Sharon Worcester

SAN DESTIN, FLA. – Many patients with mixed connective tissue disease may represent a subset of systemic scleroderma, rather than a disease involving overlapping connective tissue disorders as is commonly believed, or a subset of lupus as some have suggested over the years, Dr. Virginia Steen said at the Congress of Clinical Rheumatology.

Several factors associated with clinical presentation support this argument, said Dr. Steen, professor of medicine at Georgetown University in Washington.

Nail Fold Capillaries/Digital Ulcers

For example, data from a study of nail fold capillary abnormalities in mixed connective tissue disease (MCTD) showed that the abnormalities took a sclerodermatous pattern in 64% of 22 patients, compared with a systemic lupus erythematosus (SLE) pattern in 23%, and a nonspecific pattern in 14%, she said.

Compared with typical findings in SLE, there was significantly greater capillary loss, and more of the bushy capillary formations seen in scleroderma.

"So it did tend to be more scleroderma-like, and this is particularly important, because we do see a lot of MCTD patients who have digital ulcers," she said. In most cases, the ulcers are ischemic and are caused by vascular changes similar to scleroderma, rather than due to a lupus vasculitis, she added.

Arthritis/Joint Involvement

Arthritis in MCTD also has different characteristics than arthritis seen in lupus, and more similarities to scleroderma. The arthritis in MCTD tends to be erosive, unlike arthritis seen in SLE, and it tends to be small, marginal, and asymmetric, occurring in the wrists and fingers. Other musculoskeletal features similar to those in scleroderma include calcinosis, distal tuft resorption, and acro-osteolysis.

Although MCTD patients do tend to get Jaccoud’s subluxation, much as SLE patients do, this occurs to a lesser extent than in lupus, and the frequency of cyclic citrullinated peptides is low as well (9% in one study).

"Hand arthritis is often quite mixed," Dr. Steen said.

Muscle Involvement

Muscle involvement is rarely the presenting feature in MCTD, but it is usually present in early disease, and although the perivascular and endomysial inflammation is more typical of dermatomyositis, there tends to not be a lot of skin involvement associated with this.

Furthermore, there is an increase in the thickness of vessel walls, which is fairly unique, and the immunochemical profile in these cases differs from what is typically seen with myositis in that creatine phosphokinase levels are lower, Dr. Steen said.

Also, the effects on muscle tend to be milder in MCTD, with some patients experiencing no symptoms, and it may not progress.

Skin Involvement

Skin involvement patterns also indicate that MCTD is actually a scleroderma subset. Skin involvement is much less common in MCTD than in SLE.

"It’s a lupuslike skin disease similar to subacute cutaneous lupus, but it also has vascular ectasia, hypovascularity, or luminal occlusion of the vessels, so it’s a little bit atypical," Dr. Steen said.

Also, lupus band test positivity is uncommon, and the most common skin manifestations are more scleroderma-like, with puffy fingers and sclerodactyly, she added. Patients with skin involvement usually have limited scleroderma, but about 20% go on to develop diffuse cutaneous scleroderma.

Gastrointestinal Involvement

Providing more evidence is the fact that esophageal involvement and the very severe small bowel dysmotility commonly seen in MCTD are identical to those seen in scleroderma, Dr. Steen said.

"There doesn’t seem to be any difference in the pattern, and as in scleroderma, it doesn’t respond to steroids or immunosuppressants. You really just have to treat it symptomatically," she noted.

Interstitial Lung Disease

Interstitial lung disease is a more challenging area, according to Dr. Steen. It is common in patients diagnosed with MCTD, but there is a lack of prospective study data. In a 2010 study, 66% of 144 patients with very early nonspecific interstitial pneumonitis (NSIP) were treated with steroids; 50% responded, and 50% went on to develop more severe and progressive fibrosis requiring immunosuppressive therapy.

"So there wasn’t a clear pattern where you would think this was a unique type of inflammatory interstitial pneumonitis that is clearly steroid responsive like some of the NSIPs that aren’t associated with connective tissues disease are. There is more fibrosis, and it does seem to be more typically scleroderma related than an independent type of lung disease," she said.

Pulmonary Hypertension

Pulmonary hypertension is one of the biggest challenges in MCTD, Dr. Steen said. Several studies have shown a significant association with pulmonary hypertension and mortality in these patients.

A small study of MCTD patients showed a large decrease in the DLCO (diffusing capacity of the lung for carbon monoxide), she said. Some of these patients had increased pulmonary artery pressure, and there were seven patients who actually had pulmonary arterial hypertension. The available autopsies revealed that the patients tended to have pretty typical pulmonary arteriolopathy, similar to what we see in scleroderma, with a striking intimal proliferation of the vasculature, she said.

Also, as in scleroderma, the pulmonary vessels – even in patients who didn’t have pulmonary hypertension – had similar but less extensive disease, she added.

Based on these various findings, which together show a great deal of similarity to scleroderma while highlighting numerous differences from other connective tissue diseases, Dr. Steen said she is increasingly convinced that MCTD is not a unique entity, mixed disease, or subset of lupus, but is actually a subset of systemic scleroderma.

Dr. Steen reported having no disclosures relevant to her presentation.

SAN DESTIN, FLA. – Many patients with mixed connective tissue disease may represent a subset of systemic scleroderma, rather than a disease involving overlapping connective tissue disorders as is commonly believed, or a subset of lupus as some have suggested over the years, Dr. Virginia Steen said at the Congress of Clinical Rheumatology.

Several factors associated with clinical presentation support this argument, said Dr. Steen, professor of medicine at Georgetown University in Washington.

Nail Fold Capillaries/Digital Ulcers

For example, data from a study of nail fold capillary abnormalities in mixed connective tissue disease (MCTD) showed that the abnormalities took a sclerodermatous pattern in 64% of 22 patients, compared with a systemic lupus erythematosus (SLE) pattern in 23%, and a nonspecific pattern in 14%, she said.

Compared with typical findings in SLE, there was significantly greater capillary loss, and more of the bushy capillary formations seen in scleroderma.

"So it did tend to be more scleroderma-like, and this is particularly important, because we do see a lot of MCTD patients who have digital ulcers," she said. In most cases, the ulcers are ischemic and are caused by vascular changes similar to scleroderma, rather than due to a lupus vasculitis, she added.

Arthritis/Joint Involvement

Arthritis in MCTD also has different characteristics than arthritis seen in lupus, and more similarities to scleroderma. The arthritis in MCTD tends to be erosive, unlike arthritis seen in SLE, and it tends to be small, marginal, and asymmetric, occurring in the wrists and fingers. Other musculoskeletal features similar to those in scleroderma include calcinosis, distal tuft resorption, and acro-osteolysis.

Although MCTD patients do tend to get Jaccoud’s subluxation, much as SLE patients do, this occurs to a lesser extent than in lupus, and the frequency of cyclic citrullinated peptides is low as well (9% in one study).

"Hand arthritis is often quite mixed," Dr. Steen said.

Muscle Involvement

Muscle involvement is rarely the presenting feature in MCTD, but it is usually present in early disease, and although the perivascular and endomysial inflammation is more typical of dermatomyositis, there tends to not be a lot of skin involvement associated with this.

Furthermore, there is an increase in the thickness of vessel walls, which is fairly unique, and the immunochemical profile in these cases differs from what is typically seen with myositis in that creatine phosphokinase levels are lower, Dr. Steen said.

Also, the effects on muscle tend to be milder in MCTD, with some patients experiencing no symptoms, and it may not progress.

Skin Involvement

Skin involvement patterns also indicate that MCTD is actually a scleroderma subset. Skin involvement is much less common in MCTD than in SLE.

"It’s a lupuslike skin disease similar to subacute cutaneous lupus, but it also has vascular ectasia, hypovascularity, or luminal occlusion of the vessels, so it’s a little bit atypical," Dr. Steen said.

Also, lupus band test positivity is uncommon, and the most common skin manifestations are more scleroderma-like, with puffy fingers and sclerodactyly, she added. Patients with skin involvement usually have limited scleroderma, but about 20% go on to develop diffuse cutaneous scleroderma.

Gastrointestinal Involvement

Providing more evidence is the fact that esophageal involvement and the very severe small bowel dysmotility commonly seen in MCTD are identical to those seen in scleroderma, Dr. Steen said.

"There doesn’t seem to be any difference in the pattern, and as in scleroderma, it doesn’t respond to steroids or immunosuppressants. You really just have to treat it symptomatically," she noted.

Interstitial Lung Disease

Interstitial lung disease is a more challenging area, according to Dr. Steen. It is common in patients diagnosed with MCTD, but there is a lack of prospective study data. In a 2010 study, 66% of 144 patients with very early nonspecific interstitial pneumonitis (NSIP) were treated with steroids; 50% responded, and 50% went on to develop more severe and progressive fibrosis requiring immunosuppressive therapy.

"So there wasn’t a clear pattern where you would think this was a unique type of inflammatory interstitial pneumonitis that is clearly steroid responsive like some of the NSIPs that aren’t associated with connective tissues disease are. There is more fibrosis, and it does seem to be more typically scleroderma related than an independent type of lung disease," she said.

Pulmonary Hypertension

Pulmonary hypertension is one of the biggest challenges in MCTD, Dr. Steen said. Several studies have shown a significant association with pulmonary hypertension and mortality in these patients.

A small study of MCTD patients showed a large decrease in the DLCO (diffusing capacity of the lung for carbon monoxide), she said. Some of these patients had increased pulmonary artery pressure, and there were seven patients who actually had pulmonary arterial hypertension. The available autopsies revealed that the patients tended to have pretty typical pulmonary arteriolopathy, similar to what we see in scleroderma, with a striking intimal proliferation of the vasculature, she said.

Also, as in scleroderma, the pulmonary vessels – even in patients who didn’t have pulmonary hypertension – had similar but less extensive disease, she added.

Based on these various findings, which together show a great deal of similarity to scleroderma while highlighting numerous differences from other connective tissue diseases, Dr. Steen said she is increasingly convinced that MCTD is not a unique entity, mixed disease, or subset of lupus, but is actually a subset of systemic scleroderma.

Dr. Steen reported having no disclosures relevant to her presentation.

SAN DESTIN, FLA. – Many patients with mixed connective tissue disease may represent a subset of systemic scleroderma, rather than a disease involving overlapping connective tissue disorders as is commonly believed, or a subset of lupus as some have suggested over the years, Dr. Virginia Steen said at the Congress of Clinical Rheumatology.

Several factors associated with clinical presentation support this argument, said Dr. Steen, professor of medicine at Georgetown University in Washington.

Nail Fold Capillaries/Digital Ulcers

For example, data from a study of nail fold capillary abnormalities in mixed connective tissue disease (MCTD) showed that the abnormalities took a sclerodermatous pattern in 64% of 22 patients, compared with a systemic lupus erythematosus (SLE) pattern in 23%, and a nonspecific pattern in 14%, she said.

Compared with typical findings in SLE, there was significantly greater capillary loss, and more of the bushy capillary formations seen in scleroderma.

"So it did tend to be more scleroderma-like, and this is particularly important, because we do see a lot of MCTD patients who have digital ulcers," she said. In most cases, the ulcers are ischemic and are caused by vascular changes similar to scleroderma, rather than due to a lupus vasculitis, she added.

Arthritis/Joint Involvement

Arthritis in MCTD also has different characteristics than arthritis seen in lupus, and more similarities to scleroderma. The arthritis in MCTD tends to be erosive, unlike arthritis seen in SLE, and it tends to be small, marginal, and asymmetric, occurring in the wrists and fingers. Other musculoskeletal features similar to those in scleroderma include calcinosis, distal tuft resorption, and acro-osteolysis.

Although MCTD patients do tend to get Jaccoud’s subluxation, much as SLE patients do, this occurs to a lesser extent than in lupus, and the frequency of cyclic citrullinated peptides is low as well (9% in one study).

"Hand arthritis is often quite mixed," Dr. Steen said.

Muscle Involvement

Muscle involvement is rarely the presenting feature in MCTD, but it is usually present in early disease, and although the perivascular and endomysial inflammation is more typical of dermatomyositis, there tends to not be a lot of skin involvement associated with this.

Furthermore, there is an increase in the thickness of vessel walls, which is fairly unique, and the immunochemical profile in these cases differs from what is typically seen with myositis in that creatine phosphokinase levels are lower, Dr. Steen said.

Also, the effects on muscle tend to be milder in MCTD, with some patients experiencing no symptoms, and it may not progress.

Skin Involvement

Skin involvement patterns also indicate that MCTD is actually a scleroderma subset. Skin involvement is much less common in MCTD than in SLE.

"It’s a lupuslike skin disease similar to subacute cutaneous lupus, but it also has vascular ectasia, hypovascularity, or luminal occlusion of the vessels, so it’s a little bit atypical," Dr. Steen said.

Also, lupus band test positivity is uncommon, and the most common skin manifestations are more scleroderma-like, with puffy fingers and sclerodactyly, she added. Patients with skin involvement usually have limited scleroderma, but about 20% go on to develop diffuse cutaneous scleroderma.

Gastrointestinal Involvement

Providing more evidence is the fact that esophageal involvement and the very severe small bowel dysmotility commonly seen in MCTD are identical to those seen in scleroderma, Dr. Steen said.

"There doesn’t seem to be any difference in the pattern, and as in scleroderma, it doesn’t respond to steroids or immunosuppressants. You really just have to treat it symptomatically," she noted.

Interstitial Lung Disease

Interstitial lung disease is a more challenging area, according to Dr. Steen. It is common in patients diagnosed with MCTD, but there is a lack of prospective study data. In a 2010 study, 66% of 144 patients with very early nonspecific interstitial pneumonitis (NSIP) were treated with steroids; 50% responded, and 50% went on to develop more severe and progressive fibrosis requiring immunosuppressive therapy.

"So there wasn’t a clear pattern where you would think this was a unique type of inflammatory interstitial pneumonitis that is clearly steroid responsive like some of the NSIPs that aren’t associated with connective tissues disease are. There is more fibrosis, and it does seem to be more typically scleroderma related than an independent type of lung disease," she said.

Pulmonary Hypertension

Pulmonary hypertension is one of the biggest challenges in MCTD, Dr. Steen said. Several studies have shown a significant association with pulmonary hypertension and mortality in these patients.

A small study of MCTD patients showed a large decrease in the DLCO (diffusing capacity of the lung for carbon monoxide), she said. Some of these patients had increased pulmonary artery pressure, and there were seven patients who actually had pulmonary arterial hypertension. The available autopsies revealed that the patients tended to have pretty typical pulmonary arteriolopathy, similar to what we see in scleroderma, with a striking intimal proliferation of the vasculature, she said.

Also, as in scleroderma, the pulmonary vessels – even in patients who didn’t have pulmonary hypertension – had similar but less extensive disease, she added.

Based on these various findings, which together show a great deal of similarity to scleroderma while highlighting numerous differences from other connective tissue diseases, Dr. Steen said she is increasingly convinced that MCTD is not a unique entity, mixed disease, or subset of lupus, but is actually a subset of systemic scleroderma.

Dr. Steen reported having no disclosures relevant to her presentation.

DESTIN, FLA. – A 2010 study by Dr. Anna-Luise A. Katzenstein and her colleagues was the first to show that interstitial fibrosis is remarkably common and often severe in cigarette smokers, including those with no clinical evidence of interstitial lung disease.

Pathologic specimens showed that interstitial fibrosis occurred in 12 of 20 smokers (60%) but in none of 3 nonsmokers; three of the smokers with fibrosis had well-defined smoking-related disorders such as respiratory bronchiolitis–interstitial lung disease (RB-ILD), but 9 had pathology showing more than 10% fibrosis on their lung biopsies (Hum. Pathol. 2010;41:316-25). They were considered to have smoking-related interstitial lung disease, Dr. David Moller said at the Congress of Clinical Rheumatology.

"More recently this has been described as [combined pulmonary fibrosis and emphysema, or CPFE syndrome], and it’s largely with the advent of high resolution computed tomography scanning that it has been appreciated how common fibrosis is in association with emphysema," said Dr. Moller, professor of medicine and director of the sarcoidosis clinic at Johns Hopkins University, Baltimore.

Typically, patients with CPFE syndrome have upper-lobe emphysema and lower-lobe fibrosis, he said.

"Because of that, you can get relatively normalized lung volumes and spirometry, but what characterizes these patients is a severe reduction in diffusing capacity. This is often associated with a pulmonary hypertension, which can be a major determinant of survival," he added.

CPFE syndrome is more common in males than females, and is found in 19%-51% of smokers with emphysema on chest CT who have no defined underlying interstitial lung disease. On biopsy, a number of pathological patterns may be seen, including usual interstitial pneumonitis (UIP), nonspecific interstitial pneumonia, and RB-ILD, Dr. Moller said.

Mortality is increased in patients with this syndrome, compared with those who smoke and have chronic obstructive pulmonary disease, and survival ranges from 35% to 80% at 5 years, he added, noting that the mortality rate is unclear in patients who may have underlying idiopathic pulmonary fibrosis.

The syndrome is strongly associated with smoking but is also associated with lung cancer, asbestos and mineral dust exposures, and pulmonary hypertension. A 2011 study demonstrated that CPFE is also associated with connective tissue disease.

In that retrospective study of 34 patients with both connective tissue disease and CPFE syndrome who were followed for about 8 years, 18 had rheumatoid arthritis, 10 had systemic sclerosis, 2 had mixed connective tissues disease, 2 had overlapping connective tissue disease, 1 had Sjögren’s syndrome, and 1 had polymyositis.

High resolution CT showed emphysema of the upper lobes of the lungs and pulmonary fibrosis of the lower lobes in all patients, and all experienced dyspnea during exercise. Pulmonary hypertension was present in five of the systemic sclerosis patients, and four of these patients died during follow-up (Arthritis Rheum. 2011;63:295-304).

The patients in this study were significantly younger than a historical control group of patients with idiopathic CPFE syndrome, and were more frequently female than male, Dr. Moller noted.

Compared with patients with connective tissue disease and lung fibrosis without emphysema, however, the study patients with connective tissue disease and CPFE had higher lung volumes, lower diffusion capacity, higher pulmonary pressures and were more frequently male than female.

There was also some suggestion that those with connective tissue disease and CPFE syndrome may have less severe outcomes than did those with idiopathic CPFE syndrome, but again, pulmonary hypertension is the key to the clinical course, Dr. Moller said.

The authors of this study concluded that CPFE syndrome should be included as a novel, distinct pulmonary manifestation within the spectrum of connective tissue disease–associated lung diseases in smokers and former smokers – particularly those with rheumatoid arthritis or systemic sclerosis.

Treatment for CPFE syndrome includes smoking cessation and treating the underlying cause when it is apparent, Dr. Moller said.

Dr. Moller reported having no financial disclosures.

DESTIN, FLA. – A 2010 study by Dr. Anna-Luise A. Katzenstein and her colleagues was the first to show that interstitial fibrosis is remarkably common and often severe in cigarette smokers, including those with no clinical evidence of interstitial lung disease.

Pathologic specimens showed that interstitial fibrosis occurred in 12 of 20 smokers (60%) but in none of 3 nonsmokers; three of the smokers with fibrosis had well-defined smoking-related disorders such as respiratory bronchiolitis–interstitial lung disease (RB-ILD), but 9 had pathology showing more than 10% fibrosis on their lung biopsies (Hum. Pathol. 2010;41:316-25). They were considered to have smoking-related interstitial lung disease, Dr. David Moller said at the Congress of Clinical Rheumatology.

"More recently this has been described as [combined pulmonary fibrosis and emphysema, or CPFE syndrome], and it’s largely with the advent of high resolution computed tomography scanning that it has been appreciated how common fibrosis is in association with emphysema," said Dr. Moller, professor of medicine and director of the sarcoidosis clinic at Johns Hopkins University, Baltimore.

Typically, patients with CPFE syndrome have upper-lobe emphysema and lower-lobe fibrosis, he said.

"Because of that, you can get relatively normalized lung volumes and spirometry, but what characterizes these patients is a severe reduction in diffusing capacity. This is often associated with a pulmonary hypertension, which can be a major determinant of survival," he added.

CPFE syndrome is more common in males than females, and is found in 19%-51% of smokers with emphysema on chest CT who have no defined underlying interstitial lung disease. On biopsy, a number of pathological patterns may be seen, including usual interstitial pneumonitis (UIP), nonspecific interstitial pneumonia, and RB-ILD, Dr. Moller said.

Mortality is increased in patients with this syndrome, compared with those who smoke and have chronic obstructive pulmonary disease, and survival ranges from 35% to 80% at 5 years, he added, noting that the mortality rate is unclear in patients who may have underlying idiopathic pulmonary fibrosis.

The syndrome is strongly associated with smoking but is also associated with lung cancer, asbestos and mineral dust exposures, and pulmonary hypertension. A 2011 study demonstrated that CPFE is also associated with connective tissue disease.

In that retrospective study of 34 patients with both connective tissue disease and CPFE syndrome who were followed for about 8 years, 18 had rheumatoid arthritis, 10 had systemic sclerosis, 2 had mixed connective tissues disease, 2 had overlapping connective tissue disease, 1 had Sjögren’s syndrome, and 1 had polymyositis.

High resolution CT showed emphysema of the upper lobes of the lungs and pulmonary fibrosis of the lower lobes in all patients, and all experienced dyspnea during exercise. Pulmonary hypertension was present in five of the systemic sclerosis patients, and four of these patients died during follow-up (Arthritis Rheum. 2011;63:295-304).

The patients in this study were significantly younger than a historical control group of patients with idiopathic CPFE syndrome, and were more frequently female than male, Dr. Moller noted.

Compared with patients with connective tissue disease and lung fibrosis without emphysema, however, the study patients with connective tissue disease and CPFE had higher lung volumes, lower diffusion capacity, higher pulmonary pressures and were more frequently male than female.

There was also some suggestion that those with connective tissue disease and CPFE syndrome may have less severe outcomes than did those with idiopathic CPFE syndrome, but again, pulmonary hypertension is the key to the clinical course, Dr. Moller said.

The authors of this study concluded that CPFE syndrome should be included as a novel, distinct pulmonary manifestation within the spectrum of connective tissue disease–associated lung diseases in smokers and former smokers – particularly those with rheumatoid arthritis or systemic sclerosis.

Treatment for CPFE syndrome includes smoking cessation and treating the underlying cause when it is apparent, Dr. Moller said.

Dr. Moller reported having no financial disclosures.

DESTIN, FLA. – A 2010 study by Dr. Anna-Luise A. Katzenstein and her colleagues was the first to show that interstitial fibrosis is remarkably common and often severe in cigarette smokers, including those with no clinical evidence of interstitial lung disease.

Pathologic specimens showed that interstitial fibrosis occurred in 12 of 20 smokers (60%) but in none of 3 nonsmokers; three of the smokers with fibrosis had well-defined smoking-related disorders such as respiratory bronchiolitis–interstitial lung disease (RB-ILD), but 9 had pathology showing more than 10% fibrosis on their lung biopsies (Hum. Pathol. 2010;41:316-25). They were considered to have smoking-related interstitial lung disease, Dr. David Moller said at the Congress of Clinical Rheumatology.

"More recently this has been described as [combined pulmonary fibrosis and emphysema, or CPFE syndrome], and it’s largely with the advent of high resolution computed tomography scanning that it has been appreciated how common fibrosis is in association with emphysema," said Dr. Moller, professor of medicine and director of the sarcoidosis clinic at Johns Hopkins University, Baltimore.

Typically, patients with CPFE syndrome have upper-lobe emphysema and lower-lobe fibrosis, he said.

"Because of that, you can get relatively normalized lung volumes and spirometry, but what characterizes these patients is a severe reduction in diffusing capacity. This is often associated with a pulmonary hypertension, which can be a major determinant of survival," he added.

CPFE syndrome is more common in males than females, and is found in 19%-51% of smokers with emphysema on chest CT who have no defined underlying interstitial lung disease. On biopsy, a number of pathological patterns may be seen, including usual interstitial pneumonitis (UIP), nonspecific interstitial pneumonia, and RB-ILD, Dr. Moller said.

Mortality is increased in patients with this syndrome, compared with those who smoke and have chronic obstructive pulmonary disease, and survival ranges from 35% to 80% at 5 years, he added, noting that the mortality rate is unclear in patients who may have underlying idiopathic pulmonary fibrosis.

The syndrome is strongly associated with smoking but is also associated with lung cancer, asbestos and mineral dust exposures, and pulmonary hypertension. A 2011 study demonstrated that CPFE is also associated with connective tissue disease.

In that retrospective study of 34 patients with both connective tissue disease and CPFE syndrome who were followed for about 8 years, 18 had rheumatoid arthritis, 10 had systemic sclerosis, 2 had mixed connective tissues disease, 2 had overlapping connective tissue disease, 1 had Sjögren’s syndrome, and 1 had polymyositis.

High resolution CT showed emphysema of the upper lobes of the lungs and pulmonary fibrosis of the lower lobes in all patients, and all experienced dyspnea during exercise. Pulmonary hypertension was present in five of the systemic sclerosis patients, and four of these patients died during follow-up (Arthritis Rheum. 2011;63:295-304).

The patients in this study were significantly younger than a historical control group of patients with idiopathic CPFE syndrome, and were more frequently female than male, Dr. Moller noted.

Compared with patients with connective tissue disease and lung fibrosis without emphysema, however, the study patients with connective tissue disease and CPFE had higher lung volumes, lower diffusion capacity, higher pulmonary pressures and were more frequently male than female.

There was also some suggestion that those with connective tissue disease and CPFE syndrome may have less severe outcomes than did those with idiopathic CPFE syndrome, but again, pulmonary hypertension is the key to the clinical course, Dr. Moller said.

The authors of this study concluded that CPFE syndrome should be included as a novel, distinct pulmonary manifestation within the spectrum of connective tissue disease–associated lung diseases in smokers and former smokers – particularly those with rheumatoid arthritis or systemic sclerosis.

Treatment for CPFE syndrome includes smoking cessation and treating the underlying cause when it is apparent, Dr. Moller said.

Dr. Moller reported having no financial disclosures.

SANDESTIN, FLA. – The successful management of severe diffuse skin thickening in scleroderma patients requires early aggressive treatment, including physical therapy, according to Dr. Virginia Steen.

"We don’t have any clear-cut treatment for severe skin disease, but one of the most important things we have to do is aggressive physical therapy – and make sure that they keep moving," Dr. Steen, professor of medicine at Georgetown University, Washington, D.C., said at the Congress of Clinical Rheumatology.

Keeping these patients moving requires that they be provided with adequate analgesia, she added.

A treatment option for those with a great deal of tendon, joint, and muscle involvement (in addition to skin involvement) is methotrexate at 15-25 mg/week, she said, noting that methotrexate is known to be helpful with these aspects of scleroderma, and some additional studies have shown it may be helpful for the skin as well. One randomized, controlled study of 71 patients, for example, showed a slight advantage for methotrexate over placebo for early diffuse scleroderma (Arthritis Rheum. 2001;44:1351-8).

Similarly, mycophenolate (CellCept), which has been shown in multiple open-label studies to be useful for scleroderma patients with lung involvement, also appears to have some beneficial effects on the skin, so consider its use in patients with both lung and skin involvement, Dr. Steen advised.

Cyclophosphamide (Cytoxan) is another drug that may be helpful in those with both lung and skin involvement.

"Cytoxan isn’t very dramatic in the skin, but you certainly may want to use it if you have any lung involvement," she said, noting that the Scleroderma Lung Study demonstrated that it is better than placebo in scleroderma lung disease (Ann. Rheum. Dis. 2007;66:1641-7). "I also still use d-penicillamine," she noted, explaining she prescribes this to patients with just skin involvement who don’t need treatment that is "too aggressive otherwise."

Although the lack of straightforward answers about how to target diffuse skin thickening in scleroderma is frustrating, there is encouraging news on the horizon.

"There are a lot of things at least in the works in terms of antifibrotic processes," Dr. Steen said, explaining that alteration of myocytes and myofibroblasts in animal models has been shown to reverse fibrosis, and work is ongoing.

Protein kinase inhibitors, for example, are of interest, and although the effects are not dramatic, they may have some benefit, except that there was significant toxicity, which led to discontinuation of one study. Other potential therapies involve transforming growth factor–beta antagonists, connective tissue growth factor antagonists, peroxisome proliferator–activated receptor gamma ligands, and interleuken-6 antagonists.

Ongoing work with the anti–IL-6 tocilizumab (Actemra), for example, is showing some intriguing results that could have implications for the treatment of the subset of patients with very high IL-6 leading to a fibrotic signature, Dr. Steen said.

Some preliminary animal model studies of tocilizumab showed that it improves the skin in mice with increased IL-6 and scleroderma and there is now a controlled trial of tocilizumab in early diffuse scleroderma.

"Although, there have only been a few case reports of Actemra in scleroderma, we are excited about its potential as an effective antifibrotic agent in scleroderma," Dr. Steen said in an interview.

Dr. Steen disclosed that she has received grant funding, consulting fees, and/or speaking fees from Actelion, Genentec/Roche , Gilead Pharmaceuticals, Pfizer, and United Therapeutics.

SANDESTIN, FLA. – The successful management of severe diffuse skin thickening in scleroderma patients requires early aggressive treatment, including physical therapy, according to Dr. Virginia Steen.

"We don’t have any clear-cut treatment for severe skin disease, but one of the most important things we have to do is aggressive physical therapy – and make sure that they keep moving," Dr. Steen, professor of medicine at Georgetown University, Washington, D.C., said at the Congress of Clinical Rheumatology.

Keeping these patients moving requires that they be provided with adequate analgesia, she added.

A treatment option for those with a great deal of tendon, joint, and muscle involvement (in addition to skin involvement) is methotrexate at 15-25 mg/week, she said, noting that methotrexate is known to be helpful with these aspects of scleroderma, and some additional studies have shown it may be helpful for the skin as well. One randomized, controlled study of 71 patients, for example, showed a slight advantage for methotrexate over placebo for early diffuse scleroderma (Arthritis Rheum. 2001;44:1351-8).

Similarly, mycophenolate (CellCept), which has been shown in multiple open-label studies to be useful for scleroderma patients with lung involvement, also appears to have some beneficial effects on the skin, so consider its use in patients with both lung and skin involvement, Dr. Steen advised.

Cyclophosphamide (Cytoxan) is another drug that may be helpful in those with both lung and skin involvement.

"Cytoxan isn’t very dramatic in the skin, but you certainly may want to use it if you have any lung involvement," she said, noting that the Scleroderma Lung Study demonstrated that it is better than placebo in scleroderma lung disease (Ann. Rheum. Dis. 2007;66:1641-7). "I also still use d-penicillamine," she noted, explaining she prescribes this to patients with just skin involvement who don’t need treatment that is "too aggressive otherwise."

Although the lack of straightforward answers about how to target diffuse skin thickening in scleroderma is frustrating, there is encouraging news on the horizon.

"There are a lot of things at least in the works in terms of antifibrotic processes," Dr. Steen said, explaining that alteration of myocytes and myofibroblasts in animal models has been shown to reverse fibrosis, and work is ongoing.

Protein kinase inhibitors, for example, are of interest, and although the effects are not dramatic, they may have some benefit, except that there was significant toxicity, which led to discontinuation of one study. Other potential therapies involve transforming growth factor–beta antagonists, connective tissue growth factor antagonists, peroxisome proliferator–activated receptor gamma ligands, and interleuken-6 antagonists.

Ongoing work with the anti–IL-6 tocilizumab (Actemra), for example, is showing some intriguing results that could have implications for the treatment of the subset of patients with very high IL-6 leading to a fibrotic signature, Dr. Steen said.

Some preliminary animal model studies of tocilizumab showed that it improves the skin in mice with increased IL-6 and scleroderma and there is now a controlled trial of tocilizumab in early diffuse scleroderma.

"Although, there have only been a few case reports of Actemra in scleroderma, we are excited about its potential as an effective antifibrotic agent in scleroderma," Dr. Steen said in an interview.

Dr. Steen disclosed that she has received grant funding, consulting fees, and/or speaking fees from Actelion, Genentec/Roche , Gilead Pharmaceuticals, Pfizer, and United Therapeutics.

SANDESTIN, FLA. – The successful management of severe diffuse skin thickening in scleroderma patients requires early aggressive treatment, including physical therapy, according to Dr. Virginia Steen.

"We don’t have any clear-cut treatment for severe skin disease, but one of the most important things we have to do is aggressive physical therapy – and make sure that they keep moving," Dr. Steen, professor of medicine at Georgetown University, Washington, D.C., said at the Congress of Clinical Rheumatology.

Keeping these patients moving requires that they be provided with adequate analgesia, she added.

A treatment option for those with a great deal of tendon, joint, and muscle involvement (in addition to skin involvement) is methotrexate at 15-25 mg/week, she said, noting that methotrexate is known to be helpful with these aspects of scleroderma, and some additional studies have shown it may be helpful for the skin as well. One randomized, controlled study of 71 patients, for example, showed a slight advantage for methotrexate over placebo for early diffuse scleroderma (Arthritis Rheum. 2001;44:1351-8).

Similarly, mycophenolate (CellCept), which has been shown in multiple open-label studies to be useful for scleroderma patients with lung involvement, also appears to have some beneficial effects on the skin, so consider its use in patients with both lung and skin involvement, Dr. Steen advised.

Cyclophosphamide (Cytoxan) is another drug that may be helpful in those with both lung and skin involvement.

"Cytoxan isn’t very dramatic in the skin, but you certainly may want to use it if you have any lung involvement," she said, noting that the Scleroderma Lung Study demonstrated that it is better than placebo in scleroderma lung disease (Ann. Rheum. Dis. 2007;66:1641-7). "I also still use d-penicillamine," she noted, explaining she prescribes this to patients with just skin involvement who don’t need treatment that is "too aggressive otherwise."

Although the lack of straightforward answers about how to target diffuse skin thickening in scleroderma is frustrating, there is encouraging news on the horizon.

"There are a lot of things at least in the works in terms of antifibrotic processes," Dr. Steen said, explaining that alteration of myocytes and myofibroblasts in animal models has been shown to reverse fibrosis, and work is ongoing.

Protein kinase inhibitors, for example, are of interest, and although the effects are not dramatic, they may have some benefit, except that there was significant toxicity, which led to discontinuation of one study. Other potential therapies involve transforming growth factor–beta antagonists, connective tissue growth factor antagonists, peroxisome proliferator–activated receptor gamma ligands, and interleuken-6 antagonists.

Ongoing work with the anti–IL-6 tocilizumab (Actemra), for example, is showing some intriguing results that could have implications for the treatment of the subset of patients with very high IL-6 leading to a fibrotic signature, Dr. Steen said.

Some preliminary animal model studies of tocilizumab showed that it improves the skin in mice with increased IL-6 and scleroderma and there is now a controlled trial of tocilizumab in early diffuse scleroderma.

"Although, there have only been a few case reports of Actemra in scleroderma, we are excited about its potential as an effective antifibrotic agent in scleroderma," Dr. Steen said in an interview.

Dr. Steen disclosed that she has received grant funding, consulting fees, and/or speaking fees from Actelion, Genentec/Roche , Gilead Pharmaceuticals, Pfizer, and United Therapeutics.

PHOENIX – Vilazodone was associated with significantly higher rates of response and remission than placebo, and it demonstrated efficacy across all symptoms in patients with major depressive disorder in an analysis of pooled data from two pivotal randomized controlled trials.

The efficacy of the serotonin reuptake inhibitor and 5-HT receptor partial agonist was established in the two 8-week phase III studies, and safety and tolerability were demonstrated in a 52-week open-label phase III study. These findings led to the 2011 Food and Drug Administration approval of vilazodone hydrochloride under the trade name of Viibryd for treatment of MDD in adults.

The current post hoc pooled analysis of data from the two 8-week studies further demonstrates the drug’s efficacy across the symptoms of depression, Dr. Arif Khan and colleagues reported in a poster at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

Compared with 432 patients who received placebo, the 431 patients randomized to receive vilazodone experienced significant improvements in Montgomery-Åsberg Depression Rating Scale (MADRS) scores (least squared mean difference of –2.79), as well as significant improvement on all secondary measures, including the Hamilton Depression Rating Scale (HAMD), the Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) scales, and the Hamilton Anxiety Rating Scale (HAMA), according to Dr. Khan of the Northwest Clinical Research Center in Bellevue, Wash.

Response defined by at least 50% improvement on the MADRS occurred in 42% of vilazodone and 29% of placebo patients. Response defined by a 50% or greater improvement on the HAMD occurred in 44% and 33% of the patients, respectively, and response defined by achievement of a CGI-I score of 2 or less occurred in 49% and 35% of the patients, respectively. Remission defined as a MADRS score of 10 or less occurred in 29% of the vilazodone and 20% of the placebo patients, and remission defined as a MADRS score of 12 or less occurred in 35% vs. 22% of the patients, respectively.

Significant improvement in favor of vilazodone also was seen on change from baseline in every MADRS single item, including apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts.

The patients were adults aged 18-65 years in the first trial and 18-70 years in the second. All met diagnostic criteria for MDD according to the DSM-IV-TR, and they all underwent a washout period of at least 2 weeks, a 1-week screening period, and an 8-week double-blind treatment period. Vilazodone was titrated from a 10-mg dose once daily for 7 days to 20 mg once daily for the next 7 days and 40 mg once daily thereafter.

The findings demonstrate that vilazodone is significantly superior to placebo on all depression rating scales tested, Dr. Khan noted.

"Additionally, superiority versus placebo on all MADRS single items demonstrated the broad efficacy of vilazodone across the spectrum of depression symptoms," he wrote, also noting that "the selection of a therapeutic agent that effectively resolves a broad spectrum of symptoms and promotes a return to full functioning is an important component of depression treatment."

Dr. Khan reported having no conflicts of interest to disclose. This study was supported by Forest Laboratories. Other authors are employees of Forest Research Institute, a scientific subsidiary of Forest Laboratories.

PHOENIX – Vilazodone was associated with significantly higher rates of response and remission than placebo, and it demonstrated efficacy across all symptoms in patients with major depressive disorder in an analysis of pooled data from two pivotal randomized controlled trials.

The efficacy of the serotonin reuptake inhibitor and 5-HT receptor partial agonist was established in the two 8-week phase III studies, and safety and tolerability were demonstrated in a 52-week open-label phase III study. These findings led to the 2011 Food and Drug Administration approval of vilazodone hydrochloride under the trade name of Viibryd for treatment of MDD in adults.

The current post hoc pooled analysis of data from the two 8-week studies further demonstrates the drug’s efficacy across the symptoms of depression, Dr. Arif Khan and colleagues reported in a poster at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

Compared with 432 patients who received placebo, the 431 patients randomized to receive vilazodone experienced significant improvements in Montgomery-Åsberg Depression Rating Scale (MADRS) scores (least squared mean difference of –2.79), as well as significant improvement on all secondary measures, including the Hamilton Depression Rating Scale (HAMD), the Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) scales, and the Hamilton Anxiety Rating Scale (HAMA), according to Dr. Khan of the Northwest Clinical Research Center in Bellevue, Wash.

Response defined by at least 50% improvement on the MADRS occurred in 42% of vilazodone and 29% of placebo patients. Response defined by a 50% or greater improvement on the HAMD occurred in 44% and 33% of the patients, respectively, and response defined by achievement of a CGI-I score of 2 or less occurred in 49% and 35% of the patients, respectively. Remission defined as a MADRS score of 10 or less occurred in 29% of the vilazodone and 20% of the placebo patients, and remission defined as a MADRS score of 12 or less occurred in 35% vs. 22% of the patients, respectively.

Significant improvement in favor of vilazodone also was seen on change from baseline in every MADRS single item, including apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts.

The patients were adults aged 18-65 years in the first trial and 18-70 years in the second. All met diagnostic criteria for MDD according to the DSM-IV-TR, and they all underwent a washout period of at least 2 weeks, a 1-week screening period, and an 8-week double-blind treatment period. Vilazodone was titrated from a 10-mg dose once daily for 7 days to 20 mg once daily for the next 7 days and 40 mg once daily thereafter.

The findings demonstrate that vilazodone is significantly superior to placebo on all depression rating scales tested, Dr. Khan noted.

"Additionally, superiority versus placebo on all MADRS single items demonstrated the broad efficacy of vilazodone across the spectrum of depression symptoms," he wrote, also noting that "the selection of a therapeutic agent that effectively resolves a broad spectrum of symptoms and promotes a return to full functioning is an important component of depression treatment."

Dr. Khan reported having no conflicts of interest to disclose. This study was supported by Forest Laboratories. Other authors are employees of Forest Research Institute, a scientific subsidiary of Forest Laboratories.

PHOENIX – Vilazodone was associated with significantly higher rates of response and remission than placebo, and it demonstrated efficacy across all symptoms in patients with major depressive disorder in an analysis of pooled data from two pivotal randomized controlled trials.

The efficacy of the serotonin reuptake inhibitor and 5-HT receptor partial agonist was established in the two 8-week phase III studies, and safety and tolerability were demonstrated in a 52-week open-label phase III study. These findings led to the 2011 Food and Drug Administration approval of vilazodone hydrochloride under the trade name of Viibryd for treatment of MDD in adults.

The current post hoc pooled analysis of data from the two 8-week studies further demonstrates the drug’s efficacy across the symptoms of depression, Dr. Arif Khan and colleagues reported in a poster at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

Compared with 432 patients who received placebo, the 431 patients randomized to receive vilazodone experienced significant improvements in Montgomery-Åsberg Depression Rating Scale (MADRS) scores (least squared mean difference of –2.79), as well as significant improvement on all secondary measures, including the Hamilton Depression Rating Scale (HAMD), the Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) scales, and the Hamilton Anxiety Rating Scale (HAMA), according to Dr. Khan of the Northwest Clinical Research Center in Bellevue, Wash.

Response defined by at least 50% improvement on the MADRS occurred in 42% of vilazodone and 29% of placebo patients. Response defined by a 50% or greater improvement on the HAMD occurred in 44% and 33% of the patients, respectively, and response defined by achievement of a CGI-I score of 2 or less occurred in 49% and 35% of the patients, respectively. Remission defined as a MADRS score of 10 or less occurred in 29% of the vilazodone and 20% of the placebo patients, and remission defined as a MADRS score of 12 or less occurred in 35% vs. 22% of the patients, respectively.

Significant improvement in favor of vilazodone also was seen on change from baseline in every MADRS single item, including apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts.

The patients were adults aged 18-65 years in the first trial and 18-70 years in the second. All met diagnostic criteria for MDD according to the DSM-IV-TR, and they all underwent a washout period of at least 2 weeks, a 1-week screening period, and an 8-week double-blind treatment period. Vilazodone was titrated from a 10-mg dose once daily for 7 days to 20 mg once daily for the next 7 days and 40 mg once daily thereafter.

The findings demonstrate that vilazodone is significantly superior to placebo on all depression rating scales tested, Dr. Khan noted.

"Additionally, superiority versus placebo on all MADRS single items demonstrated the broad efficacy of vilazodone across the spectrum of depression symptoms," he wrote, also noting that "the selection of a therapeutic agent that effectively resolves a broad spectrum of symptoms and promotes a return to full functioning is an important component of depression treatment."

Dr. Khan reported having no conflicts of interest to disclose. This study was supported by Forest Laboratories. Other authors are employees of Forest Research Institute, a scientific subsidiary of Forest Laboratories.

PHOENIX – The novel atypical antipsychotic drug cariprazine is effective for the treatment of acute mania associated with bipolar I disorder, according to findings from a randomized, placebo-controlled phase III study.

In 158 patients randomized to receive 3 weeks of double-blind treatment with the orally active dopamine D3-preferring D3/D2 receptor partial agonist, the mean improvement on the Young Mania Rating Scale (YMRS), based on a mixed-effects model of repeated measures, was significantly greater than the mean improvement in 151 patients randomized to receive placebo, Anjana Bose, Ph.D. and her colleagues reported in a poster at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

Cariprazine demonstrated fast onset of action, with a statistically greater improvement vs. placebo seen by day 4 of treatment and at every visit thereafter.

Significantly more patients in the active treatment group met the YMRS criteria for response (59% vs. 44% taking placebo achieved at least a 50% score reduction from baseline) and remission (52% vs. 35% achieved a total score of 12 or less) at 3 weeks, she said.

The mean improvement on the Clinical Global Impressions-Severity scale also was significantly greater in the treatment group at week 3, as was the reduction in Positive and Negative Syndrome Scale (PANSS) score, according to Dr. Bose of Forest Research Institute, Jersey City, N.J.

Of note, cariprazine demonstrated fast onset of action, with a statistically greater improvement vs. placebo seen by day 4 of treatment and at every visit thereafter, she said.

Patients in the 6-week multicenter study were adults aged 18-65 years with acute mania associated with bipolar I disorder (as defined by the DSM-IV-TR) and a YMRS score of 20 or higher. The mean YMRS scores at baseline were similar at 32.3 (treatment group) and 32.1 (placebo).

Patients were hospitalized for a 4- to 7-day wash-out period and for at least the first 14 days of the 3-week treatment period. Those randomized to the treatment group received between 3 and 12 mg of cariprazine daily during those 3 weeks; treatment was initiated at a dose of 1.5 mg/day and increased in increments of 3 mg to a maximum of 12 mg/day by day 7, based on patient response and tolerability. The mean dose given was 7.5 mg/day.

Treatment was followed by a 2-week safety follow-up period.

A similar proportion of patients in the treatment and placebo groups (69% and 68%, respectively) completed the study; 10% of treatment-group patients and 7% of placebo-group patients discontinued treatment because of adverse effects. Treatment-emergent adverse events occurred in 80% and 63% of the patients in each group, respectively, and included worsening of mania in two treatment-group patients and five placebo-group patients and akathisia in five treatment-group patients.

The most common adverse events were akathisia, extrapyramidal disorder, tremor, dyspepsia, and vomiting. Extrapyramidal symptom–related adverse events occurred in 46% of the treatment and 12% of the placebo-group patients, Dr. Bose reported.

"Cariprazine is an orally active atypical antipsychotic candidate in clinical development for the treatment of schizophrenia and bipolar disorder. It has been hypothesized that a compound that exhibits high potency for both D3 and D2 receptors may have treatment advantages compared with currently available atypical antipsychotics," she wrote.

In this study, treatment was associated with a higher incidence of akathisia and extrapyramidal symptoms, but it was not associated with a mean increase in weight or metabolic parameters or with prolactin increase or QTc prolongation, she noted.

The drug was safe and generally well tolerated. The findings of this phase III study support those from an earlier phase II study in which cariprazine also was shown to be safe, well tolerated, and significantly superior to placebo for improvement of acute manic or mixed episodes, she concluded.

Dr. Bose is an employee of Forest Research Institute, a scientific subsidiary of Forest Laboratories, the maker of cariprazine and the sponsor of this study.

PHOENIX – The novel atypical antipsychotic drug cariprazine is effective for the treatment of acute mania associated with bipolar I disorder, according to findings from a randomized, placebo-controlled phase III study.

In 158 patients randomized to receive 3 weeks of double-blind treatment with the orally active dopamine D3-preferring D3/D2 receptor partial agonist, the mean improvement on the Young Mania Rating Scale (YMRS), based on a mixed-effects model of repeated measures, was significantly greater than the mean improvement in 151 patients randomized to receive placebo, Anjana Bose, Ph.D. and her colleagues reported in a poster at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

Cariprazine demonstrated fast onset of action, with a statistically greater improvement vs. placebo seen by day 4 of treatment and at every visit thereafter.

Significantly more patients in the active treatment group met the YMRS criteria for response (59% vs. 44% taking placebo achieved at least a 50% score reduction from baseline) and remission (52% vs. 35% achieved a total score of 12 or less) at 3 weeks, she said.

The mean improvement on the Clinical Global Impressions-Severity scale also was significantly greater in the treatment group at week 3, as was the reduction in Positive and Negative Syndrome Scale (PANSS) score, according to Dr. Bose of Forest Research Institute, Jersey City, N.J.

Of note, cariprazine demonstrated fast onset of action, with a statistically greater improvement vs. placebo seen by day 4 of treatment and at every visit thereafter, she said.

Patients in the 6-week multicenter study were adults aged 18-65 years with acute mania associated with bipolar I disorder (as defined by the DSM-IV-TR) and a YMRS score of 20 or higher. The mean YMRS scores at baseline were similar at 32.3 (treatment group) and 32.1 (placebo).

Patients were hospitalized for a 4- to 7-day wash-out period and for at least the first 14 days of the 3-week treatment period. Those randomized to the treatment group received between 3 and 12 mg of cariprazine daily during those 3 weeks; treatment was initiated at a dose of 1.5 mg/day and increased in increments of 3 mg to a maximum of 12 mg/day by day 7, based on patient response and tolerability. The mean dose given was 7.5 mg/day.

Treatment was followed by a 2-week safety follow-up period.

A similar proportion of patients in the treatment and placebo groups (69% and 68%, respectively) completed the study; 10% of treatment-group patients and 7% of placebo-group patients discontinued treatment because of adverse effects. Treatment-emergent adverse events occurred in 80% and 63% of the patients in each group, respectively, and included worsening of mania in two treatment-group patients and five placebo-group patients and akathisia in five treatment-group patients.

The most common adverse events were akathisia, extrapyramidal disorder, tremor, dyspepsia, and vomiting. Extrapyramidal symptom–related adverse events occurred in 46% of the treatment and 12% of the placebo-group patients, Dr. Bose reported.

"Cariprazine is an orally active atypical antipsychotic candidate in clinical development for the treatment of schizophrenia and bipolar disorder. It has been hypothesized that a compound that exhibits high potency for both D3 and D2 receptors may have treatment advantages compared with currently available atypical antipsychotics," she wrote.

In this study, treatment was associated with a higher incidence of akathisia and extrapyramidal symptoms, but it was not associated with a mean increase in weight or metabolic parameters or with prolactin increase or QTc prolongation, she noted.

The drug was safe and generally well tolerated. The findings of this phase III study support those from an earlier phase II study in which cariprazine also was shown to be safe, well tolerated, and significantly superior to placebo for improvement of acute manic or mixed episodes, she concluded.

Dr. Bose is an employee of Forest Research Institute, a scientific subsidiary of Forest Laboratories, the maker of cariprazine and the sponsor of this study.

PHOENIX – The novel atypical antipsychotic drug cariprazine is effective for the treatment of acute mania associated with bipolar I disorder, according to findings from a randomized, placebo-controlled phase III study.

In 158 patients randomized to receive 3 weeks of double-blind treatment with the orally active dopamine D3-preferring D3/D2 receptor partial agonist, the mean improvement on the Young Mania Rating Scale (YMRS), based on a mixed-effects model of repeated measures, was significantly greater than the mean improvement in 151 patients randomized to receive placebo, Anjana Bose, Ph.D. and her colleagues reported in a poster at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

Cariprazine demonstrated fast onset of action, with a statistically greater improvement vs. placebo seen by day 4 of treatment and at every visit thereafter.

Significantly more patients in the active treatment group met the YMRS criteria for response (59% vs. 44% taking placebo achieved at least a 50% score reduction from baseline) and remission (52% vs. 35% achieved a total score of 12 or less) at 3 weeks, she said.

The mean improvement on the Clinical Global Impressions-Severity scale also was significantly greater in the treatment group at week 3, as was the reduction in Positive and Negative Syndrome Scale (PANSS) score, according to Dr. Bose of Forest Research Institute, Jersey City, N.J.

Of note, cariprazine demonstrated fast onset of action, with a statistically greater improvement vs. placebo seen by day 4 of treatment and at every visit thereafter, she said.

Patients in the 6-week multicenter study were adults aged 18-65 years with acute mania associated with bipolar I disorder (as defined by the DSM-IV-TR) and a YMRS score of 20 or higher. The mean YMRS scores at baseline were similar at 32.3 (treatment group) and 32.1 (placebo).

Patients were hospitalized for a 4- to 7-day wash-out period and for at least the first 14 days of the 3-week treatment period. Those randomized to the treatment group received between 3 and 12 mg of cariprazine daily during those 3 weeks; treatment was initiated at a dose of 1.5 mg/day and increased in increments of 3 mg to a maximum of 12 mg/day by day 7, based on patient response and tolerability. The mean dose given was 7.5 mg/day.

Treatment was followed by a 2-week safety follow-up period.

A similar proportion of patients in the treatment and placebo groups (69% and 68%, respectively) completed the study; 10% of treatment-group patients and 7% of placebo-group patients discontinued treatment because of adverse effects. Treatment-emergent adverse events occurred in 80% and 63% of the patients in each group, respectively, and included worsening of mania in two treatment-group patients and five placebo-group patients and akathisia in five treatment-group patients.

The most common adverse events were akathisia, extrapyramidal disorder, tremor, dyspepsia, and vomiting. Extrapyramidal symptom–related adverse events occurred in 46% of the treatment and 12% of the placebo-group patients, Dr. Bose reported.

"Cariprazine is an orally active atypical antipsychotic candidate in clinical development for the treatment of schizophrenia and bipolar disorder. It has been hypothesized that a compound that exhibits high potency for both D3 and D2 receptors may have treatment advantages compared with currently available atypical antipsychotics," she wrote.

In this study, treatment was associated with a higher incidence of akathisia and extrapyramidal symptoms, but it was not associated with a mean increase in weight or metabolic parameters or with prolactin increase or QTc prolongation, she noted.

The drug was safe and generally well tolerated. The findings of this phase III study support those from an earlier phase II study in which cariprazine also was shown to be safe, well tolerated, and significantly superior to placebo for improvement of acute manic or mixed episodes, she concluded.

Dr. Bose is an employee of Forest Research Institute, a scientific subsidiary of Forest Laboratories, the maker of cariprazine and the sponsor of this study.

The number of reported wild polio virus cases decreased by 52% worldwide, from 1,352 cases in 2010 to 650 cases in 2011, according to the Centers for Disease Control and Prevention.

This progress occurred despite a shortage of funding to eradicate polio globally, a goal that the World Health Organization established in January of this year.

The achievement of polio eradication also varied significantly by region.

In India in 2011, the number of cases declined 98%, and the last identified case was in January of that year. The country is now considered polio-free.

Cases increased, however, in Afghanistan (by 69%), Nigeria (by 66%), and Pakistan (by 27%) in 2011, and circulation there continues, according to the May 18 Morbidity and Mortality Weekly Report (MMWR 2012; 61[19]:353-7).

Outbreaks continue to occur as a result of importation from polio-reservoir countries to areas previously polio free for 12 or more months; 11 different outbreaks occurred globally, including 9 new outbreaks in eight countries, including China and seven countries in Africa, according to the report.

In the first quarter of 2012, 59% fewer cases have been reported worldwide, compared with the same period in 2011, and all wild polio virus cases were reported from Afghanistan, Chad, Nigeria, and Pakistan. No new outbreaks have been reported, but persistent circulations, particularly in Nigeria and Pakistan, pose an ongoing threat to eradication efforts.

Following the WHO’s 2012 declaration regarding the public health emergency posed by ongoing poliovirus transmission, countries with endemic or reestablished transmission developed national emergency plans for interrupting transmission.

If global eradication is to be achieved, full implementation of these emergency plans is urgently needed, according to an editorial note included in the report.

The number of reported wild polio virus cases decreased by 52% worldwide, from 1,352 cases in 2010 to 650 cases in 2011, according to the Centers for Disease Control and Prevention.

This progress occurred despite a shortage of funding to eradicate polio globally, a goal that the World Health Organization established in January of this year.

The achievement of polio eradication also varied significantly by region.

In India in 2011, the number of cases declined 98%, and the last identified case was in January of that year. The country is now considered polio-free.

Cases increased, however, in Afghanistan (by 69%), Nigeria (by 66%), and Pakistan (by 27%) in 2011, and circulation there continues, according to the May 18 Morbidity and Mortality Weekly Report (MMWR 2012; 61[19]:353-7).

Outbreaks continue to occur as a result of importation from polio-reservoir countries to areas previously polio free for 12 or more months; 11 different outbreaks occurred globally, including 9 new outbreaks in eight countries, including China and seven countries in Africa, according to the report.

In the first quarter of 2012, 59% fewer cases have been reported worldwide, compared with the same period in 2011, and all wild polio virus cases were reported from Afghanistan, Chad, Nigeria, and Pakistan. No new outbreaks have been reported, but persistent circulations, particularly in Nigeria and Pakistan, pose an ongoing threat to eradication efforts.

Following the WHO’s 2012 declaration regarding the public health emergency posed by ongoing poliovirus transmission, countries with endemic or reestablished transmission developed national emergency plans for interrupting transmission.

If global eradication is to be achieved, full implementation of these emergency plans is urgently needed, according to an editorial note included in the report.

The number of reported wild polio virus cases decreased by 52% worldwide, from 1,352 cases in 2010 to 650 cases in 2011, according to the Centers for Disease Control and Prevention.

This progress occurred despite a shortage of funding to eradicate polio globally, a goal that the World Health Organization established in January of this year.

The achievement of polio eradication also varied significantly by region.

In India in 2011, the number of cases declined 98%, and the last identified case was in January of that year. The country is now considered polio-free.

Cases increased, however, in Afghanistan (by 69%), Nigeria (by 66%), and Pakistan (by 27%) in 2011, and circulation there continues, according to the May 18 Morbidity and Mortality Weekly Report (MMWR 2012; 61[19]:353-7).

Outbreaks continue to occur as a result of importation from polio-reservoir countries to areas previously polio free for 12 or more months; 11 different outbreaks occurred globally, including 9 new outbreaks in eight countries, including China and seven countries in Africa, according to the report.

In the first quarter of 2012, 59% fewer cases have been reported worldwide, compared with the same period in 2011, and all wild polio virus cases were reported from Afghanistan, Chad, Nigeria, and Pakistan. No new outbreaks have been reported, but persistent circulations, particularly in Nigeria and Pakistan, pose an ongoing threat to eradication efforts.

Following the WHO’s 2012 declaration regarding the public health emergency posed by ongoing poliovirus transmission, countries with endemic or reestablished transmission developed national emergency plans for interrupting transmission.

If global eradication is to be achieved, full implementation of these emergency plans is urgently needed, according to an editorial note included in the report.

DESTIN, FLA. – Management of lupus nephritis during pregnancy gets close attention in ACR’s new nephritis guidelines.

No treatment is necessary in pregnant women with prior lupus nephritis who have no current evidence of systemic or renal disease activity, while those with mild systemic activity may be treated with hydroxychloroquine, according to the guidelines, which are published in the June issue of Arthritis Care & Research.

"There are good data suggesting hydroxychloroquine controls lupus in women who are pregnant, resulting in fewer flares" Dr. Bevra H. Hahn said at the Congress of Clinical Rheumatology. Dr. Hahn, professor of medicine and chief of the division of rheumatology at the University of California, Los Angeles, led the ACR core working group that helped with development of the guidelines.

In patients with clinically active nephritis or with substantial extrarenal disease activity, glucocorticoids may be prescribed at doses necessary to control disease activity (Arthritis Care Res. 2012;64:797-08).

"I start at 0.5 mg/kg per day," Dr. Hahn said of glucocorticoids under these circumstances. She noted that only steroids that are metabolized by placental enzymes should be used so that the drug does not reach the fetus.

She and her coauthors cautioned, however, that high-dose glucocorticoid therapy is associated with a high risk of maternal complications – including hypertension and diabetes mellitus – in patients with systemic lupus erythematosus (SLE). They also stress that mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided in pregnancy, because they are established human teratogens.

Azathioprine, though listed as pregnancy category D indicating teratogenic risk, has been shown in cross-sectional studies to be associated with very low risk of fetal abnormalities and can be added if necessary, according to the task force panel charged with developing the guidelines.

The azathioprine dose, however, should not exceed 2 mg/kg per day in pregnant women, Dr. Hahn said.

The task force has recommended that pregnant patients with a persistently active nephritis and documented or suspected class III or IV disease with crescents may be candidates for delivery after 28 weeks if the fetus is viable. The recommendations with respect to pregnancy were based on level C evidence, indicating they were based on consensus, expert opinion, and case series.

For women with SLE and nephritis who are not pregnant, but who have concerns about fertility preservation, the task force panel recommended that mycophenolate mofetil was preferable to cyclophosphamide for induction therapy, because cyclophosphamide has been shown to cause permanent infertility in both women and men.

For example, one study showed that 6 months of high-dose intravenous cyclophosphamide with a cumulative dose of 4.4 g-10 g was associated with sustained amenorrhea in about 10% of young women, and the risk increased with age.

However, the physician should be certain the patient is not pregnant before prescribing mycophenolate mofetil or mycophenolic acid, and treatment should be stopped for at least 6 weeks before pregnancy is attempted.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, FLA. – Management of lupus nephritis during pregnancy gets close attention in ACR’s new nephritis guidelines.

No treatment is necessary in pregnant women with prior lupus nephritis who have no current evidence of systemic or renal disease activity, while those with mild systemic activity may be treated with hydroxychloroquine, according to the guidelines, which are published in the June issue of Arthritis Care & Research.

"There are good data suggesting hydroxychloroquine controls lupus in women who are pregnant, resulting in fewer flares" Dr. Bevra H. Hahn said at the Congress of Clinical Rheumatology. Dr. Hahn, professor of medicine and chief of the division of rheumatology at the University of California, Los Angeles, led the ACR core working group that helped with development of the guidelines.

In patients with clinically active nephritis or with substantial extrarenal disease activity, glucocorticoids may be prescribed at doses necessary to control disease activity (Arthritis Care Res. 2012;64:797-08).

"I start at 0.5 mg/kg per day," Dr. Hahn said of glucocorticoids under these circumstances. She noted that only steroids that are metabolized by placental enzymes should be used so that the drug does not reach the fetus.

She and her coauthors cautioned, however, that high-dose glucocorticoid therapy is associated with a high risk of maternal complications – including hypertension and diabetes mellitus – in patients with systemic lupus erythematosus (SLE). They also stress that mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided in pregnancy, because they are established human teratogens.

Azathioprine, though listed as pregnancy category D indicating teratogenic risk, has been shown in cross-sectional studies to be associated with very low risk of fetal abnormalities and can be added if necessary, according to the task force panel charged with developing the guidelines.

The azathioprine dose, however, should not exceed 2 mg/kg per day in pregnant women, Dr. Hahn said.

The task force has recommended that pregnant patients with a persistently active nephritis and documented or suspected class III or IV disease with crescents may be candidates for delivery after 28 weeks if the fetus is viable. The recommendations with respect to pregnancy were based on level C evidence, indicating they were based on consensus, expert opinion, and case series.

For women with SLE and nephritis who are not pregnant, but who have concerns about fertility preservation, the task force panel recommended that mycophenolate mofetil was preferable to cyclophosphamide for induction therapy, because cyclophosphamide has been shown to cause permanent infertility in both women and men.

For example, one study showed that 6 months of high-dose intravenous cyclophosphamide with a cumulative dose of 4.4 g-10 g was associated with sustained amenorrhea in about 10% of young women, and the risk increased with age.

However, the physician should be certain the patient is not pregnant before prescribing mycophenolate mofetil or mycophenolic acid, and treatment should be stopped for at least 6 weeks before pregnancy is attempted.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, FLA. – Management of lupus nephritis during pregnancy gets close attention in ACR’s new nephritis guidelines.

No treatment is necessary in pregnant women with prior lupus nephritis who have no current evidence of systemic or renal disease activity, while those with mild systemic activity may be treated with hydroxychloroquine, according to the guidelines, which are published in the June issue of Arthritis Care & Research.

"There are good data suggesting hydroxychloroquine controls lupus in women who are pregnant, resulting in fewer flares" Dr. Bevra H. Hahn said at the Congress of Clinical Rheumatology. Dr. Hahn, professor of medicine and chief of the division of rheumatology at the University of California, Los Angeles, led the ACR core working group that helped with development of the guidelines.

In patients with clinically active nephritis or with substantial extrarenal disease activity, glucocorticoids may be prescribed at doses necessary to control disease activity (Arthritis Care Res. 2012;64:797-08).

"I start at 0.5 mg/kg per day," Dr. Hahn said of glucocorticoids under these circumstances. She noted that only steroids that are metabolized by placental enzymes should be used so that the drug does not reach the fetus.

She and her coauthors cautioned, however, that high-dose glucocorticoid therapy is associated with a high risk of maternal complications – including hypertension and diabetes mellitus – in patients with systemic lupus erythematosus (SLE). They also stress that mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided in pregnancy, because they are established human teratogens.

Azathioprine, though listed as pregnancy category D indicating teratogenic risk, has been shown in cross-sectional studies to be associated with very low risk of fetal abnormalities and can be added if necessary, according to the task force panel charged with developing the guidelines.

The azathioprine dose, however, should not exceed 2 mg/kg per day in pregnant women, Dr. Hahn said.

The task force has recommended that pregnant patients with a persistently active nephritis and documented or suspected class III or IV disease with crescents may be candidates for delivery after 28 weeks if the fetus is viable. The recommendations with respect to pregnancy were based on level C evidence, indicating they were based on consensus, expert opinion, and case series.

For women with SLE and nephritis who are not pregnant, but who have concerns about fertility preservation, the task force panel recommended that mycophenolate mofetil was preferable to cyclophosphamide for induction therapy, because cyclophosphamide has been shown to cause permanent infertility in both women and men.

For example, one study showed that 6 months of high-dose intravenous cyclophosphamide with a cumulative dose of 4.4 g-10 g was associated with sustained amenorrhea in about 10% of young women, and the risk increased with age.

However, the physician should be certain the patient is not pregnant before prescribing mycophenolate mofetil or mycophenolic acid, and treatment should be stopped for at least 6 weeks before pregnancy is attempted.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, Fla. – Renal biopsy, unless strongly contraindicated, should be performed in every patient with clinical evidence of active lupus nephritis that has not been previously treated so that glomerular disease can be classified by current International Society of Nephrology/Renal Pathology Society classification, according to updated lupus nephritis treatment guidelines from the American College of Rheumatology.

Biopsy also will allow evaluation of disease for activity and chronicity and for tubular and vascular changes, as well as for the identification of additional or alternative causes of renal disease, according to the guidelines, which are published in the June issue of Arthritis Care and Research (Arthritis Care Res. 2012;54:797-808).

In fact, the recommended therapeutic strategies in the updated guidelines require knowledge of the classification of nephritis based on renal biopsy, according to Dr. Bevra H. Hahn, speaking at a meeting that happened to coincide with the online release of the guidelines on May 4.

For example, histologic class I and class II disease generally do not require immunosuppressive treatment; class III and class IV disease – and class V disease when combined with class III and IV disease – require aggressive therapy with glucocorticoids and immunosuppressive agents; and patients with class V disease alone (pure membranous lupus nephritis) with nephritic range proteinuria should be started on prednisone at 0.5mg/kg per day plus mycophenolate mofetil at 2-3 g total daily. Class VI disease generally requires preparation for renal replacement therapy.

The guidelines update those published in 1999, which represented a more general approach to systemic lupus erythematosus (SLE). These new guidelines more directly address nephritis, including case identification, treatment, and monitoring, and they include data on newer therapeutic modalities, including mycophenolate mofetil, mycophenolic acid, and rituximab, which were not available at the time the previous guidelines were developed, said Dr. Hahn, who led the core working group that helped develop the new guidelines.

They also address special situations such as pregnancy.

The core working group, along with a core executive group and a task force panel of experts used the validated modified RAND/University of California at Los Angeles Appropriateness Method, which involves a systematic literature view and expert opinion (based on voting by the task force panel) to develop the new guidelines.

The biopsy recommendation and the related therapeutic recommendations are based on level C evidence, indicating they were derived by consensus, expert opinion, and case series. Indications for renal biopsy, according to the task force panel include increasing serum creatinine without compelling alternative causes, confirmed proteinuria of 1 g or more/24 hours, and combinations of proteinuria of 0.5 g or more/24 hours plus hematuria (defined as 5 or more red blood cells per high power field) and proteinuria of 0.5 g or more/24 hours plus cellular casts – as long at these findings are confirmed in at least two tests conducted within a short time period and in the absence of alternative causes.

The task force panel also addressed adjunctive treatments, specifically recommending that:

• All patients with SLE be treated with a background of hydroxychloroquine unless contraindicated. This level C recommendation is based on recent cross-sectional and prospective controlled trial data indicating it is of benefit for reducing flare rates, is associated with significantly lower damage accrual (including renal damage), and may be associated with reduced risk of clotting events.

• Careful attention be paid to control of hypertension, with a target of no more than 130/80 mm Hg. This recommendation is based on level A evidence for nondiabetic chronic renal disease, indicating it is derived from multiple randomized controlled trials or a meta-analysis.

• Women of child-bearing potential who have active or prior lupus nephritis be counseled about the pregnancy risks conferred by the disease and its treatments. This recommendation is based on level C evidence.

Other task force panel recommendations specifically address induction of improvement in patients with International Society of Nephrology class III/IV lupus glomerulonephritis, induction of improvement in those with class IV or IV/V disease with cellular crescents, maintaining improvement in those who respond to induction therapy, and changing therapies in those who do not. Additional recommendations address the identification of vascular disease in patients with SLE and renal abnormalities, treatment of lupus nephritis patients who are pregnant, and monitoring the activity of lupus nephritis, Dr. Hahn said.

The new recommendations are "heavily based on induction with mycophenolate mofetil or cyclophosphamide, and on maintenance with mycophenolate mofetil or azathioprine," she noted.

"Nephritis remains one of the most devastating complications of lupus," she and her coauthors wrote, noting that the incidence increased during the 1980s and 1990s, with no decline seen as of 2004, despite the availability of new therapeutic regimens.

Standardized incidence rates for end-stage renal disease in the United States have risen in a number of populations, including younger patients, African Americans, and those living in the South.

"We hope that institution of these recommendations might lead to reductions in these trends. Furthermore, they may allow us to evaluate whether those who receive the recommended therapies are less likely to develop end-stage renal disease," they continued, concluding that while much progress has been made since lupus nephritis was associated with a near-terminal prognosis, these recommendations represent an effort to further improve outcomes and decrease morbidity and mortality in SLE.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, Fla. – Renal biopsy, unless strongly contraindicated, should be performed in every patient with clinical evidence of active lupus nephritis that has not been previously treated so that glomerular disease can be classified by current International Society of Nephrology/Renal Pathology Society classification, according to updated lupus nephritis treatment guidelines from the American College of Rheumatology.

Biopsy also will allow evaluation of disease for activity and chronicity and for tubular and vascular changes, as well as for the identification of additional or alternative causes of renal disease, according to the guidelines, which are published in the June issue of Arthritis Care and Research (Arthritis Care Res. 2012;54:797-808).

In fact, the recommended therapeutic strategies in the updated guidelines require knowledge of the classification of nephritis based on renal biopsy, according to Dr. Bevra H. Hahn, speaking at a meeting that happened to coincide with the online release of the guidelines on May 4.

For example, histologic class I and class II disease generally do not require immunosuppressive treatment; class III and class IV disease – and class V disease when combined with class III and IV disease – require aggressive therapy with glucocorticoids and immunosuppressive agents; and patients with class V disease alone (pure membranous lupus nephritis) with nephritic range proteinuria should be started on prednisone at 0.5mg/kg per day plus mycophenolate mofetil at 2-3 g total daily. Class VI disease generally requires preparation for renal replacement therapy.

The guidelines update those published in 1999, which represented a more general approach to systemic lupus erythematosus (SLE). These new guidelines more directly address nephritis, including case identification, treatment, and monitoring, and they include data on newer therapeutic modalities, including mycophenolate mofetil, mycophenolic acid, and rituximab, which were not available at the time the previous guidelines were developed, said Dr. Hahn, who led the core working group that helped develop the new guidelines.

They also address special situations such as pregnancy.

The core working group, along with a core executive group and a task force panel of experts used the validated modified RAND/University of California at Los Angeles Appropriateness Method, which involves a systematic literature view and expert opinion (based on voting by the task force panel) to develop the new guidelines.

The biopsy recommendation and the related therapeutic recommendations are based on level C evidence, indicating they were derived by consensus, expert opinion, and case series. Indications for renal biopsy, according to the task force panel include increasing serum creatinine without compelling alternative causes, confirmed proteinuria of 1 g or more/24 hours, and combinations of proteinuria of 0.5 g or more/24 hours plus hematuria (defined as 5 or more red blood cells per high power field) and proteinuria of 0.5 g or more/24 hours plus cellular casts – as long at these findings are confirmed in at least two tests conducted within a short time period and in the absence of alternative causes.

The task force panel also addressed adjunctive treatments, specifically recommending that:

• All patients with SLE be treated with a background of hydroxychloroquine unless contraindicated. This level C recommendation is based on recent cross-sectional and prospective controlled trial data indicating it is of benefit for reducing flare rates, is associated with significantly lower damage accrual (including renal damage), and may be associated with reduced risk of clotting events.

• Careful attention be paid to control of hypertension, with a target of no more than 130/80 mm Hg. This recommendation is based on level A evidence for nondiabetic chronic renal disease, indicating it is derived from multiple randomized controlled trials or a meta-analysis.

• Women of child-bearing potential who have active or prior lupus nephritis be counseled about the pregnancy risks conferred by the disease and its treatments. This recommendation is based on level C evidence.

Other task force panel recommendations specifically address induction of improvement in patients with International Society of Nephrology class III/IV lupus glomerulonephritis, induction of improvement in those with class IV or IV/V disease with cellular crescents, maintaining improvement in those who respond to induction therapy, and changing therapies in those who do not. Additional recommendations address the identification of vascular disease in patients with SLE and renal abnormalities, treatment of lupus nephritis patients who are pregnant, and monitoring the activity of lupus nephritis, Dr. Hahn said.

The new recommendations are "heavily based on induction with mycophenolate mofetil or cyclophosphamide, and on maintenance with mycophenolate mofetil or azathioprine," she noted.

"Nephritis remains one of the most devastating complications of lupus," she and her coauthors wrote, noting that the incidence increased during the 1980s and 1990s, with no decline seen as of 2004, despite the availability of new therapeutic regimens.

Standardized incidence rates for end-stage renal disease in the United States have risen in a number of populations, including younger patients, African Americans, and those living in the South.

"We hope that institution of these recommendations might lead to reductions in these trends. Furthermore, they may allow us to evaluate whether those who receive the recommended therapies are less likely to develop end-stage renal disease," they continued, concluding that while much progress has been made since lupus nephritis was associated with a near-terminal prognosis, these recommendations represent an effort to further improve outcomes and decrease morbidity and mortality in SLE.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, Fla. – Renal biopsy, unless strongly contraindicated, should be performed in every patient with clinical evidence of active lupus nephritis that has not been previously treated so that glomerular disease can be classified by current International Society of Nephrology/Renal Pathology Society classification, according to updated lupus nephritis treatment guidelines from the American College of Rheumatology.

Biopsy also will allow evaluation of disease for activity and chronicity and for tubular and vascular changes, as well as for the identification of additional or alternative causes of renal disease, according to the guidelines, which are published in the June issue of Arthritis Care and Research (Arthritis Care Res. 2012;54:797-808).

In fact, the recommended therapeutic strategies in the updated guidelines require knowledge of the classification of nephritis based on renal biopsy, according to Dr. Bevra H. Hahn, speaking at a meeting that happened to coincide with the online release of the guidelines on May 4.

For example, histologic class I and class II disease generally do not require immunosuppressive treatment; class III and class IV disease – and class V disease when combined with class III and IV disease – require aggressive therapy with glucocorticoids and immunosuppressive agents; and patients with class V disease alone (pure membranous lupus nephritis) with nephritic range proteinuria should be started on prednisone at 0.5mg/kg per day plus mycophenolate mofetil at 2-3 g total daily. Class VI disease generally requires preparation for renal replacement therapy.

The guidelines update those published in 1999, which represented a more general approach to systemic lupus erythematosus (SLE). These new guidelines more directly address nephritis, including case identification, treatment, and monitoring, and they include data on newer therapeutic modalities, including mycophenolate mofetil, mycophenolic acid, and rituximab, which were not available at the time the previous guidelines were developed, said Dr. Hahn, who led the core working group that helped develop the new guidelines.

They also address special situations such as pregnancy.

The core working group, along with a core executive group and a task force panel of experts used the validated modified RAND/University of California at Los Angeles Appropriateness Method, which involves a systematic literature view and expert opinion (based on voting by the task force panel) to develop the new guidelines.

The biopsy recommendation and the related therapeutic recommendations are based on level C evidence, indicating they were derived by consensus, expert opinion, and case series. Indications for renal biopsy, according to the task force panel include increasing serum creatinine without compelling alternative causes, confirmed proteinuria of 1 g or more/24 hours, and combinations of proteinuria of 0.5 g or more/24 hours plus hematuria (defined as 5 or more red blood cells per high power field) and proteinuria of 0.5 g or more/24 hours plus cellular casts – as long at these findings are confirmed in at least two tests conducted within a short time period and in the absence of alternative causes.

The task force panel also addressed adjunctive treatments, specifically recommending that:

• All patients with SLE be treated with a background of hydroxychloroquine unless contraindicated. This level C recommendation is based on recent cross-sectional and prospective controlled trial data indicating it is of benefit for reducing flare rates, is associated with significantly lower damage accrual (including renal damage), and may be associated with reduced risk of clotting events.

• Careful attention be paid to control of hypertension, with a target of no more than 130/80 mm Hg. This recommendation is based on level A evidence for nondiabetic chronic renal disease, indicating it is derived from multiple randomized controlled trials or a meta-analysis.

• Women of child-bearing potential who have active or prior lupus nephritis be counseled about the pregnancy risks conferred by the disease and its treatments. This recommendation is based on level C evidence.

Other task force panel recommendations specifically address induction of improvement in patients with International Society of Nephrology class III/IV lupus glomerulonephritis, induction of improvement in those with class IV or IV/V disease with cellular crescents, maintaining improvement in those who respond to induction therapy, and changing therapies in those who do not. Additional recommendations address the identification of vascular disease in patients with SLE and renal abnormalities, treatment of lupus nephritis patients who are pregnant, and monitoring the activity of lupus nephritis, Dr. Hahn said.

The new recommendations are "heavily based on induction with mycophenolate mofetil or cyclophosphamide, and on maintenance with mycophenolate mofetil or azathioprine," she noted.

"Nephritis remains one of the most devastating complications of lupus," she and her coauthors wrote, noting that the incidence increased during the 1980s and 1990s, with no decline seen as of 2004, despite the availability of new therapeutic regimens.

Standardized incidence rates for end-stage renal disease in the United States have risen in a number of populations, including younger patients, African Americans, and those living in the South.

"We hope that institution of these recommendations might lead to reductions in these trends. Furthermore, they may allow us to evaluate whether those who receive the recommended therapies are less likely to develop end-stage renal disease," they continued, concluding that while much progress has been made since lupus nephritis was associated with a near-terminal prognosis, these recommendations represent an effort to further improve outcomes and decrease morbidity and mortality in SLE.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

KISSIMMEE, FLA. – Treatment with a 2,940 Er:YAG ablative fractional laser led to a clinically significant reduction of third-degree burn scars in a prospective study of 11 patients.

Clinical and histologic findings from the laser study provide important clues as to the mechanism of action and appropriate treatment intervals, Dr. Jill S. Waibel reported at the meeting. Scars from fire or thermal injury are among the worst that are seen in clinical practice, and although fractional laser therapy is emerging as the preferred treatment for these injuries, a better understanding of the optimal laser wavelengths, clinical response patterns, scar tissue response, and histologic changes will improve outcomes.

Patients in this study underwent three ablative treatments at 4-week intervals, and – based on blinded evaluation by independent investigators – were found to have an overall modified Manchester score of 2.3 out of 3 points, indicating moderate to excellent improvement. The scores for dyschromia, hypertrophy reduction, vascularity, and scar texture improvement were 1.7, 1.9, 2.0, and 2.0, respectively, indicating mild to moderate improvement, said Dr. Waibel, a physician in private practice in Miami.

The patients, who had third-degree burn scars over an average of 80% of their body, were treated with one pass at depths ranging from 400 to 800 microns, depending on scar thickness and density.

Biopsies were performed at baseline and at 3 months after the final treatment. On biopsies taken at baseline, the scars were noted to have thickened, homogenized, dystrophic collagen structures; and on biopsies taken 3 months after the final treatment, a decrease in these dystrophic fibers was seen, she said.

Dr. Waibel hypothesized that scar improvement resulted from the complete replacement of ablated zones by newly synthesized collagen and that the collagen remodeling led to more normal-appearing skin.

She noted that the erbium laser is "very powerful" and caused a great deal of erythema in two patients, leading her to "turn the power down" over the course of the study. Although no worsening of scars was seen, the increased vascularity in the two patients suggested that intervals longer than 4 weeks between treatments – perhaps to between 2 and 3 months - may be warranted.

Although additional study is needed, the findings suggest that the 2,940 Er:YAG laser is effective for clinically improving burn scars through vaporization and by inducing an organized wound-healing response; this histologic healing response may lead to the improvement that is seen clinically, she concluded.

This study was funded by Sciton. Dr. Waibel said she had no other relevant financial disclosures.

KISSIMMEE, FLA. – Treatment with a 2,940 Er:YAG ablative fractional laser led to a clinically significant reduction of third-degree burn scars in a prospective study of 11 patients.

Clinical and histologic findings from the laser study provide important clues as to the mechanism of action and appropriate treatment intervals, Dr. Jill S. Waibel reported at the meeting. Scars from fire or thermal injury are among the worst that are seen in clinical practice, and although fractional laser therapy is emerging as the preferred treatment for these injuries, a better understanding of the optimal laser wavelengths, clinical response patterns, scar tissue response, and histologic changes will improve outcomes.

Patients in this study underwent three ablative treatments at 4-week intervals, and – based on blinded evaluation by independent investigators – were found to have an overall modified Manchester score of 2.3 out of 3 points, indicating moderate to excellent improvement. The scores for dyschromia, hypertrophy reduction, vascularity, and scar texture improvement were 1.7, 1.9, 2.0, and 2.0, respectively, indicating mild to moderate improvement, said Dr. Waibel, a physician in private practice in Miami.

The patients, who had third-degree burn scars over an average of 80% of their body, were treated with one pass at depths ranging from 400 to 800 microns, depending on scar thickness and density.

Biopsies were performed at baseline and at 3 months after the final treatment. On biopsies taken at baseline, the scars were noted to have thickened, homogenized, dystrophic collagen structures; and on biopsies taken 3 months after the final treatment, a decrease in these dystrophic fibers was seen, she said.

Dr. Waibel hypothesized that scar improvement resulted from the complete replacement of ablated zones by newly synthesized collagen and that the collagen remodeling led to more normal-appearing skin.

She noted that the erbium laser is "very powerful" and caused a great deal of erythema in two patients, leading her to "turn the power down" over the course of the study. Although no worsening of scars was seen, the increased vascularity in the two patients suggested that intervals longer than 4 weeks between treatments – perhaps to between 2 and 3 months - may be warranted.

Although additional study is needed, the findings suggest that the 2,940 Er:YAG laser is effective for clinically improving burn scars through vaporization and by inducing an organized wound-healing response; this histologic healing response may lead to the improvement that is seen clinically, she concluded.

This study was funded by Sciton. Dr. Waibel said she had no other relevant financial disclosures.

KISSIMMEE, FLA. – Treatment with a 2,940 Er:YAG ablative fractional laser led to a clinically significant reduction of third-degree burn scars in a prospective study of 11 patients.

Clinical and histologic findings from the laser study provide important clues as to the mechanism of action and appropriate treatment intervals, Dr. Jill S. Waibel reported at the meeting. Scars from fire or thermal injury are among the worst that are seen in clinical practice, and although fractional laser therapy is emerging as the preferred treatment for these injuries, a better understanding of the optimal laser wavelengths, clinical response patterns, scar tissue response, and histologic changes will improve outcomes.

Patients in this study underwent three ablative treatments at 4-week intervals, and – based on blinded evaluation by independent investigators – were found to have an overall modified Manchester score of 2.3 out of 3 points, indicating moderate to excellent improvement. The scores for dyschromia, hypertrophy reduction, vascularity, and scar texture improvement were 1.7, 1.9, 2.0, and 2.0, respectively, indicating mild to moderate improvement, said Dr. Waibel, a physician in private practice in Miami.

The patients, who had third-degree burn scars over an average of 80% of their body, were treated with one pass at depths ranging from 400 to 800 microns, depending on scar thickness and density.

Biopsies were performed at baseline and at 3 months after the final treatment. On biopsies taken at baseline, the scars were noted to have thickened, homogenized, dystrophic collagen structures; and on biopsies taken 3 months after the final treatment, a decrease in these dystrophic fibers was seen, she said.

Dr. Waibel hypothesized that scar improvement resulted from the complete replacement of ablated zones by newly synthesized collagen and that the collagen remodeling led to more normal-appearing skin.

She noted that the erbium laser is "very powerful" and caused a great deal of erythema in two patients, leading her to "turn the power down" over the course of the study. Although no worsening of scars was seen, the increased vascularity in the two patients suggested that intervals longer than 4 weeks between treatments – perhaps to between 2 and 3 months - may be warranted.

Although additional study is needed, the findings suggest that the 2,940 Er:YAG laser is effective for clinically improving burn scars through vaporization and by inducing an organized wound-healing response; this histologic healing response may lead to the improvement that is seen clinically, she concluded.

This study was funded by Sciton. Dr. Waibel said she had no other relevant financial disclosures.

KISSIMMEE, FLA. – Two new studies have found safe and effective means for improving the results of lower abdomen cryolipolysis.

In the first study, 20 patients underwent one lower abdomen cryolipolysis treatment for 60 minutes, followed by a second treatment 2 months later. A consistent and discernable decrease in the thickness of the fat layer was noted in an independent photo review 4 months following the initial treatment.

Blinded independent reviewers, including two plastic surgeons and one dermatologist, compared the follow-up photos with those taken at baseline, and correctly identified the posttreatment image 86% of the time, Dr. Flor Mayoral reported at the annual meeting of the American Society for Laser Medicine and Surgery.

"Massage appears to be a safe, effective way to further reduce the fat layer following a cryolipolysis procedure."

Patient satisfaction was also high, with 75% of study participants reporting a "somewhat to very visible" change in the treated region, said Dr. Mayoral, a dermatologist in private practice in Coral Gables, Fla.

"Patients didn’t have the advantage of looking at their own photographs to determine whether they looked better or not," she noted.

Study patients were treated using CoolSculpting, by Zeltiq Aesthetics, at a cooling intensity factor of 42. No adverse events were reported.

Additional treatment following initial cryolipolysis of the abdomen appeared to be safe and effective, Dr. Mayoral concluded.

In a separate single-center study, Dr. Gerald Boey, a dermatologist in private practice in Vancouver, B.C., found that performing manual massage to the abdominal area following cryolipolysis led to improved outcomes, compared with cryolipolysis without the manual massage.

Massage was performed on one randomly selected side of the abdomen immediately following treatment of the entire lower abdomen in 10 patients, and outcomes on each side were compared using photos taken at baseline and at the 2-month follow-up. Improvement occurred on both sides, but greater improvement was noted on the massaged side in all patients, and ultrasound measurement confirmed that the fat reduction on the massaged side was, on average, 68% greater than on the control side, Dr. Boey said.

In a separate set of seven patients, biopsies performed at baseline and at 3, 8, 13, 30, 60, and 120 days following massage demonstrated that massage was not associated with any evidence of necrosis or fibrosis.

As in Dr. Mayoral’s study, cryolipolysis in this study was performed using CoolSculpting at a cooling intensity factor of 42 for 60 minutes. Massage was performed for 1 minute using a vigorous kneading motion, followed by 1 minute using a circular motion with the pads of the fingers.

"Massage appears to be a safe, effective way to further reduce the fat layer following a cryolipolysis procedure," Dr. Boey said. As for why the massage helps, one possible explanation is that manipulation of the fat while it is in the crystalline state induced by cryolipolysis may cause an accelerated reperfusion injury.

Dr. Mayoral reported that her study was funded by Zeltiq Aesthetics. She had no other disclosures to report. Dr. Boey had no disclosures to report.

KISSIMMEE, FLA. – Two new studies have found safe and effective means for improving the results of lower abdomen cryolipolysis.

In the first study, 20 patients underwent one lower abdomen cryolipolysis treatment for 60 minutes, followed by a second treatment 2 months later. A consistent and discernable decrease in the thickness of the fat layer was noted in an independent photo review 4 months following the initial treatment.

Blinded independent reviewers, including two plastic surgeons and one dermatologist, compared the follow-up photos with those taken at baseline, and correctly identified the posttreatment image 86% of the time, Dr. Flor Mayoral reported at the annual meeting of the American Society for Laser Medicine and Surgery.

"Massage appears to be a safe, effective way to further reduce the fat layer following a cryolipolysis procedure."

Patient satisfaction was also high, with 75% of study participants reporting a "somewhat to very visible" change in the treated region, said Dr. Mayoral, a dermatologist in private practice in Coral Gables, Fla.

"Patients didn’t have the advantage of looking at their own photographs to determine whether they looked better or not," she noted.

Study patients were treated using CoolSculpting, by Zeltiq Aesthetics, at a cooling intensity factor of 42. No adverse events were reported.

Additional treatment following initial cryolipolysis of the abdomen appeared to be safe and effective, Dr. Mayoral concluded.

In a separate single-center study, Dr. Gerald Boey, a dermatologist in private practice in Vancouver, B.C., found that performing manual massage to the abdominal area following cryolipolysis led to improved outcomes, compared with cryolipolysis without the manual massage.

Massage was performed on one randomly selected side of the abdomen immediately following treatment of the entire lower abdomen in 10 patients, and outcomes on each side were compared using photos taken at baseline and at the 2-month follow-up. Improvement occurred on both sides, but greater improvement was noted on the massaged side in all patients, and ultrasound measurement confirmed that the fat reduction on the massaged side was, on average, 68% greater than on the control side, Dr. Boey said.

In a separate set of seven patients, biopsies performed at baseline and at 3, 8, 13, 30, 60, and 120 days following massage demonstrated that massage was not associated with any evidence of necrosis or fibrosis.

As in Dr. Mayoral’s study, cryolipolysis in this study was performed using CoolSculpting at a cooling intensity factor of 42 for 60 minutes. Massage was performed for 1 minute using a vigorous kneading motion, followed by 1 minute using a circular motion with the pads of the fingers.

"Massage appears to be a safe, effective way to further reduce the fat layer following a cryolipolysis procedure," Dr. Boey said. As for why the massage helps, one possible explanation is that manipulation of the fat while it is in the crystalline state induced by cryolipolysis may cause an accelerated reperfusion injury.

Dr. Mayoral reported that her study was funded by Zeltiq Aesthetics. She had no other disclosures to report. Dr. Boey had no disclosures to report.

KISSIMMEE, FLA. – Two new studies have found safe and effective means for improving the results of lower abdomen cryolipolysis.

In the first study, 20 patients underwent one lower abdomen cryolipolysis treatment for 60 minutes, followed by a second treatment 2 months later. A consistent and discernable decrease in the thickness of the fat layer was noted in an independent photo review 4 months following the initial treatment.

Blinded independent reviewers, including two plastic surgeons and one dermatologist, compared the follow-up photos with those taken at baseline, and correctly identified the posttreatment image 86% of the time, Dr. Flor Mayoral reported at the annual meeting of the American Society for Laser Medicine and Surgery.

"Massage appears to be a safe, effective way to further reduce the fat layer following a cryolipolysis procedure."

Patient satisfaction was also high, with 75% of study participants reporting a "somewhat to very visible" change in the treated region, said Dr. Mayoral, a dermatologist in private practice in Coral Gables, Fla.

"Patients didn’t have the advantage of looking at their own photographs to determine whether they looked better or not," she noted.

Study patients were treated using CoolSculpting, by Zeltiq Aesthetics, at a cooling intensity factor of 42. No adverse events were reported.

Additional treatment following initial cryolipolysis of the abdomen appeared to be safe and effective, Dr. Mayoral concluded.

In a separate single-center study, Dr. Gerald Boey, a dermatologist in private practice in Vancouver, B.C., found that performing manual massage to the abdominal area following cryolipolysis led to improved outcomes, compared with cryolipolysis without the manual massage.

Massage was performed on one randomly selected side of the abdomen immediately following treatment of the entire lower abdomen in 10 patients, and outcomes on each side were compared using photos taken at baseline and at the 2-month follow-up. Improvement occurred on both sides, but greater improvement was noted on the massaged side in all patients, and ultrasound measurement confirmed that the fat reduction on the massaged side was, on average, 68% greater than on the control side, Dr. Boey said.

In a separate set of seven patients, biopsies performed at baseline and at 3, 8, 13, 30, 60, and 120 days following massage demonstrated that massage was not associated with any evidence of necrosis or fibrosis.

As in Dr. Mayoral’s study, cryolipolysis in this study was performed using CoolSculpting at a cooling intensity factor of 42 for 60 minutes. Massage was performed for 1 minute using a vigorous kneading motion, followed by 1 minute using a circular motion with the pads of the fingers.

"Massage appears to be a safe, effective way to further reduce the fat layer following a cryolipolysis procedure," Dr. Boey said. As for why the massage helps, one possible explanation is that manipulation of the fat while it is in the crystalline state induced by cryolipolysis may cause an accelerated reperfusion injury.

Dr. Mayoral reported that her study was funded by Zeltiq Aesthetics. She had no other disclosures to report. Dr. Boey had no disclosures to report.