Canadian Rheumatology Association (CRA): Scientific Conference and Annual General Meeting

VICTORIA, B.C. – The risk for cardiovascular disease is greater in people with osteoarthritis, but the reason why remains unclear, researchers reported at the annual meeting of the Canadian Rheumatology Association.

Using diagnosis codes, a team led by M. Mushfiqur Rahman, a biostatistician at the Arthritis Research Center of the University of British Columbia, Vancouver and a doctoral student with the School of Population and Public Health there, compared risk by osteoarthritis (OA) in a random sample of adults from the province’s general population who were free of cardiovascular disease (CVD) at baseline.

In all, 12,624 people with prevalent or incident OA were matched with 61,131 unaffected people. With a mean follow-up of 13 years, there were 1.3 new cases of CVD per 100 person-years in the study sample, according to results reported in a poster session.

Analyses showed a statistically significant 19% increase in the risk of CVD in people who had OA vs. those without, after multivariate adjustment for a variety of potential confounders, such as hypertension, diabetes, and comorbidity burden.

In sex-stratified analyses, the elevation of risk was below average for men, whether they were younger than 65 years of age (12% increase in risk) or older than this age (13%). But it was notably above average for both women younger than age 65 years (41%) and women over this age (27%).

The mechanisms underlying the observed association are unknown, according to Mr. Rahman. Inflammation is one possibility, although there is no evidence to support this relationship at present.

"We cannot explain this relationship biologically," he commented in an interview. "Maybe reduced physical activity is a major factor here: After a diagnosis of OA, people are not as physically active as they were before."

"Prescription medication could also be a big factor," Mr. Rahman continued. "We didn’t adjust for any prescription drugs here," although patients with [OA] are more likely to be using acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids. "Those medications may have an effect [in elevating CVD risk]. We will see in the future."

The investigators are obtaining linked self-reported data that may shed further light on mechanisms. They will also be cross-checking the findings by assessing CVD mortality in patients with OA. If patients with OA prove to have higher CVD mortality, "that will be a good validation study."

In the meantime, physicians who see patients with OA may want to counsel them, "do more physical activity and take care of your heart," said Mr. Rahman.

Study participants were a random sample of individuals drawn from Population Data British Columbia for the years 1991 to 2009.

They were defined as having OA if the OA diagnostic code was used on either two or more visits to a health professional in 2 years or at least one discharge from the hospital. Similarly, they were defined as having CVD if they had a hospital record having a diagnosis code for ischemic heart disease, congestive heart failure, or stroke.

The mean age was about 58 years, and 59% of participants were women. About 16% had hypertension, 5% had hyperlipidemia, and 2% were obese. The mean Charlson comorbidity index was 0.41 in the OA group and 0.32 in the control group.

In addition to the elevated risk of CVD associated with OA (relative risk, 1.19), study results showed that participants were more likely to receive a CVD diagnosis if they had chronic obstructive pulmonary disease (1.18), had hypertension (1.38), were obese (1.21), or were in the lowest quintile of socioeconomic status (1.05). Also, risk increased with Charlson comorbidity index (1.11).

"There are some unmeasured confounders, for sure," Mr. Rahman acknowledged, noting that some variables, prescription drug use among them, were not available in the database used. Obesity was assessed from physician diagnoses instead of from body mass index; thus, the prevalence may have been underestimated. Also, "although we adjusted for [chronic obstructive pulmonary disease], smoking is an unmeasured confounder. And the physical activity level of the patients could be an unmeasured confounder, too."

Mr. Rahman disclosed that he had no relevant conflicts of interest.

VICTORIA, B.C. – The risk for cardiovascular disease is greater in people with osteoarthritis, but the reason why remains unclear, researchers reported at the annual meeting of the Canadian Rheumatology Association.

Using diagnosis codes, a team led by M. Mushfiqur Rahman, a biostatistician at the Arthritis Research Center of the University of British Columbia, Vancouver and a doctoral student with the School of Population and Public Health there, compared risk by osteoarthritis (OA) in a random sample of adults from the province’s general population who were free of cardiovascular disease (CVD) at baseline.

In all, 12,624 people with prevalent or incident OA were matched with 61,131 unaffected people. With a mean follow-up of 13 years, there were 1.3 new cases of CVD per 100 person-years in the study sample, according to results reported in a poster session.

Analyses showed a statistically significant 19% increase in the risk of CVD in people who had OA vs. those without, after multivariate adjustment for a variety of potential confounders, such as hypertension, diabetes, and comorbidity burden.

In sex-stratified analyses, the elevation of risk was below average for men, whether they were younger than 65 years of age (12% increase in risk) or older than this age (13%). But it was notably above average for both women younger than age 65 years (41%) and women over this age (27%).

The mechanisms underlying the observed association are unknown, according to Mr. Rahman. Inflammation is one possibility, although there is no evidence to support this relationship at present.

"We cannot explain this relationship biologically," he commented in an interview. "Maybe reduced physical activity is a major factor here: After a diagnosis of OA, people are not as physically active as they were before."

"Prescription medication could also be a big factor," Mr. Rahman continued. "We didn’t adjust for any prescription drugs here," although patients with [OA] are more likely to be using acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids. "Those medications may have an effect [in elevating CVD risk]. We will see in the future."

The investigators are obtaining linked self-reported data that may shed further light on mechanisms. They will also be cross-checking the findings by assessing CVD mortality in patients with OA. If patients with OA prove to have higher CVD mortality, "that will be a good validation study."

In the meantime, physicians who see patients with OA may want to counsel them, "do more physical activity and take care of your heart," said Mr. Rahman.

Study participants were a random sample of individuals drawn from Population Data British Columbia for the years 1991 to 2009.

They were defined as having OA if the OA diagnostic code was used on either two or more visits to a health professional in 2 years or at least one discharge from the hospital. Similarly, they were defined as having CVD if they had a hospital record having a diagnosis code for ischemic heart disease, congestive heart failure, or stroke.

The mean age was about 58 years, and 59% of participants were women. About 16% had hypertension, 5% had hyperlipidemia, and 2% were obese. The mean Charlson comorbidity index was 0.41 in the OA group and 0.32 in the control group.

In addition to the elevated risk of CVD associated with OA (relative risk, 1.19), study results showed that participants were more likely to receive a CVD diagnosis if they had chronic obstructive pulmonary disease (1.18), had hypertension (1.38), were obese (1.21), or were in the lowest quintile of socioeconomic status (1.05). Also, risk increased with Charlson comorbidity index (1.11).

"There are some unmeasured confounders, for sure," Mr. Rahman acknowledged, noting that some variables, prescription drug use among them, were not available in the database used. Obesity was assessed from physician diagnoses instead of from body mass index; thus, the prevalence may have been underestimated. Also, "although we adjusted for [chronic obstructive pulmonary disease], smoking is an unmeasured confounder. And the physical activity level of the patients could be an unmeasured confounder, too."

Mr. Rahman disclosed that he had no relevant conflicts of interest.

VICTORIA, B.C. – The risk for cardiovascular disease is greater in people with osteoarthritis, but the reason why remains unclear, researchers reported at the annual meeting of the Canadian Rheumatology Association.

Using diagnosis codes, a team led by M. Mushfiqur Rahman, a biostatistician at the Arthritis Research Center of the University of British Columbia, Vancouver and a doctoral student with the School of Population and Public Health there, compared risk by osteoarthritis (OA) in a random sample of adults from the province’s general population who were free of cardiovascular disease (CVD) at baseline.

In all, 12,624 people with prevalent or incident OA were matched with 61,131 unaffected people. With a mean follow-up of 13 years, there were 1.3 new cases of CVD per 100 person-years in the study sample, according to results reported in a poster session.

Analyses showed a statistically significant 19% increase in the risk of CVD in people who had OA vs. those without, after multivariate adjustment for a variety of potential confounders, such as hypertension, diabetes, and comorbidity burden.

In sex-stratified analyses, the elevation of risk was below average for men, whether they were younger than 65 years of age (12% increase in risk) or older than this age (13%). But it was notably above average for both women younger than age 65 years (41%) and women over this age (27%).

The mechanisms underlying the observed association are unknown, according to Mr. Rahman. Inflammation is one possibility, although there is no evidence to support this relationship at present.

"We cannot explain this relationship biologically," he commented in an interview. "Maybe reduced physical activity is a major factor here: After a diagnosis of OA, people are not as physically active as they were before."

"Prescription medication could also be a big factor," Mr. Rahman continued. "We didn’t adjust for any prescription drugs here," although patients with [OA] are more likely to be using acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids. "Those medications may have an effect [in elevating CVD risk]. We will see in the future."

The investigators are obtaining linked self-reported data that may shed further light on mechanisms. They will also be cross-checking the findings by assessing CVD mortality in patients with OA. If patients with OA prove to have higher CVD mortality, "that will be a good validation study."

In the meantime, physicians who see patients with OA may want to counsel them, "do more physical activity and take care of your heart," said Mr. Rahman.

Study participants were a random sample of individuals drawn from Population Data British Columbia for the years 1991 to 2009.

They were defined as having OA if the OA diagnostic code was used on either two or more visits to a health professional in 2 years or at least one discharge from the hospital. Similarly, they were defined as having CVD if they had a hospital record having a diagnosis code for ischemic heart disease, congestive heart failure, or stroke.

The mean age was about 58 years, and 59% of participants were women. About 16% had hypertension, 5% had hyperlipidemia, and 2% were obese. The mean Charlson comorbidity index was 0.41 in the OA group and 0.32 in the control group.

In addition to the elevated risk of CVD associated with OA (relative risk, 1.19), study results showed that participants were more likely to receive a CVD diagnosis if they had chronic obstructive pulmonary disease (1.18), had hypertension (1.38), were obese (1.21), or were in the lowest quintile of socioeconomic status (1.05). Also, risk increased with Charlson comorbidity index (1.11).

"There are some unmeasured confounders, for sure," Mr. Rahman acknowledged, noting that some variables, prescription drug use among them, were not available in the database used. Obesity was assessed from physician diagnoses instead of from body mass index; thus, the prevalence may have been underestimated. Also, "although we adjusted for [chronic obstructive pulmonary disease], smoking is an unmeasured confounder. And the physical activity level of the patients could be an unmeasured confounder, too."

Mr. Rahman disclosed that he had no relevant conflicts of interest.

VICTORIA, B.C. – The results of a cluster analysis may help streamline the diagnostic work-up in children with inflammatory brain diseases, sparing some of them invasive tests such as lumbar puncture or brain biopsy.

Investigators led by Dr. Tania Cellucci, a pediatric rheumatologist at the Hospital for Sick Children, University of Toronto, retrospectively analyzed presenting clinical, laboratory, and magnetic resonance imaging features in 147 pediatric patients having one of these diseases in an as-yet unpublished study.

The results, reported in a poster session at the annual meeting of the Canadian Rheumatology Association, identified three clusters of children who had different groups of diseases and who differed significantly with respect to the prevalence of various presenting features.

The investigators studied consecutive children seen at the hospital for inflammatory brain disease between December 1998 and June 2010, reviewing medical records to identify presenting clinical, laboratory, and imaging findings, and biopsy histology. The median age was about 9 years, and half the children were girls.

The most common disease was primary CNS vasculitis (seen in 71% of the children), Dr. Cellucci reported. That was followed by CNS vasculitis secondary to a systemic condition, such as lupus (7%), the neuronal antibody syndromes (6%), and postinfectious inflammatory brain disease (4%). The rest fell into a collective category of other diseases, such as neurosarcoidosis and inflammatory channelopathy (12%).

A k-means cluster analysis identified three distinct clusters:

• Patients in cluster 1 had angiography-negative primary CNS vasculitis and neuronal antibody syndromes that were due to antibodies against NMDA (N-methyl-d-aspartate).

• Patients in cluster 2 had angiography-negative primary CNS vasculitis and neuronal antibody syndromes that were due to antibodies against some other antigen.

• Patients in cluster 3 had angiography-positive primary CNS vasculitis and secondary CNS vasculitis.

The clusters differed significantly with respect to 14 presenting features. In terms of clinical features, patients in cluster 1 were more likely than their counterparts in the other clusters to have behavioral, cognitive, and mood changes, and seizures. Patients in cluster 2 were more likely to have ataxia, fatigue, and vision abnormalities. And patients in cluster 3 were more likely to be male and to have paresis and speech deficits.

Generally, laboratory features were not helpful in differentiating among clusters, Dr. Cellucci noted. For example, the proportions of patients having an elevated erythrocyte sedimentation rate and C-reactive protein level were essentially the same across clusters. The exception was that patients in cluster 3 were less likely to have an elevated cerebrospinal fluid white blood cell count.

In contrast, presenting MRI features were helpful (but not sufficient to confirm a diagnosis). Although the majority of patients in each cluster had some abnormalities on this imaging, the specific findings differed. Patients in cluster 3 were more likely than those in the other clusters to have unilateral lesions and ischemic lesions.

"The spectrum of childhood inflammatory brain diseases has really rapidly expanded over the past decade. A lot of new diseases have been described in the literature," Dr. Cellucci explained in an interview. Furthermore, these diseases have overlapping presenting features, leading to diagnostic uncertainty.

"So this is a new field with which a lot of people feel uncomfortable," she said. "This study is the first step in which we compare the different diseases and figure out whether can we use these findings to come up with a diagnostic algorithm."

If validated in an independent cohort, the findings may help clinicians "figure out which patient needs one test, which patient needs another test, and whether we can cut down on invasive tests, like a brain biopsy or a lumbar puncture, in patients who don’t actually need it," she said.

The study’s findings, while requiring validation, could help tailor the work-up to a child’s presenting features, according to Dr. Cellucci. "All patients will need an MRI, which is reasonable since this is not invasive. But patients in cluster 1 and 2 are those who may need a lumbar puncture, testing for neuronal antibodies, and possibly a biopsy. Patients who present with the findings typical for cluster 3 may require only an angiogram in addition to the MRI," she explained.

In addition, the findings may go a long way toward identifying children in the community whose inflammatory brain disease is misdiagnosed as some other condition, such as depression, psychosis, or seizure disorder.

"It would be a really important study to find out how many of these kids we are missing in the community," Dr. Cellucci commented. "One of the critical things is that we have treatment that works well for these patients: You treat them, and they get back to normal or almost normal, most of them. So that makes it even more critical to identify them."

She described the case of a girl who had seizures as her only symptom, but they did not improve with antiseizure medications. "As part of her work-up for more aggressive antiseizure therapy – which would be surgery – she had a brain biopsy that showed inflammation. We treated the inflammation and she is now seizure free," Dr. Cellucci said. "So I think that’s where it maybe becomes important to really figure out, how do we identify these kids and get them on the right therapy, because it is reversible for them."

Dr. Cellucci said that she had no relevant financial disclosures.

VICTORIA, B.C. – The results of a cluster analysis may help streamline the diagnostic work-up in children with inflammatory brain diseases, sparing some of them invasive tests such as lumbar puncture or brain biopsy.

Investigators led by Dr. Tania Cellucci, a pediatric rheumatologist at the Hospital for Sick Children, University of Toronto, retrospectively analyzed presenting clinical, laboratory, and magnetic resonance imaging features in 147 pediatric patients having one of these diseases in an as-yet unpublished study.

The results, reported in a poster session at the annual meeting of the Canadian Rheumatology Association, identified three clusters of children who had different groups of diseases and who differed significantly with respect to the prevalence of various presenting features.

The investigators studied consecutive children seen at the hospital for inflammatory brain disease between December 1998 and June 2010, reviewing medical records to identify presenting clinical, laboratory, and imaging findings, and biopsy histology. The median age was about 9 years, and half the children were girls.

The most common disease was primary CNS vasculitis (seen in 71% of the children), Dr. Cellucci reported. That was followed by CNS vasculitis secondary to a systemic condition, such as lupus (7%), the neuronal antibody syndromes (6%), and postinfectious inflammatory brain disease (4%). The rest fell into a collective category of other diseases, such as neurosarcoidosis and inflammatory channelopathy (12%).

A k-means cluster analysis identified three distinct clusters:

• Patients in cluster 1 had angiography-negative primary CNS vasculitis and neuronal antibody syndromes that were due to antibodies against NMDA (N-methyl-d-aspartate).

• Patients in cluster 2 had angiography-negative primary CNS vasculitis and neuronal antibody syndromes that were due to antibodies against some other antigen.

• Patients in cluster 3 had angiography-positive primary CNS vasculitis and secondary CNS vasculitis.

The clusters differed significantly with respect to 14 presenting features. In terms of clinical features, patients in cluster 1 were more likely than their counterparts in the other clusters to have behavioral, cognitive, and mood changes, and seizures. Patients in cluster 2 were more likely to have ataxia, fatigue, and vision abnormalities. And patients in cluster 3 were more likely to be male and to have paresis and speech deficits.

Generally, laboratory features were not helpful in differentiating among clusters, Dr. Cellucci noted. For example, the proportions of patients having an elevated erythrocyte sedimentation rate and C-reactive protein level were essentially the same across clusters. The exception was that patients in cluster 3 were less likely to have an elevated cerebrospinal fluid white blood cell count.

In contrast, presenting MRI features were helpful (but not sufficient to confirm a diagnosis). Although the majority of patients in each cluster had some abnormalities on this imaging, the specific findings differed. Patients in cluster 3 were more likely than those in the other clusters to have unilateral lesions and ischemic lesions.

"The spectrum of childhood inflammatory brain diseases has really rapidly expanded over the past decade. A lot of new diseases have been described in the literature," Dr. Cellucci explained in an interview. Furthermore, these diseases have overlapping presenting features, leading to diagnostic uncertainty.

"So this is a new field with which a lot of people feel uncomfortable," she said. "This study is the first step in which we compare the different diseases and figure out whether can we use these findings to come up with a diagnostic algorithm."

If validated in an independent cohort, the findings may help clinicians "figure out which patient needs one test, which patient needs another test, and whether we can cut down on invasive tests, like a brain biopsy or a lumbar puncture, in patients who don’t actually need it," she said.

The study’s findings, while requiring validation, could help tailor the work-up to a child’s presenting features, according to Dr. Cellucci. "All patients will need an MRI, which is reasonable since this is not invasive. But patients in cluster 1 and 2 are those who may need a lumbar puncture, testing for neuronal antibodies, and possibly a biopsy. Patients who present with the findings typical for cluster 3 may require only an angiogram in addition to the MRI," she explained.

In addition, the findings may go a long way toward identifying children in the community whose inflammatory brain disease is misdiagnosed as some other condition, such as depression, psychosis, or seizure disorder.

"It would be a really important study to find out how many of these kids we are missing in the community," Dr. Cellucci commented. "One of the critical things is that we have treatment that works well for these patients: You treat them, and they get back to normal or almost normal, most of them. So that makes it even more critical to identify them."

She described the case of a girl who had seizures as her only symptom, but they did not improve with antiseizure medications. "As part of her work-up for more aggressive antiseizure therapy – which would be surgery – she had a brain biopsy that showed inflammation. We treated the inflammation and she is now seizure free," Dr. Cellucci said. "So I think that’s where it maybe becomes important to really figure out, how do we identify these kids and get them on the right therapy, because it is reversible for them."

Dr. Cellucci said that she had no relevant financial disclosures.

VICTORIA, B.C. – The results of a cluster analysis may help streamline the diagnostic work-up in children with inflammatory brain diseases, sparing some of them invasive tests such as lumbar puncture or brain biopsy.

Investigators led by Dr. Tania Cellucci, a pediatric rheumatologist at the Hospital for Sick Children, University of Toronto, retrospectively analyzed presenting clinical, laboratory, and magnetic resonance imaging features in 147 pediatric patients having one of these diseases in an as-yet unpublished study.

The results, reported in a poster session at the annual meeting of the Canadian Rheumatology Association, identified three clusters of children who had different groups of diseases and who differed significantly with respect to the prevalence of various presenting features.

The investigators studied consecutive children seen at the hospital for inflammatory brain disease between December 1998 and June 2010, reviewing medical records to identify presenting clinical, laboratory, and imaging findings, and biopsy histology. The median age was about 9 years, and half the children were girls.

The most common disease was primary CNS vasculitis (seen in 71% of the children), Dr. Cellucci reported. That was followed by CNS vasculitis secondary to a systemic condition, such as lupus (7%), the neuronal antibody syndromes (6%), and postinfectious inflammatory brain disease (4%). The rest fell into a collective category of other diseases, such as neurosarcoidosis and inflammatory channelopathy (12%).

A k-means cluster analysis identified three distinct clusters:

• Patients in cluster 1 had angiography-negative primary CNS vasculitis and neuronal antibody syndromes that were due to antibodies against NMDA (N-methyl-d-aspartate).

• Patients in cluster 2 had angiography-negative primary CNS vasculitis and neuronal antibody syndromes that were due to antibodies against some other antigen.

• Patients in cluster 3 had angiography-positive primary CNS vasculitis and secondary CNS vasculitis.

The clusters differed significantly with respect to 14 presenting features. In terms of clinical features, patients in cluster 1 were more likely than their counterparts in the other clusters to have behavioral, cognitive, and mood changes, and seizures. Patients in cluster 2 were more likely to have ataxia, fatigue, and vision abnormalities. And patients in cluster 3 were more likely to be male and to have paresis and speech deficits.

Generally, laboratory features were not helpful in differentiating among clusters, Dr. Cellucci noted. For example, the proportions of patients having an elevated erythrocyte sedimentation rate and C-reactive protein level were essentially the same across clusters. The exception was that patients in cluster 3 were less likely to have an elevated cerebrospinal fluid white blood cell count.

In contrast, presenting MRI features were helpful (but not sufficient to confirm a diagnosis). Although the majority of patients in each cluster had some abnormalities on this imaging, the specific findings differed. Patients in cluster 3 were more likely than those in the other clusters to have unilateral lesions and ischemic lesions.

"The spectrum of childhood inflammatory brain diseases has really rapidly expanded over the past decade. A lot of new diseases have been described in the literature," Dr. Cellucci explained in an interview. Furthermore, these diseases have overlapping presenting features, leading to diagnostic uncertainty.

"So this is a new field with which a lot of people feel uncomfortable," she said. "This study is the first step in which we compare the different diseases and figure out whether can we use these findings to come up with a diagnostic algorithm."

If validated in an independent cohort, the findings may help clinicians "figure out which patient needs one test, which patient needs another test, and whether we can cut down on invasive tests, like a brain biopsy or a lumbar puncture, in patients who don’t actually need it," she said.

The study’s findings, while requiring validation, could help tailor the work-up to a child’s presenting features, according to Dr. Cellucci. "All patients will need an MRI, which is reasonable since this is not invasive. But patients in cluster 1 and 2 are those who may need a lumbar puncture, testing for neuronal antibodies, and possibly a biopsy. Patients who present with the findings typical for cluster 3 may require only an angiogram in addition to the MRI," she explained.

In addition, the findings may go a long way toward identifying children in the community whose inflammatory brain disease is misdiagnosed as some other condition, such as depression, psychosis, or seizure disorder.

"It would be a really important study to find out how many of these kids we are missing in the community," Dr. Cellucci commented. "One of the critical things is that we have treatment that works well for these patients: You treat them, and they get back to normal or almost normal, most of them. So that makes it even more critical to identify them."

She described the case of a girl who had seizures as her only symptom, but they did not improve with antiseizure medications. "As part of her work-up for more aggressive antiseizure therapy – which would be surgery – she had a brain biopsy that showed inflammation. We treated the inflammation and she is now seizure free," Dr. Cellucci said. "So I think that’s where it maybe becomes important to really figure out, how do we identify these kids and get them on the right therapy, because it is reversible for them."

Dr. Cellucci said that she had no relevant financial disclosures.

VICTORIA, B.C. – Patients with rheumatoid arthritis who also have common comorbidities are at increased risk for infection when starting treatment with at least one class of biologic agents, based on the findings of a cohort study.

Investigators led by Dr. Joanne Homik, director of the division of rheumatology at the University of Alberta in Edmonton, studied 1,086 patients with rheumatoid arthritis (RA) who were initiating treatment, in most cases with a biologic agent targeting tumor necrosis factor (TNF).

In adjusted analyses, patients had more than triple the risk of a serious infection, defined as one requiring hospitalization, if they had anemia, according to data from the as-yet unpublished study. In other findings, patients were 97% more likely to develop an infection if they had lung disease and 39% more likely if they had heart disease.

"The anemia variable has an unclear relationship, but we are looking into that further. Our theory is that with lung disease, that has some biologic plausibility since bronchitis and pneumonia have prominence in our list of infections seen in this cohort," Dr. Homik commented at the annual meeting of the Canadian Rheumatology Association.

The incidence density of serious infection was 1.67 cases per 100 patient-years, about half that found in some other cohorts. "One of the things we thought of when trying to explain why our serious infection risk is so low is that health care restructuring in Alberta in the mid-90s resulted in bed closures," she explained. "So hospitalizations were reduced overall, and many patients who ... could be considered seriously ill are not admitted any longer, and it can be a bit more challenging to [identify] those serious infections."

The study occurred shortly after anti-TNF agents first became available, so the patients receiving them usually had the most severe, long-standing RA, Dr. Homik noted. Over time, as the demographic of the database changes to include more patients within the first 5 years of their RA, outcomes may differ and predictors may differ as well.

The risk of any infection among patients starting anti-TNF agents did not differ from that among patients starting the disease-modifying antirheumatic drug (DMARD) leflunomide instead. However, leflunomide confers a higher infection risk than some other DMARDs, she noted.

The investigators used registry data to study a cohort of all 943 patients with RA in Alberta who started a first anti-TNF agent between January 2004 and March 2009, and also studied a comparison cohort of 143 patients who started leflunomide (Arava). The patients completed the self-administered comorbidity questionnaire at baseline and were monitored prospectively for outcomes and adverse events. Their average age was 54 years, and 70% were female.

With a mean follow-up of 2.3 years, 70% of patients developed an infection as ascertained from physician claims data or self-report; the most common were bronchitis, cellulitis, and sinusitis. Nearly 4% of patients developed a serious infection; the most common were pneumonia, cellulitis, septicemia, and septic arthritis.

In the first multivariate analysis, patients had an elevated risk of infection if they had heart disease (hazard ratio, 1.39) or lung disease (1.97), used steroids (1.2), or currently smoked (1.24). Their risk was decreased risk if they were male (HR, 0.78). When analysis was restricted to the subset who started an anti-TNF agent, infection risk was increased for those with lung disease (2.02) and decreased for men (0.80).

In the second multivariate analysis, patients had an elevated risk of serious infection if they had anemia (HR, 3.26) or used steroids (3.21), and a decreased risk if they had more than a secondary education (0.33). In the subset who started an anti-TNF agent, risk was increased for patients who had anemia (HR, 3.7) or used steroids (3.5), and decreased for those having more than a secondary education (0.3).

The risks of infection and serious infection did not differ across subgroups when patients were stratified according to whether they stayed on their first treatment or switched from one kind of DMARD to their first anti-TNF agent (or from one anti-TNF agent to another), Dr. Homik reported.

"In the cohort of patients on their first anti-TNF agent, the specific anti-TNF agent used did not predict risk of infection," she noted.

Dr. Homik disclosed that she serves as a consultant to Abbott, Amgen, Pfizer, and Roche. The Alberta Biologics Registry has received unrestricted grant support from Abbott, Amgen, Bristol-Myers Squibb, Merck/Jansson, and Pfizer.

VICTORIA, B.C. – Patients with rheumatoid arthritis who also have common comorbidities are at increased risk for infection when starting treatment with at least one class of biologic agents, based on the findings of a cohort study.

Investigators led by Dr. Joanne Homik, director of the division of rheumatology at the University of Alberta in Edmonton, studied 1,086 patients with rheumatoid arthritis (RA) who were initiating treatment, in most cases with a biologic agent targeting tumor necrosis factor (TNF).

In adjusted analyses, patients had more than triple the risk of a serious infection, defined as one requiring hospitalization, if they had anemia, according to data from the as-yet unpublished study. In other findings, patients were 97% more likely to develop an infection if they had lung disease and 39% more likely if they had heart disease.

"The anemia variable has an unclear relationship, but we are looking into that further. Our theory is that with lung disease, that has some biologic plausibility since bronchitis and pneumonia have prominence in our list of infections seen in this cohort," Dr. Homik commented at the annual meeting of the Canadian Rheumatology Association.

The incidence density of serious infection was 1.67 cases per 100 patient-years, about half that found in some other cohorts. "One of the things we thought of when trying to explain why our serious infection risk is so low is that health care restructuring in Alberta in the mid-90s resulted in bed closures," she explained. "So hospitalizations were reduced overall, and many patients who ... could be considered seriously ill are not admitted any longer, and it can be a bit more challenging to [identify] those serious infections."

The study occurred shortly after anti-TNF agents first became available, so the patients receiving them usually had the most severe, long-standing RA, Dr. Homik noted. Over time, as the demographic of the database changes to include more patients within the first 5 years of their RA, outcomes may differ and predictors may differ as well.

The risk of any infection among patients starting anti-TNF agents did not differ from that among patients starting the disease-modifying antirheumatic drug (DMARD) leflunomide instead. However, leflunomide confers a higher infection risk than some other DMARDs, she noted.

The investigators used registry data to study a cohort of all 943 patients with RA in Alberta who started a first anti-TNF agent between January 2004 and March 2009, and also studied a comparison cohort of 143 patients who started leflunomide (Arava). The patients completed the self-administered comorbidity questionnaire at baseline and were monitored prospectively for outcomes and adverse events. Their average age was 54 years, and 70% were female.

With a mean follow-up of 2.3 years, 70% of patients developed an infection as ascertained from physician claims data or self-report; the most common were bronchitis, cellulitis, and sinusitis. Nearly 4% of patients developed a serious infection; the most common were pneumonia, cellulitis, septicemia, and septic arthritis.

In the first multivariate analysis, patients had an elevated risk of infection if they had heart disease (hazard ratio, 1.39) or lung disease (1.97), used steroids (1.2), or currently smoked (1.24). Their risk was decreased risk if they were male (HR, 0.78). When analysis was restricted to the subset who started an anti-TNF agent, infection risk was increased for those with lung disease (2.02) and decreased for men (0.80).

In the second multivariate analysis, patients had an elevated risk of serious infection if they had anemia (HR, 3.26) or used steroids (3.21), and a decreased risk if they had more than a secondary education (0.33). In the subset who started an anti-TNF agent, risk was increased for patients who had anemia (HR, 3.7) or used steroids (3.5), and decreased for those having more than a secondary education (0.3).

The risks of infection and serious infection did not differ across subgroups when patients were stratified according to whether they stayed on their first treatment or switched from one kind of DMARD to their first anti-TNF agent (or from one anti-TNF agent to another), Dr. Homik reported.

"In the cohort of patients on their first anti-TNF agent, the specific anti-TNF agent used did not predict risk of infection," she noted.

Dr. Homik disclosed that she serves as a consultant to Abbott, Amgen, Pfizer, and Roche. The Alberta Biologics Registry has received unrestricted grant support from Abbott, Amgen, Bristol-Myers Squibb, Merck/Jansson, and Pfizer.

VICTORIA, B.C. – Patients with rheumatoid arthritis who also have common comorbidities are at increased risk for infection when starting treatment with at least one class of biologic agents, based on the findings of a cohort study.

Investigators led by Dr. Joanne Homik, director of the division of rheumatology at the University of Alberta in Edmonton, studied 1,086 patients with rheumatoid arthritis (RA) who were initiating treatment, in most cases with a biologic agent targeting tumor necrosis factor (TNF).

In adjusted analyses, patients had more than triple the risk of a serious infection, defined as one requiring hospitalization, if they had anemia, according to data from the as-yet unpublished study. In other findings, patients were 97% more likely to develop an infection if they had lung disease and 39% more likely if they had heart disease.

"The anemia variable has an unclear relationship, but we are looking into that further. Our theory is that with lung disease, that has some biologic plausibility since bronchitis and pneumonia have prominence in our list of infections seen in this cohort," Dr. Homik commented at the annual meeting of the Canadian Rheumatology Association.

The incidence density of serious infection was 1.67 cases per 100 patient-years, about half that found in some other cohorts. "One of the things we thought of when trying to explain why our serious infection risk is so low is that health care restructuring in Alberta in the mid-90s resulted in bed closures," she explained. "So hospitalizations were reduced overall, and many patients who ... could be considered seriously ill are not admitted any longer, and it can be a bit more challenging to [identify] those serious infections."

The study occurred shortly after anti-TNF agents first became available, so the patients receiving them usually had the most severe, long-standing RA, Dr. Homik noted. Over time, as the demographic of the database changes to include more patients within the first 5 years of their RA, outcomes may differ and predictors may differ as well.

The risk of any infection among patients starting anti-TNF agents did not differ from that among patients starting the disease-modifying antirheumatic drug (DMARD) leflunomide instead. However, leflunomide confers a higher infection risk than some other DMARDs, she noted.

The investigators used registry data to study a cohort of all 943 patients with RA in Alberta who started a first anti-TNF agent between January 2004 and March 2009, and also studied a comparison cohort of 143 patients who started leflunomide (Arava). The patients completed the self-administered comorbidity questionnaire at baseline and were monitored prospectively for outcomes and adverse events. Their average age was 54 years, and 70% were female.

With a mean follow-up of 2.3 years, 70% of patients developed an infection as ascertained from physician claims data or self-report; the most common were bronchitis, cellulitis, and sinusitis. Nearly 4% of patients developed a serious infection; the most common were pneumonia, cellulitis, septicemia, and septic arthritis.

In the first multivariate analysis, patients had an elevated risk of infection if they had heart disease (hazard ratio, 1.39) or lung disease (1.97), used steroids (1.2), or currently smoked (1.24). Their risk was decreased risk if they were male (HR, 0.78). When analysis was restricted to the subset who started an anti-TNF agent, infection risk was increased for those with lung disease (2.02) and decreased for men (0.80).

In the second multivariate analysis, patients had an elevated risk of serious infection if they had anemia (HR, 3.26) or used steroids (3.21), and a decreased risk if they had more than a secondary education (0.33). In the subset who started an anti-TNF agent, risk was increased for patients who had anemia (HR, 3.7) or used steroids (3.5), and decreased for those having more than a secondary education (0.3).

The risks of infection and serious infection did not differ across subgroups when patients were stratified according to whether they stayed on their first treatment or switched from one kind of DMARD to their first anti-TNF agent (or from one anti-TNF agent to another), Dr. Homik reported.

"In the cohort of patients on their first anti-TNF agent, the specific anti-TNF agent used did not predict risk of infection," she noted.

Dr. Homik disclosed that she serves as a consultant to Abbott, Amgen, Pfizer, and Roche. The Alberta Biologics Registry has received unrestricted grant support from Abbott, Amgen, Bristol-Myers Squibb, Merck/Jansson, and Pfizer.

VICTORIA, B.C. – Suboptimal vitamin D levels may play a role in the pathogenesis of inflammatory arthritis but not in its subsequent clinical course, judging from the findings of a study involving 264 adult patients with early disease.

Fully 77% of patients had vitamin D deficiency or insufficiency at baseline, reported lead investigator Dr. Carol A. Hitchon at the annual meeting of Canadian Rheumatology Association. But in findings that contrasted those of some earlier studies, levels were not significantly associated with disease activity at that time or with achievement of remission 1 year later.

The study also found that vitamin D levels did not correlate with levels of immunoglobulin directed against common pathogens implicated in the development of rheumatoid arthritis.

"It’s possible that vitamin D levels may not be that important in terms of clinical activity and that vitamin D status may be more important in predisposing to rheumatoid arthritis," Dr. Hitchon commented. "I don’t think vitamin D is the only answer. And I think it’s not just the level, it is probably other elements of the vitamin D pathway that might be important, in terms of how they may regulate autoimmune processes."

A session attendee wondered whether patients with inflammatory arthritis may simply have lower levels of this vitamin because they go out in the sun less.

That is a possible explanation, acknowledged Dr. Hitchon of the arthritis center at the University of Manitoba in Winnipeg. "We are hoping to measure vitamin D levels in a population that generally has more sun exposure based on where they reside, and that may give us some correlation," she added.

Accumulating data suggest that vitamin D plays a role in maintaining both tolerance and immunity to pathogens. Thus, the investigators hypothesized, "if you are deficient in vitamin D, it may lead to a break of self-tolerance and the development of autoimmunity. Similarly, deficient vitamin D can impair or alter the initial response to pathogens, leading to increased microbial load, which can also increase or affect autoimmunity," Dr. Hitchon said.

She and her colleagues studied patients from the Manitoba Early Arthritis Cohort. All of the patients had had symptoms of inflammatory arthritis for no more than 1 year, and had at least one swollen joint.

The severity of their arthritis was assessed with the DAS28-CRP (28-joint count Disease Activity Score, C-reactive protein). Circulating levels of 25-hydroxyvitamin D and antibodies to Escherichia coli and Proteus mirabilis – both of which have been implicated in rheumatoid arthritis – were measured in serum collected before the start of treatment.

The average age of the patients studied was 48 years, and 76% were women. Overall, 60% were rheumatoid factor–positive, and 49% were positive for CCP2 (cyclic citrullinated peptide, second-generation assay). Their mean DAS28-CRP score was 3.99.

Results showed that 16% of patients had vitamin D deficiency and 61% had vitamin D insufficiency, while just 23% had optimal levels. Smokers had significantly lower levels than did nonsmokers.

There was no association at baseline between vitamin D levels and rheumatoid factor or CCP2 levels, DAS28-CRP score, or several other measures of disease activity, reported Dr. Hitchon, who disclosed no relevant conflicts of interest.

In adjusted analyses, vitamin D levels were not significantly associated with DAS28-CRP score at baseline or with achievement of remission 1 year later. "As has been previously shown, the major predictor of 1-year outcome was the baseline DAS score," she noted.

During the study, 20% of patients had an improvement in their vitamin D levels, moving to a higher category, whereas 12% of patients had a worsening, moving to a lower category. "This is without any formal protocol or plan to supplement vitamin D," Dr. Hitchon pointed out.

There was also no significant correlation between vitamin D levels and levels of immunoglobulins –whether IgA, IgM, or IgG – to E. coli or P. mirabilis.

Dr. Hitchon disclosed no relevant conflicts of interest.

VICTORIA, B.C. – Suboptimal vitamin D levels may play a role in the pathogenesis of inflammatory arthritis but not in its subsequent clinical course, judging from the findings of a study involving 264 adult patients with early disease.

Fully 77% of patients had vitamin D deficiency or insufficiency at baseline, reported lead investigator Dr. Carol A. Hitchon at the annual meeting of Canadian Rheumatology Association. But in findings that contrasted those of some earlier studies, levels were not significantly associated with disease activity at that time or with achievement of remission 1 year later.

The study also found that vitamin D levels did not correlate with levels of immunoglobulin directed against common pathogens implicated in the development of rheumatoid arthritis.

"It’s possible that vitamin D levels may not be that important in terms of clinical activity and that vitamin D status may be more important in predisposing to rheumatoid arthritis," Dr. Hitchon commented. "I don’t think vitamin D is the only answer. And I think it’s not just the level, it is probably other elements of the vitamin D pathway that might be important, in terms of how they may regulate autoimmune processes."

A session attendee wondered whether patients with inflammatory arthritis may simply have lower levels of this vitamin because they go out in the sun less.

That is a possible explanation, acknowledged Dr. Hitchon of the arthritis center at the University of Manitoba in Winnipeg. "We are hoping to measure vitamin D levels in a population that generally has more sun exposure based on where they reside, and that may give us some correlation," she added.

Accumulating data suggest that vitamin D plays a role in maintaining both tolerance and immunity to pathogens. Thus, the investigators hypothesized, "if you are deficient in vitamin D, it may lead to a break of self-tolerance and the development of autoimmunity. Similarly, deficient vitamin D can impair or alter the initial response to pathogens, leading to increased microbial load, which can also increase or affect autoimmunity," Dr. Hitchon said.

She and her colleagues studied patients from the Manitoba Early Arthritis Cohort. All of the patients had had symptoms of inflammatory arthritis for no more than 1 year, and had at least one swollen joint.

The severity of their arthritis was assessed with the DAS28-CRP (28-joint count Disease Activity Score, C-reactive protein). Circulating levels of 25-hydroxyvitamin D and antibodies to Escherichia coli and Proteus mirabilis – both of which have been implicated in rheumatoid arthritis – were measured in serum collected before the start of treatment.

The average age of the patients studied was 48 years, and 76% were women. Overall, 60% were rheumatoid factor–positive, and 49% were positive for CCP2 (cyclic citrullinated peptide, second-generation assay). Their mean DAS28-CRP score was 3.99.

Results showed that 16% of patients had vitamin D deficiency and 61% had vitamin D insufficiency, while just 23% had optimal levels. Smokers had significantly lower levels than did nonsmokers.

There was no association at baseline between vitamin D levels and rheumatoid factor or CCP2 levels, DAS28-CRP score, or several other measures of disease activity, reported Dr. Hitchon, who disclosed no relevant conflicts of interest.

In adjusted analyses, vitamin D levels were not significantly associated with DAS28-CRP score at baseline or with achievement of remission 1 year later. "As has been previously shown, the major predictor of 1-year outcome was the baseline DAS score," she noted.

During the study, 20% of patients had an improvement in their vitamin D levels, moving to a higher category, whereas 12% of patients had a worsening, moving to a lower category. "This is without any formal protocol or plan to supplement vitamin D," Dr. Hitchon pointed out.

There was also no significant correlation between vitamin D levels and levels of immunoglobulins –whether IgA, IgM, or IgG – to E. coli or P. mirabilis.

Dr. Hitchon disclosed no relevant conflicts of interest.

VICTORIA, B.C. – Suboptimal vitamin D levels may play a role in the pathogenesis of inflammatory arthritis but not in its subsequent clinical course, judging from the findings of a study involving 264 adult patients with early disease.

Fully 77% of patients had vitamin D deficiency or insufficiency at baseline, reported lead investigator Dr. Carol A. Hitchon at the annual meeting of Canadian Rheumatology Association. But in findings that contrasted those of some earlier studies, levels were not significantly associated with disease activity at that time or with achievement of remission 1 year later.

The study also found that vitamin D levels did not correlate with levels of immunoglobulin directed against common pathogens implicated in the development of rheumatoid arthritis.

"It’s possible that vitamin D levels may not be that important in terms of clinical activity and that vitamin D status may be more important in predisposing to rheumatoid arthritis," Dr. Hitchon commented. "I don’t think vitamin D is the only answer. And I think it’s not just the level, it is probably other elements of the vitamin D pathway that might be important, in terms of how they may regulate autoimmune processes."

A session attendee wondered whether patients with inflammatory arthritis may simply have lower levels of this vitamin because they go out in the sun less.

That is a possible explanation, acknowledged Dr. Hitchon of the arthritis center at the University of Manitoba in Winnipeg. "We are hoping to measure vitamin D levels in a population that generally has more sun exposure based on where they reside, and that may give us some correlation," she added.

Accumulating data suggest that vitamin D plays a role in maintaining both tolerance and immunity to pathogens. Thus, the investigators hypothesized, "if you are deficient in vitamin D, it may lead to a break of self-tolerance and the development of autoimmunity. Similarly, deficient vitamin D can impair or alter the initial response to pathogens, leading to increased microbial load, which can also increase or affect autoimmunity," Dr. Hitchon said.

She and her colleagues studied patients from the Manitoba Early Arthritis Cohort. All of the patients had had symptoms of inflammatory arthritis for no more than 1 year, and had at least one swollen joint.

The severity of their arthritis was assessed with the DAS28-CRP (28-joint count Disease Activity Score, C-reactive protein). Circulating levels of 25-hydroxyvitamin D and antibodies to Escherichia coli and Proteus mirabilis – both of which have been implicated in rheumatoid arthritis – were measured in serum collected before the start of treatment.

The average age of the patients studied was 48 years, and 76% were women. Overall, 60% were rheumatoid factor–positive, and 49% were positive for CCP2 (cyclic citrullinated peptide, second-generation assay). Their mean DAS28-CRP score was 3.99.

Results showed that 16% of patients had vitamin D deficiency and 61% had vitamin D insufficiency, while just 23% had optimal levels. Smokers had significantly lower levels than did nonsmokers.

There was no association at baseline between vitamin D levels and rheumatoid factor or CCP2 levels, DAS28-CRP score, or several other measures of disease activity, reported Dr. Hitchon, who disclosed no relevant conflicts of interest.

In adjusted analyses, vitamin D levels were not significantly associated with DAS28-CRP score at baseline or with achievement of remission 1 year later. "As has been previously shown, the major predictor of 1-year outcome was the baseline DAS score," she noted.

During the study, 20% of patients had an improvement in their vitamin D levels, moving to a higher category, whereas 12% of patients had a worsening, moving to a lower category. "This is without any formal protocol or plan to supplement vitamin D," Dr. Hitchon pointed out.

There was also no significant correlation between vitamin D levels and levels of immunoglobulins –whether IgA, IgM, or IgG – to E. coli or P. mirabilis.

Dr. Hitchon disclosed no relevant conflicts of interest.