Psoriasis

The use of biologic agents to treat rheumatoid arthritis doesn’t appear to be associated with an increased risk of malignancy, compared with either placebo or with other disease-modifying drugs, according to a report in the Sept. 5 issue of JAMA.

In a meta-analysis of 63 randomized clinical trials of at least 24 weeks’ duration involving 29,423 adults with RA, there was no increase in the risk of cancer in general or in the risk of specific cancers. "Additional systematic reviews of observational studies are needed to establish risk in the longer term," said Dr. Maria A. Lopez-Olivo of the University of Texas M.D. Anderson Cancer Center, Houston, and her associates.

They described their study as the first systematic review and meta-analysis to assess the risk of any type of malignancy solely in RA patients who were taking any of the nine biologic agents approved for such use: abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab, or tocilizumab.

There has been concern that these agents could raise cancer risk because they interfere with the immune system. Some data have implicated tumor necrosis factor (TNF) inhibitors in particular, prompting the Food and Drug Administration to recommend adding a warning label citing an excess of cases of spontaneous lymphoma among children and adolescents taking TNF inhibitors.

"While trials in RA are relatively short and cannot evaluate the risk over longer-term exposure as observational studies do, we thought there was a need to conduct an updated meta-analysis of RCTs [randomized controlled trials] because of the older reports of the possible increase in malignancies and the more recent FDA advisory for TNF inhibitors, mostly based on studies in children," the researchers noted.

In the RCTs included in this meta-analysis, sample sizes ranged from 20 to 1,399 subjects. Most study subjects (79%) were white, and 76% were women. The mean duration of RA ranged from less than 1 year to 13 years.

Pharmaceutical companies sponsored 56 of the 63 trials, and another 3 did not disclose their funding sources. The remaining four trials were funded by national organizations, but the agents they used were provided free of charge by manufacturers. "There is evidence that industry-sponsored trials may overestimate the treatment effect and could possibly also overestimate safety," acacording to Dr. Lopez-Olivo and her associates.

A total of 15,989 study subjects were assigned to take biologic agents plus methotrexate and/or other disease-modifying antirheumatic drugs, while 3,615 were assigned to take the biologic agents alone and 9,819 served as control subjects who were given placebos.

A total of 211 malignancies developed during the trials, in 0.77% of the combination-therapy group, 0.64% of the monotherapy group, and 0.66% of the control group. These differences were not significant, the investigators said (JAMA 2012;308:898-908).

Skin cancers accounted for 48 of the malignancies (which included 4 melanomas), 14 were lymphomas, 26 were not specified, and 5 were hematologic nonlymphomas. The remaining 118 malignancies were solid tumors affecting a wide variety of organs including the adrenal glands, bladder, breast, GI system, liver, lung, ovary, pancreas, prostate, kidney, testes, thyroid, tongue, and uterus.

Thus there was no pattern involving a specific type of cancer.

Similarly, there was no pattern involving any of the individual biologic agents, Dr. Lopez-Olivo and her associates said.

"The only increased risk of malignancy we observed was in patients with RA treated with TNF inhibitors plus methotrexate at 52 weeks, for all cancers combined." However, this effect was not consistent across the three separate analytical methods the researchers used, did not occur in patients taking TNF inhibitors as monotherapy, and did not occur at any of the other three time points assessed.

The study findings "suggest that biologic, disease-modifying agents may be generally safe with respect to risk of malignancy in the short term," but their safety in RA patients who have concomitant cancer or risk factors for cancer remains unknown, the researchers said.

No sponsors were involved with this study, and no financial conflicts of interest were reported.

The use of biologic agents to treat rheumatoid arthritis doesn’t appear to be associated with an increased risk of malignancy, compared with either placebo or with other disease-modifying drugs, according to a report in the Sept. 5 issue of JAMA.

In a meta-analysis of 63 randomized clinical trials of at least 24 weeks’ duration involving 29,423 adults with RA, there was no increase in the risk of cancer in general or in the risk of specific cancers. "Additional systematic reviews of observational studies are needed to establish risk in the longer term," said Dr. Maria A. Lopez-Olivo of the University of Texas M.D. Anderson Cancer Center, Houston, and her associates.

They described their study as the first systematic review and meta-analysis to assess the risk of any type of malignancy solely in RA patients who were taking any of the nine biologic agents approved for such use: abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab, or tocilizumab.

There has been concern that these agents could raise cancer risk because they interfere with the immune system. Some data have implicated tumor necrosis factor (TNF) inhibitors in particular, prompting the Food and Drug Administration to recommend adding a warning label citing an excess of cases of spontaneous lymphoma among children and adolescents taking TNF inhibitors.

"While trials in RA are relatively short and cannot evaluate the risk over longer-term exposure as observational studies do, we thought there was a need to conduct an updated meta-analysis of RCTs [randomized controlled trials] because of the older reports of the possible increase in malignancies and the more recent FDA advisory for TNF inhibitors, mostly based on studies in children," the researchers noted.

In the RCTs included in this meta-analysis, sample sizes ranged from 20 to 1,399 subjects. Most study subjects (79%) were white, and 76% were women. The mean duration of RA ranged from less than 1 year to 13 years.

Pharmaceutical companies sponsored 56 of the 63 trials, and another 3 did not disclose their funding sources. The remaining four trials were funded by national organizations, but the agents they used were provided free of charge by manufacturers. "There is evidence that industry-sponsored trials may overestimate the treatment effect and could possibly also overestimate safety," acacording to Dr. Lopez-Olivo and her associates.

A total of 15,989 study subjects were assigned to take biologic agents plus methotrexate and/or other disease-modifying antirheumatic drugs, while 3,615 were assigned to take the biologic agents alone and 9,819 served as control subjects who were given placebos.

A total of 211 malignancies developed during the trials, in 0.77% of the combination-therapy group, 0.64% of the monotherapy group, and 0.66% of the control group. These differences were not significant, the investigators said (JAMA 2012;308:898-908).

Skin cancers accounted for 48 of the malignancies (which included 4 melanomas), 14 were lymphomas, 26 were not specified, and 5 were hematologic nonlymphomas. The remaining 118 malignancies were solid tumors affecting a wide variety of organs including the adrenal glands, bladder, breast, GI system, liver, lung, ovary, pancreas, prostate, kidney, testes, thyroid, tongue, and uterus.

Thus there was no pattern involving a specific type of cancer.

Similarly, there was no pattern involving any of the individual biologic agents, Dr. Lopez-Olivo and her associates said.

"The only increased risk of malignancy we observed was in patients with RA treated with TNF inhibitors plus methotrexate at 52 weeks, for all cancers combined." However, this effect was not consistent across the three separate analytical methods the researchers used, did not occur in patients taking TNF inhibitors as monotherapy, and did not occur at any of the other three time points assessed.

The study findings "suggest that biologic, disease-modifying agents may be generally safe with respect to risk of malignancy in the short term," but their safety in RA patients who have concomitant cancer or risk factors for cancer remains unknown, the researchers said.

No sponsors were involved with this study, and no financial conflicts of interest were reported.

The use of biologic agents to treat rheumatoid arthritis doesn’t appear to be associated with an increased risk of malignancy, compared with either placebo or with other disease-modifying drugs, according to a report in the Sept. 5 issue of JAMA.

In a meta-analysis of 63 randomized clinical trials of at least 24 weeks’ duration involving 29,423 adults with RA, there was no increase in the risk of cancer in general or in the risk of specific cancers. "Additional systematic reviews of observational studies are needed to establish risk in the longer term," said Dr. Maria A. Lopez-Olivo of the University of Texas M.D. Anderson Cancer Center, Houston, and her associates.

They described their study as the first systematic review and meta-analysis to assess the risk of any type of malignancy solely in RA patients who were taking any of the nine biologic agents approved for such use: abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab, or tocilizumab.

There has been concern that these agents could raise cancer risk because they interfere with the immune system. Some data have implicated tumor necrosis factor (TNF) inhibitors in particular, prompting the Food and Drug Administration to recommend adding a warning label citing an excess of cases of spontaneous lymphoma among children and adolescents taking TNF inhibitors.

"While trials in RA are relatively short and cannot evaluate the risk over longer-term exposure as observational studies do, we thought there was a need to conduct an updated meta-analysis of RCTs [randomized controlled trials] because of the older reports of the possible increase in malignancies and the more recent FDA advisory for TNF inhibitors, mostly based on studies in children," the researchers noted.

In the RCTs included in this meta-analysis, sample sizes ranged from 20 to 1,399 subjects. Most study subjects (79%) were white, and 76% were women. The mean duration of RA ranged from less than 1 year to 13 years.

Pharmaceutical companies sponsored 56 of the 63 trials, and another 3 did not disclose their funding sources. The remaining four trials were funded by national organizations, but the agents they used were provided free of charge by manufacturers. "There is evidence that industry-sponsored trials may overestimate the treatment effect and could possibly also overestimate safety," acacording to Dr. Lopez-Olivo and her associates.

A total of 15,989 study subjects were assigned to take biologic agents plus methotrexate and/or other disease-modifying antirheumatic drugs, while 3,615 were assigned to take the biologic agents alone and 9,819 served as control subjects who were given placebos.

A total of 211 malignancies developed during the trials, in 0.77% of the combination-therapy group, 0.64% of the monotherapy group, and 0.66% of the control group. These differences were not significant, the investigators said (JAMA 2012;308:898-908).

Skin cancers accounted for 48 of the malignancies (which included 4 melanomas), 14 were lymphomas, 26 were not specified, and 5 were hematologic nonlymphomas. The remaining 118 malignancies were solid tumors affecting a wide variety of organs including the adrenal glands, bladder, breast, GI system, liver, lung, ovary, pancreas, prostate, kidney, testes, thyroid, tongue, and uterus.

Thus there was no pattern involving a specific type of cancer.

Similarly, there was no pattern involving any of the individual biologic agents, Dr. Lopez-Olivo and her associates said.

"The only increased risk of malignancy we observed was in patients with RA treated with TNF inhibitors plus methotrexate at 52 weeks, for all cancers combined." However, this effect was not consistent across the three separate analytical methods the researchers used, did not occur in patients taking TNF inhibitors as monotherapy, and did not occur at any of the other three time points assessed.

The study findings "suggest that biologic, disease-modifying agents may be generally safe with respect to risk of malignancy in the short term," but their safety in RA patients who have concomitant cancer or risk factors for cancer remains unknown, the researchers said.

No sponsors were involved with this study, and no financial conflicts of interest were reported.

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.