Amy Rothman Schonfeld

NEW YORK – Current use of prednisone above 10 mg/day more than doubles the risk of cardiovascular events in patients with systemic lupus erythematosus, according to a study conducted by Dr. Michelle Petri and her colleagues.

"Do everything you can to keep patients with lupus below the 10-mg/day cutoff for prednisone," said Dr. Petri, director of the Lupus Center at Johns Hopkins Hospital, Baltimore. She presented the results of her work at a meeting sponsored by New York University.

In an observational cohort study that explored factors that might increase the risk of cardiovascular events (CVEs) in people with systemic lupus erythematosus (SLE), Dr. Petri analyzed data from 1,874 SLE patients in the Hopkins Lupus Cohort who were seen quarterly at a single clinical center for more than 23 years (April 1987 to June 2010). In patients who took 1-9 mg/day of prednisone, 32 CVEs occurred, which was not significantly different from what would be expected in the general population. But once 10 mg/day was exceeded, the risk of having a CVE increased significantly in the 10- to 19-mg/day prednisone group (relative risk 2.4, P = .002), equivalent to a rate of 20.2/1,000 person-years). A more than a fivefold increase in risk was noted in those who took 20 mg or more per day (P less than .001), which was equivalent to 35.4/1,000 person-years (Am. J. Epidemiol. 2012;176:708-19).

After adjustment for age, CVE rates were not associated with disease duration, but were associated with average past levels of lupus disease activity and recent levels of circulating anti–double-stranded DNA. Past use of corticosteroids in the absence of current use did not affect CVE rates, although a cumulative past dose of 36,500 mg or more (equivalent to 10 or more years of prednisone 10 mg/day or equivalent) more than doubled the CVE rate (P = .0066).

To reduce cardiovascular risk in patients with SLE, Dr. Petri suggested assessing and treating traditional cardiovascular risk factors (hypertension, obesity, hyperlipidemia, smoking, and a sedentary lifestyle). Clinical trials in children and adults have shown that statins do not prevent accelerated atherosclerosis in SLE, so they are not helpful. "They don’t even work in mice!" said Dr. Petri, a professor in the division of rheumatology at Johns Hopkins University School of Medicine, Baltimore.

One possible treatment might be mycophenolate mofetil (MMF), which has not been approved by the Food and Drug Administration for use in SLE. Although there is some evidence that MMF slows progression of atherosclerosis in renal transplant patients and in mice, no clinical studies have been done to support its use in SLE. But Dr. Petri discouraged treating patients with MMF because of warnings associated with its use (infection, lymphoma and malignancies, pregnancy loss and congenital malformations, neutropenia and red cell aplasia, and interference with oral contraceptives).

NSAIDs have also been associated with a 66% increased risk of cardiovascular damage in SLE, Dr. Petri said. "These findings are a driving factor behind our need for new therapies for lupus. We need to avoid steroids as well as NSAIDs."

Dr. Petri is a consultant to GlaxoSmithKline.

NEW YORK – Current use of prednisone above 10 mg/day more than doubles the risk of cardiovascular events in patients with systemic lupus erythematosus, according to a study conducted by Dr. Michelle Petri and her colleagues.

"Do everything you can to keep patients with lupus below the 10-mg/day cutoff for prednisone," said Dr. Petri, director of the Lupus Center at Johns Hopkins Hospital, Baltimore. She presented the results of her work at a meeting sponsored by New York University.

In an observational cohort study that explored factors that might increase the risk of cardiovascular events (CVEs) in people with systemic lupus erythematosus (SLE), Dr. Petri analyzed data from 1,874 SLE patients in the Hopkins Lupus Cohort who were seen quarterly at a single clinical center for more than 23 years (April 1987 to June 2010). In patients who took 1-9 mg/day of prednisone, 32 CVEs occurred, which was not significantly different from what would be expected in the general population. But once 10 mg/day was exceeded, the risk of having a CVE increased significantly in the 10- to 19-mg/day prednisone group (relative risk 2.4, P = .002), equivalent to a rate of 20.2/1,000 person-years). A more than a fivefold increase in risk was noted in those who took 20 mg or more per day (P less than .001), which was equivalent to 35.4/1,000 person-years (Am. J. Epidemiol. 2012;176:708-19).

After adjustment for age, CVE rates were not associated with disease duration, but were associated with average past levels of lupus disease activity and recent levels of circulating anti–double-stranded DNA. Past use of corticosteroids in the absence of current use did not affect CVE rates, although a cumulative past dose of 36,500 mg or more (equivalent to 10 or more years of prednisone 10 mg/day or equivalent) more than doubled the CVE rate (P = .0066).

To reduce cardiovascular risk in patients with SLE, Dr. Petri suggested assessing and treating traditional cardiovascular risk factors (hypertension, obesity, hyperlipidemia, smoking, and a sedentary lifestyle). Clinical trials in children and adults have shown that statins do not prevent accelerated atherosclerosis in SLE, so they are not helpful. "They don’t even work in mice!" said Dr. Petri, a professor in the division of rheumatology at Johns Hopkins University School of Medicine, Baltimore.

One possible treatment might be mycophenolate mofetil (MMF), which has not been approved by the Food and Drug Administration for use in SLE. Although there is some evidence that MMF slows progression of atherosclerosis in renal transplant patients and in mice, no clinical studies have been done to support its use in SLE. But Dr. Petri discouraged treating patients with MMF because of warnings associated with its use (infection, lymphoma and malignancies, pregnancy loss and congenital malformations, neutropenia and red cell aplasia, and interference with oral contraceptives).

NSAIDs have also been associated with a 66% increased risk of cardiovascular damage in SLE, Dr. Petri said. "These findings are a driving factor behind our need for new therapies for lupus. We need to avoid steroids as well as NSAIDs."

Dr. Petri is a consultant to GlaxoSmithKline.

NEW YORK – Current use of prednisone above 10 mg/day more than doubles the risk of cardiovascular events in patients with systemic lupus erythematosus, according to a study conducted by Dr. Michelle Petri and her colleagues.

"Do everything you can to keep patients with lupus below the 10-mg/day cutoff for prednisone," said Dr. Petri, director of the Lupus Center at Johns Hopkins Hospital, Baltimore. She presented the results of her work at a meeting sponsored by New York University.

In an observational cohort study that explored factors that might increase the risk of cardiovascular events (CVEs) in people with systemic lupus erythematosus (SLE), Dr. Petri analyzed data from 1,874 SLE patients in the Hopkins Lupus Cohort who were seen quarterly at a single clinical center for more than 23 years (April 1987 to June 2010). In patients who took 1-9 mg/day of prednisone, 32 CVEs occurred, which was not significantly different from what would be expected in the general population. But once 10 mg/day was exceeded, the risk of having a CVE increased significantly in the 10- to 19-mg/day prednisone group (relative risk 2.4, P = .002), equivalent to a rate of 20.2/1,000 person-years). A more than a fivefold increase in risk was noted in those who took 20 mg or more per day (P less than .001), which was equivalent to 35.4/1,000 person-years (Am. J. Epidemiol. 2012;176:708-19).

After adjustment for age, CVE rates were not associated with disease duration, but were associated with average past levels of lupus disease activity and recent levels of circulating anti–double-stranded DNA. Past use of corticosteroids in the absence of current use did not affect CVE rates, although a cumulative past dose of 36,500 mg or more (equivalent to 10 or more years of prednisone 10 mg/day or equivalent) more than doubled the CVE rate (P = .0066).

To reduce cardiovascular risk in patients with SLE, Dr. Petri suggested assessing and treating traditional cardiovascular risk factors (hypertension, obesity, hyperlipidemia, smoking, and a sedentary lifestyle). Clinical trials in children and adults have shown that statins do not prevent accelerated atherosclerosis in SLE, so they are not helpful. "They don’t even work in mice!" said Dr. Petri, a professor in the division of rheumatology at Johns Hopkins University School of Medicine, Baltimore.

One possible treatment might be mycophenolate mofetil (MMF), which has not been approved by the Food and Drug Administration for use in SLE. Although there is some evidence that MMF slows progression of atherosclerosis in renal transplant patients and in mice, no clinical studies have been done to support its use in SLE. But Dr. Petri discouraged treating patients with MMF because of warnings associated with its use (infection, lymphoma and malignancies, pregnancy loss and congenital malformations, neutropenia and red cell aplasia, and interference with oral contraceptives).

NSAIDs have also been associated with a 66% increased risk of cardiovascular damage in SLE, Dr. Petri said. "These findings are a driving factor behind our need for new therapies for lupus. We need to avoid steroids as well as NSAIDs."

Dr. Petri is a consultant to GlaxoSmithKline.

NEW YORK – Obesity appears to reduce response to anti–tumor necrosis factor–alpha treatment in individuals with psoriatic arthritis, but weight loss can improve it, according to a review of two studies by Dr. Christopher T. Ritchlin.

"These data convincingly show that if we talk to our patients and tell them to lose weight, it can have an impact on how their PsA [psoriatic arthritis] therapies are going to work," Dr. Ritchlin, director of the Translational Immunology Research Center at the University of Rochester (N.Y.), said at a meeting sponsored by New York University.

Dr. Ritchlin said these results fit in with previous epidemiologic studies that show that as body mass index goes up, so does the risk for both psoriasis and PsA (Arch. Intern. Med. 2009;167:1670-5 and Ann. Rheum. Dis. 2012;71:1273-7).

These data support a link between obesity-related chronic tissue inflammation and development of some rheumatic diseases, such as arthritis in psoriatic patients. These same inflammatory processes may also interfere with good clinical response to biologic agents.

In a study published by Dr. Matteo Nicola di Minno of Federico II University in Naples, Italy, and his colleagues, individuals with a BMI in the 30-35 kg/m² range with PsA had a nearly fourfold increased risk of not responding well to treatment with tumor necrosis factor–alpha inhibitors (TNFis). The risk of a poor response rose more than fivefold for those whose BMIs greater than 35 kg/m² (Arthritis Care Res. 2013;65:141-7).

The study prospectively followed PsA patients with active disease for 24 months who were starting TNFi therapy (30% adalimumab, 41% etanercept, 29% infliximab). The group comprised 135 obese patients (BMI greater than 30 kg/m²) and 135 controls of normal weight. The primary outcome was achievement of minimal disease activity (MDA), which meant they fulfilled five of seven outcome measures: one or fewer tender joints, one or fewer swollen joints, a score of 1 or less on the Psoriasis Area and Severity Index or body surface area = 3, a score of 15 or less on a visual analog scale (VAS) for pain, a score of 20 or less on a patient global disease severity VAS score, a score on the Health Assessment Questionnaire of 0.5 or less, or one or fewer tender entheseal points.

After 12 months, only 98 (36%) of the total group reached MDA. "What the results showed was that the odds of not achieving MDA were directly related to increased BMI," Dr. Ritchlin said.

Significantly more of the patients who did not achieve MDA were obese (64% vs. 25.5%, P less than .001). After adjustment for other variables, obesity was found to incur a nearly fivefold risk of poor response to therapy (hazard ratio 4.90, 95% confidence interval [CI] 3.04-7.87). The hazard ratios were 3.98 for those with BMI of 30-35 kg/m² and 5.4 for those with BMI greater than 35 kg/m² (both P less than .001). Among the 98 PsA patients who had achieved MDA by 12 months, those who were obese had a poor probability of sustaining MDA when tested at 24 months, according to Dr. di Minno.

In a follow-up study presented at the 2012 EULAR meeting (Ann. Rheum. Dis. 2012;71[Suppl. 3]:109), Dr. di Minno addressed the question of whether weight loss in obese PsA patients would improve treatment response. In this study, 138 obese PsA patients were divided into two groups of 69 patients each. One group received a hypocaloric diet and the controls followed a normal diet.

After 6 months, those who lost 10% of their BMI or more were almost five times more likely to achieve MDA (HR 4.79, P = .002). Those who lost 5%-10% of their BMI were twice as likely as were controls to reach MDA.

Dr. Ritchlin said that he had no relevant disclosures.

NEW YORK – Obesity appears to reduce response to anti–tumor necrosis factor–alpha treatment in individuals with psoriatic arthritis, but weight loss can improve it, according to a review of two studies by Dr. Christopher T. Ritchlin.

"These data convincingly show that if we talk to our patients and tell them to lose weight, it can have an impact on how their PsA [psoriatic arthritis] therapies are going to work," Dr. Ritchlin, director of the Translational Immunology Research Center at the University of Rochester (N.Y.), said at a meeting sponsored by New York University.

Dr. Ritchlin said these results fit in with previous epidemiologic studies that show that as body mass index goes up, so does the risk for both psoriasis and PsA (Arch. Intern. Med. 2009;167:1670-5 and Ann. Rheum. Dis. 2012;71:1273-7).

These data support a link between obesity-related chronic tissue inflammation and development of some rheumatic diseases, such as arthritis in psoriatic patients. These same inflammatory processes may also interfere with good clinical response to biologic agents.

In a study published by Dr. Matteo Nicola di Minno of Federico II University in Naples, Italy, and his colleagues, individuals with a BMI in the 30-35 kg/m² range with PsA had a nearly fourfold increased risk of not responding well to treatment with tumor necrosis factor–alpha inhibitors (TNFis). The risk of a poor response rose more than fivefold for those whose BMIs greater than 35 kg/m² (Arthritis Care Res. 2013;65:141-7).

The study prospectively followed PsA patients with active disease for 24 months who were starting TNFi therapy (30% adalimumab, 41% etanercept, 29% infliximab). The group comprised 135 obese patients (BMI greater than 30 kg/m²) and 135 controls of normal weight. The primary outcome was achievement of minimal disease activity (MDA), which meant they fulfilled five of seven outcome measures: one or fewer tender joints, one or fewer swollen joints, a score of 1 or less on the Psoriasis Area and Severity Index or body surface area = 3, a score of 15 or less on a visual analog scale (VAS) for pain, a score of 20 or less on a patient global disease severity VAS score, a score on the Health Assessment Questionnaire of 0.5 or less, or one or fewer tender entheseal points.

After 12 months, only 98 (36%) of the total group reached MDA. "What the results showed was that the odds of not achieving MDA were directly related to increased BMI," Dr. Ritchlin said.

Significantly more of the patients who did not achieve MDA were obese (64% vs. 25.5%, P less than .001). After adjustment for other variables, obesity was found to incur a nearly fivefold risk of poor response to therapy (hazard ratio 4.90, 95% confidence interval [CI] 3.04-7.87). The hazard ratios were 3.98 for those with BMI of 30-35 kg/m² and 5.4 for those with BMI greater than 35 kg/m² (both P less than .001). Among the 98 PsA patients who had achieved MDA by 12 months, those who were obese had a poor probability of sustaining MDA when tested at 24 months, according to Dr. di Minno.

In a follow-up study presented at the 2012 EULAR meeting (Ann. Rheum. Dis. 2012;71[Suppl. 3]:109), Dr. di Minno addressed the question of whether weight loss in obese PsA patients would improve treatment response. In this study, 138 obese PsA patients were divided into two groups of 69 patients each. One group received a hypocaloric diet and the controls followed a normal diet.

After 6 months, those who lost 10% of their BMI or more were almost five times more likely to achieve MDA (HR 4.79, P = .002). Those who lost 5%-10% of their BMI were twice as likely as were controls to reach MDA.

Dr. Ritchlin said that he had no relevant disclosures.

NEW YORK – Obesity appears to reduce response to anti–tumor necrosis factor–alpha treatment in individuals with psoriatic arthritis, but weight loss can improve it, according to a review of two studies by Dr. Christopher T. Ritchlin.

"These data convincingly show that if we talk to our patients and tell them to lose weight, it can have an impact on how their PsA [psoriatic arthritis] therapies are going to work," Dr. Ritchlin, director of the Translational Immunology Research Center at the University of Rochester (N.Y.), said at a meeting sponsored by New York University.

Dr. Ritchlin said these results fit in with previous epidemiologic studies that show that as body mass index goes up, so does the risk for both psoriasis and PsA (Arch. Intern. Med. 2009;167:1670-5 and Ann. Rheum. Dis. 2012;71:1273-7).

These data support a link between obesity-related chronic tissue inflammation and development of some rheumatic diseases, such as arthritis in psoriatic patients. These same inflammatory processes may also interfere with good clinical response to biologic agents.

In a study published by Dr. Matteo Nicola di Minno of Federico II University in Naples, Italy, and his colleagues, individuals with a BMI in the 30-35 kg/m² range with PsA had a nearly fourfold increased risk of not responding well to treatment with tumor necrosis factor–alpha inhibitors (TNFis). The risk of a poor response rose more than fivefold for those whose BMIs greater than 35 kg/m² (Arthritis Care Res. 2013;65:141-7).

The study prospectively followed PsA patients with active disease for 24 months who were starting TNFi therapy (30% adalimumab, 41% etanercept, 29% infliximab). The group comprised 135 obese patients (BMI greater than 30 kg/m²) and 135 controls of normal weight. The primary outcome was achievement of minimal disease activity (MDA), which meant they fulfilled five of seven outcome measures: one or fewer tender joints, one or fewer swollen joints, a score of 1 or less on the Psoriasis Area and Severity Index or body surface area = 3, a score of 15 or less on a visual analog scale (VAS) for pain, a score of 20 or less on a patient global disease severity VAS score, a score on the Health Assessment Questionnaire of 0.5 or less, or one or fewer tender entheseal points.

After 12 months, only 98 (36%) of the total group reached MDA. "What the results showed was that the odds of not achieving MDA were directly related to increased BMI," Dr. Ritchlin said.

Significantly more of the patients who did not achieve MDA were obese (64% vs. 25.5%, P less than .001). After adjustment for other variables, obesity was found to incur a nearly fivefold risk of poor response to therapy (hazard ratio 4.90, 95% confidence interval [CI] 3.04-7.87). The hazard ratios were 3.98 for those with BMI of 30-35 kg/m² and 5.4 for those with BMI greater than 35 kg/m² (both P less than .001). Among the 98 PsA patients who had achieved MDA by 12 months, those who were obese had a poor probability of sustaining MDA when tested at 24 months, according to Dr. di Minno.

In a follow-up study presented at the 2012 EULAR meeting (Ann. Rheum. Dis. 2012;71[Suppl. 3]:109), Dr. di Minno addressed the question of whether weight loss in obese PsA patients would improve treatment response. In this study, 138 obese PsA patients were divided into two groups of 69 patients each. One group received a hypocaloric diet and the controls followed a normal diet.

After 6 months, those who lost 10% of their BMI or more were almost five times more likely to achieve MDA (HR 4.79, P = .002). Those who lost 5%-10% of their BMI were twice as likely as were controls to reach MDA.

Dr. Ritchlin said that he had no relevant disclosures.

NEW YORK – Patients with rheumatoid arthritis had significantly greater aortic wall inflammation than did control patients with coronary artery disease but without autoimmune disease in an 18- fluorodeoxyglucose PET imaging study. No differences in carotid artery wall inflammation were found between the groups.

"These results suggest that part of the risk of cardiovascular disease in rheumatoid arthritis patients may not only be from systemic inflammation but truly localized inflammation that is causing plaques to become more vulnerable, less stable, and more likely to rupture," said Dr. Jeffrey D. Greenberg, who presented the results of the cross-sectional comparison at the NYU Seminar in Advanced Rheumatology, sponsored by New York University.

It has been known for some time that rheumatoid arthritis (RA) patients have systemic inflammation as well as vascular inflammation and have an increased risk of cardiovascular-related death, according to Dr. Greenberg, associate director of clinical translational sciences in the division of rheumatology at New York University Langone Medical Center and the NYU Hospital for Joint Diseases. He cited multifactorial mechanisms by which RA patients may incur heightened cardiovascular risk, including traditional cardiovascular risk factors (altered lipid balance, impaired insulin sensitivity), abnormal endothelial function, and increased plaque vulnerability. He said that the results of this study demonstrate another factor – localized inflammation causing subclinical vasculitis in the aorta and perhaps coronary vessels.

Dr. Greenberg and his associates used a 10 mCi injection of 18-fluorodeoxyglucose (18-FDG) and PET imaging in two separate cohorts of patients, one consisting of 27 RA patients (aged 35-64 years) and another of 70 controls with coronary artery disease but without autoimmune disease (aged 41-76 years). The investigators determined vascular 18-FDG uptake by calculating target to background ratios (TBRs) that served as proxies for macrophage activity and inflammation in the vessel walls.

RA patients had significantly higher TBR scores than did controls for the aorta mean TBR (1.46 vs. 1.25; P less than .0001), aorta maximum TBR (2.08 vs. 1.75; P less than .0001) and the TBR of the most diseased segment of aorta (2.23 vs. 1.87; P = .0004). These values were adjusted for differences in age, gender, and body mass index between the groups in multivariate regression models. RA patients had mean disease duration of about 11 years and mean DAS28 of 4.6, with no history of coronary artery disease, myocardial infarction, or stroke.

The results of the study were presented previously at the 2012 ACR Annual Meeting.

Dr. Greenberg serves as a consultant to the Consortium of Rheumatology Researchers of North America Inc. (CORRONA) and Pfizer and holds an ownership interest in CORRONA. He also receives grant support from the American College of Rheumatology, the Arthritis National Research Foundation, the Agency for Healthcare Research and Quality, the National Institute for Arthritis, and Musculoskeletal and Skin Diseases, and the NYU Clinical and Translational Science Institute.

NEW YORK – Patients with rheumatoid arthritis had significantly greater aortic wall inflammation than did control patients with coronary artery disease but without autoimmune disease in an 18- fluorodeoxyglucose PET imaging study. No differences in carotid artery wall inflammation were found between the groups.

"These results suggest that part of the risk of cardiovascular disease in rheumatoid arthritis patients may not only be from systemic inflammation but truly localized inflammation that is causing plaques to become more vulnerable, less stable, and more likely to rupture," said Dr. Jeffrey D. Greenberg, who presented the results of the cross-sectional comparison at the NYU Seminar in Advanced Rheumatology, sponsored by New York University.

It has been known for some time that rheumatoid arthritis (RA) patients have systemic inflammation as well as vascular inflammation and have an increased risk of cardiovascular-related death, according to Dr. Greenberg, associate director of clinical translational sciences in the division of rheumatology at New York University Langone Medical Center and the NYU Hospital for Joint Diseases. He cited multifactorial mechanisms by which RA patients may incur heightened cardiovascular risk, including traditional cardiovascular risk factors (altered lipid balance, impaired insulin sensitivity), abnormal endothelial function, and increased plaque vulnerability. He said that the results of this study demonstrate another factor – localized inflammation causing subclinical vasculitis in the aorta and perhaps coronary vessels.

Dr. Greenberg and his associates used a 10 mCi injection of 18-fluorodeoxyglucose (18-FDG) and PET imaging in two separate cohorts of patients, one consisting of 27 RA patients (aged 35-64 years) and another of 70 controls with coronary artery disease but without autoimmune disease (aged 41-76 years). The investigators determined vascular 18-FDG uptake by calculating target to background ratios (TBRs) that served as proxies for macrophage activity and inflammation in the vessel walls.

RA patients had significantly higher TBR scores than did controls for the aorta mean TBR (1.46 vs. 1.25; P less than .0001), aorta maximum TBR (2.08 vs. 1.75; P less than .0001) and the TBR of the most diseased segment of aorta (2.23 vs. 1.87; P = .0004). These values were adjusted for differences in age, gender, and body mass index between the groups in multivariate regression models. RA patients had mean disease duration of about 11 years and mean DAS28 of 4.6, with no history of coronary artery disease, myocardial infarction, or stroke.

The results of the study were presented previously at the 2012 ACR Annual Meeting.

Dr. Greenberg serves as a consultant to the Consortium of Rheumatology Researchers of North America Inc. (CORRONA) and Pfizer and holds an ownership interest in CORRONA. He also receives grant support from the American College of Rheumatology, the Arthritis National Research Foundation, the Agency for Healthcare Research and Quality, the National Institute for Arthritis, and Musculoskeletal and Skin Diseases, and the NYU Clinical and Translational Science Institute.

NEW YORK – Patients with rheumatoid arthritis had significantly greater aortic wall inflammation than did control patients with coronary artery disease but without autoimmune disease in an 18- fluorodeoxyglucose PET imaging study. No differences in carotid artery wall inflammation were found between the groups.

"These results suggest that part of the risk of cardiovascular disease in rheumatoid arthritis patients may not only be from systemic inflammation but truly localized inflammation that is causing plaques to become more vulnerable, less stable, and more likely to rupture," said Dr. Jeffrey D. Greenberg, who presented the results of the cross-sectional comparison at the NYU Seminar in Advanced Rheumatology, sponsored by New York University.

It has been known for some time that rheumatoid arthritis (RA) patients have systemic inflammation as well as vascular inflammation and have an increased risk of cardiovascular-related death, according to Dr. Greenberg, associate director of clinical translational sciences in the division of rheumatology at New York University Langone Medical Center and the NYU Hospital for Joint Diseases. He cited multifactorial mechanisms by which RA patients may incur heightened cardiovascular risk, including traditional cardiovascular risk factors (altered lipid balance, impaired insulin sensitivity), abnormal endothelial function, and increased plaque vulnerability. He said that the results of this study demonstrate another factor – localized inflammation causing subclinical vasculitis in the aorta and perhaps coronary vessels.

Dr. Greenberg and his associates used a 10 mCi injection of 18-fluorodeoxyglucose (18-FDG) and PET imaging in two separate cohorts of patients, one consisting of 27 RA patients (aged 35-64 years) and another of 70 controls with coronary artery disease but without autoimmune disease (aged 41-76 years). The investigators determined vascular 18-FDG uptake by calculating target to background ratios (TBRs) that served as proxies for macrophage activity and inflammation in the vessel walls.

RA patients had significantly higher TBR scores than did controls for the aorta mean TBR (1.46 vs. 1.25; P less than .0001), aorta maximum TBR (2.08 vs. 1.75; P less than .0001) and the TBR of the most diseased segment of aorta (2.23 vs. 1.87; P = .0004). These values were adjusted for differences in age, gender, and body mass index between the groups in multivariate regression models. RA patients had mean disease duration of about 11 years and mean DAS28 of 4.6, with no history of coronary artery disease, myocardial infarction, or stroke.

The results of the study were presented previously at the 2012 ACR Annual Meeting.

Dr. Greenberg serves as a consultant to the Consortium of Rheumatology Researchers of North America Inc. (CORRONA) and Pfizer and holds an ownership interest in CORRONA. He also receives grant support from the American College of Rheumatology, the Arthritis National Research Foundation, the Agency for Healthcare Research and Quality, the National Institute for Arthritis, and Musculoskeletal and Skin Diseases, and the NYU Clinical and Translational Science Institute.

NEW YORK – Delayed selective repair and the use of thoracic endovascular aortic surgery rather than urgent open procedures reduce mortality from blunt thoracic aortic injury, an analysis of 15 years of data has shown.

Thoracic aortic injury remains a leading cause of death following blunt trauma, second only to death from head injury. It is estimated that prehospital mortality is as high as 85%, said Dr. Anthony L. Estrera, a cardiothoracic and vascular surgeon at the University of Texas Medical School at Houston.

Between January 1997 and January 2012, more than 17,000 patients were entered into the University of Texas-Houston Trauma Center Registry. Of those, 327 (0.4%) were diagnosed with blunt thoracic aortic injury (BTAI). The overall mortality rate for these patients was 41% (135/327). Thirty-five percent (n = 114) died within 4 hours of admission, Dr. Estrera said at Aortic Symposium 2012.

Before 1999, open-clamp repair was performed in 20% of all operations. Distal aortic perfusion (DAP) with open repair was introduced in 1999, delayed selective repair in 2002, and thoracic endovascular aortic repair (TEVAR) in 2005. Delayed selective repair involves delaying intervention for traumatic aortic injury when other injuries, such as head injury or severe abdominal injuries, require immediate attention, Dr. Estrera explained in an interview.

During the 15-year study period, 56% (n = 184) underwent either open surgery (total bypass, 4%; open repair with visceral perfusion [open DAP], 42%; or open clamp, 16%), or TEVAR (39%).

Of those 184 patients, 27 (15%) died. The TEVAR mortality rate (4%) was significantly lower than that of the open-repair groups (open clamp, 31%; open DAP, 14%; total bypass, 57%, P less than .03). In fact, since 2005, TEVAR has been used for 71% of procedures, and the average annual mortality rate has dropped from 25%-40% to 0%-15%.

Urgent repair was associated with significantly more deaths than was delayed selective repair (22% [26/120] vs. 1.6% [1/64], P less than .02). Adjusting for injury severity score and calendar time, the investigators found that delayed repair resulted in a greater than 10-fold reduction in mortality compared with immediate open intervention (odds ratio, 0.07; P less than .02).

No deaths were noted in 4 of the last 6 years. Among open procedures, significantly better outcomes were seen with open DAP vs. open clamp (P less than .02) and with DAP vs. total bypass (P less than .05).

"We found that delayed selective repair was beneficial with open repair but not in conjunction with TEVAR. The benefit of delayed selective repair is likely related to allowing the patient time to recover from the initial traumatic insult before proceeding with another major insult, the open repair," Dr. Estrera said. "Delayed selective repair is considered for patients who present with severe head injury, infection (burn, sepsis, contaminated wounds), or multisystem trauma."

While surgical technique made a difference in mortality, no significant differences were found between groups with respect to complications. The three cases of paraplegia, which occurred only in the open-clamp group, did not have outcomes that were significantly different from outcomes in other groups. There was one case of stroke in the open-clamp group and two cases in the TEVAR group, but this also was not statistically significant.

As for durability of repair, Dr. Estrera noted that patients in the open-repair group have been followed for 6.2-15 years, and all-cause mortality data indicate that "if they survive beyond that first admission, they do pretty well." The available follow-up data for TEVAR is much shorter: up to 6 years with a mean of 2.5 years. "We don’t know what the long-term durability of these stent-grafts will be, especially in younger patients who may live for another 50 years," he said.

One problem with obtaining long-term survival data is that patients who survive BTAI can be very difficult to follow up. In their experience, Dr. Estrera said, compliance with TEVAR follow-up was only 32%, which may be attributed in part to patients being relatively young (median age, 32 years) and male (70%).

Dr. Estrera’s group is seeking ways to improve the diagnosis of BTAI. In a recent study, the diagnostic utility of computed tomography angiography (CTA) – the most commonly used screening test for BTAI – was compared with intravascular ultrasound (IVUS) or angiography (J. Vasc. Surg. 2011;53:608-14). Equivocal results were found to be more common with CTA images than with either IVUS or angiography (27% vs. 2.5% and 5%, respectively; overall P = .0002). Compared with angiography, IVUS changed the diagnosis in 13% of cases, identifying injuries in 11% and ruling them out in 2%. Angiography was found to be 38% as sensitive and 89% as specific as IVUS.

The symposium was sponsored by the American Association for Thoracic Surgery. Dr. Estrera had no relevant financial disclosures.

NEW YORK – Delayed selective repair and the use of thoracic endovascular aortic surgery rather than urgent open procedures reduce mortality from blunt thoracic aortic injury, an analysis of 15 years of data has shown.

Thoracic aortic injury remains a leading cause of death following blunt trauma, second only to death from head injury. It is estimated that prehospital mortality is as high as 85%, said Dr. Anthony L. Estrera, a cardiothoracic and vascular surgeon at the University of Texas Medical School at Houston.

Between January 1997 and January 2012, more than 17,000 patients were entered into the University of Texas-Houston Trauma Center Registry. Of those, 327 (0.4%) were diagnosed with blunt thoracic aortic injury (BTAI). The overall mortality rate for these patients was 41% (135/327). Thirty-five percent (n = 114) died within 4 hours of admission, Dr. Estrera said at Aortic Symposium 2012.

Before 1999, open-clamp repair was performed in 20% of all operations. Distal aortic perfusion (DAP) with open repair was introduced in 1999, delayed selective repair in 2002, and thoracic endovascular aortic repair (TEVAR) in 2005. Delayed selective repair involves delaying intervention for traumatic aortic injury when other injuries, such as head injury or severe abdominal injuries, require immediate attention, Dr. Estrera explained in an interview.

During the 15-year study period, 56% (n = 184) underwent either open surgery (total bypass, 4%; open repair with visceral perfusion [open DAP], 42%; or open clamp, 16%), or TEVAR (39%).

Of those 184 patients, 27 (15%) died. The TEVAR mortality rate (4%) was significantly lower than that of the open-repair groups (open clamp, 31%; open DAP, 14%; total bypass, 57%, P less than .03). In fact, since 2005, TEVAR has been used for 71% of procedures, and the average annual mortality rate has dropped from 25%-40% to 0%-15%.

Urgent repair was associated with significantly more deaths than was delayed selective repair (22% [26/120] vs. 1.6% [1/64], P less than .02). Adjusting for injury severity score and calendar time, the investigators found that delayed repair resulted in a greater than 10-fold reduction in mortality compared with immediate open intervention (odds ratio, 0.07; P less than .02).

No deaths were noted in 4 of the last 6 years. Among open procedures, significantly better outcomes were seen with open DAP vs. open clamp (P less than .02) and with DAP vs. total bypass (P less than .05).

"We found that delayed selective repair was beneficial with open repair but not in conjunction with TEVAR. The benefit of delayed selective repair is likely related to allowing the patient time to recover from the initial traumatic insult before proceeding with another major insult, the open repair," Dr. Estrera said. "Delayed selective repair is considered for patients who present with severe head injury, infection (burn, sepsis, contaminated wounds), or multisystem trauma."

While surgical technique made a difference in mortality, no significant differences were found between groups with respect to complications. The three cases of paraplegia, which occurred only in the open-clamp group, did not have outcomes that were significantly different from outcomes in other groups. There was one case of stroke in the open-clamp group and two cases in the TEVAR group, but this also was not statistically significant.

As for durability of repair, Dr. Estrera noted that patients in the open-repair group have been followed for 6.2-15 years, and all-cause mortality data indicate that "if they survive beyond that first admission, they do pretty well." The available follow-up data for TEVAR is much shorter: up to 6 years with a mean of 2.5 years. "We don’t know what the long-term durability of these stent-grafts will be, especially in younger patients who may live for another 50 years," he said.

One problem with obtaining long-term survival data is that patients who survive BTAI can be very difficult to follow up. In their experience, Dr. Estrera said, compliance with TEVAR follow-up was only 32%, which may be attributed in part to patients being relatively young (median age, 32 years) and male (70%).

Dr. Estrera’s group is seeking ways to improve the diagnosis of BTAI. In a recent study, the diagnostic utility of computed tomography angiography (CTA) – the most commonly used screening test for BTAI – was compared with intravascular ultrasound (IVUS) or angiography (J. Vasc. Surg. 2011;53:608-14). Equivocal results were found to be more common with CTA images than with either IVUS or angiography (27% vs. 2.5% and 5%, respectively; overall P = .0002). Compared with angiography, IVUS changed the diagnosis in 13% of cases, identifying injuries in 11% and ruling them out in 2%. Angiography was found to be 38% as sensitive and 89% as specific as IVUS.

The symposium was sponsored by the American Association for Thoracic Surgery. Dr. Estrera had no relevant financial disclosures.

NEW YORK – Delayed selective repair and the use of thoracic endovascular aortic surgery rather than urgent open procedures reduce mortality from blunt thoracic aortic injury, an analysis of 15 years of data has shown.

Thoracic aortic injury remains a leading cause of death following blunt trauma, second only to death from head injury. It is estimated that prehospital mortality is as high as 85%, said Dr. Anthony L. Estrera, a cardiothoracic and vascular surgeon at the University of Texas Medical School at Houston.

Between January 1997 and January 2012, more than 17,000 patients were entered into the University of Texas-Houston Trauma Center Registry. Of those, 327 (0.4%) were diagnosed with blunt thoracic aortic injury (BTAI). The overall mortality rate for these patients was 41% (135/327). Thirty-five percent (n = 114) died within 4 hours of admission, Dr. Estrera said at Aortic Symposium 2012.

Before 1999, open-clamp repair was performed in 20% of all operations. Distal aortic perfusion (DAP) with open repair was introduced in 1999, delayed selective repair in 2002, and thoracic endovascular aortic repair (TEVAR) in 2005. Delayed selective repair involves delaying intervention for traumatic aortic injury when other injuries, such as head injury or severe abdominal injuries, require immediate attention, Dr. Estrera explained in an interview.

During the 15-year study period, 56% (n = 184) underwent either open surgery (total bypass, 4%; open repair with visceral perfusion [open DAP], 42%; or open clamp, 16%), or TEVAR (39%).

Of those 184 patients, 27 (15%) died. The TEVAR mortality rate (4%) was significantly lower than that of the open-repair groups (open clamp, 31%; open DAP, 14%; total bypass, 57%, P less than .03). In fact, since 2005, TEVAR has been used for 71% of procedures, and the average annual mortality rate has dropped from 25%-40% to 0%-15%.

Urgent repair was associated with significantly more deaths than was delayed selective repair (22% [26/120] vs. 1.6% [1/64], P less than .02). Adjusting for injury severity score and calendar time, the investigators found that delayed repair resulted in a greater than 10-fold reduction in mortality compared with immediate open intervention (odds ratio, 0.07; P less than .02).

No deaths were noted in 4 of the last 6 years. Among open procedures, significantly better outcomes were seen with open DAP vs. open clamp (P less than .02) and with DAP vs. total bypass (P less than .05).

"We found that delayed selective repair was beneficial with open repair but not in conjunction with TEVAR. The benefit of delayed selective repair is likely related to allowing the patient time to recover from the initial traumatic insult before proceeding with another major insult, the open repair," Dr. Estrera said. "Delayed selective repair is considered for patients who present with severe head injury, infection (burn, sepsis, contaminated wounds), or multisystem trauma."

While surgical technique made a difference in mortality, no significant differences were found between groups with respect to complications. The three cases of paraplegia, which occurred only in the open-clamp group, did not have outcomes that were significantly different from outcomes in other groups. There was one case of stroke in the open-clamp group and two cases in the TEVAR group, but this also was not statistically significant.

As for durability of repair, Dr. Estrera noted that patients in the open-repair group have been followed for 6.2-15 years, and all-cause mortality data indicate that "if they survive beyond that first admission, they do pretty well." The available follow-up data for TEVAR is much shorter: up to 6 years with a mean of 2.5 years. "We don’t know what the long-term durability of these stent-grafts will be, especially in younger patients who may live for another 50 years," he said.

One problem with obtaining long-term survival data is that patients who survive BTAI can be very difficult to follow up. In their experience, Dr. Estrera said, compliance with TEVAR follow-up was only 32%, which may be attributed in part to patients being relatively young (median age, 32 years) and male (70%).

Dr. Estrera’s group is seeking ways to improve the diagnosis of BTAI. In a recent study, the diagnostic utility of computed tomography angiography (CTA) – the most commonly used screening test for BTAI – was compared with intravascular ultrasound (IVUS) or angiography (J. Vasc. Surg. 2011;53:608-14). Equivocal results were found to be more common with CTA images than with either IVUS or angiography (27% vs. 2.5% and 5%, respectively; overall P = .0002). Compared with angiography, IVUS changed the diagnosis in 13% of cases, identifying injuries in 11% and ruling them out in 2%. Angiography was found to be 38% as sensitive and 89% as specific as IVUS.

The symposium was sponsored by the American Association for Thoracic Surgery. Dr. Estrera had no relevant financial disclosures.

NEW YORK – Handy mnemonic devices can help predict vaccine response in patients taking biologics for rheumatoid arthritis, according to Dr. Daniel E. Furst.

Vaccinating patients taking biologic agents for rheumatoid arthritis is tricky. The effects of both the vaccine and biologic can be T-cell dependent or independent, or sometimes both, and when the mechanisms match, the vaccine’s response will likely be attenuated, he said at a rheumatology meeting sponsored by New York University.

Think ‘PITH’ – (Human) Papillomavirus, Influenza A/B, Tetanus, and Hepatitis B – to remember which vaccines have protein-based antigens and are T-cell dependent, said Dr. Furst, a rheumatology professor at the University of California in Los Angeles.

For vaccines that have carbohydrate-based antigens, which are largely T-cell independent (B-cell dependent), remember ‘PHIM’: Pneumococcus, H. influenzae B, Influenza A/B, and Meningococcus.

Biologic agents that affect T-cells include methotrexate, the TNF inhibitors, abatacept, and tocilizumab. As a general rule, biologics that affect T-cells decrease one’s response to T-cell dependent vaccines. For example, etanercept has been shown to decrease by as much as half, as well as delay the response to, the hepatitis B vaccine in both normal controls and patients with RA.

In normal volunteers abatacept blunted the response to tetanus vaccine given 2 weeks later by about 50% and given 8 weeks later by about 20%, compared to normal controls (Arthritis Res. Ther. 2007;9:R38).

Likewise, tocilizumab has been shown to reduce the response to the influenza vaccine by about 15%, according to a study presented at EULAR 2007 in Barcelona.

B-cell dependent vaccine responses are diminished by B-cell directed therapy. For example, the SIERRA study of pneumococcal vaccination in rituximab-treated patients showed that, compared to methotrexate alone, a combination of rituximab plus methotrexate decreased the response to the vaccination at 4 weeks by 30% to 60% (Arthritis Rheum. 2010;62:64-74). "That’s just what we would expect," Dr. Furst noted.

It is important to note that biologics that affect T-cell independent mechanisms (B-cell directed therapy), such as rituximab, will not usually affect T-cell mediated vaccine responses. For example, rituximab does not change the response to tetanus toxoid, said Dr. Furst. Similarly, T-cell dependent biologics will not affect T-cell independent vaccinations, citing as an example the lack of effect of adalimumab on the response to the pneumococcal vaccine, according to a paper presented at EULAR in 2006.

The influenza A/B vaccine is an exception to the rule, because it first requires an early B-cell response followed by a T-cell response.

Dr. Furst recommends avoiding live attenuated virus vaccines in patients on biologics or immunosuppressive agents. Vaccines that are likely to be affected include those for varicella/zoster, intranasal influenza/H1N1, measles/mumps/rubella (MMR), yellow fever, oral polio, typhoid (Ty21a oral), vaccinia (smallpox), the BCG vaccine for tuberculosis, and rotavirus. Live viruses can result in disseminated disease in such patients, he said. Ideally patients should be immunized with these vaccines as needed before starting a biologic or any other immunosuppressive therapy.

Dr. Furst is the recipient of research funding/consultant/advisory board member of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor Ortho Biotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Handy mnemonic devices can help predict vaccine response in patients taking biologics for rheumatoid arthritis, according to Dr. Daniel E. Furst.

Vaccinating patients taking biologic agents for rheumatoid arthritis is tricky. The effects of both the vaccine and biologic can be T-cell dependent or independent, or sometimes both, and when the mechanisms match, the vaccine’s response will likely be attenuated, he said at a rheumatology meeting sponsored by New York University.

Think ‘PITH’ – (Human) Papillomavirus, Influenza A/B, Tetanus, and Hepatitis B – to remember which vaccines have protein-based antigens and are T-cell dependent, said Dr. Furst, a rheumatology professor at the University of California in Los Angeles.

For vaccines that have carbohydrate-based antigens, which are largely T-cell independent (B-cell dependent), remember ‘PHIM’: Pneumococcus, H. influenzae B, Influenza A/B, and Meningococcus.

Biologic agents that affect T-cells include methotrexate, the TNF inhibitors, abatacept, and tocilizumab. As a general rule, biologics that affect T-cells decrease one’s response to T-cell dependent vaccines. For example, etanercept has been shown to decrease by as much as half, as well as delay the response to, the hepatitis B vaccine in both normal controls and patients with RA.

In normal volunteers abatacept blunted the response to tetanus vaccine given 2 weeks later by about 50% and given 8 weeks later by about 20%, compared to normal controls (Arthritis Res. Ther. 2007;9:R38).

Likewise, tocilizumab has been shown to reduce the response to the influenza vaccine by about 15%, according to a study presented at EULAR 2007 in Barcelona.

B-cell dependent vaccine responses are diminished by B-cell directed therapy. For example, the SIERRA study of pneumococcal vaccination in rituximab-treated patients showed that, compared to methotrexate alone, a combination of rituximab plus methotrexate decreased the response to the vaccination at 4 weeks by 30% to 60% (Arthritis Rheum. 2010;62:64-74). "That’s just what we would expect," Dr. Furst noted.

It is important to note that biologics that affect T-cell independent mechanisms (B-cell directed therapy), such as rituximab, will not usually affect T-cell mediated vaccine responses. For example, rituximab does not change the response to tetanus toxoid, said Dr. Furst. Similarly, T-cell dependent biologics will not affect T-cell independent vaccinations, citing as an example the lack of effect of adalimumab on the response to the pneumococcal vaccine, according to a paper presented at EULAR in 2006.

The influenza A/B vaccine is an exception to the rule, because it first requires an early B-cell response followed by a T-cell response.

Dr. Furst recommends avoiding live attenuated virus vaccines in patients on biologics or immunosuppressive agents. Vaccines that are likely to be affected include those for varicella/zoster, intranasal influenza/H1N1, measles/mumps/rubella (MMR), yellow fever, oral polio, typhoid (Ty21a oral), vaccinia (smallpox), the BCG vaccine for tuberculosis, and rotavirus. Live viruses can result in disseminated disease in such patients, he said. Ideally patients should be immunized with these vaccines as needed before starting a biologic or any other immunosuppressive therapy.

Dr. Furst is the recipient of research funding/consultant/advisory board member of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor Ortho Biotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Handy mnemonic devices can help predict vaccine response in patients taking biologics for rheumatoid arthritis, according to Dr. Daniel E. Furst.

Vaccinating patients taking biologic agents for rheumatoid arthritis is tricky. The effects of both the vaccine and biologic can be T-cell dependent or independent, or sometimes both, and when the mechanisms match, the vaccine’s response will likely be attenuated, he said at a rheumatology meeting sponsored by New York University.

Think ‘PITH’ – (Human) Papillomavirus, Influenza A/B, Tetanus, and Hepatitis B – to remember which vaccines have protein-based antigens and are T-cell dependent, said Dr. Furst, a rheumatology professor at the University of California in Los Angeles.

For vaccines that have carbohydrate-based antigens, which are largely T-cell independent (B-cell dependent), remember ‘PHIM’: Pneumococcus, H. influenzae B, Influenza A/B, and Meningococcus.

Biologic agents that affect T-cells include methotrexate, the TNF inhibitors, abatacept, and tocilizumab. As a general rule, biologics that affect T-cells decrease one’s response to T-cell dependent vaccines. For example, etanercept has been shown to decrease by as much as half, as well as delay the response to, the hepatitis B vaccine in both normal controls and patients with RA.

In normal volunteers abatacept blunted the response to tetanus vaccine given 2 weeks later by about 50% and given 8 weeks later by about 20%, compared to normal controls (Arthritis Res. Ther. 2007;9:R38).

Likewise, tocilizumab has been shown to reduce the response to the influenza vaccine by about 15%, according to a study presented at EULAR 2007 in Barcelona.

B-cell dependent vaccine responses are diminished by B-cell directed therapy. For example, the SIERRA study of pneumococcal vaccination in rituximab-treated patients showed that, compared to methotrexate alone, a combination of rituximab plus methotrexate decreased the response to the vaccination at 4 weeks by 30% to 60% (Arthritis Rheum. 2010;62:64-74). "That’s just what we would expect," Dr. Furst noted.

It is important to note that biologics that affect T-cell independent mechanisms (B-cell directed therapy), such as rituximab, will not usually affect T-cell mediated vaccine responses. For example, rituximab does not change the response to tetanus toxoid, said Dr. Furst. Similarly, T-cell dependent biologics will not affect T-cell independent vaccinations, citing as an example the lack of effect of adalimumab on the response to the pneumococcal vaccine, according to a paper presented at EULAR in 2006.

The influenza A/B vaccine is an exception to the rule, because it first requires an early B-cell response followed by a T-cell response.

Dr. Furst recommends avoiding live attenuated virus vaccines in patients on biologics or immunosuppressive agents. Vaccines that are likely to be affected include those for varicella/zoster, intranasal influenza/H1N1, measles/mumps/rubella (MMR), yellow fever, oral polio, typhoid (Ty21a oral), vaccinia (smallpox), the BCG vaccine for tuberculosis, and rotavirus. Live viruses can result in disseminated disease in such patients, he said. Ideally patients should be immunized with these vaccines as needed before starting a biologic or any other immunosuppressive therapy.

Dr. Furst is the recipient of research funding/consultant/advisory board member of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor Ortho Biotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Musculoskeletal ultrasound is emerging as a technique for early detection of gout and rheumatoid arthritis, Dr. Jonathan Samuels said in a discussion that included a review of recent studies published by other researchers.

To its advantage, musculoskeletal ultrasound (US) is noninvasive, painless, and does not require exposure to radiation or contrast material. Dynamic assessment allows multiple joints to be viewed quickly during one sitting. Compared with MRI, musculoskeletal ultrasound is less costly, does not require the patient to lie still for prolonged periods, and is suitable for the claustrophobic patient, said Dr. Samuels, a rheumatologist at NYU Langone Medical Center, at a rheumatology meeting sponsored by New York University.

According to the American College of Rheumatology Musculoskeletal Ultrasound Task Force, "a future for US in American rheumatology seems certain. The improved clinical assessments and patient outcomes arising from the use of US should augment American rheumatology practice." (Arthritis Care Res. 2010;62:1206-19).

Yet, not many rheumatologists have incorporated musculoskeletal ultrasound into their practices. When Dr. Samuels surveyed the meeting attendees, roughly 50% indicated by a show of hands that they had taken a course in musculoskeletal ultrasound and 75% said it should become a standard clinical tool – but only 10% said they routinely used ultrasound.

One reason may be that learning opportunities are relatively sparse, and credentialing has not yet been standardized. While most European rheumatology fellowships include training in musculoskeletal ultrasound, such training is not standard or required in the United States. The UltraSound School of North American Rheumatologists (USSONAR) provides a suggested curriculum and on-line teaching and guidance, mostly for fellows and attendings interested in teaching ultrasound. It also offers an annual competency exam. The ACR began offering intensive, 2-day introductory training courses in 2010, providing the fundamentals of musculoskeletal US for rheumatologists who want to integrate ultrasound into their practices. New this year is a 3-day intermediate course for rheumatologists who have performed 60-100 scans within the past 2 years and have taken at least one beginner-level course.

The American Institute of Ultrasound in Medicine (AIUM) released Training Guidelines for the Performance of Musculoskeletal Ultrasound Examinations, but the ACR has not fully accepted the guidelines. There is currently no official certification process for musculoskeletal ultrasound, but that may be about to change. In February 2012, the ACR voted to develop and take ownership of a certification exam.

Dr. Samuels summarized two of the studies that suggest musculoskeletal ultrasound may allow early detection and treatment of subclinical rheumatoid arthritis and gout.

In a study from the Diakonhjemmet Hospital in Oslo (Norway) (Ann. Rheum. Dis. 2011;70:176-9), patients with baseline wrist synovitis as detected with ultrasound were twice as likely to develop erosions at 12 months, while the risk was only 28% for those with baseline MRI marrow edema.

Musculoskeletal ultrasound also was successfully used to detect monosodium urate deposits in gout patients and in patients with asymptomatic hyperuricemia in a nonrandomized prospective cohort study of 50 men. Early detection of uric acid deposits could permit early therapeutic intervention, possibly preventing future tophi and erosions.

For the study, 50 men aged 55-85 years were consecutively recruited during routine primary care visits to the Department of Veterans Affairs (Arthritis Care Res. 2011;63:1456-62). Exclusion criteria included current or prior history of inflammatory arthritis other than gout, asymptomatic chondrocalcinosis of the knee, total knee replacement, and history of severe knee trauma. Subjects were assessed for gout using ACR clinical criteria and serum uric acid levels measurement.

Subjects underwent musculoskeletal ultrasound of the knees and first metatarsophalangeal joints. Images were read by two blinded rheumatologists, who looked for such characteristic findings as the "double contour" sign (a hyperechoic band) over the femoral articular cartilage of the knees and tophi (heterogenous material often surrounded by a small anechoic rim).

Deposits were found in 7 of 14 gout patients, 5 of 17 with asymptomatic hyperuricemia. and 1 of 19 controls. Most of those with asymptomatic hyperuricemia and deposits met none of the ACR gout criteria. Even in those who met several of the gout criteria, there was no association between the number of ACR criteria met and level of deposits.

Serum uric acid measures did not differentiate subjects with asymptomatic hyperuricemia (mean of 8.0 mg/dL) from those with gout (mean of 8.1 mg/dL). The mean value in controls was 5.5 mg/dL.

The presence of deposits was associated with higher uric acid levels in the gout patients, at 9.4 mg/ dL for the seven patients with crystal deposits and 6.9 mg/ dL for the seven without deposits. Mean serum uric acid level did not differ in asymptomatic hyperuricemia subjects with and without deposits.

Within the 14 gout patients, less crystal deposition was seen in the subgroup of 8 patients on therapy. None of the asymptomatic hyperuricemia patients were being treated, but it would seem plausible that therapy would reduce the risk of deposits based on data observed in the gout group.

Dr. Samuels said he has no disclosures.

NEW YORK – Musculoskeletal ultrasound is emerging as a technique for early detection of gout and rheumatoid arthritis, Dr. Jonathan Samuels said in a discussion that included a review of recent studies published by other researchers.

To its advantage, musculoskeletal ultrasound (US) is noninvasive, painless, and does not require exposure to radiation or contrast material. Dynamic assessment allows multiple joints to be viewed quickly during one sitting. Compared with MRI, musculoskeletal ultrasound is less costly, does not require the patient to lie still for prolonged periods, and is suitable for the claustrophobic patient, said Dr. Samuels, a rheumatologist at NYU Langone Medical Center, at a rheumatology meeting sponsored by New York University.

According to the American College of Rheumatology Musculoskeletal Ultrasound Task Force, "a future for US in American rheumatology seems certain. The improved clinical assessments and patient outcomes arising from the use of US should augment American rheumatology practice." (Arthritis Care Res. 2010;62:1206-19).

Yet, not many rheumatologists have incorporated musculoskeletal ultrasound into their practices. When Dr. Samuels surveyed the meeting attendees, roughly 50% indicated by a show of hands that they had taken a course in musculoskeletal ultrasound and 75% said it should become a standard clinical tool – but only 10% said they routinely used ultrasound.

One reason may be that learning opportunities are relatively sparse, and credentialing has not yet been standardized. While most European rheumatology fellowships include training in musculoskeletal ultrasound, such training is not standard or required in the United States. The UltraSound School of North American Rheumatologists (USSONAR) provides a suggested curriculum and on-line teaching and guidance, mostly for fellows and attendings interested in teaching ultrasound. It also offers an annual competency exam. The ACR began offering intensive, 2-day introductory training courses in 2010, providing the fundamentals of musculoskeletal US for rheumatologists who want to integrate ultrasound into their practices. New this year is a 3-day intermediate course for rheumatologists who have performed 60-100 scans within the past 2 years and have taken at least one beginner-level course.

The American Institute of Ultrasound in Medicine (AIUM) released Training Guidelines for the Performance of Musculoskeletal Ultrasound Examinations, but the ACR has not fully accepted the guidelines. There is currently no official certification process for musculoskeletal ultrasound, but that may be about to change. In February 2012, the ACR voted to develop and take ownership of a certification exam.

Dr. Samuels summarized two of the studies that suggest musculoskeletal ultrasound may allow early detection and treatment of subclinical rheumatoid arthritis and gout.

In a study from the Diakonhjemmet Hospital in Oslo (Norway) (Ann. Rheum. Dis. 2011;70:176-9), patients with baseline wrist synovitis as detected with ultrasound were twice as likely to develop erosions at 12 months, while the risk was only 28% for those with baseline MRI marrow edema.

Musculoskeletal ultrasound also was successfully used to detect monosodium urate deposits in gout patients and in patients with asymptomatic hyperuricemia in a nonrandomized prospective cohort study of 50 men. Early detection of uric acid deposits could permit early therapeutic intervention, possibly preventing future tophi and erosions.

For the study, 50 men aged 55-85 years were consecutively recruited during routine primary care visits to the Department of Veterans Affairs (Arthritis Care Res. 2011;63:1456-62). Exclusion criteria included current or prior history of inflammatory arthritis other than gout, asymptomatic chondrocalcinosis of the knee, total knee replacement, and history of severe knee trauma. Subjects were assessed for gout using ACR clinical criteria and serum uric acid levels measurement.

Subjects underwent musculoskeletal ultrasound of the knees and first metatarsophalangeal joints. Images were read by two blinded rheumatologists, who looked for such characteristic findings as the "double contour" sign (a hyperechoic band) over the femoral articular cartilage of the knees and tophi (heterogenous material often surrounded by a small anechoic rim).

Deposits were found in 7 of 14 gout patients, 5 of 17 with asymptomatic hyperuricemia. and 1 of 19 controls. Most of those with asymptomatic hyperuricemia and deposits met none of the ACR gout criteria. Even in those who met several of the gout criteria, there was no association between the number of ACR criteria met and level of deposits.

Serum uric acid measures did not differentiate subjects with asymptomatic hyperuricemia (mean of 8.0 mg/dL) from those with gout (mean of 8.1 mg/dL). The mean value in controls was 5.5 mg/dL.

The presence of deposits was associated with higher uric acid levels in the gout patients, at 9.4 mg/ dL for the seven patients with crystal deposits and 6.9 mg/ dL for the seven without deposits. Mean serum uric acid level did not differ in asymptomatic hyperuricemia subjects with and without deposits.

Within the 14 gout patients, less crystal deposition was seen in the subgroup of 8 patients on therapy. None of the asymptomatic hyperuricemia patients were being treated, but it would seem plausible that therapy would reduce the risk of deposits based on data observed in the gout group.

Dr. Samuels said he has no disclosures.

NEW YORK – Musculoskeletal ultrasound is emerging as a technique for early detection of gout and rheumatoid arthritis, Dr. Jonathan Samuels said in a discussion that included a review of recent studies published by other researchers.

To its advantage, musculoskeletal ultrasound (US) is noninvasive, painless, and does not require exposure to radiation or contrast material. Dynamic assessment allows multiple joints to be viewed quickly during one sitting. Compared with MRI, musculoskeletal ultrasound is less costly, does not require the patient to lie still for prolonged periods, and is suitable for the claustrophobic patient, said Dr. Samuels, a rheumatologist at NYU Langone Medical Center, at a rheumatology meeting sponsored by New York University.

According to the American College of Rheumatology Musculoskeletal Ultrasound Task Force, "a future for US in American rheumatology seems certain. The improved clinical assessments and patient outcomes arising from the use of US should augment American rheumatology practice." (Arthritis Care Res. 2010;62:1206-19).

Yet, not many rheumatologists have incorporated musculoskeletal ultrasound into their practices. When Dr. Samuels surveyed the meeting attendees, roughly 50% indicated by a show of hands that they had taken a course in musculoskeletal ultrasound and 75% said it should become a standard clinical tool – but only 10% said they routinely used ultrasound.

One reason may be that learning opportunities are relatively sparse, and credentialing has not yet been standardized. While most European rheumatology fellowships include training in musculoskeletal ultrasound, such training is not standard or required in the United States. The UltraSound School of North American Rheumatologists (USSONAR) provides a suggested curriculum and on-line teaching and guidance, mostly for fellows and attendings interested in teaching ultrasound. It also offers an annual competency exam. The ACR began offering intensive, 2-day introductory training courses in 2010, providing the fundamentals of musculoskeletal US for rheumatologists who want to integrate ultrasound into their practices. New this year is a 3-day intermediate course for rheumatologists who have performed 60-100 scans within the past 2 years and have taken at least one beginner-level course.

The American Institute of Ultrasound in Medicine (AIUM) released Training Guidelines for the Performance of Musculoskeletal Ultrasound Examinations, but the ACR has not fully accepted the guidelines. There is currently no official certification process for musculoskeletal ultrasound, but that may be about to change. In February 2012, the ACR voted to develop and take ownership of a certification exam.

Dr. Samuels summarized two of the studies that suggest musculoskeletal ultrasound may allow early detection and treatment of subclinical rheumatoid arthritis and gout.

In a study from the Diakonhjemmet Hospital in Oslo (Norway) (Ann. Rheum. Dis. 2011;70:176-9), patients with baseline wrist synovitis as detected with ultrasound were twice as likely to develop erosions at 12 months, while the risk was only 28% for those with baseline MRI marrow edema.

Musculoskeletal ultrasound also was successfully used to detect monosodium urate deposits in gout patients and in patients with asymptomatic hyperuricemia in a nonrandomized prospective cohort study of 50 men. Early detection of uric acid deposits could permit early therapeutic intervention, possibly preventing future tophi and erosions.

For the study, 50 men aged 55-85 years were consecutively recruited during routine primary care visits to the Department of Veterans Affairs (Arthritis Care Res. 2011;63:1456-62). Exclusion criteria included current or prior history of inflammatory arthritis other than gout, asymptomatic chondrocalcinosis of the knee, total knee replacement, and history of severe knee trauma. Subjects were assessed for gout using ACR clinical criteria and serum uric acid levels measurement.

Subjects underwent musculoskeletal ultrasound of the knees and first metatarsophalangeal joints. Images were read by two blinded rheumatologists, who looked for such characteristic findings as the "double contour" sign (a hyperechoic band) over the femoral articular cartilage of the knees and tophi (heterogenous material often surrounded by a small anechoic rim).

Deposits were found in 7 of 14 gout patients, 5 of 17 with asymptomatic hyperuricemia. and 1 of 19 controls. Most of those with asymptomatic hyperuricemia and deposits met none of the ACR gout criteria. Even in those who met several of the gout criteria, there was no association between the number of ACR criteria met and level of deposits.

Serum uric acid measures did not differentiate subjects with asymptomatic hyperuricemia (mean of 8.0 mg/dL) from those with gout (mean of 8.1 mg/dL). The mean value in controls was 5.5 mg/dL.

The presence of deposits was associated with higher uric acid levels in the gout patients, at 9.4 mg/ dL for the seven patients with crystal deposits and 6.9 mg/ dL for the seven without deposits. Mean serum uric acid level did not differ in asymptomatic hyperuricemia subjects with and without deposits.

Within the 14 gout patients, less crystal deposition was seen in the subgroup of 8 patients on therapy. None of the asymptomatic hyperuricemia patients were being treated, but it would seem plausible that therapy would reduce the risk of deposits based on data observed in the gout group.

Dr. Samuels said he has no disclosures.

NEW YORK – Abatacept may be helpful for treating rheumatoid arthritis in patients with concurrent hepatitis B, as long as patients are also given antiviral prophylaxis to prevent reactivation of their infection, according to the results of a small retrospective study presented at a rheumatology meeting sponsored by New York University.

"RA therapy in hepatitis B patients is complex. Flare of disease following immunosuppression is the primary concern. The major risk of hepatitis B comes not during but following immunosuppression, where reactivation can lead to severe, even fatal, hepatitis," said Dr. Daniel Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.

In this study, 5 women and 3 men with RA were treated with abatacept and followed for a mean of 18 months. At baseline, all were positive for hepatitis B, as indicated by the presence of hepatitis B surface antigen (HBsAg), hepatitis B virus DNA greater than 20,000 IU/mL, or intermittently positive AST/ALT on liver biopsy. Six patients tested negative for hepatitis C. All patients had used disease-modifying antirheumatic drugs (DMARDs) previously, and 3 had previously used a biologic agent. At baseline, the mean DAS 28 (Disease Activity Score 28) was 5.

When abatacept treatment was initiated, four of the eight patients were already on antiviral therapy, with three patients on entecavir and one on tenofavir.

A statistically significant decrease in DAS 28 scores was seen in patients treated with abatacept plus an antiviral, compared with those not treated with the antiviral. The statistical differences developed slowly and became noticeable after 10-12 months of treatment; the response continued through the 18 months of follow-up. DAS 28 scores remained stable but did not improve in those treated with abatacept but not with an antiviral.

All four patients who did not receive antiviral prophylaxis had a reactivation of hepatitis B, as indicated by a more than 10-fold increase in hepatitis B virus DNA. In contrast, none of those who took antiviral medications had reactivation.

"There may be a place for abatacept when treating RA patients with hepatitis B. It must be used with background antiviral therapy and used continuously for a number of months. We are now doing a prospective, double-blind study," said Dr. Furst in discussing the recently published findings (Arthritis Care Res. 2012 March 5 [doi: 10.1002/acr.21654]).

As far as the use of other biologics, rituximab is probably contraindicated in patients with a history of hepatitis B, suggested Dr. Furst. Although there are not a lot of data to support this contraindication, the results of one study (J. Clin. Oncol. 2009;27:605-11) demonstrated reactivation of hepatitis B virus in 25% of lymphoma patients treated with rituximab plus cyclophosphamide, hydroxydoxorubicin, Oncovin (vincristine), and prednisone (CHOP), compared with no reactivation in those receiving CHOP alone, he said.

Dr. Furst said that he is reluctant to use tumor necrosis factor (TNF) inhibitors for RA patients with a history of hepatitis B. He said that he makes an exception in cases where hepatitis B is controlled, such as in patients who are negative for hepatitis B virus DNA.

Dr. Furst presented a literature review that identified 9 cases of hepatitis B reactivation in patients treated with TNF inhibitors, including 5 cases of severe illness. On the other hand, in a retrospective analysis of 67 HbsAg-positive patients, none of the patients experienced HBV activation. "I think the idea that TNF inhibitors will cause problems afterwards makes sense. I think they are tricky to use in patients with hepatitis B."

According to the World Health Organization, about 2 billion people worldwide have been infected with the hepatitis B virus, 350 million live with chronic infection, and 600,000 die each year due to the acute or chronic consequences of hepatitis B, such as liver cancer or cirrhosis. In Southeast Asia, 8%-10% of adults are chronically infected.

According to Dr. Furst, after exposure to the hepatitis B virus, 70% of people will develop acute hepatitis B but will remain asymptomatic. About 30% will have clinical symptoms, and 0.5%-1% will progress to fulminant hepatitis. Chronic infection occurs in 5%. "This means you probably have a good number of patients with some hepatitis B in their backgrounds. If you see many patients from Asia or South America, one really must screen for hepatitis B before starting the patient on biologics," he said.

Dr. Furst has received research funding from, been a consultant to, or served on the advisory boards of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor OrthoBiotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Abatacept may be helpful for treating rheumatoid arthritis in patients with concurrent hepatitis B, as long as patients are also given antiviral prophylaxis to prevent reactivation of their infection, according to the results of a small retrospective study presented at a rheumatology meeting sponsored by New York University.

"RA therapy in hepatitis B patients is complex. Flare of disease following immunosuppression is the primary concern. The major risk of hepatitis B comes not during but following immunosuppression, where reactivation can lead to severe, even fatal, hepatitis," said Dr. Daniel Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.

In this study, 5 women and 3 men with RA were treated with abatacept and followed for a mean of 18 months. At baseline, all were positive for hepatitis B, as indicated by the presence of hepatitis B surface antigen (HBsAg), hepatitis B virus DNA greater than 20,000 IU/mL, or intermittently positive AST/ALT on liver biopsy. Six patients tested negative for hepatitis C. All patients had used disease-modifying antirheumatic drugs (DMARDs) previously, and 3 had previously used a biologic agent. At baseline, the mean DAS 28 (Disease Activity Score 28) was 5.

When abatacept treatment was initiated, four of the eight patients were already on antiviral therapy, with three patients on entecavir and one on tenofavir.

A statistically significant decrease in DAS 28 scores was seen in patients treated with abatacept plus an antiviral, compared with those not treated with the antiviral. The statistical differences developed slowly and became noticeable after 10-12 months of treatment; the response continued through the 18 months of follow-up. DAS 28 scores remained stable but did not improve in those treated with abatacept but not with an antiviral.

All four patients who did not receive antiviral prophylaxis had a reactivation of hepatitis B, as indicated by a more than 10-fold increase in hepatitis B virus DNA. In contrast, none of those who took antiviral medications had reactivation.

"There may be a place for abatacept when treating RA patients with hepatitis B. It must be used with background antiviral therapy and used continuously for a number of months. We are now doing a prospective, double-blind study," said Dr. Furst in discussing the recently published findings (Arthritis Care Res. 2012 March 5 [doi: 10.1002/acr.21654]).

As far as the use of other biologics, rituximab is probably contraindicated in patients with a history of hepatitis B, suggested Dr. Furst. Although there are not a lot of data to support this contraindication, the results of one study (J. Clin. Oncol. 2009;27:605-11) demonstrated reactivation of hepatitis B virus in 25% of lymphoma patients treated with rituximab plus cyclophosphamide, hydroxydoxorubicin, Oncovin (vincristine), and prednisone (CHOP), compared with no reactivation in those receiving CHOP alone, he said.

Dr. Furst said that he is reluctant to use tumor necrosis factor (TNF) inhibitors for RA patients with a history of hepatitis B. He said that he makes an exception in cases where hepatitis B is controlled, such as in patients who are negative for hepatitis B virus DNA.

Dr. Furst presented a literature review that identified 9 cases of hepatitis B reactivation in patients treated with TNF inhibitors, including 5 cases of severe illness. On the other hand, in a retrospective analysis of 67 HbsAg-positive patients, none of the patients experienced HBV activation. "I think the idea that TNF inhibitors will cause problems afterwards makes sense. I think they are tricky to use in patients with hepatitis B."

According to the World Health Organization, about 2 billion people worldwide have been infected with the hepatitis B virus, 350 million live with chronic infection, and 600,000 die each year due to the acute or chronic consequences of hepatitis B, such as liver cancer or cirrhosis. In Southeast Asia, 8%-10% of adults are chronically infected.

According to Dr. Furst, after exposure to the hepatitis B virus, 70% of people will develop acute hepatitis B but will remain asymptomatic. About 30% will have clinical symptoms, and 0.5%-1% will progress to fulminant hepatitis. Chronic infection occurs in 5%. "This means you probably have a good number of patients with some hepatitis B in their backgrounds. If you see many patients from Asia or South America, one really must screen for hepatitis B before starting the patient on biologics," he said.

Dr. Furst has received research funding from, been a consultant to, or served on the advisory boards of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor OrthoBiotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Abatacept may be helpful for treating rheumatoid arthritis in patients with concurrent hepatitis B, as long as patients are also given antiviral prophylaxis to prevent reactivation of their infection, according to the results of a small retrospective study presented at a rheumatology meeting sponsored by New York University.

"RA therapy in hepatitis B patients is complex. Flare of disease following immunosuppression is the primary concern. The major risk of hepatitis B comes not during but following immunosuppression, where reactivation can lead to severe, even fatal, hepatitis," said Dr. Daniel Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.

In this study, 5 women and 3 men with RA were treated with abatacept and followed for a mean of 18 months. At baseline, all were positive for hepatitis B, as indicated by the presence of hepatitis B surface antigen (HBsAg), hepatitis B virus DNA greater than 20,000 IU/mL, or intermittently positive AST/ALT on liver biopsy. Six patients tested negative for hepatitis C. All patients had used disease-modifying antirheumatic drugs (DMARDs) previously, and 3 had previously used a biologic agent. At baseline, the mean DAS 28 (Disease Activity Score 28) was 5.

When abatacept treatment was initiated, four of the eight patients were already on antiviral therapy, with three patients on entecavir and one on tenofavir.

A statistically significant decrease in DAS 28 scores was seen in patients treated with abatacept plus an antiviral, compared with those not treated with the antiviral. The statistical differences developed slowly and became noticeable after 10-12 months of treatment; the response continued through the 18 months of follow-up. DAS 28 scores remained stable but did not improve in those treated with abatacept but not with an antiviral.

All four patients who did not receive antiviral prophylaxis had a reactivation of hepatitis B, as indicated by a more than 10-fold increase in hepatitis B virus DNA. In contrast, none of those who took antiviral medications had reactivation.

"There may be a place for abatacept when treating RA patients with hepatitis B. It must be used with background antiviral therapy and used continuously for a number of months. We are now doing a prospective, double-blind study," said Dr. Furst in discussing the recently published findings (Arthritis Care Res. 2012 March 5 [doi: 10.1002/acr.21654]).

As far as the use of other biologics, rituximab is probably contraindicated in patients with a history of hepatitis B, suggested Dr. Furst. Although there are not a lot of data to support this contraindication, the results of one study (J. Clin. Oncol. 2009;27:605-11) demonstrated reactivation of hepatitis B virus in 25% of lymphoma patients treated with rituximab plus cyclophosphamide, hydroxydoxorubicin, Oncovin (vincristine), and prednisone (CHOP), compared with no reactivation in those receiving CHOP alone, he said.

Dr. Furst said that he is reluctant to use tumor necrosis factor (TNF) inhibitors for RA patients with a history of hepatitis B. He said that he makes an exception in cases where hepatitis B is controlled, such as in patients who are negative for hepatitis B virus DNA.

Dr. Furst presented a literature review that identified 9 cases of hepatitis B reactivation in patients treated with TNF inhibitors, including 5 cases of severe illness. On the other hand, in a retrospective analysis of 67 HbsAg-positive patients, none of the patients experienced HBV activation. "I think the idea that TNF inhibitors will cause problems afterwards makes sense. I think they are tricky to use in patients with hepatitis B."

According to the World Health Organization, about 2 billion people worldwide have been infected with the hepatitis B virus, 350 million live with chronic infection, and 600,000 die each year due to the acute or chronic consequences of hepatitis B, such as liver cancer or cirrhosis. In Southeast Asia, 8%-10% of adults are chronically infected.

According to Dr. Furst, after exposure to the hepatitis B virus, 70% of people will develop acute hepatitis B but will remain asymptomatic. About 30% will have clinical symptoms, and 0.5%-1% will progress to fulminant hepatitis. Chronic infection occurs in 5%. "This means you probably have a good number of patients with some hepatitis B in their backgrounds. If you see many patients from Asia or South America, one really must screen for hepatitis B before starting the patient on biologics," he said.

Dr. Furst has received research funding from, been a consultant to, or served on the advisory boards of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor OrthoBiotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Smoking worsened the course of axial spondyloarthritis, leading to earlier onset of inflammatory back pain, more severe disease, more frequent inflammation and structural lesions of the sacroiliac joints and spine, and an increased risk of developing severe radiographic sacroiliitis, according to Dr. Christopher T. Ritchlin, who discussed the findings from two studies.

Unlike most other risk factors, smoking is modifiable, noted Dr. Ritchlin, professor of medicine and director of the translational immunology research center at the University of Rochester (N.Y.) Medical Center.

The studies involved patients who were in their 30s and early 40s. "These findings help us to focus on the risk factors we should be worried about in [spondyloarthritis (SpA)]," Dr. Ritchlin said at a rheumatology meeting sponsored by New York University.

At the 2011 American College of Rheumatology annual meeting, Dr. Pedro Machado of Leiden (the Netherlands) University Medical Center presented results from the DESIR (Devenir des Spondyloarthropathies Indifferenciées Récentes) cohort, a multicenter study in France (Ann. Rheum. Dis. 2011 Oct. 11 [doi:10.1136/annrheumdis-2011-200180]). This retrospective analysis looked at the records of 654 patients who met at least one set of international criteria for SpA. The patients were young (mean age, 33.6 years) and had back pain of relatively short duration (mean, 1.5 years). About one-third of the patients were classified as smokers, which was determined by physician interview. Information as to whether the patients were current smokers or how much they smoked was not provided. Multivariate analyses were adjusted for age, sex, duration of inflammatory back pain, race, and HLA-B27 status (Rheumatology News, June 2011, p. 38).

Smoking was found to be associated with a significantly earlier onset of back pain (P = .04) and higher disease activity, as measured on both the Ankylosing Spondylitis Disease Activity Index (P = .03) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P = .003). Those who smoked also had worse functional status, as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) (P = .02). Quality of life was impaired for smokers, as measured by the Ankylosing Spondylitis Quality of Life Score (ASQol, P less than .001) and Short Form 36 physical and mental component scores (both P less than .001).

For the first time, smoking was determined to be associated with the presence of MRI inflammation and structural damage, according to Dr. Machado. MRI findings showed that those who smoked had more inflammation of the sacroiliac joints (odds ratio, 1.57; P = .02) and spine (OR, 2.33; P less than .001). Smoking was also associated with more extensive structural lesions of the sacroiliac joints (OR, 1.54; P = .03) and spine (OR, 2.02; P = .01) and a higher modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, P = .03), a measure of new bone formation.

"Taking into account that smoking is a potentially modifiable lifestyle factor, axial SpA patients who smoke should be strongly advised to quit this habit, as there seem to be disease-specific benefits that go beyond those described for the general population," Dr. Machado said.

Findings from the second study discussed by Dr. Ritchlin showed that smoking was also found to be a risk factor for severe radiographic sacroiliitis in patients with bilateral axial SpA in a cohort study of 151 patients meeting ASAS (Assessment of Spondyloarthritis International Society) criteria for axial SpA (Arthritis Rheum. 2011;63[suppl. 10]:512). Patients were divided into those who had mild disease (sacroilitis less than grade 4, n = 109) and those with more severe disease (sacroiliitis grade 4, n = 42). Most patients were in their late 30s or early 40s, and had the disease for 13 years or more. The study was presented at the 2011 American College of Rheumatology meeting by Grace Yoon of the University of California at San Francisco, where she is in the rheumatology division of the department of medicine.

In a multivariate logistic regression analysis, after adjustment for age and sex, smoking increased the risk of severe radiographic sacroiliitis (OR, 1.13, P = .006). The disease duration also increased the risk of severe radiographic sacroiliitis (OR, 1.07; P = .05) as did nonwhite ethnicity (OR, 3.3; P = .02), total hip arthroplasty (OR, 27.9; P = .0004), and a family history of ankylosing spondylitis (OR, 4.65; P = .01).

"What was really intriguing to me was the finding on MRI that there was an increase in inflammation seen in smokers," said Dr. Ritchlin. "The big question is, How does inflammation lead to osteoproliferation or new bone formation?" He suggested that both genetic factors and mechanobiologic factors such as axial myofascial tonicity influence the process.

Dr. Ritchlin reported financial relationships with Abbott, Amgen, Janssen, Pfizer, and UCB. Dr. Machado and Ms. Yoon reported that they had no relevant financial disclosures.

NEW YORK – Smoking worsened the course of axial spondyloarthritis, leading to earlier onset of inflammatory back pain, more severe disease, more frequent inflammation and structural lesions of the sacroiliac joints and spine, and an increased risk of developing severe radiographic sacroiliitis, according to Dr. Christopher T. Ritchlin, who discussed the findings from two studies.

Unlike most other risk factors, smoking is modifiable, noted Dr. Ritchlin, professor of medicine and director of the translational immunology research center at the University of Rochester (N.Y.) Medical Center.

The studies involved patients who were in their 30s and early 40s. "These findings help us to focus on the risk factors we should be worried about in [spondyloarthritis (SpA)]," Dr. Ritchlin said at a rheumatology meeting sponsored by New York University.

At the 2011 American College of Rheumatology annual meeting, Dr. Pedro Machado of Leiden (the Netherlands) University Medical Center presented results from the DESIR (Devenir des Spondyloarthropathies Indifferenciées Récentes) cohort, a multicenter study in France (Ann. Rheum. Dis. 2011 Oct. 11 [doi:10.1136/annrheumdis-2011-200180]). This retrospective analysis looked at the records of 654 patients who met at least one set of international criteria for SpA. The patients were young (mean age, 33.6 years) and had back pain of relatively short duration (mean, 1.5 years). About one-third of the patients were classified as smokers, which was determined by physician interview. Information as to whether the patients were current smokers or how much they smoked was not provided. Multivariate analyses were adjusted for age, sex, duration of inflammatory back pain, race, and HLA-B27 status (Rheumatology News, June 2011, p. 38).

Smoking was found to be associated with a significantly earlier onset of back pain (P = .04) and higher disease activity, as measured on both the Ankylosing Spondylitis Disease Activity Index (P = .03) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P = .003). Those who smoked also had worse functional status, as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) (P = .02). Quality of life was impaired for smokers, as measured by the Ankylosing Spondylitis Quality of Life Score (ASQol, P less than .001) and Short Form 36 physical and mental component scores (both P less than .001).

For the first time, smoking was determined to be associated with the presence of MRI inflammation and structural damage, according to Dr. Machado. MRI findings showed that those who smoked had more inflammation of the sacroiliac joints (odds ratio, 1.57; P = .02) and spine (OR, 2.33; P less than .001). Smoking was also associated with more extensive structural lesions of the sacroiliac joints (OR, 1.54; P = .03) and spine (OR, 2.02; P = .01) and a higher modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, P = .03), a measure of new bone formation.

"Taking into account that smoking is a potentially modifiable lifestyle factor, axial SpA patients who smoke should be strongly advised to quit this habit, as there seem to be disease-specific benefits that go beyond those described for the general population," Dr. Machado said.

Findings from the second study discussed by Dr. Ritchlin showed that smoking was also found to be a risk factor for severe radiographic sacroiliitis in patients with bilateral axial SpA in a cohort study of 151 patients meeting ASAS (Assessment of Spondyloarthritis International Society) criteria for axial SpA (Arthritis Rheum. 2011;63[suppl. 10]:512). Patients were divided into those who had mild disease (sacroilitis less than grade 4, n = 109) and those with more severe disease (sacroiliitis grade 4, n = 42). Most patients were in their late 30s or early 40s, and had the disease for 13 years or more. The study was presented at the 2011 American College of Rheumatology meeting by Grace Yoon of the University of California at San Francisco, where she is in the rheumatology division of the department of medicine.

In a multivariate logistic regression analysis, after adjustment for age and sex, smoking increased the risk of severe radiographic sacroiliitis (OR, 1.13, P = .006). The disease duration also increased the risk of severe radiographic sacroiliitis (OR, 1.07; P = .05) as did nonwhite ethnicity (OR, 3.3; P = .02), total hip arthroplasty (OR, 27.9; P = .0004), and a family history of ankylosing spondylitis (OR, 4.65; P = .01).

"What was really intriguing to me was the finding on MRI that there was an increase in inflammation seen in smokers," said Dr. Ritchlin. "The big question is, How does inflammation lead to osteoproliferation or new bone formation?" He suggested that both genetic factors and mechanobiologic factors such as axial myofascial tonicity influence the process.

Dr. Ritchlin reported financial relationships with Abbott, Amgen, Janssen, Pfizer, and UCB. Dr. Machado and Ms. Yoon reported that they had no relevant financial disclosures.

NEW YORK – Smoking worsened the course of axial spondyloarthritis, leading to earlier onset of inflammatory back pain, more severe disease, more frequent inflammation and structural lesions of the sacroiliac joints and spine, and an increased risk of developing severe radiographic sacroiliitis, according to Dr. Christopher T. Ritchlin, who discussed the findings from two studies.

Unlike most other risk factors, smoking is modifiable, noted Dr. Ritchlin, professor of medicine and director of the translational immunology research center at the University of Rochester (N.Y.) Medical Center.

The studies involved patients who were in their 30s and early 40s. "These findings help us to focus on the risk factors we should be worried about in [spondyloarthritis (SpA)]," Dr. Ritchlin said at a rheumatology meeting sponsored by New York University.

At the 2011 American College of Rheumatology annual meeting, Dr. Pedro Machado of Leiden (the Netherlands) University Medical Center presented results from the DESIR (Devenir des Spondyloarthropathies Indifferenciées Récentes) cohort, a multicenter study in France (Ann. Rheum. Dis. 2011 Oct. 11 [doi:10.1136/annrheumdis-2011-200180]). This retrospective analysis looked at the records of 654 patients who met at least one set of international criteria for SpA. The patients were young (mean age, 33.6 years) and had back pain of relatively short duration (mean, 1.5 years). About one-third of the patients were classified as smokers, which was determined by physician interview. Information as to whether the patients were current smokers or how much they smoked was not provided. Multivariate analyses were adjusted for age, sex, duration of inflammatory back pain, race, and HLA-B27 status (Rheumatology News, June 2011, p. 38).

Smoking was found to be associated with a significantly earlier onset of back pain (P = .04) and higher disease activity, as measured on both the Ankylosing Spondylitis Disease Activity Index (P = .03) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P = .003). Those who smoked also had worse functional status, as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) (P = .02). Quality of life was impaired for smokers, as measured by the Ankylosing Spondylitis Quality of Life Score (ASQol, P less than .001) and Short Form 36 physical and mental component scores (both P less than .001).

For the first time, smoking was determined to be associated with the presence of MRI inflammation and structural damage, according to Dr. Machado. MRI findings showed that those who smoked had more inflammation of the sacroiliac joints (odds ratio, 1.57; P = .02) and spine (OR, 2.33; P less than .001). Smoking was also associated with more extensive structural lesions of the sacroiliac joints (OR, 1.54; P = .03) and spine (OR, 2.02; P = .01) and a higher modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, P = .03), a measure of new bone formation.

"Taking into account that smoking is a potentially modifiable lifestyle factor, axial SpA patients who smoke should be strongly advised to quit this habit, as there seem to be disease-specific benefits that go beyond those described for the general population," Dr. Machado said.

Findings from the second study discussed by Dr. Ritchlin showed that smoking was also found to be a risk factor for severe radiographic sacroiliitis in patients with bilateral axial SpA in a cohort study of 151 patients meeting ASAS (Assessment of Spondyloarthritis International Society) criteria for axial SpA (Arthritis Rheum. 2011;63[suppl. 10]:512). Patients were divided into those who had mild disease (sacroilitis less than grade 4, n = 109) and those with more severe disease (sacroiliitis grade 4, n = 42). Most patients were in their late 30s or early 40s, and had the disease for 13 years or more. The study was presented at the 2011 American College of Rheumatology meeting by Grace Yoon of the University of California at San Francisco, where she is in the rheumatology division of the department of medicine.

In a multivariate logistic regression analysis, after adjustment for age and sex, smoking increased the risk of severe radiographic sacroiliitis (OR, 1.13, P = .006). The disease duration also increased the risk of severe radiographic sacroiliitis (OR, 1.07; P = .05) as did nonwhite ethnicity (OR, 3.3; P = .02), total hip arthroplasty (OR, 27.9; P = .0004), and a family history of ankylosing spondylitis (OR, 4.65; P = .01).

"What was really intriguing to me was the finding on MRI that there was an increase in inflammation seen in smokers," said Dr. Ritchlin. "The big question is, How does inflammation lead to osteoproliferation or new bone formation?" He suggested that both genetic factors and mechanobiologic factors such as axial myofascial tonicity influence the process.

Dr. Ritchlin reported financial relationships with Abbott, Amgen, Janssen, Pfizer, and UCB. Dr. Machado and Ms. Yoon reported that they had no relevant financial disclosures.

NEW YORK – In the first prospective study of endometriosis in teenagers undergoing complete laparoscopic excision of all areas of abnormal peritoneum, no recurrence was found during up to 5 years of follow-up, according to Dr. Patrick Yeung Jr., director of the center for endometriosis at St. Louis University.

These findings support one of the key themes of the annual congress of the Endometriosis Foundation of America, as expressed by cofounder Dr. Tamer Seckin: Early diagnosis and complete excision are "the best prevention."

In this observational study conducted by Dr. Yeung and his colleagues at an Atlanta-based specialty endometriosis practice, 20 young women aged 12-19 years with symptoms suspicious for endometriosis underwent complete laparoscopic excision of all areas of abnormal peritoneum. The most common suspicious symptoms included moderate to severe chronic pelvic pain, dysmenorrhea, and dyschezia; other symptoms reported were painful bladder, pain with exercise, and intestinal cramping. Quality of life was described as "awful" or "poor" for 65% of the girls. The majority had previous hormonal (82.4%) or surgical (76.5%) treatment (Fertil. Steril. 2011;95:1909-12).

At surgery, histologic analysis confirmed endometriosis in 17 of the 20 (85%) patients. Using the revised American Society for Reproductive Medicine staging criteria (Fertil. Steril. 1997;67:817-21), 29.5% of patients had stage I disease, 64.7% had stage II, and 5.9% had stage III.

After surgery, fewer girls reported pain symptoms such as dysmenorrhea (82.4% before surgery, reduced to 41.2% after surgery), dyschezia (76.5%, reduced to 17.6%), painful exercise (70.6%, reduced to 5.8%), intestinal cramping (58.8%, reduced to 5.8%) and bladder pain (52.9%, reduced to 11.8%) (all P less than .05). Quality of life scores also significantly improved (P less than .05).

During follow-up of up to 66 months (average, 23.1 months), 8 of 17 (47%) patients underwent a subsequent laparoscopy for persistent recurrent pain. None of these patients had endometriosis diagnosed visually or histologically. Half of the girls had pelvic adhesions.

One-third of the girls in the study took postoperative hormonal suppression medication; no recommendations were made about such treatment by the surgeons. The zero recurrence rate of endometriosis observed did not depend on postoperative hormonal suppression. "Postoperative suppression was not specifically recommended because it was felt [that] complete excision was achieved," said Dr. Yeung.

Dr. Yeung is an advocate of "see and treat" laparoscopy. He echoes the American College of Obstetricians and Gynecologists’ position that that diagnosis of endometriosis cannot be made by determining the response to empiric therapy (such as Lupron), but rather by seeing the lesions and getting histological confirmation of the diagnosis (Obstet. Gynecol. 2010;116:223-36).

Noting that younger women with endometriosis often have more atypical and subtle findings, such as red or white lesions and clear papules, he emphasized that it is critical to visualize the field well using high-definition optics with laparoscopy that can provide the benefits of both magnification and illumination. "In the younger patient, you have to look closely and systematically with ‘near contact’ laparoscopy to find it all." (Near contact laparoscopy refers to the camera tip’s being brought close to the tissue being examined to allow for adequate magnification and illumination of all peritoneal surfaces.)

Dr. Yeung uses the noncontact carbon dioxide (CO₂)laser as his "cutting tool of choice," but states that complete excision of all abnormal areas of peritoneum (both typical and atypical) is the most important. "Half the battle is finding it all, especially in younger women, and the other half of the battle is cutting it all out wherever it is found."

During the meeting, several patients recounted their difficult journeys with endometriosis. A common complaint was that their symptoms – including severe menstrual-related pelvic pain – were considered to be "normal."

Dr. Yeung confirmed that the average time from symptom onset to surgical diagnosis of endometriosis is nearly 12 years (Hum. Reprod. 1996:11;878-80).

Some believe that "invisible endometriosis" exists, so that endometriosis will always come back. This idea came from an article published 25 years ago when endometriosis was identified with the naked eye at open surgery (Fertil. Steril. 1986:46;522-4). Dr. Yeung cited a graph by Dr. David B. Redwine, an ob.gyn in Bend, Ore., who specializes in endometriosis, that shows that the more closely one looks at the tissue and the more one knows what endometriosis looks like in all of its forms (typical and atypical or subtle), the rate of "invisible endometriosis approaches zero especially by experienced surgeons" (Gynecol. Obstet. Invest. 2003;63-7).

It is important to note that pain is only one aspect of endometriosis as a disease, and, therefore, the potential benefits of removing of endometriosis cannot be fully described in terms of pain relief or quality of life benefit alone. Eradication of disease may prevent progression of disease (which may include formation of endometriomas and distortion of anatomy), and may have profound benefits on present or future fertility (Fertil. Steril. 2011;95:1909-12), he commented.

To screen for patients at high risk for having endometriosis, Dr. Yeung asks them several important questions, such as "Have you missed school or work due to pelvic pain or painful periods?" When a patient is asked these questions, "if she has any symptoms, her face lights up as she say ‘yes,’ " said Dr. Yeung. "These symptoms are not normal."

Dr. Yeung said he had no relevant disclosures.

NEW YORK – In the first prospective study of endometriosis in teenagers undergoing complete laparoscopic excision of all areas of abnormal peritoneum, no recurrence was found during up to 5 years of follow-up, according to Dr. Patrick Yeung Jr., director of the center for endometriosis at St. Louis University.

These findings support one of the key themes of the annual congress of the Endometriosis Foundation of America, as expressed by cofounder Dr. Tamer Seckin: Early diagnosis and complete excision are "the best prevention."

In this observational study conducted by Dr. Yeung and his colleagues at an Atlanta-based specialty endometriosis practice, 20 young women aged 12-19 years with symptoms suspicious for endometriosis underwent complete laparoscopic excision of all areas of abnormal peritoneum. The most common suspicious symptoms included moderate to severe chronic pelvic pain, dysmenorrhea, and dyschezia; other symptoms reported were painful bladder, pain with exercise, and intestinal cramping. Quality of life was described as "awful" or "poor" for 65% of the girls. The majority had previous hormonal (82.4%) or surgical (76.5%) treatment (Fertil. Steril. 2011;95:1909-12).

At surgery, histologic analysis confirmed endometriosis in 17 of the 20 (85%) patients. Using the revised American Society for Reproductive Medicine staging criteria (Fertil. Steril. 1997;67:817-21), 29.5% of patients had stage I disease, 64.7% had stage II, and 5.9% had stage III.

After surgery, fewer girls reported pain symptoms such as dysmenorrhea (82.4% before surgery, reduced to 41.2% after surgery), dyschezia (76.5%, reduced to 17.6%), painful exercise (70.6%, reduced to 5.8%), intestinal cramping (58.8%, reduced to 5.8%) and bladder pain (52.9%, reduced to 11.8%) (all P less than .05). Quality of life scores also significantly improved (P less than .05).

During follow-up of up to 66 months (average, 23.1 months), 8 of 17 (47%) patients underwent a subsequent laparoscopy for persistent recurrent pain. None of these patients had endometriosis diagnosed visually or histologically. Half of the girls had pelvic adhesions.

One-third of the girls in the study took postoperative hormonal suppression medication; no recommendations were made about such treatment by the surgeons. The zero recurrence rate of endometriosis observed did not depend on postoperative hormonal suppression. "Postoperative suppression was not specifically recommended because it was felt [that] complete excision was achieved," said Dr. Yeung.

Dr. Yeung is an advocate of "see and treat" laparoscopy. He echoes the American College of Obstetricians and Gynecologists’ position that that diagnosis of endometriosis cannot be made by determining the response to empiric therapy (such as Lupron), but rather by seeing the lesions and getting histological confirmation of the diagnosis (Obstet. Gynecol. 2010;116:223-36).

Noting that younger women with endometriosis often have more atypical and subtle findings, such as red or white lesions and clear papules, he emphasized that it is critical to visualize the field well using high-definition optics with laparoscopy that can provide the benefits of both magnification and illumination. "In the younger patient, you have to look closely and systematically with ‘near contact’ laparoscopy to find it all." (Near contact laparoscopy refers to the camera tip’s being brought close to the tissue being examined to allow for adequate magnification and illumination of all peritoneal surfaces.)

Dr. Yeung uses the noncontact carbon dioxide (CO₂)laser as his "cutting tool of choice," but states that complete excision of all abnormal areas of peritoneum (both typical and atypical) is the most important. "Half the battle is finding it all, especially in younger women, and the other half of the battle is cutting it all out wherever it is found."

During the meeting, several patients recounted their difficult journeys with endometriosis. A common complaint was that their symptoms – including severe menstrual-related pelvic pain – were considered to be "normal."

Dr. Yeung confirmed that the average time from symptom onset to surgical diagnosis of endometriosis is nearly 12 years (Hum. Reprod. 1996:11;878-80).

Some believe that "invisible endometriosis" exists, so that endometriosis will always come back. This idea came from an article published 25 years ago when endometriosis was identified with the naked eye at open surgery (Fertil. Steril. 1986:46;522-4). Dr. Yeung cited a graph by Dr. David B. Redwine, an ob.gyn in Bend, Ore., who specializes in endometriosis, that shows that the more closely one looks at the tissue and the more one knows what endometriosis looks like in all of its forms (typical and atypical or subtle), the rate of "invisible endometriosis approaches zero especially by experienced surgeons" (Gynecol. Obstet. Invest. 2003;63-7).

It is important to note that pain is only one aspect of endometriosis as a disease, and, therefore, the potential benefits of removing of endometriosis cannot be fully described in terms of pain relief or quality of life benefit alone. Eradication of disease may prevent progression of disease (which may include formation of endometriomas and distortion of anatomy), and may have profound benefits on present or future fertility (Fertil. Steril. 2011;95:1909-12), he commented.

To screen for patients at high risk for having endometriosis, Dr. Yeung asks them several important questions, such as "Have you missed school or work due to pelvic pain or painful periods?" When a patient is asked these questions, "if she has any symptoms, her face lights up as she say ‘yes,’ " said Dr. Yeung. "These symptoms are not normal."

Dr. Yeung said he had no relevant disclosures.

NEW YORK – In the first prospective study of endometriosis in teenagers undergoing complete laparoscopic excision of all areas of abnormal peritoneum, no recurrence was found during up to 5 years of follow-up, according to Dr. Patrick Yeung Jr., director of the center for endometriosis at St. Louis University.

These findings support one of the key themes of the annual congress of the Endometriosis Foundation of America, as expressed by cofounder Dr. Tamer Seckin: Early diagnosis and complete excision are "the best prevention."

In this observational study conducted by Dr. Yeung and his colleagues at an Atlanta-based specialty endometriosis practice, 20 young women aged 12-19 years with symptoms suspicious for endometriosis underwent complete laparoscopic excision of all areas of abnormal peritoneum. The most common suspicious symptoms included moderate to severe chronic pelvic pain, dysmenorrhea, and dyschezia; other symptoms reported were painful bladder, pain with exercise, and intestinal cramping. Quality of life was described as "awful" or "poor" for 65% of the girls. The majority had previous hormonal (82.4%) or surgical (76.5%) treatment (Fertil. Steril. 2011;95:1909-12).

At surgery, histologic analysis confirmed endometriosis in 17 of the 20 (85%) patients. Using the revised American Society for Reproductive Medicine staging criteria (Fertil. Steril. 1997;67:817-21), 29.5% of patients had stage I disease, 64.7% had stage II, and 5.9% had stage III.

After surgery, fewer girls reported pain symptoms such as dysmenorrhea (82.4% before surgery, reduced to 41.2% after surgery), dyschezia (76.5%, reduced to 17.6%), painful exercise (70.6%, reduced to 5.8%), intestinal cramping (58.8%, reduced to 5.8%) and bladder pain (52.9%, reduced to 11.8%) (all P less than .05). Quality of life scores also significantly improved (P less than .05).

During follow-up of up to 66 months (average, 23.1 months), 8 of 17 (47%) patients underwent a subsequent laparoscopy for persistent recurrent pain. None of these patients had endometriosis diagnosed visually or histologically. Half of the girls had pelvic adhesions.

One-third of the girls in the study took postoperative hormonal suppression medication; no recommendations were made about such treatment by the surgeons. The zero recurrence rate of endometriosis observed did not depend on postoperative hormonal suppression. "Postoperative suppression was not specifically recommended because it was felt [that] complete excision was achieved," said Dr. Yeung.

Dr. Yeung is an advocate of "see and treat" laparoscopy. He echoes the American College of Obstetricians and Gynecologists’ position that that diagnosis of endometriosis cannot be made by determining the response to empiric therapy (such as Lupron), but rather by seeing the lesions and getting histological confirmation of the diagnosis (Obstet. Gynecol. 2010;116:223-36).

Noting that younger women with endometriosis often have more atypical and subtle findings, such as red or white lesions and clear papules, he emphasized that it is critical to visualize the field well using high-definition optics with laparoscopy that can provide the benefits of both magnification and illumination. "In the younger patient, you have to look closely and systematically with ‘near contact’ laparoscopy to find it all." (Near contact laparoscopy refers to the camera tip’s being brought close to the tissue being examined to allow for adequate magnification and illumination of all peritoneal surfaces.)

Dr. Yeung uses the noncontact carbon dioxide (CO₂)laser as his "cutting tool of choice," but states that complete excision of all abnormal areas of peritoneum (both typical and atypical) is the most important. "Half the battle is finding it all, especially in younger women, and the other half of the battle is cutting it all out wherever it is found."

During the meeting, several patients recounted their difficult journeys with endometriosis. A common complaint was that their symptoms – including severe menstrual-related pelvic pain – were considered to be "normal."

Dr. Yeung confirmed that the average time from symptom onset to surgical diagnosis of endometriosis is nearly 12 years (Hum. Reprod. 1996:11;878-80).

Some believe that "invisible endometriosis" exists, so that endometriosis will always come back. This idea came from an article published 25 years ago when endometriosis was identified with the naked eye at open surgery (Fertil. Steril. 1986:46;522-4). Dr. Yeung cited a graph by Dr. David B. Redwine, an ob.gyn in Bend, Ore., who specializes in endometriosis, that shows that the more closely one looks at the tissue and the more one knows what endometriosis looks like in all of its forms (typical and atypical or subtle), the rate of "invisible endometriosis approaches zero especially by experienced surgeons" (Gynecol. Obstet. Invest. 2003;63-7).

It is important to note that pain is only one aspect of endometriosis as a disease, and, therefore, the potential benefits of removing of endometriosis cannot be fully described in terms of pain relief or quality of life benefit alone. Eradication of disease may prevent progression of disease (which may include formation of endometriomas and distortion of anatomy), and may have profound benefits on present or future fertility (Fertil. Steril. 2011;95:1909-12), he commented.

To screen for patients at high risk for having endometriosis, Dr. Yeung asks them several important questions, such as "Have you missed school or work due to pelvic pain or painful periods?" When a patient is asked these questions, "if she has any symptoms, her face lights up as she say ‘yes,’ " said Dr. Yeung. "These symptoms are not normal."

Dr. Yeung said he had no relevant disclosures.

NEW YORK – Management of systemic sclerosis is likely to improve as soon as an ongoing convergence of mechanistic insights, improved understanding of clinical trial design, and interest by industry results in new treatments, according to Dr. Robert F. Spiera.

Of particular note are recent trials, with both positive and negative results, of tyrosine kinase inhibitors (TKIs) and autologous stem cell transplantation, he said at a rheumatology meeting sponsored by New York University.

Even while awaiting a big breakthrough in treatment, "we can now do a lot for our patients with scleroderma," said Dr. Spiera, director of the Scleroderma and Vasculitis Center at the Hospital for Special Surgery in New York.

Therapy for systemic sclerosis (SSc) falls into two categories: treatment of organ-specific complications and disease modification. Major advances have been made in treating organ-specific complications affecting the gastrointestinal system, kidneys, heart and lungs, and musculoskeletal organs, according to Dr. Spiera. Many agents are available to manage symptoms of Raynaud’s phenomenon.

While there are no proven disease-modifying therapies as yet, the search for such therapies in scleroderma has intensified. Immunosuppressive therapy is one approach, and limited success has been achieved with cyclophosphamide. There have been several recent reports investigating immunoablative therapy combined with bone marrow transplantation.

In the ASSIST (American Scleroderma Stem Cell vs. Immune Suppression) Trial, an open-label, randomized, controlled phase II trial, 10 patients received hemopoietic stem-cell transplantation (HSCT) plus 200 mg/kg of intravenous cyclophosphamide and 6.5 mg/kg of IV rabbit antithymocyte globulin. The 9 control patients received 1.0 g/m² of IV cyclophosphamide once a month for 6 months. The authors reported that all 10 HSCT patients improved at or before follow-up at 12 months, compared with none of the 9 treated only with cyclophosphamide (odds ratio, 110; P = .00001) (Lancet 2011;378:498-506). Of the 9 controls, 8 had disease progression, compared with none of those treated by HSCT (P = .0001), and 7 controls eventually underwent HSCT. The outcomes were considered to be an improvement, defined as a decrease in the modified Rodnan skin scores (mRSS) of more than 25% or an increase in forced vital capacity (FVC) of more than 10%.

"These results surprised a lot of people in the scleroderma community," commented Dr. Spiera. He noted that some of the inclusion criteria could be subject to challenge, as they potentially allowed for enrollment of patients with relatively mild disease. He also noted that it was a single-center study, which limits the generalizability of the results, as the morbidity of the intervention is likely center- and experience-dependent.

Another single-center study from Germany reported the outcomes of autologous stem cell transplantation in 26 patients with SSc. Patients received cyclophosphamide and granulocyte colony-stimulating factor for mobilization and cyclophosphamide plus antithymocyte globulin for conditioning before retransfusion of CD34-selected stem cells. Six months after transplantation, 91% of patients improved, as measured by a reduction in the mRSS of 25% or more (Rheumatol. 2012;39:269-75). However, 3 patients died between the mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was thought to be treatment related. Seven patients relapsed during 4.4 years of follow-up. Progression-free survival was 74%. During follow-up, 4 patients died, mostly due to pulmonary or cardiac complications of SSc.

More definitive evidence regarding scleroderma may be forthcoming from the ongoing National Institutes of Health SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial. The study will compare the potential benefits of autologous stem cell transplant with those of cyclophosphamide (12 IV treatments at monthly intervals). A composite end point will include mortality, organ failure, change in FVC of more than 10%, change in mRSS of more than 25%, and the Scleroderma Health Assessment Questionnaire (SHAQ). Enrollment in SCOT was completed in May 2011, and randomization continued until Oct. 1, 2011.

Another avenue of active research is the search for antifibrotic therapy. The TKI imatinib is one agent undergoing active scrutiny. According to Dr. Spiera, there are good preclinical data available for imatinib, including reports that imatinib treatment in a mouse model of SSc reduced dermal thickening and prevented the differentiation of resting fibroblasts into myofibroblasts, perhaps by blocking noncanonical transforming growth factor-beta (TGF-beta) pathways and platelet-derived growth factor receptor (PDGFR) signaling (Arthritis Rheum. 2009;60:219-24; Oncogene 2009;28:1285-97).

Clinical findings for the treatment of SSc with imatinib have been mixed. In the largest and longest-observed cohort, Dr. Spiera conducted a prospective, phase IIa, open-label, single-arm clinical trial of 30 patients with diffuse cutaneous SSc of less than 4 years’ duration treated with imatinib 400 mg daily. Patients with both early and late disease were included, and about three-quarters had previously received other treatments, including corticosteroids (46.7%), methotrexate (30.0%), mycophenolate mofetil (20.0%), and autologous stem cell transplantation (3.3%). Twenty-four patients completed 12 months of therapy (Ann. Rheum. Dis. 2011;70:1003-9). Improvements in skin thickening and FVC were observed. The mRSS decreased by 22.4% at 12 months (P = .001), and changes were noted 6 months after initiation of therapy. Patients with early disease (less than 18 months) improved the most. FVC improved by 6.4% predicted (P = .008), and diffusion capacity remained stable. Dr. Spiera questioned the clinical significance of the change in FVC, since not all the patients had interstitial lung disease at baseline.

Treatment with imatinib was tolerated by most patients. Adverse events – including edema, nausea, and myalgias – were common (n = 171), although most (98%) were mild to moderate. There were 24 serious adverse events, and 2 were attributed to imatinib.

Steps were taken to improve tolerability. In 83% of patients, the imatinib dose was adjusted due to myalgia; edema and effusions; gastrointestinal complaints; or other illness. About 60% of patients who developed edema were given furosemide, which proved helpful.

These results stand in contrast to those of another group of investigators who set out to do a 6-month, randomized, double-blind, placebo-controlled proof-of-concept pilot study of imatinib in patients with active diffuse cutaneous SSc (Arthritis Rheum. 2011;63:3547-51). A 4:1 randomization strategy was used, stratifying patients according to current use of methotrexate. Imatinib 200 mg was given twice daily. The goal of the study was to enroll 20 patients. However, the study was discontinued after 10 patients were enrolled (9 who received imatinib and 1 placebo) due to poor tolerability and high rates of adverse events. These events were similar to those reported by Dr. Spiera: edema, fluid retention, fatigue, nausea, cramps/myalgias, and diarrhea, but also alopecia and anemia. According to the authors, the side effects occurred even when the imatinib dose was reduced to 200 mg daily. Two patients were hospitalized because of medication side effects.

No differences were found in any measures of efficacy (that is, changes in mRSS, physician’s global assessment, patient’s global assessment, or HAQ scores), but this was attributed to the small number of patients who actually completed the study.

"I think we are going to see more about [TKIs] for systemic sclerosis," said Dr. Spiera. He noted that clinical trials were underway for other TKIs, such as dasatinib and nilotinib. The TKI BIBF 1120 was shown in a phase II, randomized, placebo-controlled trial to slow down the rate of decline of FVC in patients with idiopathic pulmonary fibrosis (N. Engl. J. Med. 2011;365:1079-87).

While Dr. Spiera called for more randomized controlled trials, he also highlighted some of the challenges faced by those conducting clinical trials in scleroderma. These include the difficulty of recruiting patients with such an uncommon disease, the variety in disease phenotypes, the variable natural history, uncertainty as to what are the most relevant and valid outcome measures, and the ethical ramifications of randomizing patients to placebo.

Dr. Spiera listed research support from BMS, Boehringer Ingelheim, Novartis, Roche/Genentech, and United Therapeutics.

NEW YORK – Management of systemic sclerosis is likely to improve as soon as an ongoing convergence of mechanistic insights, improved understanding of clinical trial design, and interest by industry results in new treatments, according to Dr. Robert F. Spiera.

Of particular note are recent trials, with both positive and negative results, of tyrosine kinase inhibitors (TKIs) and autologous stem cell transplantation, he said at a rheumatology meeting sponsored by New York University.

Even while awaiting a big breakthrough in treatment, "we can now do a lot for our patients with scleroderma," said Dr. Spiera, director of the Scleroderma and Vasculitis Center at the Hospital for Special Surgery in New York.

Therapy for systemic sclerosis (SSc) falls into two categories: treatment of organ-specific complications and disease modification. Major advances have been made in treating organ-specific complications affecting the gastrointestinal system, kidneys, heart and lungs, and musculoskeletal organs, according to Dr. Spiera. Many agents are available to manage symptoms of Raynaud’s phenomenon.

While there are no proven disease-modifying therapies as yet, the search for such therapies in scleroderma has intensified. Immunosuppressive therapy is one approach, and limited success has been achieved with cyclophosphamide. There have been several recent reports investigating immunoablative therapy combined with bone marrow transplantation.

In the ASSIST (American Scleroderma Stem Cell vs. Immune Suppression) Trial, an open-label, randomized, controlled phase II trial, 10 patients received hemopoietic stem-cell transplantation (HSCT) plus 200 mg/kg of intravenous cyclophosphamide and 6.5 mg/kg of IV rabbit antithymocyte globulin. The 9 control patients received 1.0 g/m² of IV cyclophosphamide once a month for 6 months. The authors reported that all 10 HSCT patients improved at or before follow-up at 12 months, compared with none of the 9 treated only with cyclophosphamide (odds ratio, 110; P = .00001) (Lancet 2011;378:498-506). Of the 9 controls, 8 had disease progression, compared with none of those treated by HSCT (P = .0001), and 7 controls eventually underwent HSCT. The outcomes were considered to be an improvement, defined as a decrease in the modified Rodnan skin scores (mRSS) of more than 25% or an increase in forced vital capacity (FVC) of more than 10%.

"These results surprised a lot of people in the scleroderma community," commented Dr. Spiera. He noted that some of the inclusion criteria could be subject to challenge, as they potentially allowed for enrollment of patients with relatively mild disease. He also noted that it was a single-center study, which limits the generalizability of the results, as the morbidity of the intervention is likely center- and experience-dependent.

Another single-center study from Germany reported the outcomes of autologous stem cell transplantation in 26 patients with SSc. Patients received cyclophosphamide and granulocyte colony-stimulating factor for mobilization and cyclophosphamide plus antithymocyte globulin for conditioning before retransfusion of CD34-selected stem cells. Six months after transplantation, 91% of patients improved, as measured by a reduction in the mRSS of 25% or more (Rheumatol. 2012;39:269-75). However, 3 patients died between the mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was thought to be treatment related. Seven patients relapsed during 4.4 years of follow-up. Progression-free survival was 74%. During follow-up, 4 patients died, mostly due to pulmonary or cardiac complications of SSc.

More definitive evidence regarding scleroderma may be forthcoming from the ongoing National Institutes of Health SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial. The study will compare the potential benefits of autologous stem cell transplant with those of cyclophosphamide (12 IV treatments at monthly intervals). A composite end point will include mortality, organ failure, change in FVC of more than 10%, change in mRSS of more than 25%, and the Scleroderma Health Assessment Questionnaire (SHAQ). Enrollment in SCOT was completed in May 2011, and randomization continued until Oct. 1, 2011.

Another avenue of active research is the search for antifibrotic therapy. The TKI imatinib is one agent undergoing active scrutiny. According to Dr. Spiera, there are good preclinical data available for imatinib, including reports that imatinib treatment in a mouse model of SSc reduced dermal thickening and prevented the differentiation of resting fibroblasts into myofibroblasts, perhaps by blocking noncanonical transforming growth factor-beta (TGF-beta) pathways and platelet-derived growth factor receptor (PDGFR) signaling (Arthritis Rheum. 2009;60:219-24; Oncogene 2009;28:1285-97).

Clinical findings for the treatment of SSc with imatinib have been mixed. In the largest and longest-observed cohort, Dr. Spiera conducted a prospective, phase IIa, open-label, single-arm clinical trial of 30 patients with diffuse cutaneous SSc of less than 4 years’ duration treated with imatinib 400 mg daily. Patients with both early and late disease were included, and about three-quarters had previously received other treatments, including corticosteroids (46.7%), methotrexate (30.0%), mycophenolate mofetil (20.0%), and autologous stem cell transplantation (3.3%). Twenty-four patients completed 12 months of therapy (Ann. Rheum. Dis. 2011;70:1003-9). Improvements in skin thickening and FVC were observed. The mRSS decreased by 22.4% at 12 months (P = .001), and changes were noted 6 months after initiation of therapy. Patients with early disease (less than 18 months) improved the most. FVC improved by 6.4% predicted (P = .008), and diffusion capacity remained stable. Dr. Spiera questioned the clinical significance of the change in FVC, since not all the patients had interstitial lung disease at baseline.

Treatment with imatinib was tolerated by most patients. Adverse events – including edema, nausea, and myalgias – were common (n = 171), although most (98%) were mild to moderate. There were 24 serious adverse events, and 2 were attributed to imatinib.

Steps were taken to improve tolerability. In 83% of patients, the imatinib dose was adjusted due to myalgia; edema and effusions; gastrointestinal complaints; or other illness. About 60% of patients who developed edema were given furosemide, which proved helpful.

These results stand in contrast to those of another group of investigators who set out to do a 6-month, randomized, double-blind, placebo-controlled proof-of-concept pilot study of imatinib in patients with active diffuse cutaneous SSc (Arthritis Rheum. 2011;63:3547-51). A 4:1 randomization strategy was used, stratifying patients according to current use of methotrexate. Imatinib 200 mg was given twice daily. The goal of the study was to enroll 20 patients. However, the study was discontinued after 10 patients were enrolled (9 who received imatinib and 1 placebo) due to poor tolerability and high rates of adverse events. These events were similar to those reported by Dr. Spiera: edema, fluid retention, fatigue, nausea, cramps/myalgias, and diarrhea, but also alopecia and anemia. According to the authors, the side effects occurred even when the imatinib dose was reduced to 200 mg daily. Two patients were hospitalized because of medication side effects.

No differences were found in any measures of efficacy (that is, changes in mRSS, physician’s global assessment, patient’s global assessment, or HAQ scores), but this was attributed to the small number of patients who actually completed the study.

"I think we are going to see more about [TKIs] for systemic sclerosis," said Dr. Spiera. He noted that clinical trials were underway for other TKIs, such as dasatinib and nilotinib. The TKI BIBF 1120 was shown in a phase II, randomized, placebo-controlled trial to slow down the rate of decline of FVC in patients with idiopathic pulmonary fibrosis (N. Engl. J. Med. 2011;365:1079-87).

While Dr. Spiera called for more randomized controlled trials, he also highlighted some of the challenges faced by those conducting clinical trials in scleroderma. These include the difficulty of recruiting patients with such an uncommon disease, the variety in disease phenotypes, the variable natural history, uncertainty as to what are the most relevant and valid outcome measures, and the ethical ramifications of randomizing patients to placebo.

Dr. Spiera listed research support from BMS, Boehringer Ingelheim, Novartis, Roche/Genentech, and United Therapeutics.

NEW YORK – Management of systemic sclerosis is likely to improve as soon as an ongoing convergence of mechanistic insights, improved understanding of clinical trial design, and interest by industry results in new treatments, according to Dr. Robert F. Spiera.

Of particular note are recent trials, with both positive and negative results, of tyrosine kinase inhibitors (TKIs) and autologous stem cell transplantation, he said at a rheumatology meeting sponsored by New York University.

Even while awaiting a big breakthrough in treatment, "we can now do a lot for our patients with scleroderma," said Dr. Spiera, director of the Scleroderma and Vasculitis Center at the Hospital for Special Surgery in New York.

Therapy for systemic sclerosis (SSc) falls into two categories: treatment of organ-specific complications and disease modification. Major advances have been made in treating organ-specific complications affecting the gastrointestinal system, kidneys, heart and lungs, and musculoskeletal organs, according to Dr. Spiera. Many agents are available to manage symptoms of Raynaud’s phenomenon.

While there are no proven disease-modifying therapies as yet, the search for such therapies in scleroderma has intensified. Immunosuppressive therapy is one approach, and limited success has been achieved with cyclophosphamide. There have been several recent reports investigating immunoablative therapy combined with bone marrow transplantation.

In the ASSIST (American Scleroderma Stem Cell vs. Immune Suppression) Trial, an open-label, randomized, controlled phase II trial, 10 patients received hemopoietic stem-cell transplantation (HSCT) plus 200 mg/kg of intravenous cyclophosphamide and 6.5 mg/kg of IV rabbit antithymocyte globulin. The 9 control patients received 1.0 g/m² of IV cyclophosphamide once a month for 6 months. The authors reported that all 10 HSCT patients improved at or before follow-up at 12 months, compared with none of the 9 treated only with cyclophosphamide (odds ratio, 110; P = .00001) (Lancet 2011;378:498-506). Of the 9 controls, 8 had disease progression, compared with none of those treated by HSCT (P = .0001), and 7 controls eventually underwent HSCT. The outcomes were considered to be an improvement, defined as a decrease in the modified Rodnan skin scores (mRSS) of more than 25% or an increase in forced vital capacity (FVC) of more than 10%.

"These results surprised a lot of people in the scleroderma community," commented Dr. Spiera. He noted that some of the inclusion criteria could be subject to challenge, as they potentially allowed for enrollment of patients with relatively mild disease. He also noted that it was a single-center study, which limits the generalizability of the results, as the morbidity of the intervention is likely center- and experience-dependent.

Another single-center study from Germany reported the outcomes of autologous stem cell transplantation in 26 patients with SSc. Patients received cyclophosphamide and granulocyte colony-stimulating factor for mobilization and cyclophosphamide plus antithymocyte globulin for conditioning before retransfusion of CD34-selected stem cells. Six months after transplantation, 91% of patients improved, as measured by a reduction in the mRSS of 25% or more (Rheumatol. 2012;39:269-75). However, 3 patients died between the mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was thought to be treatment related. Seven patients relapsed during 4.4 years of follow-up. Progression-free survival was 74%. During follow-up, 4 patients died, mostly due to pulmonary or cardiac complications of SSc.

More definitive evidence regarding scleroderma may be forthcoming from the ongoing National Institutes of Health SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial. The study will compare the potential benefits of autologous stem cell transplant with those of cyclophosphamide (12 IV treatments at monthly intervals). A composite end point will include mortality, organ failure, change in FVC of more than 10%, change in mRSS of more than 25%, and the Scleroderma Health Assessment Questionnaire (SHAQ). Enrollment in SCOT was completed in May 2011, and randomization continued until Oct. 1, 2011.

Another avenue of active research is the search for antifibrotic therapy. The TKI imatinib is one agent undergoing active scrutiny. According to Dr. Spiera, there are good preclinical data available for imatinib, including reports that imatinib treatment in a mouse model of SSc reduced dermal thickening and prevented the differentiation of resting fibroblasts into myofibroblasts, perhaps by blocking noncanonical transforming growth factor-beta (TGF-beta) pathways and platelet-derived growth factor receptor (PDGFR) signaling (Arthritis Rheum. 2009;60:219-24; Oncogene 2009;28:1285-97).

Clinical findings for the treatment of SSc with imatinib have been mixed. In the largest and longest-observed cohort, Dr. Spiera conducted a prospective, phase IIa, open-label, single-arm clinical trial of 30 patients with diffuse cutaneous SSc of less than 4 years’ duration treated with imatinib 400 mg daily. Patients with both early and late disease were included, and about three-quarters had previously received other treatments, including corticosteroids (46.7%), methotrexate (30.0%), mycophenolate mofetil (20.0%), and autologous stem cell transplantation (3.3%). Twenty-four patients completed 12 months of therapy (Ann. Rheum. Dis. 2011;70:1003-9). Improvements in skin thickening and FVC were observed. The mRSS decreased by 22.4% at 12 months (P = .001), and changes were noted 6 months after initiation of therapy. Patients with early disease (less than 18 months) improved the most. FVC improved by 6.4% predicted (P = .008), and diffusion capacity remained stable. Dr. Spiera questioned the clinical significance of the change in FVC, since not all the patients had interstitial lung disease at baseline.

Treatment with imatinib was tolerated by most patients. Adverse events – including edema, nausea, and myalgias – were common (n = 171), although most (98%) were mild to moderate. There were 24 serious adverse events, and 2 were attributed to imatinib.

Steps were taken to improve tolerability. In 83% of patients, the imatinib dose was adjusted due to myalgia; edema and effusions; gastrointestinal complaints; or other illness. About 60% of patients who developed edema were given furosemide, which proved helpful.

These results stand in contrast to those of another group of investigators who set out to do a 6-month, randomized, double-blind, placebo-controlled proof-of-concept pilot study of imatinib in patients with active diffuse cutaneous SSc (Arthritis Rheum. 2011;63:3547-51). A 4:1 randomization strategy was used, stratifying patients according to current use of methotrexate. Imatinib 200 mg was given twice daily. The goal of the study was to enroll 20 patients. However, the study was discontinued after 10 patients were enrolled (9 who received imatinib and 1 placebo) due to poor tolerability and high rates of adverse events. These events were similar to those reported by Dr. Spiera: edema, fluid retention, fatigue, nausea, cramps/myalgias, and diarrhea, but also alopecia and anemia. According to the authors, the side effects occurred even when the imatinib dose was reduced to 200 mg daily. Two patients were hospitalized because of medication side effects.

No differences were found in any measures of efficacy (that is, changes in mRSS, physician’s global assessment, patient’s global assessment, or HAQ scores), but this was attributed to the small number of patients who actually completed the study.

"I think we are going to see more about [TKIs] for systemic sclerosis," said Dr. Spiera. He noted that clinical trials were underway for other TKIs, such as dasatinib and nilotinib. The TKI BIBF 1120 was shown in a phase II, randomized, placebo-controlled trial to slow down the rate of decline of FVC in patients with idiopathic pulmonary fibrosis (N. Engl. J. Med. 2011;365:1079-87).

While Dr. Spiera called for more randomized controlled trials, he also highlighted some of the challenges faced by those conducting clinical trials in scleroderma. These include the difficulty of recruiting patients with such an uncommon disease, the variety in disease phenotypes, the variable natural history, uncertainty as to what are the most relevant and valid outcome measures, and the ethical ramifications of randomizing patients to placebo.

Dr. Spiera listed research support from BMS, Boehringer Ingelheim, Novartis, Roche/Genentech, and United Therapeutics.