ACR Annual Meeting 2012

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

WASHINGTON – Tocilizumab led to a rapid clinical improvement in polyarticular juvenile idiopathic arthritis that was sustained at 40 weeks.

Moreover, the interleukin-6 (IL-6) receptor inhibitor was relatively safe in this population, with a profile similar to that of other populations treated with tocilizumab, for instance systemic juvenile idiopathic arthritis (JIA) patients. The Food and Drug Administration approved tocilizumab for use in children with systemic JIA in 2011 and a year earlier for use in adults with moderately to severely active RA.

That was the finding from the phase III CHERISH trial presented here by Dr. Hermine Brunner on Nov. 12 at the annual meeting of the American College of Rheumatology.

Dr. Brunner of the Cincinnati Children’s Hospital Medical Center and her colleagues looked at 188 patients aged 2-17 years with active polyarticular JIA.

For the first 16 weeks, all patients received open-label tocilizumab injections every 4 weeks according to body weight, with patients who were at least 30 kg receiving 8 mg/kg (n = 119) and patients less than 30 kg randomized to receive either 8 mg/kg (n = 34) or 10 mg/kg (n = 35).

The primary end point was achievement of a JIA ACR30 response, indicating a 30% improvement from baseline in at least three of six criteria without a worsening of greater than 30% in one remaining measure, including active joint count, limitation of motion joint count, physician global assessment, patient/parent global assessment, Childhood Health Assessment Questionnaire, and acute-phase reactant level (either erythrocyte sedimentation rate or C-reactive protein).

By the end of the 16 weeks, 93% of the heavier patients (who received 8 mg/kg) had achieved a JIA ACR30 response; 89% of the lighter patients taking 10 mg/kg achieved that level, and 77% of the lighter 8 mg/kg patients.

Moreover, 25% of patients in the heavier group achieved a JIA ACR90 at the end of 16 weeks, as did 31% of the 10 mg/kg lower-weight group and 24% of the 8 mg/kg lower-weight group, reported Dr. Brunner.

At week 16, patients who achieved a JIA-ACR30 response moved on to the second part of the study, a 24-week, double-blind randomization to either placebo or to continue tocilizumab at the same dose.

By week 40, only 54% of placebo patients were at JIA ACR30, compared with 74% of the treatment group (P = .0084).

Moreover, "nearly half" (45%) of the treatment group patients maintained a JIA ACR90 at the end of part two, said Dr. Brunner.

Looking at adverse events, the most commonly reported were infections and infestations, with 164 infections/100-person-years, followed by gastrointestinal disorders, with 71 incidences/100 person-years.

Neutropenia occurred in 3.7% of patients, though Dr. Brunner stated it was "not clearly associated" with any infectious event.

LDL cholesterol levels were elevated to 110 mg/dL or greater in 11.4% of patients, but there were no grade IV lab abnormalities reported, nor were there any deaths in the study.

"The safety profile is quite comparable to what has been seen and reported in other studies" of patients taking tocilizumab, said Dr. Brunner.

However, she added that longer term safety data are forthcoming from this ongoing trial.

Several investigators disclosed multiple relationships to pharmaceutical companies including the maker of tocilizumab, Roche Pharmaceuticals, who also sponsored the study.

WASHINGTON – Tocilizumab led to a rapid clinical improvement in polyarticular juvenile idiopathic arthritis that was sustained at 40 weeks.

Moreover, the interleukin-6 (IL-6) receptor inhibitor was relatively safe in this population, with a profile similar to that of other populations treated with tocilizumab, for instance systemic juvenile idiopathic arthritis (JIA) patients. The Food and Drug Administration approved tocilizumab for use in children with systemic JIA in 2011 and a year earlier for use in adults with moderately to severely active RA.

That was the finding from the phase III CHERISH trial presented here by Dr. Hermine Brunner on Nov. 12 at the annual meeting of the American College of Rheumatology.

Dr. Brunner of the Cincinnati Children’s Hospital Medical Center and her colleagues looked at 188 patients aged 2-17 years with active polyarticular JIA.

For the first 16 weeks, all patients received open-label tocilizumab injections every 4 weeks according to body weight, with patients who were at least 30 kg receiving 8 mg/kg (n = 119) and patients less than 30 kg randomized to receive either 8 mg/kg (n = 34) or 10 mg/kg (n = 35).

The primary end point was achievement of a JIA ACR30 response, indicating a 30% improvement from baseline in at least three of six criteria without a worsening of greater than 30% in one remaining measure, including active joint count, limitation of motion joint count, physician global assessment, patient/parent global assessment, Childhood Health Assessment Questionnaire, and acute-phase reactant level (either erythrocyte sedimentation rate or C-reactive protein).

By the end of the 16 weeks, 93% of the heavier patients (who received 8 mg/kg) had achieved a JIA ACR30 response; 89% of the lighter patients taking 10 mg/kg achieved that level, and 77% of the lighter 8 mg/kg patients.

Moreover, 25% of patients in the heavier group achieved a JIA ACR90 at the end of 16 weeks, as did 31% of the 10 mg/kg lower-weight group and 24% of the 8 mg/kg lower-weight group, reported Dr. Brunner.

At week 16, patients who achieved a JIA-ACR30 response moved on to the second part of the study, a 24-week, double-blind randomization to either placebo or to continue tocilizumab at the same dose.

By week 40, only 54% of placebo patients were at JIA ACR30, compared with 74% of the treatment group (P = .0084).

Moreover, "nearly half" (45%) of the treatment group patients maintained a JIA ACR90 at the end of part two, said Dr. Brunner.

Looking at adverse events, the most commonly reported were infections and infestations, with 164 infections/100-person-years, followed by gastrointestinal disorders, with 71 incidences/100 person-years.

Neutropenia occurred in 3.7% of patients, though Dr. Brunner stated it was "not clearly associated" with any infectious event.

LDL cholesterol levels were elevated to 110 mg/dL or greater in 11.4% of patients, but there were no grade IV lab abnormalities reported, nor were there any deaths in the study.

"The safety profile is quite comparable to what has been seen and reported in other studies" of patients taking tocilizumab, said Dr. Brunner.

However, she added that longer term safety data are forthcoming from this ongoing trial.

Several investigators disclosed multiple relationships to pharmaceutical companies including the maker of tocilizumab, Roche Pharmaceuticals, who also sponsored the study.

WASHINGTON – Tocilizumab led to a rapid clinical improvement in polyarticular juvenile idiopathic arthritis that was sustained at 40 weeks.

Moreover, the interleukin-6 (IL-6) receptor inhibitor was relatively safe in this population, with a profile similar to that of other populations treated with tocilizumab, for instance systemic juvenile idiopathic arthritis (JIA) patients. The Food and Drug Administration approved tocilizumab for use in children with systemic JIA in 2011 and a year earlier for use in adults with moderately to severely active RA.

That was the finding from the phase III CHERISH trial presented here by Dr. Hermine Brunner on Nov. 12 at the annual meeting of the American College of Rheumatology.

Dr. Brunner of the Cincinnati Children’s Hospital Medical Center and her colleagues looked at 188 patients aged 2-17 years with active polyarticular JIA.

For the first 16 weeks, all patients received open-label tocilizumab injections every 4 weeks according to body weight, with patients who were at least 30 kg receiving 8 mg/kg (n = 119) and patients less than 30 kg randomized to receive either 8 mg/kg (n = 34) or 10 mg/kg (n = 35).

The primary end point was achievement of a JIA ACR30 response, indicating a 30% improvement from baseline in at least three of six criteria without a worsening of greater than 30% in one remaining measure, including active joint count, limitation of motion joint count, physician global assessment, patient/parent global assessment, Childhood Health Assessment Questionnaire, and acute-phase reactant level (either erythrocyte sedimentation rate or C-reactive protein).

By the end of the 16 weeks, 93% of the heavier patients (who received 8 mg/kg) had achieved a JIA ACR30 response; 89% of the lighter patients taking 10 mg/kg achieved that level, and 77% of the lighter 8 mg/kg patients.

Moreover, 25% of patients in the heavier group achieved a JIA ACR90 at the end of 16 weeks, as did 31% of the 10 mg/kg lower-weight group and 24% of the 8 mg/kg lower-weight group, reported Dr. Brunner.

At week 16, patients who achieved a JIA-ACR30 response moved on to the second part of the study, a 24-week, double-blind randomization to either placebo or to continue tocilizumab at the same dose.

By week 40, only 54% of placebo patients were at JIA ACR30, compared with 74% of the treatment group (P = .0084).

Moreover, "nearly half" (45%) of the treatment group patients maintained a JIA ACR90 at the end of part two, said Dr. Brunner.

Looking at adverse events, the most commonly reported were infections and infestations, with 164 infections/100-person-years, followed by gastrointestinal disorders, with 71 incidences/100 person-years.

Neutropenia occurred in 3.7% of patients, though Dr. Brunner stated it was "not clearly associated" with any infectious event.

LDL cholesterol levels were elevated to 110 mg/dL or greater in 11.4% of patients, but there were no grade IV lab abnormalities reported, nor were there any deaths in the study.

"The safety profile is quite comparable to what has been seen and reported in other studies" of patients taking tocilizumab, said Dr. Brunner.

However, she added that longer term safety data are forthcoming from this ongoing trial.

Several investigators disclosed multiple relationships to pharmaceutical companies including the maker of tocilizumab, Roche Pharmaceuticals, who also sponsored the study.

The cell phone continues to expand its job description: camera, alarm clock, bargain hunter, restaurant finder, interactive map, and, oh yes, a phone. Turns out your patients’ phones might also help them get the most from their rheumatoid arthritis treatment, according to data from a study of a new mobile phone text messaging program. The findings were presented at the annual meeting of the American College of Rheumatology.

Dr. Tuulikki Sokka of Jyväskylä Central Hospital in Finland, and colleagues, assessed how RA could be more effectively controlled if patients received monitoring messages via their cell phones.*

Central Hospital in Finland, and colleagues, assessed how RA could be more effectively controlled if patients received monitoring messages via their cell phones.

Louise Koenig/IMNG Medical Media

The idea of remote monitoring is appealing to many people because it can cut down on visits to a clinic that might not be right down the street (especially in Finland, where it might be a long, snowy drive away).

The Finnish team developed an automated system called SandRA (Showing any need for Re-Assessment). The program sends text messages to enrolled participants every 2 weeks for the first 6 months of their treatment. The first two questions relate to medication use: "Have you used the prescribed drug treatments?" and "Have you experienced any problems with the drug?" Patients have the option to respond with a simple Y or N. At 6 weeks, patients are asked to rate their RA severity on a scale of 1-10 as a global assessment measure. A positive response generates a confirmation that the message was received. A negative response prompts a message saying that the patient will get a phone call from a rheumatology nurse within 2 working days to discuss the problem. The nurses can determine whether a patient needs to make that extra trip to the clinic, said Dr. Sokka. "We think this system will allow us to direct our resources in the clinic to the patients who really need it," she said.

Data from 137 consecutive patients showed that a majority achieved their treatment goals, as measured by the patient’s global assessment scores. Patients were scheduled for regular clinic visits 3 and 6 months after the initial visit. At 6, 10, 18, and 22 weeks, SandRA identified 34%, 31%, 29%, and 31% of the patients for assessment outside of their regularly scheduled appointments. Lappeenranta Central Hospital sponsored the research.

By Heidi Splete

(on Twitter @hsplete)

*CORRECTION: 11/14/12: The original version of this story misidentified the hospital where Dr. Sokka works. The sentence should have read: "Dr. Tuulikki Sokka of Jyväskylä Central Hospital in Finland, and colleagues, assessed how RA could be more effectively controlled if patients received monitoring messages via their cell phones."

The cell phone continues to expand its job description: camera, alarm clock, bargain hunter, restaurant finder, interactive map, and, oh yes, a phone. Turns out your patients’ phones might also help them get the most from their rheumatoid arthritis treatment, according to data from a study of a new mobile phone text messaging program. The findings were presented at the annual meeting of the American College of Rheumatology.

Dr. Tuulikki Sokka of Jyväskylä Central Hospital in Finland, and colleagues, assessed how RA could be more effectively controlled if patients received monitoring messages via their cell phones.*

Central Hospital in Finland, and colleagues, assessed how RA could be more effectively controlled if patients received monitoring messages via their cell phones.

Louise Koenig/IMNG Medical Media

The idea of remote monitoring is appealing to many people because it can cut down on visits to a clinic that might not be right down the street (especially in Finland, where it might be a long, snowy drive away).

The Finnish team developed an automated system called SandRA (Showing any need for Re-Assessment). The program sends text messages to enrolled participants every 2 weeks for the first 6 months of their treatment. The first two questions relate to medication use: "Have you used the prescribed drug treatments?" and "Have you experienced any problems with the drug?" Patients have the option to respond with a simple Y or N. At 6 weeks, patients are asked to rate their RA severity on a scale of 1-10 as a global assessment measure. A positive response generates a confirmation that the message was received. A negative response prompts a message saying that the patient will get a phone call from a rheumatology nurse within 2 working days to discuss the problem. The nurses can determine whether a patient needs to make that extra trip to the clinic, said Dr. Sokka. "We think this system will allow us to direct our resources in the clinic to the patients who really need it," she said.

Data from 137 consecutive patients showed that a majority achieved their treatment goals, as measured by the patient’s global assessment scores. Patients were scheduled for regular clinic visits 3 and 6 months after the initial visit. At 6, 10, 18, and 22 weeks, SandRA identified 34%, 31%, 29%, and 31% of the patients for assessment outside of their regularly scheduled appointments. Lappeenranta Central Hospital sponsored the research.

By Heidi Splete

(on Twitter @hsplete)

*CORRECTION: 11/14/12: The original version of this story misidentified the hospital where Dr. Sokka works. The sentence should have read: "Dr. Tuulikki Sokka of Jyväskylä Central Hospital in Finland, and colleagues, assessed how RA could be more effectively controlled if patients received monitoring messages via their cell phones."

The cell phone continues to expand its job description: camera, alarm clock, bargain hunter, restaurant finder, interactive map, and, oh yes, a phone. Turns out your patients’ phones might also help them get the most from their rheumatoid arthritis treatment, according to data from a study of a new mobile phone text messaging program. The findings were presented at the annual meeting of the American College of Rheumatology.

Dr. Tuulikki Sokka of Jyväskylä Central Hospital in Finland, and colleagues, assessed how RA could be more effectively controlled if patients received monitoring messages via their cell phones.*

Central Hospital in Finland, and colleagues, assessed how RA could be more effectively controlled if patients received monitoring messages via their cell phones.

Louise Koenig/IMNG Medical Media

The idea of remote monitoring is appealing to many people because it can cut down on visits to a clinic that might not be right down the street (especially in Finland, where it might be a long, snowy drive away).

The Finnish team developed an automated system called SandRA (Showing any need for Re-Assessment). The program sends text messages to enrolled participants every 2 weeks for the first 6 months of their treatment. The first two questions relate to medication use: "Have you used the prescribed drug treatments?" and "Have you experienced any problems with the drug?" Patients have the option to respond with a simple Y or N. At 6 weeks, patients are asked to rate their RA severity on a scale of 1-10 as a global assessment measure. A positive response generates a confirmation that the message was received. A negative response prompts a message saying that the patient will get a phone call from a rheumatology nurse within 2 working days to discuss the problem. The nurses can determine whether a patient needs to make that extra trip to the clinic, said Dr. Sokka. "We think this system will allow us to direct our resources in the clinic to the patients who really need it," she said.

Data from 137 consecutive patients showed that a majority achieved their treatment goals, as measured by the patient’s global assessment scores. Patients were scheduled for regular clinic visits 3 and 6 months after the initial visit. At 6, 10, 18, and 22 weeks, SandRA identified 34%, 31%, 29%, and 31% of the patients for assessment outside of their regularly scheduled appointments. Lappeenranta Central Hospital sponsored the research.

By Heidi Splete

(on Twitter @hsplete)

*CORRECTION: 11/14/12: The original version of this story misidentified the hospital where Dr. Sokka works. The sentence should have read: "Dr. Tuulikki Sokka of Jyväskylä Central Hospital in Finland, and colleagues, assessed how RA could be more effectively controlled if patients received monitoring messages via their cell phones."

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

WASHINGTON – A daily dose of strontium ranelate was associated with a significant delay in joint space narrowing in adults with symptomatic primary knee osteoarthritis, based on data from the phase III Strontium Ranelate Knee Osteoarthritis Trial (SEKOIA).

Strontium renalate currently is not approved in the United States, but it is approved in more than 100 countries for treating osteoporosis, said Dr. Jean-Yves Reginster, who is head of the Center for Investigation in Bone and Articular Cartilage Metabolism at the University of Liège (Belgium).

Data from nonclinical studies have shown that strontium’s bone-building activity has a positive impact on cartilage as well, he noted at the annual meeting of the American College of Rheumatology.

To examine the effectiveness of strontium ranelate on the progression of knee osteoarthritis (OA), Dr. Reginster and his colleagues randomized 1,683 adults with symptomatic primary knee OA to 1 g of strontium ranelate per day (566 patients), 2 g/day (558 patients), or a placebo (559 patients). Complete data were available for 1,371 patients. The average age of the patients was 63 years, and 69% were women.

Overall, treatment with either dose of strontium was associated with a significant delay in the radiographic progression of knee OA, which was assessed by measuring the radiological joint space narrowing (JSN) of the medial tibiofemoral compartment of the knee joint.

After 1 year, joint space width decreased by 0.27 mm in the 2-g/day group, 0.23 mm in the 1-g/day group, and 0.37 mm in the placebo group. The differences between the 2-g/day and 1-g/day groups and the placebo group were 0.10 mm and 0.14 mm, respectively.

Significantly less radiological progression was noted in both strontium groups, compared with the placebo group. The percentage of patients with radiological progression (defined as joint space narrowing of at least 0.5 mm) was 26% in the 2-g/day group, 22% in the 1-g/day group, and 33% in the placebo group.

"The structural effect is translated clinically into a lower number of patients having a radiological progression over thresholds predictive of OA-related surgery," Dr. Reginster said. The findings suggest that strontium ranelate could reduce the need for knee surgery in OA patients, he added.

In addition, significantly more patients in the 2-g/day group exceeded the minimally perceptible clinical improvement (MCPI) threshold, compared with the placebo patients, on subscores of pain, stiffness, and physical function. The percentage of patients in the 1-g/day group above this threshold was not significantly higher than in the placebo group.

No significant differences in adverse events were observed among the three groups, and the incidence of serious adverse events was 17% in all groups.

The study findings also appeared online on Nov. 9 (Ann. Rheum. Dis. 2012 [doi:10.1136/annrheumdis-2012-202231]).

The study was sponsored by Servier. Dr. Reginster disclosed financial relationships with multiple companies, including Servier.

WASHINGTON – A daily dose of strontium ranelate was associated with a significant delay in joint space narrowing in adults with symptomatic primary knee osteoarthritis, based on data from the phase III Strontium Ranelate Knee Osteoarthritis Trial (SEKOIA).

Strontium renalate currently is not approved in the United States, but it is approved in more than 100 countries for treating osteoporosis, said Dr. Jean-Yves Reginster, who is head of the Center for Investigation in Bone and Articular Cartilage Metabolism at the University of Liège (Belgium).

Data from nonclinical studies have shown that strontium’s bone-building activity has a positive impact on cartilage as well, he noted at the annual meeting of the American College of Rheumatology.

To examine the effectiveness of strontium ranelate on the progression of knee osteoarthritis (OA), Dr. Reginster and his colleagues randomized 1,683 adults with symptomatic primary knee OA to 1 g of strontium ranelate per day (566 patients), 2 g/day (558 patients), or a placebo (559 patients). Complete data were available for 1,371 patients. The average age of the patients was 63 years, and 69% were women.

Overall, treatment with either dose of strontium was associated with a significant delay in the radiographic progression of knee OA, which was assessed by measuring the radiological joint space narrowing (JSN) of the medial tibiofemoral compartment of the knee joint.

After 1 year, joint space width decreased by 0.27 mm in the 2-g/day group, 0.23 mm in the 1-g/day group, and 0.37 mm in the placebo group. The differences between the 2-g/day and 1-g/day groups and the placebo group were 0.10 mm and 0.14 mm, respectively.

Significantly less radiological progression was noted in both strontium groups, compared with the placebo group. The percentage of patients with radiological progression (defined as joint space narrowing of at least 0.5 mm) was 26% in the 2-g/day group, 22% in the 1-g/day group, and 33% in the placebo group.

"The structural effect is translated clinically into a lower number of patients having a radiological progression over thresholds predictive of OA-related surgery," Dr. Reginster said. The findings suggest that strontium ranelate could reduce the need for knee surgery in OA patients, he added.

In addition, significantly more patients in the 2-g/day group exceeded the minimally perceptible clinical improvement (MCPI) threshold, compared with the placebo patients, on subscores of pain, stiffness, and physical function. The percentage of patients in the 1-g/day group above this threshold was not significantly higher than in the placebo group.

No significant differences in adverse events were observed among the three groups, and the incidence of serious adverse events was 17% in all groups.

The study findings also appeared online on Nov. 9 (Ann. Rheum. Dis. 2012 [doi:10.1136/annrheumdis-2012-202231]).

The study was sponsored by Servier. Dr. Reginster disclosed financial relationships with multiple companies, including Servier.

WASHINGTON – A daily dose of strontium ranelate was associated with a significant delay in joint space narrowing in adults with symptomatic primary knee osteoarthritis, based on data from the phase III Strontium Ranelate Knee Osteoarthritis Trial (SEKOIA).

Strontium renalate currently is not approved in the United States, but it is approved in more than 100 countries for treating osteoporosis, said Dr. Jean-Yves Reginster, who is head of the Center for Investigation in Bone and Articular Cartilage Metabolism at the University of Liège (Belgium).

Data from nonclinical studies have shown that strontium’s bone-building activity has a positive impact on cartilage as well, he noted at the annual meeting of the American College of Rheumatology.

To examine the effectiveness of strontium ranelate on the progression of knee osteoarthritis (OA), Dr. Reginster and his colleagues randomized 1,683 adults with symptomatic primary knee OA to 1 g of strontium ranelate per day (566 patients), 2 g/day (558 patients), or a placebo (559 patients). Complete data were available for 1,371 patients. The average age of the patients was 63 years, and 69% were women.

Overall, treatment with either dose of strontium was associated with a significant delay in the radiographic progression of knee OA, which was assessed by measuring the radiological joint space narrowing (JSN) of the medial tibiofemoral compartment of the knee joint.

After 1 year, joint space width decreased by 0.27 mm in the 2-g/day group, 0.23 mm in the 1-g/day group, and 0.37 mm in the placebo group. The differences between the 2-g/day and 1-g/day groups and the placebo group were 0.10 mm and 0.14 mm, respectively.

Significantly less radiological progression was noted in both strontium groups, compared with the placebo group. The percentage of patients with radiological progression (defined as joint space narrowing of at least 0.5 mm) was 26% in the 2-g/day group, 22% in the 1-g/day group, and 33% in the placebo group.

"The structural effect is translated clinically into a lower number of patients having a radiological progression over thresholds predictive of OA-related surgery," Dr. Reginster said. The findings suggest that strontium ranelate could reduce the need for knee surgery in OA patients, he added.

In addition, significantly more patients in the 2-g/day group exceeded the minimally perceptible clinical improvement (MCPI) threshold, compared with the placebo patients, on subscores of pain, stiffness, and physical function. The percentage of patients in the 1-g/day group above this threshold was not significantly higher than in the placebo group.

No significant differences in adverse events were observed among the three groups, and the incidence of serious adverse events was 17% in all groups.

The study findings also appeared online on Nov. 9 (Ann. Rheum. Dis. 2012 [doi:10.1136/annrheumdis-2012-202231]).

The study was sponsored by Servier. Dr. Reginster disclosed financial relationships with multiple companies, including Servier.

WASHINGTON – Exposure to angiotensin-converting enzyme inhibitors prior to the onset of renal crisis in patients with scleroderma increases the risk of death, according to 1-year findings from the prospective observational International Scleroderma Renal Crisis Survey.

The findings, which contrast with those from a preliminary analysis reported last year, suggest that clinicians caring for patients with systemic scleroderma should exercise caution when prescribing angiotensin-converting enzyme (ACE) inhibitors, Dr. Marie Hudson said at the annual meeting of the American College of Rheumatology, where she reported the survey results.

Of 75 patients who experienced scleroderma renal crisis (SRC) in the course of the study, 16 were taking an ACE inhibitor prior to onset of SRC. At the 1-year follow-up, 27 (36%) of the patients had died and 25% remained on dialysis. After adjusting for differences in prednisone exposure and history of systemic hypertension, ACE inhibitor exposure prior to SRC, compared with no such exposure, was associated with significantly increased risk of death (adjusted hazard ratio, 2.52), said Dr. Hudson of the division of rheumatology at McGill University, Montreal.

SRC is a rare but life-threatening complication of systemic sclerosis that typically presents with malignant hypertension and acute renal failure.

"Prior to the advent of ACE inhibitors, it was almost a universally deadly complication of scleroderma, but since the advent of ACE inhibitors, the outcomes of patients with scleroderma renal crisis have improved tremendously," Dr. Hudson said, noting also that some evidence suggest that the incidence of SRC has decreased over the past two decades as well – due, perhaps, to more liberal use of ACE inhibitors.

"So, given the benefits of ACE inhibitors to treat SRC along with this perceived decrease in the incidence of SRC, the prophylactic use of ACE inhibitors to prevent SRC has been considered. However, some would argue that there’s no clear physiologic rationale for this," she said, explaining that most patients with SRC are not hyperreninemic prior to renal crisis and that prophylactic treatment could mask hypertension and delay diagnosis, thus leading to worse outcomes in those who develop SRC.

In fact, recent retrospective data support the idea that those exposed prior to SRC may have worse outcomes, she noted.

The findings of this survey, which are important given the widespread availability of ACE inhibitors, confirm that, she said.

Patients included in the study were identified by physicians from numerous practices around the world who had agreed to participate in the survey. A total of 589 physicians were asked biweekly if they had made a diagnosis of SRC, and if so, they filled out a short case report form at that time and then submitted another 1 year later.

The patients had a mean age of 52 years, and 67% were women. Most (76%) had diffuse systemic scleroderma with a median disease duration of 1.5 years. SRC was hypertensive in 71 patients; only 5 patients had normotensive SRC, she noted.

The rate of prednisone use was surprisingly high at nearly 50% overall, but, more importantly, the mean daily dose was twice as high in the group of patients who were not exposed to ACE inhibitors prior to SRC (mean dose of 18 mg/day vs. 9 mg/day in the exposed group), Dr. Hudson said.

However, even after adjusting for prednisone use, the risk of death in exposed patients was more than twice that of nonexposed patients, and the difference was statistically significant, she said.

Although the precise risk of death after SRC remains uncertain, it does appear that caution when using ACE inhibitors in these patients is warranted, especially early in disease when the risk of SRC is the greatest, she said.

Dr. Hudson had no disclosures to report.

WASHINGTON – Exposure to angiotensin-converting enzyme inhibitors prior to the onset of renal crisis in patients with scleroderma increases the risk of death, according to 1-year findings from the prospective observational International Scleroderma Renal Crisis Survey.

The findings, which contrast with those from a preliminary analysis reported last year, suggest that clinicians caring for patients with systemic scleroderma should exercise caution when prescribing angiotensin-converting enzyme (ACE) inhibitors, Dr. Marie Hudson said at the annual meeting of the American College of Rheumatology, where she reported the survey results.

Of 75 patients who experienced scleroderma renal crisis (SRC) in the course of the study, 16 were taking an ACE inhibitor prior to onset of SRC. At the 1-year follow-up, 27 (36%) of the patients had died and 25% remained on dialysis. After adjusting for differences in prednisone exposure and history of systemic hypertension, ACE inhibitor exposure prior to SRC, compared with no such exposure, was associated with significantly increased risk of death (adjusted hazard ratio, 2.52), said Dr. Hudson of the division of rheumatology at McGill University, Montreal.

SRC is a rare but life-threatening complication of systemic sclerosis that typically presents with malignant hypertension and acute renal failure.

"Prior to the advent of ACE inhibitors, it was almost a universally deadly complication of scleroderma, but since the advent of ACE inhibitors, the outcomes of patients with scleroderma renal crisis have improved tremendously," Dr. Hudson said, noting also that some evidence suggest that the incidence of SRC has decreased over the past two decades as well – due, perhaps, to more liberal use of ACE inhibitors.

"So, given the benefits of ACE inhibitors to treat SRC along with this perceived decrease in the incidence of SRC, the prophylactic use of ACE inhibitors to prevent SRC has been considered. However, some would argue that there’s no clear physiologic rationale for this," she said, explaining that most patients with SRC are not hyperreninemic prior to renal crisis and that prophylactic treatment could mask hypertension and delay diagnosis, thus leading to worse outcomes in those who develop SRC.

In fact, recent retrospective data support the idea that those exposed prior to SRC may have worse outcomes, she noted.

The findings of this survey, which are important given the widespread availability of ACE inhibitors, confirm that, she said.

Patients included in the study were identified by physicians from numerous practices around the world who had agreed to participate in the survey. A total of 589 physicians were asked biweekly if they had made a diagnosis of SRC, and if so, they filled out a short case report form at that time and then submitted another 1 year later.

The patients had a mean age of 52 years, and 67% were women. Most (76%) had diffuse systemic scleroderma with a median disease duration of 1.5 years. SRC was hypertensive in 71 patients; only 5 patients had normotensive SRC, she noted.

The rate of prednisone use was surprisingly high at nearly 50% overall, but, more importantly, the mean daily dose was twice as high in the group of patients who were not exposed to ACE inhibitors prior to SRC (mean dose of 18 mg/day vs. 9 mg/day in the exposed group), Dr. Hudson said.

However, even after adjusting for prednisone use, the risk of death in exposed patients was more than twice that of nonexposed patients, and the difference was statistically significant, she said.

Although the precise risk of death after SRC remains uncertain, it does appear that caution when using ACE inhibitors in these patients is warranted, especially early in disease when the risk of SRC is the greatest, she said.

Dr. Hudson had no disclosures to report.

WASHINGTON – Exposure to angiotensin-converting enzyme inhibitors prior to the onset of renal crisis in patients with scleroderma increases the risk of death, according to 1-year findings from the prospective observational International Scleroderma Renal Crisis Survey.

The findings, which contrast with those from a preliminary analysis reported last year, suggest that clinicians caring for patients with systemic scleroderma should exercise caution when prescribing angiotensin-converting enzyme (ACE) inhibitors, Dr. Marie Hudson said at the annual meeting of the American College of Rheumatology, where she reported the survey results.

Of 75 patients who experienced scleroderma renal crisis (SRC) in the course of the study, 16 were taking an ACE inhibitor prior to onset of SRC. At the 1-year follow-up, 27 (36%) of the patients had died and 25% remained on dialysis. After adjusting for differences in prednisone exposure and history of systemic hypertension, ACE inhibitor exposure prior to SRC, compared with no such exposure, was associated with significantly increased risk of death (adjusted hazard ratio, 2.52), said Dr. Hudson of the division of rheumatology at McGill University, Montreal.

SRC is a rare but life-threatening complication of systemic sclerosis that typically presents with malignant hypertension and acute renal failure.

"Prior to the advent of ACE inhibitors, it was almost a universally deadly complication of scleroderma, but since the advent of ACE inhibitors, the outcomes of patients with scleroderma renal crisis have improved tremendously," Dr. Hudson said, noting also that some evidence suggest that the incidence of SRC has decreased over the past two decades as well – due, perhaps, to more liberal use of ACE inhibitors.

"So, given the benefits of ACE inhibitors to treat SRC along with this perceived decrease in the incidence of SRC, the prophylactic use of ACE inhibitors to prevent SRC has been considered. However, some would argue that there’s no clear physiologic rationale for this," she said, explaining that most patients with SRC are not hyperreninemic prior to renal crisis and that prophylactic treatment could mask hypertension and delay diagnosis, thus leading to worse outcomes in those who develop SRC.

In fact, recent retrospective data support the idea that those exposed prior to SRC may have worse outcomes, she noted.

The findings of this survey, which are important given the widespread availability of ACE inhibitors, confirm that, she said.

Patients included in the study were identified by physicians from numerous practices around the world who had agreed to participate in the survey. A total of 589 physicians were asked biweekly if they had made a diagnosis of SRC, and if so, they filled out a short case report form at that time and then submitted another 1 year later.

The patients had a mean age of 52 years, and 67% were women. Most (76%) had diffuse systemic scleroderma with a median disease duration of 1.5 years. SRC was hypertensive in 71 patients; only 5 patients had normotensive SRC, she noted.

The rate of prednisone use was surprisingly high at nearly 50% overall, but, more importantly, the mean daily dose was twice as high in the group of patients who were not exposed to ACE inhibitors prior to SRC (mean dose of 18 mg/day vs. 9 mg/day in the exposed group), Dr. Hudson said.

However, even after adjusting for prednisone use, the risk of death in exposed patients was more than twice that of nonexposed patients, and the difference was statistically significant, she said.

Although the precise risk of death after SRC remains uncertain, it does appear that caution when using ACE inhibitors in these patients is warranted, especially early in disease when the risk of SRC is the greatest, she said.

Dr. Hudson had no disclosures to report.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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