionnaire score, prior nbDMARD use, steroid use at baseline, year of entry to the study, smoking, baseline drugs, and history of cancer, hypertension, ischemic heart disease, diabetes, depression, and chronic lung disease (hazard ratio, 0.88), said Dr. Low of the University of Manchester (England).

Patients in the British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA) were recruited during 2001-2008 and were followed semiannually for 3 years, then annually thereafter. All serious adverse events, such as stroke, and all drug therapy were reported. Events reported through Oct. 21, 2010, were included in this analysis.

The investigators also linked study subjects to the national death register and collected information from medical records; a concerted effort was made to classify stroke types.

The anti-TNF and nbDMARD groups differed with respect to several factors: The anti-TNF cohort was younger, included more women, and had higher disease activity, longer disease duration, and higher levels of disability. That cohort also used more DMARDs, more steroids, and more nonsteroidal cyclo-oxygenase-2 (COX-2) inhibitors. However, the rates of hypertension and diabetes were similar in the anti-TNF and nbDMARD cohorts.

This study is among the largest to show that anti-TNF therapy does not increase stroke risk in RA patients, when compared with nbDMARDS, Dr. Low said.

"We know that patients with RA are at risk of increased cardiovascular morbidity and mortality, and that includes stroke," she said, noting that several other observational studies and meta-analyses have demonstrated an overall increase in that risk.

However, outcomes have varied in studies comparing anti-TNF–treated RA patients and controls, with some showing as much as a 60% increase in ischemic stroke risk and others demonstrating a 30% reduction in risk.

In this large cohort of European patients with RA, no association was seen between the short-term risk of ischemic stroke and the use of anti-TNF therapy, she said, adding that additional follow-up is needed to assess risk over time.

Dr. Low reported having no relevant financial disclosures.

WASHINGTON – Exposure to anti-tumor necrosis factor therapy does not appear to be associated with a greater short-term risk of ischemic stroke in patients with rheumatoid arthritis when compared with exposure to nonbiologic disease-modifying antirheumatic drug therapy, according to findings from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis.

Of 130 verified incident ischemic cerebrovascular accidents that occurred among participants in that large prospective cohort study of RA patients, 109 occurred in 11,642 patients treated with anti–tumor necrosis factor drugs (anti-TNFs) for an incidence rate of 178/100,000 person-years, and 21 occurred in 3,271 patients in a comparator group of biologic-naive patients who had been treated with only nonbiologic disease-modifying antirheumatic drugs (nbDMARDs) for an incident rate of 175/100,000 person-years, Dr. Audrey S. Low reported at the annual meeting of the American College of Rheumatology.

The incident rates did not differ significantly, and no association was seen between ever exposure to anti-TNF drugs and ischemic stroke risk after adjustment for confounders using a propensity score based on age, sex, ethnicity, body mass index, disease activity score, disease duration, Health Assessment Questionnaire score, prior nbDMARD use, steroid use at baseline, year of entry to the study, smoking, baseline drugs, and history of cancer, hypertension, ischemic heart disease, diabetes, depression, and chronic lung disease (hazard ratio, 0.88), said Dr. Low of the University of Manchester (England).

Patients in the British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA) were recruited during 2001-2008 and were followed semiannually for 3 years, then annually thereafter. All serious adverse events, such as stroke, and all drug therapy were reported. Events reported through Oct. 21, 2010, were included in this analysis.

The investigators also linked study subjects to the national death register and collected information from medical records; a concerted effort was made to classify stroke types.

The anti-TNF and nbDMARD groups differed with respect to several factors: The anti-TNF cohort was younger, included more women, and had higher disease activity, longer disease duration, and higher levels of disability. That cohort also used more DMARDs, more steroids, and more nonsteroidal cyclo-oxygenase-2 (COX-2) inhibitors. However, the rates of hypertension and diabetes were similar in the anti-TNF and nbDMARD cohorts.

This study is among the largest to show that anti-TNF therapy does not increase stroke risk in RA patients, when compared with nbDMARDS, Dr. Low said.

"We know that patients with RA are at risk of increased cardiovascular morbidity and mortality, and that includes stroke," she said, noting that several other observational studies and meta-analyses have demonstrated an overall increase in that risk.

However, outcomes have varied in studies comparing anti-TNF–treated RA patients and controls, with some showing as much as a 60% increase in ischemic stroke risk and others demonstrating a 30% reduction in risk.

In this large cohort of European patients with RA, no association was seen between the short-term risk of ischemic stroke and the use of anti-TNF therapy, she said, adding that additional follow-up is needed to assess risk over time.

Dr. Low reported having no relevant financial disclosures.

WASHINGTON – Exposure to anti-tumor necrosis factor therapy does not appear to be associated with a greater short-term risk of ischemic stroke in patients with rheumatoid arthritis when compared with exposure to nonbiologic disease-modifying antirheumatic drug therapy, according to findings from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis.

Of 130 verified incident ischemic cerebrovascular accidents that occurred among participants in that large prospective cohort study of RA patients, 109 occurred in 11,642 patients treated with anti–tumor necrosis factor drugs (anti-TNFs) for an incidence rate of 178/100,000 person-years, and 21 occurred in 3,271 patients in a comparator group of biologic-naive patients who had been treated with only nonbiologic disease-modifying antirheumatic drugs (nbDMARDs) for an incident rate of 175/100,000 person-years, Dr. Audrey S. Low reported at the annual meeting of the American College of Rheumatology.

The incident rates did not differ significantly, and no association was seen between ever exposure to anti-TNF drugs and ischemic stroke risk after adjustment for confounders using a propensity score based on age, sex, ethnicity, body mass index, disease activity score, disease duration, Health Assessment Questionnaire score, prior nbDMARD use, steroid use at baseline, year of entry to the study, smoking, baseline drugs, and history of cancer, hypertension, ischemic heart disease, diabetes, depression, and chronic lung disease (hazard ratio, 0.88), said Dr. Low of the University of Manchester (England).

Patients in the British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA) were recruited during 2001-2008 and were followed semiannually for 3 years, then annually thereafter. All serious adverse events, such as stroke, and all drug therapy were reported. Events reported through Oct. 21, 2010, were included in this analysis.

The investigators also linked study subjects to the national death register and collected information from medical records; a concerted effort was made to classify stroke types.

The anti-TNF and nbDMARD groups differed with respect to several factors: The anti-TNF cohort was younger, included more women, and had higher disease activity, longer disease duration, and higher levels of disability. That cohort also used more DMARDs, more steroids, and more nonsteroidal cyclo-oxygenase-2 (COX-2) inhibitors. However, the rates of hypertension and diabetes were similar in the anti-TNF and nbDMARD cohorts.

This study is among the largest to show that anti-TNF therapy does not increase stroke risk in RA patients, when compared with nbDMARDS, Dr. Low said.

"We know that patients with RA are at risk of increased cardiovascular morbidity and mortality, and that includes stroke," she said, noting that several other observational studies and meta-analyses have demonstrated an overall increase in that risk.

However, outcomes have varied in studies comparing anti-TNF–treated RA patients and controls, with some showing as much as a 60% increase in ischemic stroke risk and others demonstrating a 30% reduction in risk.

In this large cohort of European patients with RA, no association was seen between the short-term risk of ischemic stroke and the use of anti-TNF therapy, she said, adding that additional follow-up is needed to assess risk over time.

Dr. Low reported having no relevant financial disclosures.

WASHINGTON – Low bone mineral density and the presence of vertebral fractures in patients with rheumatoid arthritis not only signal the likely presence of osteoporosis but also appear to signal increased cardiovascular disease risk, according to findings from a cross-sectional study.*

The findings suggest that dual-energy x-ray absorptiometry (DEXA) scans commonly performed in rheumatoid arthritis (RA) patients to assess for osteoporosis could also serve as an assessment of cardiovascular disease risk, Dr. Ausaf Mohammad reported at the annual meeting of the American College of Rheumatology.

Of 603 patients from a convenience sample of adults who met 1987 ACR criteria for RA classification, 230 had at least one documented cardiovascular disease event, and those patients, compared with patients without a cardiovascular disease event, had significantly lower total hip and lumbar spine bone mineral density, and were four times as likely to have osteoporosis (60% vs. 15%) and twice as likely to have a vertebral fracture (24% vs. 12%), said Dr. Mohammad of Galway (Ireland) University Hospitals.

Low bone mineral density and the presence of vertebral fractures were independently associated with cardiovascular disease after adjustment for age, sex, smoking, hypertension, diabetes, and hypercholesterolemia. These measures outperformed traditional risk factors and RA disease activity scores for predicting cardiovascular disease.*

For example, the age- and sex-adjusted odds ratios for osteoporosis and vertebral fractures in those with cardiovascular disease were 2.70 and 2.67; the odds ratios for diabetes mellitus, smoking history, hypertension, hyperlipidemia, C-reactive protein, and Disease Activity Score (DAS-28) indicative of active RA were 1.61, 1.18, 1.58, 1.02, 1.73, and 1.63, respectively.

Patients in the RA cohort included 446 women and 157 men over age 40 years (mean, 56 years) who had a prior DEXA scan with vertebral fracture assessment available for analysis. The scans were evaluated by blinded musculoskeletal radiologists, and osteoporosis diagnoses were made using World Health Organization DEXA criteria; 32% of patients had osteoporosis by bone mineral density criteria, and 13% had one or more vertebral fractures on vertebral fracture assessment.

Cardiovascular events in the cohort included myocardial infarction in 45 patients, stent in 145, heart failure in 33, and stroke in 7.

The findings are of note given that traditional risk factors for cardiovascular disease tend to underperform in patients with RA, and that cardiovascular disease remains the leading cause of mortality in this population, Dr. Mohammad said.

"The risk of cardiovascular disease rises shortly after onset of arthritis, but does not precede it, and the risk appears similar to what is seen in non-RA subjects with diabetes and non-RA subjects who are 5-10 years older, so this tells us we are looking at a very high-risk population," he said.

However, despite a similar distribution in RA and non-RA patients, risk factors for cardiovascular disease "behave differently" in RA patients, and multiple studies have shown that methods for assessing risk, such as the Framingham risk score, underestimate risk in those with RA.

Indeed, the Framingham risk score did not differ significantly between those with and without cardiovascular disease events in the current study, Dr. Mohammad said, adding: "This poses a significant challenge. Therefore we need better markers and better prediction tools."

It appears, based on these findings, that bone mineral density could serve as such a marker, and that DEXA scans could be a good prediction tool, he said.

Since RA patients are also at increased risk for osteoporosis and fractures, many are already referred for DEXA scans.

"So DEXA may provide an opportunity to assess RA subjects at the time of osteoporosis for cardiovascular disease without the need for additional testing," he said.

Although this study has inherent limitations associated with its cross-sectional design, it does have several strengths, including the large cohort size and the fact that participating radiologists were blinded to patient status. Also, the findings are in keeping with those from multiple prior studies in non-RA populations, demonstrating strong associations between osteoporosis and cardiovascular disease, he added, noting that the findings underscore a need for interventions to reduce cardiovascular disease risk in RA patients with osteoporosis.

Dr. Mohammad reported having no relevant financial disclosures.

*Correction: 12/04/2012: An earlier version of this story misstated Dr. Mohammad's findings. 

WASHINGTON – Low bone mineral density and the presence of vertebral fractures in patients with rheumatoid arthritis not only signal the likely presence of osteoporosis but also appear to signal increased cardiovascular disease risk, according to findings from a cross-sectional study.*

The findings suggest that dual-energy x-ray absorptiometry (DEXA) scans commonly performed in rheumatoid arthritis (RA) patients to assess for osteoporosis could also serve as an assessment of cardiovascular disease risk, Dr. Ausaf Mohammad reported at the annual meeting of the American College of Rheumatology.

Of 603 patients from a convenience sample of adults who met 1987 ACR criteria for RA classification, 230 had at least one documented cardiovascular disease event, and those patients, compared with patients without a cardiovascular disease event, had significantly lower total hip and lumbar spine bone mineral density, and were four times as likely to have osteoporosis (60% vs. 15%) and twice as likely to have a vertebral fracture (24% vs. 12%), said Dr. Mohammad of Galway (Ireland) University Hospitals.

Low bone mineral density and the presence of vertebral fractures were independently associated with cardiovascular disease after adjustment for age, sex, smoking, hypertension, diabetes, and hypercholesterolemia. These measures outperformed traditional risk factors and RA disease activity scores for predicting cardiovascular disease.*

For example, the age- and sex-adjusted odds ratios for osteoporosis and vertebral fractures in those with cardiovascular disease were 2.70 and 2.67; the odds ratios for diabetes mellitus, smoking history, hypertension, hyperlipidemia, C-reactive protein, and Disease Activity Score (DAS-28) indicative of active RA were 1.61, 1.18, 1.58, 1.02, 1.73, and 1.63, respectively.

Patients in the RA cohort included 446 women and 157 men over age 40 years (mean, 56 years) who had a prior DEXA scan with vertebral fracture assessment available for analysis. The scans were evaluated by blinded musculoskeletal radiologists, and osteoporosis diagnoses were made using World Health Organization DEXA criteria; 32% of patients had osteoporosis by bone mineral density criteria, and 13% had one or more vertebral fractures on vertebral fracture assessment.

Cardiovascular events in the cohort included myocardial infarction in 45 patients, stent in 145, heart failure in 33, and stroke in 7.

The findings are of note given that traditional risk factors for cardiovascular disease tend to underperform in patients with RA, and that cardiovascular disease remains the leading cause of mortality in this population, Dr. Mohammad said.

"The risk of cardiovascular disease rises shortly after onset of arthritis, but does not precede it, and the risk appears similar to what is seen in non-RA subjects with diabetes and non-RA subjects who are 5-10 years older, so this tells us we are looking at a very high-risk population," he said.

However, despite a similar distribution in RA and non-RA patients, risk factors for cardiovascular disease "behave differently" in RA patients, and multiple studies have shown that methods for assessing risk, such as the Framingham risk score, underestimate risk in those with RA.

Indeed, the Framingham risk score did not differ significantly between those with and without cardiovascular disease events in the current study, Dr. Mohammad said, adding: "This poses a significant challenge. Therefore we need better markers and better prediction tools."

It appears, based on these findings, that bone mineral density could serve as such a marker, and that DEXA scans could be a good prediction tool, he said.

Since RA patients are also at increased risk for osteoporosis and fractures, many are already referred for DEXA scans.

"So DEXA may provide an opportunity to assess RA subjects at the time of osteoporosis for cardiovascular disease without the need for additional testing," he said.

Although this study has inherent limitations associated with its cross-sectional design, it does have several strengths, including the large cohort size and the fact that participating radiologists were blinded to patient status. Also, the findings are in keeping with those from multiple prior studies in non-RA populations, demonstrating strong associations between osteoporosis and cardiovascular disease, he added, noting that the findings underscore a need for interventions to reduce cardiovascular disease risk in RA patients with osteoporosis.

Dr. Mohammad reported having no relevant financial disclosures.

*Correction: 12/04/2012: An earlier version of this story misstated Dr. Mohammad's findings. 

WASHINGTON – Low bone mineral density and the presence of vertebral fractures in patients with rheumatoid arthritis not only signal the likely presence of osteoporosis but also appear to signal increased cardiovascular disease risk, according to findings from a cross-sectional study.*

The findings suggest that dual-energy x-ray absorptiometry (DEXA) scans commonly performed in rheumatoid arthritis (RA) patients to assess for osteoporosis could also serve as an assessment of cardiovascular disease risk, Dr. Ausaf Mohammad reported at the annual meeting of the American College of Rheumatology.

Of 603 patients from a convenience sample of adults who met 1987 ACR criteria for RA classification, 230 had at least one documented cardiovascular disease event, and those patients, compared with patients without a cardiovascular disease event, had significantly lower total hip and lumbar spine bone mineral density, and were four times as likely to have osteoporosis (60% vs. 15%) and twice as likely to have a vertebral fracture (24% vs. 12%), said Dr. Mohammad of Galway (Ireland) University Hospitals.

Low bone mineral density and the presence of vertebral fractures were independently associated with cardiovascular disease after adjustment for age, sex, smoking, hypertension, diabetes, and hypercholesterolemia. These measures outperformed traditional risk factors and RA disease activity scores for predicting cardiovascular disease.*

For example, the age- and sex-adjusted odds ratios for osteoporosis and vertebral fractures in those with cardiovascular disease were 2.70 and 2.67; the odds ratios for diabetes mellitus, smoking history, hypertension, hyperlipidemia, C-reactive protein, and Disease Activity Score (DAS-28) indicative of active RA were 1.61, 1.18, 1.58, 1.02, 1.73, and 1.63, respectively.

Patients in the RA cohort included 446 women and 157 men over age 40 years (mean, 56 years) who had a prior DEXA scan with vertebral fracture assessment available for analysis. The scans were evaluated by blinded musculoskeletal radiologists, and osteoporosis diagnoses were made using World Health Organization DEXA criteria; 32% of patients had osteoporosis by bone mineral density criteria, and 13% had one or more vertebral fractures on vertebral fracture assessment.

Cardiovascular events in the cohort included myocardial infarction in 45 patients, stent in 145, heart failure in 33, and stroke in 7.

The findings are of note given that traditional risk factors for cardiovascular disease tend to underperform in patients with RA, and that cardiovascular disease remains the leading cause of mortality in this population, Dr. Mohammad said.

"The risk of cardiovascular disease rises shortly after onset of arthritis, but does not precede it, and the risk appears similar to what is seen in non-RA subjects with diabetes and non-RA subjects who are 5-10 years older, so this tells us we are looking at a very high-risk population," he said.

However, despite a similar distribution in RA and non-RA patients, risk factors for cardiovascular disease "behave differently" in RA patients, and multiple studies have shown that methods for assessing risk, such as the Framingham risk score, underestimate risk in those with RA.

Indeed, the Framingham risk score did not differ significantly between those with and without cardiovascular disease events in the current study, Dr. Mohammad said, adding: "This poses a significant challenge. Therefore we need better markers and better prediction tools."

It appears, based on these findings, that bone mineral density could serve as such a marker, and that DEXA scans could be a good prediction tool, he said.

Since RA patients are also at increased risk for osteoporosis and fractures, many are already referred for DEXA scans.

"So DEXA may provide an opportunity to assess RA subjects at the time of osteoporosis for cardiovascular disease without the need for additional testing," he said.

Although this study has inherent limitations associated with its cross-sectional design, it does have several strengths, including the large cohort size and the fact that participating radiologists were blinded to patient status. Also, the findings are in keeping with those from multiple prior studies in non-RA populations, demonstrating strong associations between osteoporosis and cardiovascular disease, he added, noting that the findings underscore a need for interventions to reduce cardiovascular disease risk in RA patients with osteoporosis.

Dr. Mohammad reported having no relevant financial disclosures.

*Correction: 12/04/2012: An earlier version of this story misstated Dr. Mohammad's findings. 

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

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

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

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

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

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

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

Dr. van Sijl reported having no disclosures.

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

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

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

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

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

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

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

Dr. van Sijl reported having no disclosures.

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

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

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

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

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

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

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

Dr. van Sijl reported having no disclosures.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

She reported having no relevant financial disclosures.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

She reported having no relevant financial disclosures.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

She reported having no relevant financial disclosures.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Significant variations in respiratory symptoms during different stages of the menstrual cycle were identified in a study of almost 4,000 women in Northern Europe, with patterns that varied by body mass index, asthma, and smoking status.

"The findings suggest substantial hormonal influences in interplay with metabolic factors on airway physiology and on pathophysiological processes in respiratory diseases like asthma," concluded Dr. Ferenc Macsali, of the department of gynecology and obstetrics at Haukeland University Hospital, Bergen, Norway, and his associates. The study was published online in November (Am. J. Respir. Crit. Care Med. 2012 [doi: 10.1164/rccm.201206-1112OC]).

The study obtained information from questionnaires mailed to the Nordic-Baltic population of women, with questions about respiratory symptoms, menstrual symptoms, BMI, and smoking status, from 3,926 women (mean age 39 years), with regular cycles no greater than 28 days, who were not on any hormonal medications. The study is part of Respiratory Health in Northern Europe (RHINE), a population-based multicenter questionnaire study. Almost 29% of the women were regular smokers, almost 8% said they had been diagnosed with asthma, and their mean BMI was 23 kg/m².

Based on their analysis of the responses, the investigators identified significant variations during the menstrual cycle for each of the three symptoms analyzed – wheezing, shortness of breath, and coughing – including reports of wheezing that were higher during cycle days 10-22, with a "dramatic" drop in the middle of the cycle at about days 14-16, the "putative time of ovulation," in most subgroups. Wheezing was lower before and after menses. The daily incidence of shortness of breath was highest on days 7-21, dropping just before the middle of the cycle "in a number of subgroups." And there were peaks in the incidence of cough before and after midcycle, around the time of "putative" ovulation, and before the onset of menses; the incidence of coughs was lower after menses..

The effects of the menstrual cycle on respiratory symptoms in the general female population have not been well studied, and "our finding that respiratory symptoms vary according to the stage of the menstrual cycle is novel, as is our finding that these patterns vary according to BMI and smoking status," Dr. Macsali said in a statement issued by the American Thoracic Society, which publishes the American Journal of Respiratory and Critical Care Medicine.

"These relationships indicate a link between respiratory symptoms and hormonal changes through the menstrual cycle," he added.

"Our results point to the potential for individualizing therapy for respiratory diseases according to individual symptom patterns," Dr. Macsali said in the statement. As an example, he noted, adjusting asthma medication "according to a woman’s menstrual cycle might improve its efficacy and help reduce disability and the costs of care."

The authors acknowledged that the use of the questionnaire to obtain the data, as well as variations in the length of the menstrual cycle among those who responded, were limitations of the study.

No author disclosures were listed in the study. RHINE receives financial support from organizations that include the Swedish Heart and Lung Foundation, the Norwegian Asthma and Allergy Association, and the Danish Lung Association, according to the RHINE website.

Significant variations in respiratory symptoms during different stages of the menstrual cycle were identified in a study of almost 4,000 women in Northern Europe, with patterns that varied by body mass index, asthma, and smoking status.

"The findings suggest substantial hormonal influences in interplay with metabolic factors on airway physiology and on pathophysiological processes in respiratory diseases like asthma," concluded Dr. Ferenc Macsali, of the department of gynecology and obstetrics at Haukeland University Hospital, Bergen, Norway, and his associates. The study was published online in November (Am. J. Respir. Crit. Care Med. 2012 [doi: 10.1164/rccm.201206-1112OC]).

The study obtained information from questionnaires mailed to the Nordic-Baltic population of women, with questions about respiratory symptoms, menstrual symptoms, BMI, and smoking status, from 3,926 women (mean age 39 years), with regular cycles no greater than 28 days, who were not on any hormonal medications. The study is part of Respiratory Health in Northern Europe (RHINE), a population-based multicenter questionnaire study. Almost 29% of the women were regular smokers, almost 8% said they had been diagnosed with asthma, and their mean BMI was 23 kg/m².

Based on their analysis of the responses, the investigators identified significant variations during the menstrual cycle for each of the three symptoms analyzed – wheezing, shortness of breath, and coughing – including reports of wheezing that were higher during cycle days 10-22, with a "dramatic" drop in the middle of the cycle at about days 14-16, the "putative time of ovulation," in most subgroups. Wheezing was lower before and after menses. The daily incidence of shortness of breath was highest on days 7-21, dropping just before the middle of the cycle "in a number of subgroups." And there were peaks in the incidence of cough before and after midcycle, around the time of "putative" ovulation, and before the onset of menses; the incidence of coughs was lower after menses..

The effects of the menstrual cycle on respiratory symptoms in the general female population have not been well studied, and "our finding that respiratory symptoms vary according to the stage of the menstrual cycle is novel, as is our finding that these patterns vary according to BMI and smoking status," Dr. Macsali said in a statement issued by the American Thoracic Society, which publishes the American Journal of Respiratory and Critical Care Medicine.

"These relationships indicate a link between respiratory symptoms and hormonal changes through the menstrual cycle," he added.

"Our results point to the potential for individualizing therapy for respiratory diseases according to individual symptom patterns," Dr. Macsali said in the statement. As an example, he noted, adjusting asthma medication "according to a woman’s menstrual cycle might improve its efficacy and help reduce disability and the costs of care."

The authors acknowledged that the use of the questionnaire to obtain the data, as well as variations in the length of the menstrual cycle among those who responded, were limitations of the study.

No author disclosures were listed in the study. RHINE receives financial support from organizations that include the Swedish Heart and Lung Foundation, the Norwegian Asthma and Allergy Association, and the Danish Lung Association, according to the RHINE website.

Significant variations in respiratory symptoms during different stages of the menstrual cycle were identified in a study of almost 4,000 women in Northern Europe, with patterns that varied by body mass index, asthma, and smoking status.

"The findings suggest substantial hormonal influences in interplay with metabolic factors on airway physiology and on pathophysiological processes in respiratory diseases like asthma," concluded Dr. Ferenc Macsali, of the department of gynecology and obstetrics at Haukeland University Hospital, Bergen, Norway, and his associates. The study was published online in November (Am. J. Respir. Crit. Care Med. 2012 [doi: 10.1164/rccm.201206-1112OC]).

The study obtained information from questionnaires mailed to the Nordic-Baltic population of women, with questions about respiratory symptoms, menstrual symptoms, BMI, and smoking status, from 3,926 women (mean age 39 years), with regular cycles no greater than 28 days, who were not on any hormonal medications. The study is part of Respiratory Health in Northern Europe (RHINE), a population-based multicenter questionnaire study. Almost 29% of the women were regular smokers, almost 8% said they had been diagnosed with asthma, and their mean BMI was 23 kg/m².

Based on their analysis of the responses, the investigators identified significant variations during the menstrual cycle for each of the three symptoms analyzed – wheezing, shortness of breath, and coughing – including reports of wheezing that were higher during cycle days 10-22, with a "dramatic" drop in the middle of the cycle at about days 14-16, the "putative time of ovulation," in most subgroups. Wheezing was lower before and after menses. The daily incidence of shortness of breath was highest on days 7-21, dropping just before the middle of the cycle "in a number of subgroups." And there were peaks in the incidence of cough before and after midcycle, around the time of "putative" ovulation, and before the onset of menses; the incidence of coughs was lower after menses..

The effects of the menstrual cycle on respiratory symptoms in the general female population have not been well studied, and "our finding that respiratory symptoms vary according to the stage of the menstrual cycle is novel, as is our finding that these patterns vary according to BMI and smoking status," Dr. Macsali said in a statement issued by the American Thoracic Society, which publishes the American Journal of Respiratory and Critical Care Medicine.

"These relationships indicate a link between respiratory symptoms and hormonal changes through the menstrual cycle," he added.

"Our results point to the potential for individualizing therapy for respiratory diseases according to individual symptom patterns," Dr. Macsali said in the statement. As an example, he noted, adjusting asthma medication "according to a woman’s menstrual cycle might improve its efficacy and help reduce disability and the costs of care."

The authors acknowledged that the use of the questionnaire to obtain the data, as well as variations in the length of the menstrual cycle among those who responded, were limitations of the study.

No author disclosures were listed in the study. RHINE receives financial support from organizations that include the Swedish Heart and Lung Foundation, the Norwegian Asthma and Allergy Association, and the Danish Lung Association, according to the RHINE website.