Psoriasis

ESTES PARK, COLO. – The high false-positive rates for autoimmune serologies make them unsuitable as screening tests for connective tissue diseases, according to Dr. Robert W. Janson.

Moreover, the prearranged test panels often pitched to primary care physicians are a particularly bad idea, he said. These panels might combine, for example, rheumatoid factor (RF), antinuclear antibodies, erythrocyte sedimentation rate (ESR), and C-reactive protein.

"I call them ‘rheum rally packs.’ They should be avoided. They can multiply testing errors, leading to additional unnecessary testing, needless angst, and inappropriate treatment," said Dr. Janson, chief of the rheumatology section at the Denver Veterans Affairs Medical Center.

Selectivity is the watchword when ordering autoimmune serologic tests. Their value comes when suspicion of a connective tissue disease (CTD) is already high based on history and physical examination, that is, when the pretest probability is relatively high, he explained at an update on internal medicine sponsored by the University of Colorado.

Take, for example, rheumatoid factor. The very name is a misnomer, suggesting a high test specificity that’s completely undeserved. While 80% of patients with rheumatoid arthritis are indeed RF+, the test is also positive in the majority of individuals with Sjögren’s syndrome or mixed CDT; in many patients with chronic infection, malignancy, or fibrotic pulmonary disorders; and even in 5% of healthy individuals. As a result, the test’s positive predictive value for rheumatoid arthritis is a mere 24%, although its negative predictive value is much better at 89%.

"Rheumatoid factor has little value as a screening test to diagnose or exclude CTD in patients with just plain arthralgias. It has a much higher positive predictive value if ordered selectively in patients with a higher probability of a CTD: morning stiffness, sicca symptoms, and arthralgias or synovitis in a rheumatoid arthritis distribution," the rheumatologist continued.

The combination of a positive RF and a positive test for anticyclic citrullinated peptide antibodies (ACPAs) is associated with a nearly 100% likelihood that an appropriately symptomatic patient has rheumatoid arthritis. Also, when both tests are positive, it’s an indicator of a more serious case of rheumatoid arthritis that will involve joint damage and disability.

"These patients need more aggressive therapy," Dr. Janson noted.

On the other hand, he said he’d urge that a patient with morning stiffness lasting longer than 1 hour, tenderness of the metacarpophalangeal or metatarsophalangeal joints, and suspected synovitis on physical examination be referred to a rheumatologist to see if an early inflammatory arthritis is involved, even if the RF and/or ACPA tests are negative. In this era of highly effective biologic therapy, negative serologic tests don’t preclude early and aggressive therapy, he noted.

Nearly all patients with SLE will have a positive antinuclear antibody (ANA) test. A negative test rules out SLE with 95% certainty. But the test’s positive predictive value for SLE is only 11%-30% because so many other conditions are associated with a positive ANA. These include numerous other CTDs, organ-specific autoimmune diseases such as Hashimoto’s thyroiditis, a variety of chronic infections, and lymphoproliferative disorders. In addition, low-titer positive ANA tests are not uncommon in normal women and the elderly.

In sum, ANA testing is useful to help establish a diagnosis when a patient’s clinical features suggest a CTD, as well as for excluding CTDs in patients with uncertain clinical findings, and in monitoring CTD disease activity. Rheumatologists consider ANA titers of 1:320 or higher to be more clinically meaningful, according to Dr. Janson.

He singled out a particular ANA subantibody test – that for antihistone antibodies – as one that "approaches being the perfect test." That’s because patients with drug-induced lupus don’t make antibodies to nonhistone nuclear antigens. As a result, antihistone antibody testing enjoys greater than 95% sensitivity and specificity for drug-induced lupus.

Two ANA subantibody tests are highly diagnostic for SLE. These are anti–double-stranded DNA and anti–Smith antibody tests, each with a specificity in excess of 95% for SLE.

The antineutrophil cytoplasmic antibody (ANCA) tests are the first serologies to order when a patient is suspected of having some kind of vasculitis as manifest, for example, by diffuse alveolar hemorrhage, nephritis without another explanation, or a pulmonary-renal syndrome.

ANCAs come in two types: cytoplasmic (cANCA), which are antibodies directed against proteinase 3, and perinuclear (pANCA), directed most often against myeloperoxidase.

The cANCA test has 98% specificity for active generalized granulomatosis with polyangiitis, formerly known as Wegener’s granulomatosis. However, limited granulomatosis with polyangiitis affecting, say, the sinuses but without kidney involvement may be ANCA negative in 40% of cases.

The pANCA test has 60%-90% sensitivity for microscopic polyangiitis, but poor sensitivity, as the test can be positive in rheumatoid arthritis and several other CTDs. However, the specificity for microscopic polyangiitis improves to greater than 95% in the setting of both positive pANCA and antimyeloperoxidase ELISA tests.

The acute phase reactants – C-reactive protein and ESR are useful in assessing patients with a suspected malignancy or infection, as well as in those in whom inflammatory arthritides or vasculitis is a concern. A CRP greater than 1.0 mg/dL indicates significant inflammation, and a value in excess of 10 mg/dL is due either to metastatic cancer, bacterial infection, or systemic vasculitis. And if both the ESR and CRP are normal, the probability that a patient has a vasculitis is "incredibly low," Dr. Janson said.

At least 80% of patients with polymyalgia rheumatica will have an elevated ESR, and the CRP should be elevated in those that don’t.

Dr. Janson reported having no relevant financial conflicts.

ESTES PARK, COLO. – The high false-positive rates for autoimmune serologies make them unsuitable as screening tests for connective tissue diseases, according to Dr. Robert W. Janson.

Moreover, the prearranged test panels often pitched to primary care physicians are a particularly bad idea, he said. These panels might combine, for example, rheumatoid factor (RF), antinuclear antibodies, erythrocyte sedimentation rate (ESR), and C-reactive protein.

"I call them ‘rheum rally packs.’ They should be avoided. They can multiply testing errors, leading to additional unnecessary testing, needless angst, and inappropriate treatment," said Dr. Janson, chief of the rheumatology section at the Denver Veterans Affairs Medical Center.

Selectivity is the watchword when ordering autoimmune serologic tests. Their value comes when suspicion of a connective tissue disease (CTD) is already high based on history and physical examination, that is, when the pretest probability is relatively high, he explained at an update on internal medicine sponsored by the University of Colorado.

Take, for example, rheumatoid factor. The very name is a misnomer, suggesting a high test specificity that’s completely undeserved. While 80% of patients with rheumatoid arthritis are indeed RF+, the test is also positive in the majority of individuals with Sjögren’s syndrome or mixed CDT; in many patients with chronic infection, malignancy, or fibrotic pulmonary disorders; and even in 5% of healthy individuals. As a result, the test’s positive predictive value for rheumatoid arthritis is a mere 24%, although its negative predictive value is much better at 89%.

"Rheumatoid factor has little value as a screening test to diagnose or exclude CTD in patients with just plain arthralgias. It has a much higher positive predictive value if ordered selectively in patients with a higher probability of a CTD: morning stiffness, sicca symptoms, and arthralgias or synovitis in a rheumatoid arthritis distribution," the rheumatologist continued.

The combination of a positive RF and a positive test for anticyclic citrullinated peptide antibodies (ACPAs) is associated with a nearly 100% likelihood that an appropriately symptomatic patient has rheumatoid arthritis. Also, when both tests are positive, it’s an indicator of a more serious case of rheumatoid arthritis that will involve joint damage and disability.

"These patients need more aggressive therapy," Dr. Janson noted.

On the other hand, he said he’d urge that a patient with morning stiffness lasting longer than 1 hour, tenderness of the metacarpophalangeal or metatarsophalangeal joints, and suspected synovitis on physical examination be referred to a rheumatologist to see if an early inflammatory arthritis is involved, even if the RF and/or ACPA tests are negative. In this era of highly effective biologic therapy, negative serologic tests don’t preclude early and aggressive therapy, he noted.

Nearly all patients with SLE will have a positive antinuclear antibody (ANA) test. A negative test rules out SLE with 95% certainty. But the test’s positive predictive value for SLE is only 11%-30% because so many other conditions are associated with a positive ANA. These include numerous other CTDs, organ-specific autoimmune diseases such as Hashimoto’s thyroiditis, a variety of chronic infections, and lymphoproliferative disorders. In addition, low-titer positive ANA tests are not uncommon in normal women and the elderly.

In sum, ANA testing is useful to help establish a diagnosis when a patient’s clinical features suggest a CTD, as well as for excluding CTDs in patients with uncertain clinical findings, and in monitoring CTD disease activity. Rheumatologists consider ANA titers of 1:320 or higher to be more clinically meaningful, according to Dr. Janson.

He singled out a particular ANA subantibody test – that for antihistone antibodies – as one that "approaches being the perfect test." That’s because patients with drug-induced lupus don’t make antibodies to nonhistone nuclear antigens. As a result, antihistone antibody testing enjoys greater than 95% sensitivity and specificity for drug-induced lupus.

Two ANA subantibody tests are highly diagnostic for SLE. These are anti–double-stranded DNA and anti–Smith antibody tests, each with a specificity in excess of 95% for SLE.

The antineutrophil cytoplasmic antibody (ANCA) tests are the first serologies to order when a patient is suspected of having some kind of vasculitis as manifest, for example, by diffuse alveolar hemorrhage, nephritis without another explanation, or a pulmonary-renal syndrome.

ANCAs come in two types: cytoplasmic (cANCA), which are antibodies directed against proteinase 3, and perinuclear (pANCA), directed most often against myeloperoxidase.

The cANCA test has 98% specificity for active generalized granulomatosis with polyangiitis, formerly known as Wegener’s granulomatosis. However, limited granulomatosis with polyangiitis affecting, say, the sinuses but without kidney involvement may be ANCA negative in 40% of cases.

The pANCA test has 60%-90% sensitivity for microscopic polyangiitis, but poor sensitivity, as the test can be positive in rheumatoid arthritis and several other CTDs. However, the specificity for microscopic polyangiitis improves to greater than 95% in the setting of both positive pANCA and antimyeloperoxidase ELISA tests.

The acute phase reactants – C-reactive protein and ESR are useful in assessing patients with a suspected malignancy or infection, as well as in those in whom inflammatory arthritides or vasculitis is a concern. A CRP greater than 1.0 mg/dL indicates significant inflammation, and a value in excess of 10 mg/dL is due either to metastatic cancer, bacterial infection, or systemic vasculitis. And if both the ESR and CRP are normal, the probability that a patient has a vasculitis is "incredibly low," Dr. Janson said.

At least 80% of patients with polymyalgia rheumatica will have an elevated ESR, and the CRP should be elevated in those that don’t.

Dr. Janson reported having no relevant financial conflicts.

ESTES PARK, COLO. – The high false-positive rates for autoimmune serologies make them unsuitable as screening tests for connective tissue diseases, according to Dr. Robert W. Janson.

Moreover, the prearranged test panels often pitched to primary care physicians are a particularly bad idea, he said. These panels might combine, for example, rheumatoid factor (RF), antinuclear antibodies, erythrocyte sedimentation rate (ESR), and C-reactive protein.

"I call them ‘rheum rally packs.’ They should be avoided. They can multiply testing errors, leading to additional unnecessary testing, needless angst, and inappropriate treatment," said Dr. Janson, chief of the rheumatology section at the Denver Veterans Affairs Medical Center.

Selectivity is the watchword when ordering autoimmune serologic tests. Their value comes when suspicion of a connective tissue disease (CTD) is already high based on history and physical examination, that is, when the pretest probability is relatively high, he explained at an update on internal medicine sponsored by the University of Colorado.

Take, for example, rheumatoid factor. The very name is a misnomer, suggesting a high test specificity that’s completely undeserved. While 80% of patients with rheumatoid arthritis are indeed RF+, the test is also positive in the majority of individuals with Sjögren’s syndrome or mixed CDT; in many patients with chronic infection, malignancy, or fibrotic pulmonary disorders; and even in 5% of healthy individuals. As a result, the test’s positive predictive value for rheumatoid arthritis is a mere 24%, although its negative predictive value is much better at 89%.

"Rheumatoid factor has little value as a screening test to diagnose or exclude CTD in patients with just plain arthralgias. It has a much higher positive predictive value if ordered selectively in patients with a higher probability of a CTD: morning stiffness, sicca symptoms, and arthralgias or synovitis in a rheumatoid arthritis distribution," the rheumatologist continued.

The combination of a positive RF and a positive test for anticyclic citrullinated peptide antibodies (ACPAs) is associated with a nearly 100% likelihood that an appropriately symptomatic patient has rheumatoid arthritis. Also, when both tests are positive, it’s an indicator of a more serious case of rheumatoid arthritis that will involve joint damage and disability.

"These patients need more aggressive therapy," Dr. Janson noted.

On the other hand, he said he’d urge that a patient with morning stiffness lasting longer than 1 hour, tenderness of the metacarpophalangeal or metatarsophalangeal joints, and suspected synovitis on physical examination be referred to a rheumatologist to see if an early inflammatory arthritis is involved, even if the RF and/or ACPA tests are negative. In this era of highly effective biologic therapy, negative serologic tests don’t preclude early and aggressive therapy, he noted.

Nearly all patients with SLE will have a positive antinuclear antibody (ANA) test. A negative test rules out SLE with 95% certainty. But the test’s positive predictive value for SLE is only 11%-30% because so many other conditions are associated with a positive ANA. These include numerous other CTDs, organ-specific autoimmune diseases such as Hashimoto’s thyroiditis, a variety of chronic infections, and lymphoproliferative disorders. In addition, low-titer positive ANA tests are not uncommon in normal women and the elderly.

In sum, ANA testing is useful to help establish a diagnosis when a patient’s clinical features suggest a CTD, as well as for excluding CTDs in patients with uncertain clinical findings, and in monitoring CTD disease activity. Rheumatologists consider ANA titers of 1:320 or higher to be more clinically meaningful, according to Dr. Janson.

He singled out a particular ANA subantibody test – that for antihistone antibodies – as one that "approaches being the perfect test." That’s because patients with drug-induced lupus don’t make antibodies to nonhistone nuclear antigens. As a result, antihistone antibody testing enjoys greater than 95% sensitivity and specificity for drug-induced lupus.

Two ANA subantibody tests are highly diagnostic for SLE. These are anti–double-stranded DNA and anti–Smith antibody tests, each with a specificity in excess of 95% for SLE.

The antineutrophil cytoplasmic antibody (ANCA) tests are the first serologies to order when a patient is suspected of having some kind of vasculitis as manifest, for example, by diffuse alveolar hemorrhage, nephritis without another explanation, or a pulmonary-renal syndrome.

ANCAs come in two types: cytoplasmic (cANCA), which are antibodies directed against proteinase 3, and perinuclear (pANCA), directed most often against myeloperoxidase.

The cANCA test has 98% specificity for active generalized granulomatosis with polyangiitis, formerly known as Wegener’s granulomatosis. However, limited granulomatosis with polyangiitis affecting, say, the sinuses but without kidney involvement may be ANCA negative in 40% of cases.

The pANCA test has 60%-90% sensitivity for microscopic polyangiitis, but poor sensitivity, as the test can be positive in rheumatoid arthritis and several other CTDs. However, the specificity for microscopic polyangiitis improves to greater than 95% in the setting of both positive pANCA and antimyeloperoxidase ELISA tests.

The acute phase reactants – C-reactive protein and ESR are useful in assessing patients with a suspected malignancy or infection, as well as in those in whom inflammatory arthritides or vasculitis is a concern. A CRP greater than 1.0 mg/dL indicates significant inflammation, and a value in excess of 10 mg/dL is due either to metastatic cancer, bacterial infection, or systemic vasculitis. And if both the ESR and CRP are normal, the probability that a patient has a vasculitis is "incredibly low," Dr. Janson said.

At least 80% of patients with polymyalgia rheumatica will have an elevated ESR, and the CRP should be elevated in those that don’t.

Dr. Janson reported having no relevant financial conflicts.

Systemic treatments for psoriasis – including tumor necrosis factor inhibitors, oral drugs, and phototherapy – reduce the risk of myocardial infarction by approximately half, according to a study published online Aug. 20 in the Archives of Dermatology.

Psoriasis is a systemic inflammatory disease known to raise the risk of cardiovascular disorders, which also have a major inflammatory component. "It seems that controlling psoriasis with aggressive therapy and, thus, lowering inflammation, leads to a reduction in MI risk," said Dr. Jashin J. Wu of Kaiser Permanente Los Angeles Medical Center, and his associates.

The effect of systemic psoriasis therapy on cardiovascular disease "has been largely unexplored" until now. Dr. Wu and his colleagues performed a retrospective cohort study to examine the issue, using their HMO’s large database to examine the medical and prescription data on 8,845 adults who were diagnosed as having psoriasis between 2004 and 2009, and were followed for a median of 4 years for incident MI. The mean age of these study subjects was 53 years at baseline; half were men and half were women.

In all, 1,673 subjects (19%) were treated with TNF inhibitors, 2,097 (24%) were treated with oral systemic agents or phototherapy, and the remaining 5,075 received only topical treatment.

There were 221 incident MIs during follow-up.

For patients who took TNF inhibitors, the rate of MI was 3.05 per 1,000 patient-years, and for those who received systemic drugs or phototherapy, the rate of MI was 3.85 per 1,000 patient-years. These rates were not significantly different from each other, but were significantly lower than the rate of 6.73 MIs per 1,000 patient-years seen in the topical therapy–only group.

Compared with patients who used only topical treatment, those who took TNF inhibitors showed a 55% reduction in MI incidence and those who used other systemic treatments showed a 43% reduction in MI incidence, the investigators said (Arch. Dermatol. 2012 Aug. 20 [doi:10.1001/archdermatol.2012.2502]).

This is the first large-scale study to show that TNF inhibitors in particular, when they are taken for the treatment of psoriasis, reduce the incidence of MI. A previous study using a large database of patients with rheumatoid arthritis, another inflammatory disease associated with cardiovascular disease, found that therapy with TNF agonists also reduced the rate of cardiovascular events in that patient population, Dr. Wu and his associates noted.

In their study, an analysis of the data that stratified study subjects by age suggested that TNF inhibitors, oral agents, and phototherapy all exerted stronger protective effects in those older than 60 years, compared with younger patients. One explanation may be that older patients are more likely to develop type 2 diabetes, and these systemic therapies may cut the risk of that disease as well, they said.

This study was limited in that it could not account for study subjects’ use of nonprescription drugs, such as NSAIDs.

This study was supported by Kaiser Permanente’s Garfield Memorial Fund. Dr. Wu reported ties to Abbott Laboratories, Amgen, and Pfizer.

Systemic treatments for psoriasis – including tumor necrosis factor inhibitors, oral drugs, and phototherapy – reduce the risk of myocardial infarction by approximately half, according to a study published online Aug. 20 in the Archives of Dermatology.

Psoriasis is a systemic inflammatory disease known to raise the risk of cardiovascular disorders, which also have a major inflammatory component. "It seems that controlling psoriasis with aggressive therapy and, thus, lowering inflammation, leads to a reduction in MI risk," said Dr. Jashin J. Wu of Kaiser Permanente Los Angeles Medical Center, and his associates.

The effect of systemic psoriasis therapy on cardiovascular disease "has been largely unexplored" until now. Dr. Wu and his colleagues performed a retrospective cohort study to examine the issue, using their HMO’s large database to examine the medical and prescription data on 8,845 adults who were diagnosed as having psoriasis between 2004 and 2009, and were followed for a median of 4 years for incident MI. The mean age of these study subjects was 53 years at baseline; half were men and half were women.

In all, 1,673 subjects (19%) were treated with TNF inhibitors, 2,097 (24%) were treated with oral systemic agents or phototherapy, and the remaining 5,075 received only topical treatment.

There were 221 incident MIs during follow-up.

For patients who took TNF inhibitors, the rate of MI was 3.05 per 1,000 patient-years, and for those who received systemic drugs or phototherapy, the rate of MI was 3.85 per 1,000 patient-years. These rates were not significantly different from each other, but were significantly lower than the rate of 6.73 MIs per 1,000 patient-years seen in the topical therapy–only group.

Compared with patients who used only topical treatment, those who took TNF inhibitors showed a 55% reduction in MI incidence and those who used other systemic treatments showed a 43% reduction in MI incidence, the investigators said (Arch. Dermatol. 2012 Aug. 20 [doi:10.1001/archdermatol.2012.2502]).

This is the first large-scale study to show that TNF inhibitors in particular, when they are taken for the treatment of psoriasis, reduce the incidence of MI. A previous study using a large database of patients with rheumatoid arthritis, another inflammatory disease associated with cardiovascular disease, found that therapy with TNF agonists also reduced the rate of cardiovascular events in that patient population, Dr. Wu and his associates noted.

In their study, an analysis of the data that stratified study subjects by age suggested that TNF inhibitors, oral agents, and phototherapy all exerted stronger protective effects in those older than 60 years, compared with younger patients. One explanation may be that older patients are more likely to develop type 2 diabetes, and these systemic therapies may cut the risk of that disease as well, they said.

This study was limited in that it could not account for study subjects’ use of nonprescription drugs, such as NSAIDs.

This study was supported by Kaiser Permanente’s Garfield Memorial Fund. Dr. Wu reported ties to Abbott Laboratories, Amgen, and Pfizer.

Systemic treatments for psoriasis – including tumor necrosis factor inhibitors, oral drugs, and phototherapy – reduce the risk of myocardial infarction by approximately half, according to a study published online Aug. 20 in the Archives of Dermatology.

Psoriasis is a systemic inflammatory disease known to raise the risk of cardiovascular disorders, which also have a major inflammatory component. "It seems that controlling psoriasis with aggressive therapy and, thus, lowering inflammation, leads to a reduction in MI risk," said Dr. Jashin J. Wu of Kaiser Permanente Los Angeles Medical Center, and his associates.

The effect of systemic psoriasis therapy on cardiovascular disease "has been largely unexplored" until now. Dr. Wu and his colleagues performed a retrospective cohort study to examine the issue, using their HMO’s large database to examine the medical and prescription data on 8,845 adults who were diagnosed as having psoriasis between 2004 and 2009, and were followed for a median of 4 years for incident MI. The mean age of these study subjects was 53 years at baseline; half were men and half were women.

In all, 1,673 subjects (19%) were treated with TNF inhibitors, 2,097 (24%) were treated with oral systemic agents or phototherapy, and the remaining 5,075 received only topical treatment.

There were 221 incident MIs during follow-up.

For patients who took TNF inhibitors, the rate of MI was 3.05 per 1,000 patient-years, and for those who received systemic drugs or phototherapy, the rate of MI was 3.85 per 1,000 patient-years. These rates were not significantly different from each other, but were significantly lower than the rate of 6.73 MIs per 1,000 patient-years seen in the topical therapy–only group.

Compared with patients who used only topical treatment, those who took TNF inhibitors showed a 55% reduction in MI incidence and those who used other systemic treatments showed a 43% reduction in MI incidence, the investigators said (Arch. Dermatol. 2012 Aug. 20 [doi:10.1001/archdermatol.2012.2502]).

This is the first large-scale study to show that TNF inhibitors in particular, when they are taken for the treatment of psoriasis, reduce the incidence of MI. A previous study using a large database of patients with rheumatoid arthritis, another inflammatory disease associated with cardiovascular disease, found that therapy with TNF agonists also reduced the rate of cardiovascular events in that patient population, Dr. Wu and his associates noted.

In their study, an analysis of the data that stratified study subjects by age suggested that TNF inhibitors, oral agents, and phototherapy all exerted stronger protective effects in those older than 60 years, compared with younger patients. One explanation may be that older patients are more likely to develop type 2 diabetes, and these systemic therapies may cut the risk of that disease as well, they said.

This study was limited in that it could not account for study subjects’ use of nonprescription drugs, such as NSAIDs.

This study was supported by Kaiser Permanente’s Garfield Memorial Fund. Dr. Wu reported ties to Abbott Laboratories, Amgen, and Pfizer.

ORLANDO – A recent study that found a high prevalence of undiagnosed or untreated cardiovascular risk factors among patients with moderate to severe psoriasis reinforces the need for routine screening, said Dr. Jeffrey P. Callen.

Cardiovascular disease risk "seems to be increased in our patients with moderate to severe psoriasis, the kinds of patients who require systemic therapy," said Dr. Callen.

In the study, a total 59% of patients had at least two established cardiovascular risk factors, and 29% had three or more. Importantly, using Framingham risk scores, the investigators found 19% were at high risk for a cardiovascular event (J. Am. Acad. Dermatol. 2012;67:76-85).

Although comorbidities of psoriasis have garnered a lot of research, "what is relatively new is some of our systemic therapies might moderate or lessen these comorbidities and lessen patient risks in the future," said Dr. Callen, chief of the division of dermatology at the University of Louisville (Ky.).

Methotrexate therapy, for example, reduced the incidence of vascular disease in veterans with psoriasis or rheumatoid arthritis (J. Am. Acad. Dermatol. 2005;52:262-7). A lower to moderate cumulative dose appeared to be more beneficial than higher dose methotrexate, he said at the annual meeting of the Florida Society of Dermatology and Dermatologic Surgery.

In a more recent study, tumor necrosis factor (TNF) antagonist therapy improved aortic stiffness among 60 patients with inflammatory arthropathies, including psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis (Hypertension 2010;55:333-8). "Those treated had a decrease in aortic stiffness, suggesting there is something we are doing with our systemic therapies," Dr. Callen said. "At least in the short run, this intervention might have some impact on cardiovascular disease."

How much of a concern is aortic stiffness? A comparison of 58 normotensive patients with psoriasis and 36 controls found significantly higher rates of abnormal aortic stiffness in the psoriasis group (Blood Press. 2010:19:351-8).

Another study suggests that treatment with a TNF inhibitor or hydroxychloroquine reduces the risk for new-onset diabetes mellitus among patients with psoriasis or rheumatoid arthritis (JAMA 2011;305:2525-31). The decrease was statistically significant, compared with treatment with other nonbiologic disease-modifying antirheumatic drugs.

"Dermatologists often overlook systemic aspects of skin disease, including psoriasis," said Dr. Callen.

For this reason, Dr. Callen recommends a comprehensive comorbidity monitoring plan, especially for patients with severe psoriasis. Assess blood pressure, heart rate, and body mass index every 2 years, for example. Order a lipid profile and check fasting blood glucose every 5 years (or more frequently in the presence of other risk factors). Ask patients questions about arthritis symptoms regularly, as well. He adapted these recommendations from a report in the British Medical Journal (2010;340:b5666).

Also ask your psoriasis patients about the other medical professionals they consult. "There are patients with severe psoriasis who are not seeing other doctors. I see patients who come in and list me as their primary care physician. I’m not a PCP," he said.

Dr. Callen said he is a consultant to Amgen and a member of the safety monitoring committee for Celgene.

ORLANDO – A recent study that found a high prevalence of undiagnosed or untreated cardiovascular risk factors among patients with moderate to severe psoriasis reinforces the need for routine screening, said Dr. Jeffrey P. Callen.

Cardiovascular disease risk "seems to be increased in our patients with moderate to severe psoriasis, the kinds of patients who require systemic therapy," said Dr. Callen.

In the study, a total 59% of patients had at least two established cardiovascular risk factors, and 29% had three or more. Importantly, using Framingham risk scores, the investigators found 19% were at high risk for a cardiovascular event (J. Am. Acad. Dermatol. 2012;67:76-85).

Although comorbidities of psoriasis have garnered a lot of research, "what is relatively new is some of our systemic therapies might moderate or lessen these comorbidities and lessen patient risks in the future," said Dr. Callen, chief of the division of dermatology at the University of Louisville (Ky.).

Methotrexate therapy, for example, reduced the incidence of vascular disease in veterans with psoriasis or rheumatoid arthritis (J. Am. Acad. Dermatol. 2005;52:262-7). A lower to moderate cumulative dose appeared to be more beneficial than higher dose methotrexate, he said at the annual meeting of the Florida Society of Dermatology and Dermatologic Surgery.

In a more recent study, tumor necrosis factor (TNF) antagonist therapy improved aortic stiffness among 60 patients with inflammatory arthropathies, including psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis (Hypertension 2010;55:333-8). "Those treated had a decrease in aortic stiffness, suggesting there is something we are doing with our systemic therapies," Dr. Callen said. "At least in the short run, this intervention might have some impact on cardiovascular disease."

How much of a concern is aortic stiffness? A comparison of 58 normotensive patients with psoriasis and 36 controls found significantly higher rates of abnormal aortic stiffness in the psoriasis group (Blood Press. 2010:19:351-8).

Another study suggests that treatment with a TNF inhibitor or hydroxychloroquine reduces the risk for new-onset diabetes mellitus among patients with psoriasis or rheumatoid arthritis (JAMA 2011;305:2525-31). The decrease was statistically significant, compared with treatment with other nonbiologic disease-modifying antirheumatic drugs.

"Dermatologists often overlook systemic aspects of skin disease, including psoriasis," said Dr. Callen.

For this reason, Dr. Callen recommends a comprehensive comorbidity monitoring plan, especially for patients with severe psoriasis. Assess blood pressure, heart rate, and body mass index every 2 years, for example. Order a lipid profile and check fasting blood glucose every 5 years (or more frequently in the presence of other risk factors). Ask patients questions about arthritis symptoms regularly, as well. He adapted these recommendations from a report in the British Medical Journal (2010;340:b5666).

Also ask your psoriasis patients about the other medical professionals they consult. "There are patients with severe psoriasis who are not seeing other doctors. I see patients who come in and list me as their primary care physician. I’m not a PCP," he said.

Dr. Callen said he is a consultant to Amgen and a member of the safety monitoring committee for Celgene.

ORLANDO – A recent study that found a high prevalence of undiagnosed or untreated cardiovascular risk factors among patients with moderate to severe psoriasis reinforces the need for routine screening, said Dr. Jeffrey P. Callen.

Cardiovascular disease risk "seems to be increased in our patients with moderate to severe psoriasis, the kinds of patients who require systemic therapy," said Dr. Callen.

In the study, a total 59% of patients had at least two established cardiovascular risk factors, and 29% had three or more. Importantly, using Framingham risk scores, the investigators found 19% were at high risk for a cardiovascular event (J. Am. Acad. Dermatol. 2012;67:76-85).

Although comorbidities of psoriasis have garnered a lot of research, "what is relatively new is some of our systemic therapies might moderate or lessen these comorbidities and lessen patient risks in the future," said Dr. Callen, chief of the division of dermatology at the University of Louisville (Ky.).

Methotrexate therapy, for example, reduced the incidence of vascular disease in veterans with psoriasis or rheumatoid arthritis (J. Am. Acad. Dermatol. 2005;52:262-7). A lower to moderate cumulative dose appeared to be more beneficial than higher dose methotrexate, he said at the annual meeting of the Florida Society of Dermatology and Dermatologic Surgery.

In a more recent study, tumor necrosis factor (TNF) antagonist therapy improved aortic stiffness among 60 patients with inflammatory arthropathies, including psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis (Hypertension 2010;55:333-8). "Those treated had a decrease in aortic stiffness, suggesting there is something we are doing with our systemic therapies," Dr. Callen said. "At least in the short run, this intervention might have some impact on cardiovascular disease."

How much of a concern is aortic stiffness? A comparison of 58 normotensive patients with psoriasis and 36 controls found significantly higher rates of abnormal aortic stiffness in the psoriasis group (Blood Press. 2010:19:351-8).

Another study suggests that treatment with a TNF inhibitor or hydroxychloroquine reduces the risk for new-onset diabetes mellitus among patients with psoriasis or rheumatoid arthritis (JAMA 2011;305:2525-31). The decrease was statistically significant, compared with treatment with other nonbiologic disease-modifying antirheumatic drugs.

"Dermatologists often overlook systemic aspects of skin disease, including psoriasis," said Dr. Callen.

For this reason, Dr. Callen recommends a comprehensive comorbidity monitoring plan, especially for patients with severe psoriasis. Assess blood pressure, heart rate, and body mass index every 2 years, for example. Order a lipid profile and check fasting blood glucose every 5 years (or more frequently in the presence of other risk factors). Ask patients questions about arthritis symptoms regularly, as well. He adapted these recommendations from a report in the British Medical Journal (2010;340:b5666).

Also ask your psoriasis patients about the other medical professionals they consult. "There are patients with severe psoriasis who are not seeing other doctors. I see patients who come in and list me as their primary care physician. I’m not a PCP," he said.

Dr. Callen said he is a consultant to Amgen and a member of the safety monitoring committee for Celgene.

BERLIN – Medical therapy might prove to be the preferred approach for treating patients with early-stage Dupuytren’s contracture, suggest the findings of a small retrospective study.

Injection of collagenase Clostridium histolyticum in patients with early-stage Dupuytren’s contracture resulted in significantly better clinical outcomes than those that were seen in patients with advanced disease. Collagenase C. histolyticum (Xiaflex) injections are generally given only after patients with Dupuytren’s contracture develop fixed-flexion contracture angles of 30 degrees or more.

The retrospective study suggests a new treatment paradigm: The early injection of palpable cords with lesser fixed-flexion contracture angles results in near normal correction, bringing improvement that’s significantly greater than that achieved with delayed therapy, according to Dr. Clayton A. Peimer, an orthopedic surgeon at Michigan State University, East Lansing.

This is off-label therapy. At present, Xiaflex is approved in the United States and Europe under more restrictive conditions (injection of only a single palpable cord at a time, with a 4-week hiatus before either a repeat injection or an injection of another affected cord).

The finding warrants confirmation in prospective longitudinal studies aimed at determining whether collagenase injections into early-stage joints slows progression of Dupuytren’s contracture and improves upon the high contracture recurrence rate that follows surgical release, he added.

In a separate Australian study presented at the annual European Congress of Rheumatology, Dr. David Gilpin of the Brisbane (Queensland) Hand and Upper Limb Clinic reported that concurrent injections of collagenase C. histolyticum into two affected palpable cords in the same hand proved safe, effective, and well tolerated.

The advantages of being able to safely treat multiple contractures at the same time include shortened recovery times, fewer office visits for patients, and more efficient use of physicians’ time, noted Dr. Gilpin.

His study included 12 patients with three or more fixed-flexion contractures of 20% or greater in the proximal interphalangeal (PIP) and/or metacarpophalangeal (MP) joints on the same hand. The participants initially received a single collagenase injection in one palpable cord, followed roughly 24 hours later by the standard finger extension procedure that breaks the now-weakened cord. After 30 days, the patients received two injections into two different palpable cords on the same hand, followed by finger extension procedures the next day.

The first injection resulted in a mean 81% reduction in the degree of fixed-flexion contracture in treated MP joints, and a 66% decrease in PIP joints. The subsequent two concurrent injections of other affected cords showed near identical effectiveness (mean reduction in fixed-flexion contractures, 80% in MP and 63% in PIP joints).

Blood samples that were obtained 24 hours after the dual injections showed no detectable systemic levels of the biologic agent.

Not surprisingly, several treatment-related adverse events were more common when patients received two injections rather than one. These included injection site pain or discomfort, skin discoloration, itching, and blood blisters.

Dr. Peimer reviewed the charts of 302 patients with Dupuytren’s contracture who were treated with collagenase injections at 10 U.S. community and academic practices. Of affected joints, 20% were treated at an early stage (defined as a fixed-flexion contracture angle of 30 degrees or less). Their mean initial fixed-flexion contracture angle was 25 degrees, improving to 3.8 degrees after treatment. In contrast, the mean baseline fixed-flexion contracture angle in patients with advanced disease was 58 degrees, with an improvement to 14 degrees following collagenase treatment. No serious treatment-related adverse events occurred.

Dupuytren’s contracture is the result of a usually painless progressive thickening and shortening of the palmar fascia. This leads to curling of the fingers and impaired hand function. The most common surgical treatment, limited fasciectomy, can result in complications including digital nerve injury, hematoma, and complex regional pain syndrome. Xiaflex was approved in the United States in 2010 as the first nonsurgical treatment for Dupuytren’s contracture. European approval followed the next year.

The studies were sponsored by Auxillium Pharmaceuticals, which markets Xiaflex. Dr. Peimer and Dr. Gilpin were paid by the company for their research, and Dr. Gilpin owns stock in Auxillium.

BERLIN – Medical therapy might prove to be the preferred approach for treating patients with early-stage Dupuytren’s contracture, suggest the findings of a small retrospective study.

Injection of collagenase Clostridium histolyticum in patients with early-stage Dupuytren’s contracture resulted in significantly better clinical outcomes than those that were seen in patients with advanced disease. Collagenase C. histolyticum (Xiaflex) injections are generally given only after patients with Dupuytren’s contracture develop fixed-flexion contracture angles of 30 degrees or more.

The retrospective study suggests a new treatment paradigm: The early injection of palpable cords with lesser fixed-flexion contracture angles results in near normal correction, bringing improvement that’s significantly greater than that achieved with delayed therapy, according to Dr. Clayton A. Peimer, an orthopedic surgeon at Michigan State University, East Lansing.

This is off-label therapy. At present, Xiaflex is approved in the United States and Europe under more restrictive conditions (injection of only a single palpable cord at a time, with a 4-week hiatus before either a repeat injection or an injection of another affected cord).

The finding warrants confirmation in prospective longitudinal studies aimed at determining whether collagenase injections into early-stage joints slows progression of Dupuytren’s contracture and improves upon the high contracture recurrence rate that follows surgical release, he added.

In a separate Australian study presented at the annual European Congress of Rheumatology, Dr. David Gilpin of the Brisbane (Queensland) Hand and Upper Limb Clinic reported that concurrent injections of collagenase C. histolyticum into two affected palpable cords in the same hand proved safe, effective, and well tolerated.

The advantages of being able to safely treat multiple contractures at the same time include shortened recovery times, fewer office visits for patients, and more efficient use of physicians’ time, noted Dr. Gilpin.

His study included 12 patients with three or more fixed-flexion contractures of 20% or greater in the proximal interphalangeal (PIP) and/or metacarpophalangeal (MP) joints on the same hand. The participants initially received a single collagenase injection in one palpable cord, followed roughly 24 hours later by the standard finger extension procedure that breaks the now-weakened cord. After 30 days, the patients received two injections into two different palpable cords on the same hand, followed by finger extension procedures the next day.

The first injection resulted in a mean 81% reduction in the degree of fixed-flexion contracture in treated MP joints, and a 66% decrease in PIP joints. The subsequent two concurrent injections of other affected cords showed near identical effectiveness (mean reduction in fixed-flexion contractures, 80% in MP and 63% in PIP joints).

Blood samples that were obtained 24 hours after the dual injections showed no detectable systemic levels of the biologic agent.

Not surprisingly, several treatment-related adverse events were more common when patients received two injections rather than one. These included injection site pain or discomfort, skin discoloration, itching, and blood blisters.

Dr. Peimer reviewed the charts of 302 patients with Dupuytren’s contracture who were treated with collagenase injections at 10 U.S. community and academic practices. Of affected joints, 20% were treated at an early stage (defined as a fixed-flexion contracture angle of 30 degrees or less). Their mean initial fixed-flexion contracture angle was 25 degrees, improving to 3.8 degrees after treatment. In contrast, the mean baseline fixed-flexion contracture angle in patients with advanced disease was 58 degrees, with an improvement to 14 degrees following collagenase treatment. No serious treatment-related adverse events occurred.

Dupuytren’s contracture is the result of a usually painless progressive thickening and shortening of the palmar fascia. This leads to curling of the fingers and impaired hand function. The most common surgical treatment, limited fasciectomy, can result in complications including digital nerve injury, hematoma, and complex regional pain syndrome. Xiaflex was approved in the United States in 2010 as the first nonsurgical treatment for Dupuytren’s contracture. European approval followed the next year.

The studies were sponsored by Auxillium Pharmaceuticals, which markets Xiaflex. Dr. Peimer and Dr. Gilpin were paid by the company for their research, and Dr. Gilpin owns stock in Auxillium.

BERLIN – Medical therapy might prove to be the preferred approach for treating patients with early-stage Dupuytren’s contracture, suggest the findings of a small retrospective study.

Injection of collagenase Clostridium histolyticum in patients with early-stage Dupuytren’s contracture resulted in significantly better clinical outcomes than those that were seen in patients with advanced disease. Collagenase C. histolyticum (Xiaflex) injections are generally given only after patients with Dupuytren’s contracture develop fixed-flexion contracture angles of 30 degrees or more.

The retrospective study suggests a new treatment paradigm: The early injection of palpable cords with lesser fixed-flexion contracture angles results in near normal correction, bringing improvement that’s significantly greater than that achieved with delayed therapy, according to Dr. Clayton A. Peimer, an orthopedic surgeon at Michigan State University, East Lansing.

This is off-label therapy. At present, Xiaflex is approved in the United States and Europe under more restrictive conditions (injection of only a single palpable cord at a time, with a 4-week hiatus before either a repeat injection or an injection of another affected cord).

The finding warrants confirmation in prospective longitudinal studies aimed at determining whether collagenase injections into early-stage joints slows progression of Dupuytren’s contracture and improves upon the high contracture recurrence rate that follows surgical release, he added.

In a separate Australian study presented at the annual European Congress of Rheumatology, Dr. David Gilpin of the Brisbane (Queensland) Hand and Upper Limb Clinic reported that concurrent injections of collagenase C. histolyticum into two affected palpable cords in the same hand proved safe, effective, and well tolerated.

The advantages of being able to safely treat multiple contractures at the same time include shortened recovery times, fewer office visits for patients, and more efficient use of physicians’ time, noted Dr. Gilpin.

His study included 12 patients with three or more fixed-flexion contractures of 20% or greater in the proximal interphalangeal (PIP) and/or metacarpophalangeal (MP) joints on the same hand. The participants initially received a single collagenase injection in one palpable cord, followed roughly 24 hours later by the standard finger extension procedure that breaks the now-weakened cord. After 30 days, the patients received two injections into two different palpable cords on the same hand, followed by finger extension procedures the next day.

The first injection resulted in a mean 81% reduction in the degree of fixed-flexion contracture in treated MP joints, and a 66% decrease in PIP joints. The subsequent two concurrent injections of other affected cords showed near identical effectiveness (mean reduction in fixed-flexion contractures, 80% in MP and 63% in PIP joints).

Blood samples that were obtained 24 hours after the dual injections showed no detectable systemic levels of the biologic agent.

Not surprisingly, several treatment-related adverse events were more common when patients received two injections rather than one. These included injection site pain or discomfort, skin discoloration, itching, and blood blisters.

Dr. Peimer reviewed the charts of 302 patients with Dupuytren’s contracture who were treated with collagenase injections at 10 U.S. community and academic practices. Of affected joints, 20% were treated at an early stage (defined as a fixed-flexion contracture angle of 30 degrees or less). Their mean initial fixed-flexion contracture angle was 25 degrees, improving to 3.8 degrees after treatment. In contrast, the mean baseline fixed-flexion contracture angle in patients with advanced disease was 58 degrees, with an improvement to 14 degrees following collagenase treatment. No serious treatment-related adverse events occurred.

Dupuytren’s contracture is the result of a usually painless progressive thickening and shortening of the palmar fascia. This leads to curling of the fingers and impaired hand function. The most common surgical treatment, limited fasciectomy, can result in complications including digital nerve injury, hematoma, and complex regional pain syndrome. Xiaflex was approved in the United States in 2010 as the first nonsurgical treatment for Dupuytren’s contracture. European approval followed the next year.

The studies were sponsored by Auxillium Pharmaceuticals, which markets Xiaflex. Dr. Peimer and Dr. Gilpin were paid by the company for their research, and Dr. Gilpin owns stock in Auxillium.

VICTORIA, B.C. – Subclinical enthesitis occurs more commonly in patients with psoriatic arthritis than in those with psoriasis, possibly as a result of age and obesity rather than disease severity, to judge from the findings of a cross-sectional study conducted by investigators at Toronto Western Hospital.

The investigators used ultrasound as well as clinical examination to assess the extent, if any, of enthesitis in study participants, who were 59 patients with psoriatic arthritis and 79 patients with psoriasis. Study participants were recruited from longitudinal cohorts. The control group was made up of 60 healthy volunteers who did not have any personal or family history of spondyloarthropathy. They were evaluated for enthesitis at sites in the calcaneus, knee, and olecranon.

Findings on ultrasound – any enthesophytes, bony erosions, tendon thickness, and bursitis, within tendons – were scored using GUESS (Glasgow Ultrasound Enthesitis Scoring System), which reflects the overall burden bilaterally of enthesitis from abnormalities in five lower limb sites, and the MASEI (Madrid Sonography Enthesitis Index), which additionally includes calcifications and Doppler signals as elemental lesions as well as abnormalities of the olecranon tuberosity enthesis.

The average ages were 52, 53, and 42 years in the psoriasis, psoriatic arthritis, and healthy volunteer groups, respectively, and men accounted for 64%, 57%, and 32% of participants. Corresponding mean body mass indices were 27, 30, and 26 kg/m², respectively.

In all, 12 anatomical sites were assessed. The mean number showing ultrasonographic enthesitis differed significantly across groups, reported study coauthor Jai P. Jayakar at the annual meeting of the Canadian Rheumatology Association. The number of anatomical sites that showed enthesitis was highest in the psoriatic arthritis group (7.1), intermediate in the psoriasis group (5), and lowest in healthy volunteers (4).

There was also a significant, graded difference across groups in GUESS scores (8.9, 5.6, and 4.4 out of a possible 36, respectively, for psoriatic arthritis, psoriasis, and healthy controls) and in MASEI scores (18.5, 9.9, and 7.7 respectively for psoriatic arthritis, psoriasis, and healthy controls out of a possible 136). However, in multivariate analyses, disease status was not associated with these scores; only increasing age and BMI showed significant associations.

"Our study is one of the first comparative assessments of subclinical enthesitis in psoriasis vs. psoriatic arthritis," noted Mr. Jayakar. "Our results reveal that the prevalence of ultrasonographic entheseal abnormalities and indices of entheseal burden ... are greater in psoriatic arthritis than in psoriasis; however, this relationship may be modulated in a multifactorial manner by factors other than disease status, such as age and body mass index.

"Now, it is possible that enthesitis could be of predictive value in specific patient subgroups – for example, age- or obesity-stratified subgroups," he added. "However, larger studies are needed to confirm the utility of subclinical enthesitis as a predictive factor for the development of psoriatic arthritis in patients with psoriasis."

How could the investigators be certain, a session attendee asked, that they were detecting disease-related enthesitis and not simply mechanical tendonitis?

That is a valid concern, given the lack of consensus among rheumatologists as to which ultrasonographic abnormalities result from degeneration, inflammation, mechanical stress, or other etiologies, acknowledged Mr. Jayakar, a medical student at the University of Western Ontario, London. Large cohorts with well-defined disease status would be required to investigate this further, he said.

"One direction in which we could move forward is if we can find specific elemental lesions – or aggregates of elemental lesions – that are of predictive value, then perhaps those could be used pragmatically to help us in our clinical management," he noted. "But as of now, the pathophysiological underpinnings of these abnormalities are not very well described."

Mr. Jayakar disclosed no relevant conflicts of interest.

VICTORIA, B.C. – Subclinical enthesitis occurs more commonly in patients with psoriatic arthritis than in those with psoriasis, possibly as a result of age and obesity rather than disease severity, to judge from the findings of a cross-sectional study conducted by investigators at Toronto Western Hospital.

The investigators used ultrasound as well as clinical examination to assess the extent, if any, of enthesitis in study participants, who were 59 patients with psoriatic arthritis and 79 patients with psoriasis. Study participants were recruited from longitudinal cohorts. The control group was made up of 60 healthy volunteers who did not have any personal or family history of spondyloarthropathy. They were evaluated for enthesitis at sites in the calcaneus, knee, and olecranon.

Findings on ultrasound – any enthesophytes, bony erosions, tendon thickness, and bursitis, within tendons – were scored using GUESS (Glasgow Ultrasound Enthesitis Scoring System), which reflects the overall burden bilaterally of enthesitis from abnormalities in five lower limb sites, and the MASEI (Madrid Sonography Enthesitis Index), which additionally includes calcifications and Doppler signals as elemental lesions as well as abnormalities of the olecranon tuberosity enthesis.

The average ages were 52, 53, and 42 years in the psoriasis, psoriatic arthritis, and healthy volunteer groups, respectively, and men accounted for 64%, 57%, and 32% of participants. Corresponding mean body mass indices were 27, 30, and 26 kg/m², respectively.

In all, 12 anatomical sites were assessed. The mean number showing ultrasonographic enthesitis differed significantly across groups, reported study coauthor Jai P. Jayakar at the annual meeting of the Canadian Rheumatology Association. The number of anatomical sites that showed enthesitis was highest in the psoriatic arthritis group (7.1), intermediate in the psoriasis group (5), and lowest in healthy volunteers (4).

There was also a significant, graded difference across groups in GUESS scores (8.9, 5.6, and 4.4 out of a possible 36, respectively, for psoriatic arthritis, psoriasis, and healthy controls) and in MASEI scores (18.5, 9.9, and 7.7 respectively for psoriatic arthritis, psoriasis, and healthy controls out of a possible 136). However, in multivariate analyses, disease status was not associated with these scores; only increasing age and BMI showed significant associations.

"Our study is one of the first comparative assessments of subclinical enthesitis in psoriasis vs. psoriatic arthritis," noted Mr. Jayakar. "Our results reveal that the prevalence of ultrasonographic entheseal abnormalities and indices of entheseal burden ... are greater in psoriatic arthritis than in psoriasis; however, this relationship may be modulated in a multifactorial manner by factors other than disease status, such as age and body mass index.

"Now, it is possible that enthesitis could be of predictive value in specific patient subgroups – for example, age- or obesity-stratified subgroups," he added. "However, larger studies are needed to confirm the utility of subclinical enthesitis as a predictive factor for the development of psoriatic arthritis in patients with psoriasis."

How could the investigators be certain, a session attendee asked, that they were detecting disease-related enthesitis and not simply mechanical tendonitis?

That is a valid concern, given the lack of consensus among rheumatologists as to which ultrasonographic abnormalities result from degeneration, inflammation, mechanical stress, or other etiologies, acknowledged Mr. Jayakar, a medical student at the University of Western Ontario, London. Large cohorts with well-defined disease status would be required to investigate this further, he said.

"One direction in which we could move forward is if we can find specific elemental lesions – or aggregates of elemental lesions – that are of predictive value, then perhaps those could be used pragmatically to help us in our clinical management," he noted. "But as of now, the pathophysiological underpinnings of these abnormalities are not very well described."

Mr. Jayakar disclosed no relevant conflicts of interest.

VICTORIA, B.C. – Subclinical enthesitis occurs more commonly in patients with psoriatic arthritis than in those with psoriasis, possibly as a result of age and obesity rather than disease severity, to judge from the findings of a cross-sectional study conducted by investigators at Toronto Western Hospital.

The investigators used ultrasound as well as clinical examination to assess the extent, if any, of enthesitis in study participants, who were 59 patients with psoriatic arthritis and 79 patients with psoriasis. Study participants were recruited from longitudinal cohorts. The control group was made up of 60 healthy volunteers who did not have any personal or family history of spondyloarthropathy. They were evaluated for enthesitis at sites in the calcaneus, knee, and olecranon.

Findings on ultrasound – any enthesophytes, bony erosions, tendon thickness, and bursitis, within tendons – were scored using GUESS (Glasgow Ultrasound Enthesitis Scoring System), which reflects the overall burden bilaterally of enthesitis from abnormalities in five lower limb sites, and the MASEI (Madrid Sonography Enthesitis Index), which additionally includes calcifications and Doppler signals as elemental lesions as well as abnormalities of the olecranon tuberosity enthesis.

The average ages were 52, 53, and 42 years in the psoriasis, psoriatic arthritis, and healthy volunteer groups, respectively, and men accounted for 64%, 57%, and 32% of participants. Corresponding mean body mass indices were 27, 30, and 26 kg/m², respectively.

In all, 12 anatomical sites were assessed. The mean number showing ultrasonographic enthesitis differed significantly across groups, reported study coauthor Jai P. Jayakar at the annual meeting of the Canadian Rheumatology Association. The number of anatomical sites that showed enthesitis was highest in the psoriatic arthritis group (7.1), intermediate in the psoriasis group (5), and lowest in healthy volunteers (4).

There was also a significant, graded difference across groups in GUESS scores (8.9, 5.6, and 4.4 out of a possible 36, respectively, for psoriatic arthritis, psoriasis, and healthy controls) and in MASEI scores (18.5, 9.9, and 7.7 respectively for psoriatic arthritis, psoriasis, and healthy controls out of a possible 136). However, in multivariate analyses, disease status was not associated with these scores; only increasing age and BMI showed significant associations.

"Our study is one of the first comparative assessments of subclinical enthesitis in psoriasis vs. psoriatic arthritis," noted Mr. Jayakar. "Our results reveal that the prevalence of ultrasonographic entheseal abnormalities and indices of entheseal burden ... are greater in psoriatic arthritis than in psoriasis; however, this relationship may be modulated in a multifactorial manner by factors other than disease status, such as age and body mass index.

"Now, it is possible that enthesitis could be of predictive value in specific patient subgroups – for example, age- or obesity-stratified subgroups," he added. "However, larger studies are needed to confirm the utility of subclinical enthesitis as a predictive factor for the development of psoriatic arthritis in patients with psoriasis."

How could the investigators be certain, a session attendee asked, that they were detecting disease-related enthesitis and not simply mechanical tendonitis?

That is a valid concern, given the lack of consensus among rheumatologists as to which ultrasonographic abnormalities result from degeneration, inflammation, mechanical stress, or other etiologies, acknowledged Mr. Jayakar, a medical student at the University of Western Ontario, London. Large cohorts with well-defined disease status would be required to investigate this further, he said.

"One direction in which we could move forward is if we can find specific elemental lesions – or aggregates of elemental lesions – that are of predictive value, then perhaps those could be used pragmatically to help us in our clinical management," he noted. "But as of now, the pathophysiological underpinnings of these abnormalities are not very well described."

Mr. Jayakar disclosed no relevant conflicts of interest.

Genes play a key role in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis, and genetic distinctions exist between two of the condition’s main clinical syndromes: granulomatosis with polyangiitis and microscopic polyangiitis, judging from data from a genomewide association study.

The findings also support the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. If true, those findings could have both immunopathogenic and therapeutic implications, according to Paul A. Lyons, Ph.D., of the Cambridge (England) Institute for Medical Research, and his colleagues in their online report in the July 19 issue of the New England Journal of Medicine.

"There is debate as to whether the clinical syndromes of granulomatosis with polyangiitis and microscopic polyangiitis represent distinct diseases or are part of a single disease spectrum," the investigators wrote. The concept of a single disease spectrum has resulted in similar treatment strategies being used in trials regardless of which of these two clinical syndromes are present, and also in the suggestion that genetic studies should consider the two syndromes together, they explained.

"Clear evidence that these clinical syndromes are etiologically distinct might provide a rationale for devising syndrome-specific therapeutic strategies," the investigators noted (N. Engl. J. Med. 2012 July 19 [doi: 10.1056/NEJMoa1108735]).

To identify genetic risk factors and evaluate whether a common or distinct genetic background exists for granulomatosis with polyangiitis and microscopic polyangiitis, they performed genotyping in a discovery cohort of 1,233 patients with ANCA-associated vasculitis from the United Kingdom and 5,884 controls, as well as in a replication cohort of 1,454 Northern European case patients and 1,666 controls.

Combined analysis of the discovery and replication cohorts demonstrated that four single nucleotide polymorphisms (SNPs) exceeded the significance threshold for genomewide association, including three from the major histocompatibility complex (MHC). The most significant of these three was within the gene encoding HLA-DPB1. The fourth was in the SERPINA1 locus at 14q32.

Another SNP in PRTN3, which was added to the replication analysis on the bases of a priori hypotheses, was also found to be significantly associated with disease.

"Together, these data provide evidence of a genetic base of ANCA-associated vasculitis that extends beyond the MHC," the investigators said.

Additional analysis of the discovery cohort after subdivision on the basis of whether patients were diagnosed with granulomatosis with polyangiitis or with microscopic polyangiitis showed that all three MHC-associated SNPs differed between the two groups, with "essentially all of the association" found in those with granulomatosis with polyangiitis.

"This was also true of SERPINA1 – while it did not show a significant difference when granulomatosis with polyangiitis and microscopic polyangiitis were compared directly, perhaps owing to small numbers of patients and thus reduced power, it was associated with granulomatosis with polyangiitis, but not microscopic polyangiitis, when each subtype was compared with controls," they added.

There also was a suggestion of an association between PRTN3 and granulomatosis with polyangiitis rather than with microscopic polyangiitis, and also between some less significant SNPs and granulomatosis with polyangiitis, they said.

"Overall, there was evidence that granulomatosis with polyangiitis had genetic associations distinct from microscopic polyangiitis at both the MHC and SERPIN loci," they said.

Additional subgroup analysis based on proteinase 3 and myeloperoxidase ANCA specificity showed significant differences at the MHC, SERPINA1, and PRTN3 loci, all of which included a genetic association with proteinase 3 ANCA but not with myeloperoxidase ANCA. Further analysis demonstrated associations of HLA-DP and the related SNPs SERPINA1 and PRTN3 in patients with proteinase 3 ANCA associated with granulomatosis with polyangiitis but not myeloperoxidase ANCA. The findings were the same in the microscopic polyangiitis group, showing an association of proteinase 3 ANCA and the HLA-DP SNP and SERPINA1. The converse was true for the HLA-DQ SNP, which was associated with myeloperoxidase ANCA rather than proteinase 3 ANCA in patients with microscopic polyangiitis.

The clear association of genetic background with autoantibody specificity suggests that it might contribute to the clinical classifications of granulomatosis with polyangiitis and microscopic polyangiitis, the investigators said.

"The genetic difference between proteinase 3 ANCA and myeloperoxidase ANCA polyangiitis could have immunopathogenic and therapeutic implications, ... and will require future genetic studies powered to detect associations with these conditions rather than with ANCA-associated vasculitis as a whole," they said.

The investigators concluded that this study "provides clear evidence of a genetic contribution to disease susceptibility, which differs between granulomatosis with polyangiitis and microscopic polyangiitis."

Further, "associations with HLA, SERPINA1, and PRTN3 are primarily aligned with ANCA specificity rather than with the clinically defined syndromes granulomatosis with polyangiitis and microscopic polyangiitis, making it logical to consider including ANCA specificity in the diagnostic criteria for ANCA-associated vasculitis," they argued.

Dr. Lyons and his associates disclosed that they had no relevant financial disclosures relevant to this research other than its funding. This study was supported by the British Heart Foundation; the Wellcome Trust; the National Institute of Health Research Biomedical Research Centres of Cambridge, Imperial College, and Manchester; the Medical Research Council and Kidney Research UK; the West Anglia Comprehensive Local Research Network; the Norfolk and Suffolk Comprehensive Local Research network; the German Research Foundation; and the European Union FP7 Infectious Triggers of Chronic Autoimmunity Consortium. Author disclosure forms for both the study authors and editorial author are available with the full text of the article at NEMJ.org.

Genes play a key role in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis, and genetic distinctions exist between two of the condition’s main clinical syndromes: granulomatosis with polyangiitis and microscopic polyangiitis, judging from data from a genomewide association study.

The findings also support the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. If true, those findings could have both immunopathogenic and therapeutic implications, according to Paul A. Lyons, Ph.D., of the Cambridge (England) Institute for Medical Research, and his colleagues in their online report in the July 19 issue of the New England Journal of Medicine.

"There is debate as to whether the clinical syndromes of granulomatosis with polyangiitis and microscopic polyangiitis represent distinct diseases or are part of a single disease spectrum," the investigators wrote. The concept of a single disease spectrum has resulted in similar treatment strategies being used in trials regardless of which of these two clinical syndromes are present, and also in the suggestion that genetic studies should consider the two syndromes together, they explained.

"Clear evidence that these clinical syndromes are etiologically distinct might provide a rationale for devising syndrome-specific therapeutic strategies," the investigators noted (N. Engl. J. Med. 2012 July 19 [doi: 10.1056/NEJMoa1108735]).

To identify genetic risk factors and evaluate whether a common or distinct genetic background exists for granulomatosis with polyangiitis and microscopic polyangiitis, they performed genotyping in a discovery cohort of 1,233 patients with ANCA-associated vasculitis from the United Kingdom and 5,884 controls, as well as in a replication cohort of 1,454 Northern European case patients and 1,666 controls.

Combined analysis of the discovery and replication cohorts demonstrated that four single nucleotide polymorphisms (SNPs) exceeded the significance threshold for genomewide association, including three from the major histocompatibility complex (MHC). The most significant of these three was within the gene encoding HLA-DPB1. The fourth was in the SERPINA1 locus at 14q32.

Another SNP in PRTN3, which was added to the replication analysis on the bases of a priori hypotheses, was also found to be significantly associated with disease.

"Together, these data provide evidence of a genetic base of ANCA-associated vasculitis that extends beyond the MHC," the investigators said.

Additional analysis of the discovery cohort after subdivision on the basis of whether patients were diagnosed with granulomatosis with polyangiitis or with microscopic polyangiitis showed that all three MHC-associated SNPs differed between the two groups, with "essentially all of the association" found in those with granulomatosis with polyangiitis.

"This was also true of SERPINA1 – while it did not show a significant difference when granulomatosis with polyangiitis and microscopic polyangiitis were compared directly, perhaps owing to small numbers of patients and thus reduced power, it was associated with granulomatosis with polyangiitis, but not microscopic polyangiitis, when each subtype was compared with controls," they added.

There also was a suggestion of an association between PRTN3 and granulomatosis with polyangiitis rather than with microscopic polyangiitis, and also between some less significant SNPs and granulomatosis with polyangiitis, they said.

"Overall, there was evidence that granulomatosis with polyangiitis had genetic associations distinct from microscopic polyangiitis at both the MHC and SERPIN loci," they said.

Additional subgroup analysis based on proteinase 3 and myeloperoxidase ANCA specificity showed significant differences at the MHC, SERPINA1, and PRTN3 loci, all of which included a genetic association with proteinase 3 ANCA but not with myeloperoxidase ANCA. Further analysis demonstrated associations of HLA-DP and the related SNPs SERPINA1 and PRTN3 in patients with proteinase 3 ANCA associated with granulomatosis with polyangiitis but not myeloperoxidase ANCA. The findings were the same in the microscopic polyangiitis group, showing an association of proteinase 3 ANCA and the HLA-DP SNP and SERPINA1. The converse was true for the HLA-DQ SNP, which was associated with myeloperoxidase ANCA rather than proteinase 3 ANCA in patients with microscopic polyangiitis.

The clear association of genetic background with autoantibody specificity suggests that it might contribute to the clinical classifications of granulomatosis with polyangiitis and microscopic polyangiitis, the investigators said.

"The genetic difference between proteinase 3 ANCA and myeloperoxidase ANCA polyangiitis could have immunopathogenic and therapeutic implications, ... and will require future genetic studies powered to detect associations with these conditions rather than with ANCA-associated vasculitis as a whole," they said.

The investigators concluded that this study "provides clear evidence of a genetic contribution to disease susceptibility, which differs between granulomatosis with polyangiitis and microscopic polyangiitis."

Further, "associations with HLA, SERPINA1, and PRTN3 are primarily aligned with ANCA specificity rather than with the clinically defined syndromes granulomatosis with polyangiitis and microscopic polyangiitis, making it logical to consider including ANCA specificity in the diagnostic criteria for ANCA-associated vasculitis," they argued.

Dr. Lyons and his associates disclosed that they had no relevant financial disclosures relevant to this research other than its funding. This study was supported by the British Heart Foundation; the Wellcome Trust; the National Institute of Health Research Biomedical Research Centres of Cambridge, Imperial College, and Manchester; the Medical Research Council and Kidney Research UK; the West Anglia Comprehensive Local Research Network; the Norfolk and Suffolk Comprehensive Local Research network; the German Research Foundation; and the European Union FP7 Infectious Triggers of Chronic Autoimmunity Consortium. Author disclosure forms for both the study authors and editorial author are available with the full text of the article at NEMJ.org.

Genes play a key role in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis, and genetic distinctions exist between two of the condition’s main clinical syndromes: granulomatosis with polyangiitis and microscopic polyangiitis, judging from data from a genomewide association study.

The findings also support the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. If true, those findings could have both immunopathogenic and therapeutic implications, according to Paul A. Lyons, Ph.D., of the Cambridge (England) Institute for Medical Research, and his colleagues in their online report in the July 19 issue of the New England Journal of Medicine.

"There is debate as to whether the clinical syndromes of granulomatosis with polyangiitis and microscopic polyangiitis represent distinct diseases or are part of a single disease spectrum," the investigators wrote. The concept of a single disease spectrum has resulted in similar treatment strategies being used in trials regardless of which of these two clinical syndromes are present, and also in the suggestion that genetic studies should consider the two syndromes together, they explained.

"Clear evidence that these clinical syndromes are etiologically distinct might provide a rationale for devising syndrome-specific therapeutic strategies," the investigators noted (N. Engl. J. Med. 2012 July 19 [doi: 10.1056/NEJMoa1108735]).

To identify genetic risk factors and evaluate whether a common or distinct genetic background exists for granulomatosis with polyangiitis and microscopic polyangiitis, they performed genotyping in a discovery cohort of 1,233 patients with ANCA-associated vasculitis from the United Kingdom and 5,884 controls, as well as in a replication cohort of 1,454 Northern European case patients and 1,666 controls.

Combined analysis of the discovery and replication cohorts demonstrated that four single nucleotide polymorphisms (SNPs) exceeded the significance threshold for genomewide association, including three from the major histocompatibility complex (MHC). The most significant of these three was within the gene encoding HLA-DPB1. The fourth was in the SERPINA1 locus at 14q32.

Another SNP in PRTN3, which was added to the replication analysis on the bases of a priori hypotheses, was also found to be significantly associated with disease.

"Together, these data provide evidence of a genetic base of ANCA-associated vasculitis that extends beyond the MHC," the investigators said.

Additional analysis of the discovery cohort after subdivision on the basis of whether patients were diagnosed with granulomatosis with polyangiitis or with microscopic polyangiitis showed that all three MHC-associated SNPs differed between the two groups, with "essentially all of the association" found in those with granulomatosis with polyangiitis.

"This was also true of SERPINA1 – while it did not show a significant difference when granulomatosis with polyangiitis and microscopic polyangiitis were compared directly, perhaps owing to small numbers of patients and thus reduced power, it was associated with granulomatosis with polyangiitis, but not microscopic polyangiitis, when each subtype was compared with controls," they added.

There also was a suggestion of an association between PRTN3 and granulomatosis with polyangiitis rather than with microscopic polyangiitis, and also between some less significant SNPs and granulomatosis with polyangiitis, they said.

"Overall, there was evidence that granulomatosis with polyangiitis had genetic associations distinct from microscopic polyangiitis at both the MHC and SERPIN loci," they said.

Additional subgroup analysis based on proteinase 3 and myeloperoxidase ANCA specificity showed significant differences at the MHC, SERPINA1, and PRTN3 loci, all of which included a genetic association with proteinase 3 ANCA but not with myeloperoxidase ANCA. Further analysis demonstrated associations of HLA-DP and the related SNPs SERPINA1 and PRTN3 in patients with proteinase 3 ANCA associated with granulomatosis with polyangiitis but not myeloperoxidase ANCA. The findings were the same in the microscopic polyangiitis group, showing an association of proteinase 3 ANCA and the HLA-DP SNP and SERPINA1. The converse was true for the HLA-DQ SNP, which was associated with myeloperoxidase ANCA rather than proteinase 3 ANCA in patients with microscopic polyangiitis.

The clear association of genetic background with autoantibody specificity suggests that it might contribute to the clinical classifications of granulomatosis with polyangiitis and microscopic polyangiitis, the investigators said.

"The genetic difference between proteinase 3 ANCA and myeloperoxidase ANCA polyangiitis could have immunopathogenic and therapeutic implications, ... and will require future genetic studies powered to detect associations with these conditions rather than with ANCA-associated vasculitis as a whole," they said.

The investigators concluded that this study "provides clear evidence of a genetic contribution to disease susceptibility, which differs between granulomatosis with polyangiitis and microscopic polyangiitis."

Further, "associations with HLA, SERPINA1, and PRTN3 are primarily aligned with ANCA specificity rather than with the clinically defined syndromes granulomatosis with polyangiitis and microscopic polyangiitis, making it logical to consider including ANCA specificity in the diagnostic criteria for ANCA-associated vasculitis," they argued.

Dr. Lyons and his associates disclosed that they had no relevant financial disclosures relevant to this research other than its funding. This study was supported by the British Heart Foundation; the Wellcome Trust; the National Institute of Health Research Biomedical Research Centres of Cambridge, Imperial College, and Manchester; the Medical Research Council and Kidney Research UK; the West Anglia Comprehensive Local Research Network; the Norfolk and Suffolk Comprehensive Local Research network; the German Research Foundation; and the European Union FP7 Infectious Triggers of Chronic Autoimmunity Consortium. Author disclosure forms for both the study authors and editorial author are available with the full text of the article at NEMJ.org.

BERLIN – The risk of cardiovascular events in patients with systemic lupus erythematosus is sevenfold higher than the risk predicted by the Framingham equation, a study shows.

The role of risk factors varies widely, with the presence of high triglyceride levels upping the risk nearly fourfold while use of cyclophosphamide, which may be a proxy for disease severity, raises the risk almost 17-fold, Dr. Sarah Skeoch, a clinical research fellow at the Arthritis Research UK Epidemiology Unit at the University of Manchester, England, said at the annual European Congress of Rheumatology.

The research also showed that triglyceride level was the only independent traditional risk factor, with a 3.6-fold increased risk association. Damage related to lupus, according to the Systemic Lupus International Collaborating Clinics (SLICC) damage index, increased risk 10-fold. Cyclophosphamide therapy was associated with a 16.7-fold increase in risk.

Although the patients have more of the classical risk factors, this does not seem to account for all the increased risk. Disease characteristics such as chronic inflammation or treatments may contribute, she suggested.

"We wanted to look at the association between risk and disease, for example, how active their lupus is, damage accrued over time, whether they have renal disease, and also whether their treatments are associated with CV events like heart disease and stroke," Dr. Skeoch added.

The study looked at these factors in 200 patients who were diagnosed between 2000 and 2003.

At baseline, 12 patients of the eventual 124 who were followed up had experienced a prior CV event. Also at baseline, the SLE disease activity index (SLEDAI) score was 1, indicating low disease activity, and the SLICC damage index was low.

All patients included in the study were over 18 years of age, female, and white. Their lupus was stable with therapy for at least 2 months prior to inclusion in the study. "They were a relatively well population of patients," said Dr. Skeoch.

Blood tests and clinical assessments were carried out to determine levels of traditional risk factors, lupus disease activity, and lupus-related damage, as well as measurements related to disease therapies.

After a 5-year interval, patients were invited back for assessments and the incidence of CV events, including coronary events, cerebral events, and peripheral vascular disease over the elapsed time period, was recorded.

Next, a comparison was made between the predicted CV risk at baseline according to the Framingham equation and the observed results in 112 patients with no prior CV disease.

CV Risk Higher Than Expected

Upon follow-up, patients were, on average, 56 years old and had had disease for approximately 16 years. Out of the 124 patients followed up over approximately 5 years, 12 (9.7%) had a CV event. Coronary events accounted for seven of these, cerebrovascular events were recorded in five patients, and peripheral vascular disease occurred in one patient. "One patient had both a coronary event and a cerebral event within the follow up," Dr. Skeoch said.

In those who had no prior CV event at baseline, predicted risk of a CV event according to the Framingham equation suggested that 1% of patients should have an event in the next 5 years. "In fact, we found 7% had an event – so seven times higher than predicted. This excess risk is most likely attributed to uncaptured traditional risk factors or alternatively, the disease itself, which is more likely," she commented.

The investigators looked at independent risk factors for a CV event regardless of which other risk factors a patient had and found that triglyceride levels were the only traditional risk factor, with an odds ratio (OR) of 3.61 (95% confidence interval, 1.23-10.56). Triglyceride levels often were not the primary target of lipid-lowering therapy, which was usually aimed at reducing total cholesterol or cholesterol ratio, she noted.

Other multivariable analyses of baseline characteristics associated with CV events suggested that the risk was elevated by two factors: the SLICC damage score (OR, 9.62; CI, 1.46-63.5) and cyclophosphamide therapy (OR, 16.7; CI, 1.46-123). "Factors associated with the patients’ lupus disease included having had a venous thromboembolism, damage related to SLE in the past, cyclophosphamide exposure, and a higher steroid dose at baseline which predisposed the patient to having an event," Dr. Skeoch said.

Marker for Disease Severity

"This is the first time cyclophosphamide [therapy] has been marked as an example of an independent predictor of CV risk. We don’t think it is the cyclophosphamide itself because it has been used in a number of diseases and there’s no known evidence to suggest it causes heart disease, but we think it is a measure of people with severe disease. Also, patients exposed to cyclophosphamide tend to have had more steroids," she explained.

If patients with lupus had severe disease, then they might be more likely to be at risk of CV events in the future, she concluded. "We have found that patients with SLE are at higher risk than expected of CV disease and that those with severe disease may be most at risk. We should endeavor to monitor and treat traditional risk factors and aim for good control of SLE disease activity in order to minimize this risk."

Dr. Skeoch has no relevant conflicts of interest. She is funded by the UK Medical Research Council.

BERLIN – The risk of cardiovascular events in patients with systemic lupus erythematosus is sevenfold higher than the risk predicted by the Framingham equation, a study shows.

The role of risk factors varies widely, with the presence of high triglyceride levels upping the risk nearly fourfold while use of cyclophosphamide, which may be a proxy for disease severity, raises the risk almost 17-fold, Dr. Sarah Skeoch, a clinical research fellow at the Arthritis Research UK Epidemiology Unit at the University of Manchester, England, said at the annual European Congress of Rheumatology.

The research also showed that triglyceride level was the only independent traditional risk factor, with a 3.6-fold increased risk association. Damage related to lupus, according to the Systemic Lupus International Collaborating Clinics (SLICC) damage index, increased risk 10-fold. Cyclophosphamide therapy was associated with a 16.7-fold increase in risk.

Although the patients have more of the classical risk factors, this does not seem to account for all the increased risk. Disease characteristics such as chronic inflammation or treatments may contribute, she suggested.

"We wanted to look at the association between risk and disease, for example, how active their lupus is, damage accrued over time, whether they have renal disease, and also whether their treatments are associated with CV events like heart disease and stroke," Dr. Skeoch added.

The study looked at these factors in 200 patients who were diagnosed between 2000 and 2003.

At baseline, 12 patients of the eventual 124 who were followed up had experienced a prior CV event. Also at baseline, the SLE disease activity index (SLEDAI) score was 1, indicating low disease activity, and the SLICC damage index was low.

All patients included in the study were over 18 years of age, female, and white. Their lupus was stable with therapy for at least 2 months prior to inclusion in the study. "They were a relatively well population of patients," said Dr. Skeoch.

Blood tests and clinical assessments were carried out to determine levels of traditional risk factors, lupus disease activity, and lupus-related damage, as well as measurements related to disease therapies.

After a 5-year interval, patients were invited back for assessments and the incidence of CV events, including coronary events, cerebral events, and peripheral vascular disease over the elapsed time period, was recorded.

Next, a comparison was made between the predicted CV risk at baseline according to the Framingham equation and the observed results in 112 patients with no prior CV disease.

CV Risk Higher Than Expected

Upon follow-up, patients were, on average, 56 years old and had had disease for approximately 16 years. Out of the 124 patients followed up over approximately 5 years, 12 (9.7%) had a CV event. Coronary events accounted for seven of these, cerebrovascular events were recorded in five patients, and peripheral vascular disease occurred in one patient. "One patient had both a coronary event and a cerebral event within the follow up," Dr. Skeoch said.

In those who had no prior CV event at baseline, predicted risk of a CV event according to the Framingham equation suggested that 1% of patients should have an event in the next 5 years. "In fact, we found 7% had an event – so seven times higher than predicted. This excess risk is most likely attributed to uncaptured traditional risk factors or alternatively, the disease itself, which is more likely," she commented.

The investigators looked at independent risk factors for a CV event regardless of which other risk factors a patient had and found that triglyceride levels were the only traditional risk factor, with an odds ratio (OR) of 3.61 (95% confidence interval, 1.23-10.56). Triglyceride levels often were not the primary target of lipid-lowering therapy, which was usually aimed at reducing total cholesterol or cholesterol ratio, she noted.

Other multivariable analyses of baseline characteristics associated with CV events suggested that the risk was elevated by two factors: the SLICC damage score (OR, 9.62; CI, 1.46-63.5) and cyclophosphamide therapy (OR, 16.7; CI, 1.46-123). "Factors associated with the patients’ lupus disease included having had a venous thromboembolism, damage related to SLE in the past, cyclophosphamide exposure, and a higher steroid dose at baseline which predisposed the patient to having an event," Dr. Skeoch said.

Marker for Disease Severity

"This is the first time cyclophosphamide [therapy] has been marked as an example of an independent predictor of CV risk. We don’t think it is the cyclophosphamide itself because it has been used in a number of diseases and there’s no known evidence to suggest it causes heart disease, but we think it is a measure of people with severe disease. Also, patients exposed to cyclophosphamide tend to have had more steroids," she explained.

If patients with lupus had severe disease, then they might be more likely to be at risk of CV events in the future, she concluded. "We have found that patients with SLE are at higher risk than expected of CV disease and that those with severe disease may be most at risk. We should endeavor to monitor and treat traditional risk factors and aim for good control of SLE disease activity in order to minimize this risk."

Dr. Skeoch has no relevant conflicts of interest. She is funded by the UK Medical Research Council.

BERLIN – The risk of cardiovascular events in patients with systemic lupus erythematosus is sevenfold higher than the risk predicted by the Framingham equation, a study shows.

The role of risk factors varies widely, with the presence of high triglyceride levels upping the risk nearly fourfold while use of cyclophosphamide, which may be a proxy for disease severity, raises the risk almost 17-fold, Dr. Sarah Skeoch, a clinical research fellow at the Arthritis Research UK Epidemiology Unit at the University of Manchester, England, said at the annual European Congress of Rheumatology.

The research also showed that triglyceride level was the only independent traditional risk factor, with a 3.6-fold increased risk association. Damage related to lupus, according to the Systemic Lupus International Collaborating Clinics (SLICC) damage index, increased risk 10-fold. Cyclophosphamide therapy was associated with a 16.7-fold increase in risk.

Although the patients have more of the classical risk factors, this does not seem to account for all the increased risk. Disease characteristics such as chronic inflammation or treatments may contribute, she suggested.

"We wanted to look at the association between risk and disease, for example, how active their lupus is, damage accrued over time, whether they have renal disease, and also whether their treatments are associated with CV events like heart disease and stroke," Dr. Skeoch added.

The study looked at these factors in 200 patients who were diagnosed between 2000 and 2003.

At baseline, 12 patients of the eventual 124 who were followed up had experienced a prior CV event. Also at baseline, the SLE disease activity index (SLEDAI) score was 1, indicating low disease activity, and the SLICC damage index was low.

All patients included in the study were over 18 years of age, female, and white. Their lupus was stable with therapy for at least 2 months prior to inclusion in the study. "They were a relatively well population of patients," said Dr. Skeoch.

Blood tests and clinical assessments were carried out to determine levels of traditional risk factors, lupus disease activity, and lupus-related damage, as well as measurements related to disease therapies.

After a 5-year interval, patients were invited back for assessments and the incidence of CV events, including coronary events, cerebral events, and peripheral vascular disease over the elapsed time period, was recorded.

Next, a comparison was made between the predicted CV risk at baseline according to the Framingham equation and the observed results in 112 patients with no prior CV disease.

CV Risk Higher Than Expected

Upon follow-up, patients were, on average, 56 years old and had had disease for approximately 16 years. Out of the 124 patients followed up over approximately 5 years, 12 (9.7%) had a CV event. Coronary events accounted for seven of these, cerebrovascular events were recorded in five patients, and peripheral vascular disease occurred in one patient. "One patient had both a coronary event and a cerebral event within the follow up," Dr. Skeoch said.

In those who had no prior CV event at baseline, predicted risk of a CV event according to the Framingham equation suggested that 1% of patients should have an event in the next 5 years. "In fact, we found 7% had an event – so seven times higher than predicted. This excess risk is most likely attributed to uncaptured traditional risk factors or alternatively, the disease itself, which is more likely," she commented.

The investigators looked at independent risk factors for a CV event regardless of which other risk factors a patient had and found that triglyceride levels were the only traditional risk factor, with an odds ratio (OR) of 3.61 (95% confidence interval, 1.23-10.56). Triglyceride levels often were not the primary target of lipid-lowering therapy, which was usually aimed at reducing total cholesterol or cholesterol ratio, she noted.

Other multivariable analyses of baseline characteristics associated with CV events suggested that the risk was elevated by two factors: the SLICC damage score (OR, 9.62; CI, 1.46-63.5) and cyclophosphamide therapy (OR, 16.7; CI, 1.46-123). "Factors associated with the patients’ lupus disease included having had a venous thromboembolism, damage related to SLE in the past, cyclophosphamide exposure, and a higher steroid dose at baseline which predisposed the patient to having an event," Dr. Skeoch said.

Marker for Disease Severity

"This is the first time cyclophosphamide [therapy] has been marked as an example of an independent predictor of CV risk. We don’t think it is the cyclophosphamide itself because it has been used in a number of diseases and there’s no known evidence to suggest it causes heart disease, but we think it is a measure of people with severe disease. Also, patients exposed to cyclophosphamide tend to have had more steroids," she explained.

If patients with lupus had severe disease, then they might be more likely to be at risk of CV events in the future, she concluded. "We have found that patients with SLE are at higher risk than expected of CV disease and that those with severe disease may be most at risk. We should endeavor to monitor and treat traditional risk factors and aim for good control of SLE disease activity in order to minimize this risk."

Dr. Skeoch has no relevant conflicts of interest. She is funded by the UK Medical Research Council.

RALEIGH, N.C. – Absolute differences in response rates for treatments of moderate to severe plaque psoriasis as commonly used in everyday clinical practice "are small and may not be clinically significant," Dr. Joy Wan said at the annual meeting of the Society for Investigative Dermatology.

The results of a multicenter, comparative effectiveness study provide a picture of how psoriasis treatments are performing in real-world practice as opposed to the setting of clinical trials, which typically feature a nonrepresentative patient population and physician investigators having expertise in the treatment under study, according to Dr. Wan.

The results suggest that the go-to treatments for moderate to severe plaque psoriasis aren’t as effective in routine practice as they were in randomized trials (Arch. Dermatol. 2012;148:487-94). For example, only 48% of patients on adalimumab (Humira) were clear or almost clear based on Physician Global Assessment (PGA) ratings, compared with a 73% rate in an earlier clinical trial, noted Dr. Wan of the University of Pennsylvania, Philadelphia.

The comparative effectiveness study was cross sectional, and involved 713 consecutive patients with moderate to severe plaque psoriasis seen for routine follow-up care in 10 practices participating in the Dermatology Clinical Effectiveness Research Network (DCERN), a nationwide network of private and academic dermatology practices established in 2010.

The study participants (mean age, 49 years; 50% men) had a median 19-year duration of psoriasis; 23% also had psoriatic arthritis. All patients in the study were on monotherapy with methotrexate, etanercept, adalimumab, ustekinumab, or narrow-band UVB phototherapy (NBUVB). In all, 27% of the patients were on etanercept, 24% on methotrexate, 21% on adalimumab, 17% on NBUVB, and the rest on ustekinumab. Patients had been on methotrexate, adalimumab, or etanercept for a median of 12 months; ustekinumab for 4 months; and NBUVB for 2 months. On average, participants had been on only one systemic therapy or phototherapy prior to their current treatment. Patients were evaluated using PGA ratings and the Dermatology Life Quality Index.

One striking finding, noted Dr. Wan, was that recommended dosing often was not optimal. Notably, 36% of patients on etanercept were on 50 mg twice weekly and 12% on adalimumab were on 40 mg once weekly; those are double the recommended maintenance doses based on clinical trial data. And only 11% of patients on NBUVB received the optimal dosing frequency of at least 12 sessions within the previous 4 weeks.

The primary study end point was the proportion of patients rated clear or almost clear on PGA. The rates were 24% with methotrexate, 48% with adalimumab, 34% with etanercept, 36% for ustekinumab, and 28% with NBUVB.

Using methotrexate as the reference standard in analyses adjusted for more than 20 factors, including patient age, gender, and treatment duration, patients on adalimumab were 2.15-fold more likely to have clear or almost clear skin. Patients on ustekinumab were 1.57-fold more likely and those on etanercept 1.45-fold more likely to have clear or almost clear skin than those on methotrexate. The response rate to NBUVB wasn’t significantly different from that for methotrexate.

The results suggest that the biologic agents are outperforming methotrexate. That being said, the median PGA scores for all of the therapies hovered in the range of 1.3-1.7 on a scale of 0 to 5. This indicates that the absolute differences in treatment effectiveness are "quite small," Dr. Wan said. Moreover, there were no significant differences between treatments in terms of quality of life.

"The proportion of patients who said psoriasis had no or only a small effect on their quality of life was generally high across the board, ranging from 68% with narrow-band UVB to 78% with adalimumab," she said.

The number of patients who would need to be treated with a given agent in order to achieve one additional "clear" or "almost clear" response beyond what would be expected if patients were treated with methotrexate – was 4 for adalimumab, 8 for ustekinumab, 10 for etanercept, and 12 for NBUVB.

This cross-sectional study provides a useful snapshot of how psoriasis therapies are performing in current practice. The next step will be to perform a longitudinal comparative effectiveness study, according to Dr. Wan.

The DCERN network was formed in response to the fact that comparative effectiveness research was becoming a hot research trend, she said. The Institute of Medicine has identified comparative effectiveness research as a top priority, with psoriasis and acne as the main diseases of interest within dermatology.

"Congress has spent billions of dollars to jump-start comparative effectiveness research efforts," Dr. Wan noted.

Dr. Alexa B. Kimball rose from the audience to comment on the interpretation of the study data.

"There’s a relatively consistent pattern in clinical practice: Many patients are started on methotrexate; then if need be they are moved to etanercept or adalimumab, then to ustekinumab. So in a sense, since you’re finding that the clinical improvement is not so different across these therapies, doesn’t that suggest that patients get to a certain level of improvement and then are no longer switched? In fact, it may be that what you’re really showing is the level of improvement patients tend to be satisfied at," said Dr. Kimball of Harvard Medical School, Boston.

The study was sponsored by the National Institutes of Health. Dr. Wan reported having no financial conflicts. Dr. Kimball is a clinical trial investigator of biologic agents.

RALEIGH, N.C. – Absolute differences in response rates for treatments of moderate to severe plaque psoriasis as commonly used in everyday clinical practice "are small and may not be clinically significant," Dr. Joy Wan said at the annual meeting of the Society for Investigative Dermatology.

The results of a multicenter, comparative effectiveness study provide a picture of how psoriasis treatments are performing in real-world practice as opposed to the setting of clinical trials, which typically feature a nonrepresentative patient population and physician investigators having expertise in the treatment under study, according to Dr. Wan.

The results suggest that the go-to treatments for moderate to severe plaque psoriasis aren’t as effective in routine practice as they were in randomized trials (Arch. Dermatol. 2012;148:487-94). For example, only 48% of patients on adalimumab (Humira) were clear or almost clear based on Physician Global Assessment (PGA) ratings, compared with a 73% rate in an earlier clinical trial, noted Dr. Wan of the University of Pennsylvania, Philadelphia.

The comparative effectiveness study was cross sectional, and involved 713 consecutive patients with moderate to severe plaque psoriasis seen for routine follow-up care in 10 practices participating in the Dermatology Clinical Effectiveness Research Network (DCERN), a nationwide network of private and academic dermatology practices established in 2010.

The study participants (mean age, 49 years; 50% men) had a median 19-year duration of psoriasis; 23% also had psoriatic arthritis. All patients in the study were on monotherapy with methotrexate, etanercept, adalimumab, ustekinumab, or narrow-band UVB phototherapy (NBUVB). In all, 27% of the patients were on etanercept, 24% on methotrexate, 21% on adalimumab, 17% on NBUVB, and the rest on ustekinumab. Patients had been on methotrexate, adalimumab, or etanercept for a median of 12 months; ustekinumab for 4 months; and NBUVB for 2 months. On average, participants had been on only one systemic therapy or phototherapy prior to their current treatment. Patients were evaluated using PGA ratings and the Dermatology Life Quality Index.

One striking finding, noted Dr. Wan, was that recommended dosing often was not optimal. Notably, 36% of patients on etanercept were on 50 mg twice weekly and 12% on adalimumab were on 40 mg once weekly; those are double the recommended maintenance doses based on clinical trial data. And only 11% of patients on NBUVB received the optimal dosing frequency of at least 12 sessions within the previous 4 weeks.

The primary study end point was the proportion of patients rated clear or almost clear on PGA. The rates were 24% with methotrexate, 48% with adalimumab, 34% with etanercept, 36% for ustekinumab, and 28% with NBUVB.

Using methotrexate as the reference standard in analyses adjusted for more than 20 factors, including patient age, gender, and treatment duration, patients on adalimumab were 2.15-fold more likely to have clear or almost clear skin. Patients on ustekinumab were 1.57-fold more likely and those on etanercept 1.45-fold more likely to have clear or almost clear skin than those on methotrexate. The response rate to NBUVB wasn’t significantly different from that for methotrexate.

The results suggest that the biologic agents are outperforming methotrexate. That being said, the median PGA scores for all of the therapies hovered in the range of 1.3-1.7 on a scale of 0 to 5. This indicates that the absolute differences in treatment effectiveness are "quite small," Dr. Wan said. Moreover, there were no significant differences between treatments in terms of quality of life.

"The proportion of patients who said psoriasis had no or only a small effect on their quality of life was generally high across the board, ranging from 68% with narrow-band UVB to 78% with adalimumab," she said.

The number of patients who would need to be treated with a given agent in order to achieve one additional "clear" or "almost clear" response beyond what would be expected if patients were treated with methotrexate – was 4 for adalimumab, 8 for ustekinumab, 10 for etanercept, and 12 for NBUVB.

This cross-sectional study provides a useful snapshot of how psoriasis therapies are performing in current practice. The next step will be to perform a longitudinal comparative effectiveness study, according to Dr. Wan.

The DCERN network was formed in response to the fact that comparative effectiveness research was becoming a hot research trend, she said. The Institute of Medicine has identified comparative effectiveness research as a top priority, with psoriasis and acne as the main diseases of interest within dermatology.

"Congress has spent billions of dollars to jump-start comparative effectiveness research efforts," Dr. Wan noted.

Dr. Alexa B. Kimball rose from the audience to comment on the interpretation of the study data.

"There’s a relatively consistent pattern in clinical practice: Many patients are started on methotrexate; then if need be they are moved to etanercept or adalimumab, then to ustekinumab. So in a sense, since you’re finding that the clinical improvement is not so different across these therapies, doesn’t that suggest that patients get to a certain level of improvement and then are no longer switched? In fact, it may be that what you’re really showing is the level of improvement patients tend to be satisfied at," said Dr. Kimball of Harvard Medical School, Boston.

The study was sponsored by the National Institutes of Health. Dr. Wan reported having no financial conflicts. Dr. Kimball is a clinical trial investigator of biologic agents.

RALEIGH, N.C. – Absolute differences in response rates for treatments of moderate to severe plaque psoriasis as commonly used in everyday clinical practice "are small and may not be clinically significant," Dr. Joy Wan said at the annual meeting of the Society for Investigative Dermatology.

The results of a multicenter, comparative effectiveness study provide a picture of how psoriasis treatments are performing in real-world practice as opposed to the setting of clinical trials, which typically feature a nonrepresentative patient population and physician investigators having expertise in the treatment under study, according to Dr. Wan.

The results suggest that the go-to treatments for moderate to severe plaque psoriasis aren’t as effective in routine practice as they were in randomized trials (Arch. Dermatol. 2012;148:487-94). For example, only 48% of patients on adalimumab (Humira) were clear or almost clear based on Physician Global Assessment (PGA) ratings, compared with a 73% rate in an earlier clinical trial, noted Dr. Wan of the University of Pennsylvania, Philadelphia.

The comparative effectiveness study was cross sectional, and involved 713 consecutive patients with moderate to severe plaque psoriasis seen for routine follow-up care in 10 practices participating in the Dermatology Clinical Effectiveness Research Network (DCERN), a nationwide network of private and academic dermatology practices established in 2010.

The study participants (mean age, 49 years; 50% men) had a median 19-year duration of psoriasis; 23% also had psoriatic arthritis. All patients in the study were on monotherapy with methotrexate, etanercept, adalimumab, ustekinumab, or narrow-band UVB phototherapy (NBUVB). In all, 27% of the patients were on etanercept, 24% on methotrexate, 21% on adalimumab, 17% on NBUVB, and the rest on ustekinumab. Patients had been on methotrexate, adalimumab, or etanercept for a median of 12 months; ustekinumab for 4 months; and NBUVB for 2 months. On average, participants had been on only one systemic therapy or phototherapy prior to their current treatment. Patients were evaluated using PGA ratings and the Dermatology Life Quality Index.

One striking finding, noted Dr. Wan, was that recommended dosing often was not optimal. Notably, 36% of patients on etanercept were on 50 mg twice weekly and 12% on adalimumab were on 40 mg once weekly; those are double the recommended maintenance doses based on clinical trial data. And only 11% of patients on NBUVB received the optimal dosing frequency of at least 12 sessions within the previous 4 weeks.

The primary study end point was the proportion of patients rated clear or almost clear on PGA. The rates were 24% with methotrexate, 48% with adalimumab, 34% with etanercept, 36% for ustekinumab, and 28% with NBUVB.

Using methotrexate as the reference standard in analyses adjusted for more than 20 factors, including patient age, gender, and treatment duration, patients on adalimumab were 2.15-fold more likely to have clear or almost clear skin. Patients on ustekinumab were 1.57-fold more likely and those on etanercept 1.45-fold more likely to have clear or almost clear skin than those on methotrexate. The response rate to NBUVB wasn’t significantly different from that for methotrexate.

The results suggest that the biologic agents are outperforming methotrexate. That being said, the median PGA scores for all of the therapies hovered in the range of 1.3-1.7 on a scale of 0 to 5. This indicates that the absolute differences in treatment effectiveness are "quite small," Dr. Wan said. Moreover, there were no significant differences between treatments in terms of quality of life.

"The proportion of patients who said psoriasis had no or only a small effect on their quality of life was generally high across the board, ranging from 68% with narrow-band UVB to 78% with adalimumab," she said.

The number of patients who would need to be treated with a given agent in order to achieve one additional "clear" or "almost clear" response beyond what would be expected if patients were treated with methotrexate – was 4 for adalimumab, 8 for ustekinumab, 10 for etanercept, and 12 for NBUVB.

This cross-sectional study provides a useful snapshot of how psoriasis therapies are performing in current practice. The next step will be to perform a longitudinal comparative effectiveness study, according to Dr. Wan.

The DCERN network was formed in response to the fact that comparative effectiveness research was becoming a hot research trend, she said. The Institute of Medicine has identified comparative effectiveness research as a top priority, with psoriasis and acne as the main diseases of interest within dermatology.

"Congress has spent billions of dollars to jump-start comparative effectiveness research efforts," Dr. Wan noted.

Dr. Alexa B. Kimball rose from the audience to comment on the interpretation of the study data.

"There’s a relatively consistent pattern in clinical practice: Many patients are started on methotrexate; then if need be they are moved to etanercept or adalimumab, then to ustekinumab. So in a sense, since you’re finding that the clinical improvement is not so different across these therapies, doesn’t that suggest that patients get to a certain level of improvement and then are no longer switched? In fact, it may be that what you’re really showing is the level of improvement patients tend to be satisfied at," said Dr. Kimball of Harvard Medical School, Boston.

The study was sponsored by the National Institutes of Health. Dr. Wan reported having no financial conflicts. Dr. Kimball is a clinical trial investigator of biologic agents.