Doug Brunk

TORONTO – If you don’t think clinicians should be worried about the current state of cardiovascular disease (CVD) prevention, consider the arresting data from the 2011 World Health Organization Global Atlas on CVD Prevention and Control.

The atlas showed that CVD accounts for 31% of deaths worldwide: 17.5 million deaths in 2012, projected to increase to 23.3 million deaths in 2030.

At the same time, the American Heart Association projects that by 2030, more than 40% of the U.S. population will have some form of CVD, with total direct costs projected to increase from $273 billion to $818 billion – and real indirect costs because of lost productivity will increase from $172 billion to $276 billion.

“We are not preventing CVD, and the worldwide prevalence of risk factors predicts a grim future,” Dr. Brian W. McCrindle, a staff cardiologist at the Hospital for Sick Children, Toronto, said at the International Society on Thrombosis and Haemostasis congress.

“One of the biggest problems is that we don’t give health and we don’t give prevention their fair due,” Dr. McCrindle continued. “We spend proportionately more health care dollars on providing care for acute and chronic illnesses, much of which are preventable. Our expenditures are growing, leaving little for prevention, and even less for children.”

Courtesy International Society on Thrombosis and Haemostasis

According to Dr. McCrindle, today’s clinicians miss the mark on preventing CVD “because we focus our efforts on tertiary prevention – the treatment of existing symptomatic disease in order to ameliorate its effects, or treatment to delay or prevent progression; or on secondary prevention – the early detection of the potential for development of a disease, or the prevention of events in those with asymptomatic disease.

“We do make some effort regarding primary prevention – the reduction of risk factors before the occurrence of disease, but tend to delay these efforts until much later in adulthood,” he noted. “We do very little regarding primordial prevention – the prevention of risk factors from developing.”

Dr. McCrindle noted that atherosclerosis has been shown to begin in youth, and that obesity and other cardiovascular risk factors in children track into adulthood. “These findings are of concern regarding current prevention strategies,” he said.

“However, there are some important evidence gaps that need to be addressed before embarking on screening and intervention strategies in youth,” Dr. McCrindle cautioned. “Unfortunately, direct evidence does not exist to assert that risk factors measured in childhood are related to clinical events in adults, although long-term follow-up of existing cohorts may provide that.

“We may never have direct evidence that detection and management of risk factors in children reduce CVD events in adults, since a 50- to 60-year-long randomized trial can never be done,” Dr. McCrindle noted. “However, a chain of indirect evidence can be established.”

Key to current efforts, he continued, are the use of noninvasive ways to measure subclinical atherosclerosis, including ultrasound to assess endothelial function, arterial stiffness and intima-media thickness, and ultrafast computed tomography to detect coronary artery calcium. “These have been important predictors of events in adults, and are increasingly used in pediatric studies,” he said.

While he characterized the current health care landscape as being “at odds with the current reality facing today’s youth,” Dr. McCrindle suggested several ways that attendees can improve the CVD outlook in children, starting with being a role model for a healthy lifestyle. “We need to practice what we preach,” he said.

He also encouraged clinicians to implement existing pediatric guidelines on CVD health, assess and intervene on risk factors in children, and become more effective counselors.

“Instead of telling children what to do, we need to use techniques such as motivational interviewing to guide our young patients in discovering what they want to achieve,” Dr. McCrindle said. “We need to let kids set their own agenda and respect their autonomy. We also need to focus on ideal health across the lifespan, particularly on preventing risk factors and behaviors.”

Dr. McCrindle had no disclosures.

[email protected]

TORONTO – If you don’t think clinicians should be worried about the current state of cardiovascular disease (CVD) prevention, consider the arresting data from the 2011 World Health Organization Global Atlas on CVD Prevention and Control.

The atlas showed that CVD accounts for 31% of deaths worldwide: 17.5 million deaths in 2012, projected to increase to 23.3 million deaths in 2030.

At the same time, the American Heart Association projects that by 2030, more than 40% of the U.S. population will have some form of CVD, with total direct costs projected to increase from $273 billion to $818 billion – and real indirect costs because of lost productivity will increase from $172 billion to $276 billion.

“We are not preventing CVD, and the worldwide prevalence of risk factors predicts a grim future,” Dr. Brian W. McCrindle, a staff cardiologist at the Hospital for Sick Children, Toronto, said at the International Society on Thrombosis and Haemostasis congress.

“One of the biggest problems is that we don’t give health and we don’t give prevention their fair due,” Dr. McCrindle continued. “We spend proportionately more health care dollars on providing care for acute and chronic illnesses, much of which are preventable. Our expenditures are growing, leaving little for prevention, and even less for children.”

Courtesy International Society on Thrombosis and Haemostasis

According to Dr. McCrindle, today’s clinicians miss the mark on preventing CVD “because we focus our efforts on tertiary prevention – the treatment of existing symptomatic disease in order to ameliorate its effects, or treatment to delay or prevent progression; or on secondary prevention – the early detection of the potential for development of a disease, or the prevention of events in those with asymptomatic disease.

“We do make some effort regarding primary prevention – the reduction of risk factors before the occurrence of disease, but tend to delay these efforts until much later in adulthood,” he noted. “We do very little regarding primordial prevention – the prevention of risk factors from developing.”

Dr. McCrindle noted that atherosclerosis has been shown to begin in youth, and that obesity and other cardiovascular risk factors in children track into adulthood. “These findings are of concern regarding current prevention strategies,” he said.

“However, there are some important evidence gaps that need to be addressed before embarking on screening and intervention strategies in youth,” Dr. McCrindle cautioned. “Unfortunately, direct evidence does not exist to assert that risk factors measured in childhood are related to clinical events in adults, although long-term follow-up of existing cohorts may provide that.

“We may never have direct evidence that detection and management of risk factors in children reduce CVD events in adults, since a 50- to 60-year-long randomized trial can never be done,” Dr. McCrindle noted. “However, a chain of indirect evidence can be established.”

Key to current efforts, he continued, are the use of noninvasive ways to measure subclinical atherosclerosis, including ultrasound to assess endothelial function, arterial stiffness and intima-media thickness, and ultrafast computed tomography to detect coronary artery calcium. “These have been important predictors of events in adults, and are increasingly used in pediatric studies,” he said.

While he characterized the current health care landscape as being “at odds with the current reality facing today’s youth,” Dr. McCrindle suggested several ways that attendees can improve the CVD outlook in children, starting with being a role model for a healthy lifestyle. “We need to practice what we preach,” he said.

He also encouraged clinicians to implement existing pediatric guidelines on CVD health, assess and intervene on risk factors in children, and become more effective counselors.

“Instead of telling children what to do, we need to use techniques such as motivational interviewing to guide our young patients in discovering what they want to achieve,” Dr. McCrindle said. “We need to let kids set their own agenda and respect their autonomy. We also need to focus on ideal health across the lifespan, particularly on preventing risk factors and behaviors.”

Dr. McCrindle had no disclosures.

[email protected]

TORONTO – If you don’t think clinicians should be worried about the current state of cardiovascular disease (CVD) prevention, consider the arresting data from the 2011 World Health Organization Global Atlas on CVD Prevention and Control.

The atlas showed that CVD accounts for 31% of deaths worldwide: 17.5 million deaths in 2012, projected to increase to 23.3 million deaths in 2030.

At the same time, the American Heart Association projects that by 2030, more than 40% of the U.S. population will have some form of CVD, with total direct costs projected to increase from $273 billion to $818 billion – and real indirect costs because of lost productivity will increase from $172 billion to $276 billion.

“We are not preventing CVD, and the worldwide prevalence of risk factors predicts a grim future,” Dr. Brian W. McCrindle, a staff cardiologist at the Hospital for Sick Children, Toronto, said at the International Society on Thrombosis and Haemostasis congress.

“One of the biggest problems is that we don’t give health and we don’t give prevention their fair due,” Dr. McCrindle continued. “We spend proportionately more health care dollars on providing care for acute and chronic illnesses, much of which are preventable. Our expenditures are growing, leaving little for prevention, and even less for children.”

Courtesy International Society on Thrombosis and Haemostasis

According to Dr. McCrindle, today’s clinicians miss the mark on preventing CVD “because we focus our efforts on tertiary prevention – the treatment of existing symptomatic disease in order to ameliorate its effects, or treatment to delay or prevent progression; or on secondary prevention – the early detection of the potential for development of a disease, or the prevention of events in those with asymptomatic disease.

“We do make some effort regarding primary prevention – the reduction of risk factors before the occurrence of disease, but tend to delay these efforts until much later in adulthood,” he noted. “We do very little regarding primordial prevention – the prevention of risk factors from developing.”

Dr. McCrindle noted that atherosclerosis has been shown to begin in youth, and that obesity and other cardiovascular risk factors in children track into adulthood. “These findings are of concern regarding current prevention strategies,” he said.

“However, there are some important evidence gaps that need to be addressed before embarking on screening and intervention strategies in youth,” Dr. McCrindle cautioned. “Unfortunately, direct evidence does not exist to assert that risk factors measured in childhood are related to clinical events in adults, although long-term follow-up of existing cohorts may provide that.

“We may never have direct evidence that detection and management of risk factors in children reduce CVD events in adults, since a 50- to 60-year-long randomized trial can never be done,” Dr. McCrindle noted. “However, a chain of indirect evidence can be established.”

Key to current efforts, he continued, are the use of noninvasive ways to measure subclinical atherosclerosis, including ultrasound to assess endothelial function, arterial stiffness and intima-media thickness, and ultrafast computed tomography to detect coronary artery calcium. “These have been important predictors of events in adults, and are increasingly used in pediatric studies,” he said.

While he characterized the current health care landscape as being “at odds with the current reality facing today’s youth,” Dr. McCrindle suggested several ways that attendees can improve the CVD outlook in children, starting with being a role model for a healthy lifestyle. “We need to practice what we preach,” he said.

He also encouraged clinicians to implement existing pediatric guidelines on CVD health, assess and intervene on risk factors in children, and become more effective counselors.

“Instead of telling children what to do, we need to use techniques such as motivational interviewing to guide our young patients in discovering what they want to achieve,” Dr. McCrindle said. “We need to let kids set their own agenda and respect their autonomy. We also need to focus on ideal health across the lifespan, particularly on preventing risk factors and behaviors.”

Dr. McCrindle had no disclosures.

[email protected]

The periconceptional use of some selective serotonin reuptake inhibitors (SSRIs) appears to have no impact on the development of birth defects, but some birth defects occur more frequently among infants of women treated with paroxetine or fluoxetine early in pregnancy, results from a Bayesian analysis demonstrated.

“Recent meta-analyses and systematic reviews combining data from more than 20 epidemiological studies have reached conflicting conclusions and this uncertainty influences perceptions of the safety of antidepressant use in pregnancy,” researchers led by Jennita Reefhuis, Ph.D., of the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention, Atlanta, wrote in the British Medical Journal on July 8.

© Alliance/Thinkstock

“SSRIs are increasingly used by women of reproductive age and during pregnancy, but the inconsistent reports have limited opportunities for clinicians to carefully evaluate the risk compared with benefit of specific SSRIs for a given patient during pregnancy,” they said.

In an effort to evaluate the association between individual SSRIs and birth defects, the researchers used Bayesian methods to summarize independent findings identified in the literature and to update those findings using data from the U.S. National Birth Defects Prevention Study (NBDPS).

The analysis drew from 10 centers in the United States and included 17,952 mothers of infants with birth defects and 9,857 mothers of infants without birth defects, with estimated dates of delivery between 1997 and 2009. Exposures included the use of citalopram, escitalopram, fluoxetine, paroxetine, or sertraline in the month before through the third month of pregnancy (BMJ 2015;350:h3190 [doi:10.1136/bmj.h3190]).

The main outcome measure was the 14 categories of birth defects that, according to the medical literature, had associations with SSRIs: neural tube defects, anencephaly, all septal defects, ventricular septal defects, right ventricular outflow tract obstructions, cleft palate, cleft lip with or without cleft palate, esophageal atresia, anal atresia, hypospadias, any limb reduction defect, craniosynostosis, gastroschisis, and omphalocele.

The researchers found that sertraline was the most commonly used SSRI (reported use in early pregnancy was about 40%), but none of five previously reported birth defects associated with use of sertraline was confirmed. For nine previously reported associations between maternal SSRI use and birth defects in infants, the researchers found no association.

High posterior odds ratios were observed for five birth defects with paroxetine use: anencephaly (3.2); atrial septal defects (1.8); right ventricular outflow tract obstruction defects (2.4); gastroschisis (2.5); and omphalocele (3.5). Additionally, higher posterior odds ratios were observed for two defects with fluoxetine use: right ventricular outflow tract obstruction cardiac defects (2.0) and craniosynostosis (1.9).

“Although our analysis strongly supports the validity of the associations that were observed, the increase in the absolute risks, if the associations are causal, is small,” the researchers wrote.

They noted that the two strongest posterior odds ratios were seen for maternal paroxetine treatment and anencephaly or right ventricular outflow tract obstruction cardiac defects in the infant. If these associations are causal, the absolute risks in the children of women who are treated with paroxetine early in pregnancy would increase for anencephaly from 2 per 10,000 to 7 per 10,000. For right ventricular outflow tract obstruction cardiac defects, the absolute risk would increase from 10 per 10,000 to 24 per 10,000.

“The absolute risks for these birth defects are still low,” the researchers wrote.

The authors pointed out that their study confirms the need to assess the association between specific SSRIs and specific birth defects, rather than combining an entire drug class or a heterogeneous group of birth defects.

“Although SSRIs are similar pharmacologically, there are chemical differences, and if any of them do have teratogenic activity, it may be completely unrelated to the inhibition of serotonin receptors,” they wrote. ”SSRIs also differ pharmacokinetically, and this could account for differences in teratogenic activity, whether or not the mechanism involved inhibition of serotonin receptors.”

Data collection for the study was funded by the CDC. The authors reported having no financial disclosures.

[email protected]

The periconceptional use of some selective serotonin reuptake inhibitors (SSRIs) appears to have no impact on the development of birth defects, but some birth defects occur more frequently among infants of women treated with paroxetine or fluoxetine early in pregnancy, results from a Bayesian analysis demonstrated.

“Recent meta-analyses and systematic reviews combining data from more than 20 epidemiological studies have reached conflicting conclusions and this uncertainty influences perceptions of the safety of antidepressant use in pregnancy,” researchers led by Jennita Reefhuis, Ph.D., of the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention, Atlanta, wrote in the British Medical Journal on July 8.

© Alliance/Thinkstock

“SSRIs are increasingly used by women of reproductive age and during pregnancy, but the inconsistent reports have limited opportunities for clinicians to carefully evaluate the risk compared with benefit of specific SSRIs for a given patient during pregnancy,” they said.

In an effort to evaluate the association between individual SSRIs and birth defects, the researchers used Bayesian methods to summarize independent findings identified in the literature and to update those findings using data from the U.S. National Birth Defects Prevention Study (NBDPS).

The analysis drew from 10 centers in the United States and included 17,952 mothers of infants with birth defects and 9,857 mothers of infants without birth defects, with estimated dates of delivery between 1997 and 2009. Exposures included the use of citalopram, escitalopram, fluoxetine, paroxetine, or sertraline in the month before through the third month of pregnancy (BMJ 2015;350:h3190 [doi:10.1136/bmj.h3190]).

The main outcome measure was the 14 categories of birth defects that, according to the medical literature, had associations with SSRIs: neural tube defects, anencephaly, all septal defects, ventricular septal defects, right ventricular outflow tract obstructions, cleft palate, cleft lip with or without cleft palate, esophageal atresia, anal atresia, hypospadias, any limb reduction defect, craniosynostosis, gastroschisis, and omphalocele.

The researchers found that sertraline was the most commonly used SSRI (reported use in early pregnancy was about 40%), but none of five previously reported birth defects associated with use of sertraline was confirmed. For nine previously reported associations between maternal SSRI use and birth defects in infants, the researchers found no association.

High posterior odds ratios were observed for five birth defects with paroxetine use: anencephaly (3.2); atrial septal defects (1.8); right ventricular outflow tract obstruction defects (2.4); gastroschisis (2.5); and omphalocele (3.5). Additionally, higher posterior odds ratios were observed for two defects with fluoxetine use: right ventricular outflow tract obstruction cardiac defects (2.0) and craniosynostosis (1.9).

“Although our analysis strongly supports the validity of the associations that were observed, the increase in the absolute risks, if the associations are causal, is small,” the researchers wrote.

They noted that the two strongest posterior odds ratios were seen for maternal paroxetine treatment and anencephaly or right ventricular outflow tract obstruction cardiac defects in the infant. If these associations are causal, the absolute risks in the children of women who are treated with paroxetine early in pregnancy would increase for anencephaly from 2 per 10,000 to 7 per 10,000. For right ventricular outflow tract obstruction cardiac defects, the absolute risk would increase from 10 per 10,000 to 24 per 10,000.

“The absolute risks for these birth defects are still low,” the researchers wrote.

The authors pointed out that their study confirms the need to assess the association between specific SSRIs and specific birth defects, rather than combining an entire drug class or a heterogeneous group of birth defects.

“Although SSRIs are similar pharmacologically, there are chemical differences, and if any of them do have teratogenic activity, it may be completely unrelated to the inhibition of serotonin receptors,” they wrote. ”SSRIs also differ pharmacokinetically, and this could account for differences in teratogenic activity, whether or not the mechanism involved inhibition of serotonin receptors.”

Data collection for the study was funded by the CDC. The authors reported having no financial disclosures.

[email protected]

The periconceptional use of some selective serotonin reuptake inhibitors (SSRIs) appears to have no impact on the development of birth defects, but some birth defects occur more frequently among infants of women treated with paroxetine or fluoxetine early in pregnancy, results from a Bayesian analysis demonstrated.

“Recent meta-analyses and systematic reviews combining data from more than 20 epidemiological studies have reached conflicting conclusions and this uncertainty influences perceptions of the safety of antidepressant use in pregnancy,” researchers led by Jennita Reefhuis, Ph.D., of the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention, Atlanta, wrote in the British Medical Journal on July 8.

© Alliance/Thinkstock

“SSRIs are increasingly used by women of reproductive age and during pregnancy, but the inconsistent reports have limited opportunities for clinicians to carefully evaluate the risk compared with benefit of specific SSRIs for a given patient during pregnancy,” they said.

In an effort to evaluate the association between individual SSRIs and birth defects, the researchers used Bayesian methods to summarize independent findings identified in the literature and to update those findings using data from the U.S. National Birth Defects Prevention Study (NBDPS).

The analysis drew from 10 centers in the United States and included 17,952 mothers of infants with birth defects and 9,857 mothers of infants without birth defects, with estimated dates of delivery between 1997 and 2009. Exposures included the use of citalopram, escitalopram, fluoxetine, paroxetine, or sertraline in the month before through the third month of pregnancy (BMJ 2015;350:h3190 [doi:10.1136/bmj.h3190]).

The main outcome measure was the 14 categories of birth defects that, according to the medical literature, had associations with SSRIs: neural tube defects, anencephaly, all septal defects, ventricular septal defects, right ventricular outflow tract obstructions, cleft palate, cleft lip with or without cleft palate, esophageal atresia, anal atresia, hypospadias, any limb reduction defect, craniosynostosis, gastroschisis, and omphalocele.

The researchers found that sertraline was the most commonly used SSRI (reported use in early pregnancy was about 40%), but none of five previously reported birth defects associated with use of sertraline was confirmed. For nine previously reported associations between maternal SSRI use and birth defects in infants, the researchers found no association.

High posterior odds ratios were observed for five birth defects with paroxetine use: anencephaly (3.2); atrial septal defects (1.8); right ventricular outflow tract obstruction defects (2.4); gastroschisis (2.5); and omphalocele (3.5). Additionally, higher posterior odds ratios were observed for two defects with fluoxetine use: right ventricular outflow tract obstruction cardiac defects (2.0) and craniosynostosis (1.9).

“Although our analysis strongly supports the validity of the associations that were observed, the increase in the absolute risks, if the associations are causal, is small,” the researchers wrote.

They noted that the two strongest posterior odds ratios were seen for maternal paroxetine treatment and anencephaly or right ventricular outflow tract obstruction cardiac defects in the infant. If these associations are causal, the absolute risks in the children of women who are treated with paroxetine early in pregnancy would increase for anencephaly from 2 per 10,000 to 7 per 10,000. For right ventricular outflow tract obstruction cardiac defects, the absolute risk would increase from 10 per 10,000 to 24 per 10,000.

“The absolute risks for these birth defects are still low,” the researchers wrote.

The authors pointed out that their study confirms the need to assess the association between specific SSRIs and specific birth defects, rather than combining an entire drug class or a heterogeneous group of birth defects.

“Although SSRIs are similar pharmacologically, there are chemical differences, and if any of them do have teratogenic activity, it may be completely unrelated to the inhibition of serotonin receptors,” they wrote. ”SSRIs also differ pharmacokinetically, and this could account for differences in teratogenic activity, whether or not the mechanism involved inhibition of serotonin receptors.”

Data collection for the study was funded by the CDC. The authors reported having no financial disclosures.

[email protected]

After years of overtreatment for men with low-risk prostate cancer, the practice of active surveillance/watchful waiting increased sharply in 2010 through 2013. At the same time, high-risk disease was more often treated with potentially curative local treatment rather than with androgen deprivation therapy alone, though not in patients aged 75 and older.

Those are key findings from a snapshot of data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a registry that since 1995 has accrued men with prostate cancer diagnosed at 45 urology practices in the United States.

In a JAMA article published online on July 7, Dr. Matthew R. Cooperberg and Dr. Peter R. Carroll, of the department of urology at the University of California, San Francisco, reported findings from 10,472 men included in the analysis. Their mean age was 66 years and their median Cancer of the Prostate Risk Assessment (CAPRA) score was 2.

Surveillance for low-risk prostate cancer varied between 7% and 14% from 1990 through 2009, but increased to 40% between 2010 through 2013 (P less than .001). At the same time, treatment with androgen deprivation for intermediate- and high-risk tumors, which had been increasing between 1990 through 2009 (to 10% and 30%, respectively), decreased sharply (to 4% and 24%).

The researchers found that among men aged 75 and older, the rate of surveillance was 54% from 1990 through 1994, decreased to 22% from 2000 through 2004, and increased to 76% from 2010 through 2013. “There was an increase in the use of surgery for men aged 75 years or older with low-risk cancer to 9.5% and intermediate-risk cancer to 15%,” they wrote. “However, these was not an increase in use for those with high-risk cancer, among whom androgen deprivation accounted for 66.7% of treatment.”

Rates of overall surveillance among participating centers ranged widely during the time period studied, from 8% to 64%.

“Given that overtreatment of low-risk disease is a major driver of arguments against prostate cancer screening efforts, these observations may help inform a renewed discussion regarding early detection policy in the United States,” the authors concluded.

CapSURE is currently funded by a grant from the U.S. Department of Defense and by UCSF. Dr. Cooperberg disclosed that he has received grants and personal fees from Myriad Genetics, grants from Genomic Health and GenomeDx, and personal fees from Dendreon, Astellas, and Bayer. Dr. Carroll reported having no financial disclosures.

After years of overtreatment for men with low-risk prostate cancer, the practice of active surveillance/watchful waiting increased sharply in 2010 through 2013. At the same time, high-risk disease was more often treated with potentially curative local treatment rather than with androgen deprivation therapy alone, though not in patients aged 75 and older.

Those are key findings from a snapshot of data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a registry that since 1995 has accrued men with prostate cancer diagnosed at 45 urology practices in the United States.

In a JAMA article published online on July 7, Dr. Matthew R. Cooperberg and Dr. Peter R. Carroll, of the department of urology at the University of California, San Francisco, reported findings from 10,472 men included in the analysis. Their mean age was 66 years and their median Cancer of the Prostate Risk Assessment (CAPRA) score was 2.

Surveillance for low-risk prostate cancer varied between 7% and 14% from 1990 through 2009, but increased to 40% between 2010 through 2013 (P less than .001). At the same time, treatment with androgen deprivation for intermediate- and high-risk tumors, which had been increasing between 1990 through 2009 (to 10% and 30%, respectively), decreased sharply (to 4% and 24%).

The researchers found that among men aged 75 and older, the rate of surveillance was 54% from 1990 through 1994, decreased to 22% from 2000 through 2004, and increased to 76% from 2010 through 2013. “There was an increase in the use of surgery for men aged 75 years or older with low-risk cancer to 9.5% and intermediate-risk cancer to 15%,” they wrote. “However, these was not an increase in use for those with high-risk cancer, among whom androgen deprivation accounted for 66.7% of treatment.”

Rates of overall surveillance among participating centers ranged widely during the time period studied, from 8% to 64%.

“Given that overtreatment of low-risk disease is a major driver of arguments against prostate cancer screening efforts, these observations may help inform a renewed discussion regarding early detection policy in the United States,” the authors concluded.

CapSURE is currently funded by a grant from the U.S. Department of Defense and by UCSF. Dr. Cooperberg disclosed that he has received grants and personal fees from Myriad Genetics, grants from Genomic Health and GenomeDx, and personal fees from Dendreon, Astellas, and Bayer. Dr. Carroll reported having no financial disclosures.

After years of overtreatment for men with low-risk prostate cancer, the practice of active surveillance/watchful waiting increased sharply in 2010 through 2013. At the same time, high-risk disease was more often treated with potentially curative local treatment rather than with androgen deprivation therapy alone, though not in patients aged 75 and older.

Those are key findings from a snapshot of data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a registry that since 1995 has accrued men with prostate cancer diagnosed at 45 urology practices in the United States.

In a JAMA article published online on July 7, Dr. Matthew R. Cooperberg and Dr. Peter R. Carroll, of the department of urology at the University of California, San Francisco, reported findings from 10,472 men included in the analysis. Their mean age was 66 years and their median Cancer of the Prostate Risk Assessment (CAPRA) score was 2.

Surveillance for low-risk prostate cancer varied between 7% and 14% from 1990 through 2009, but increased to 40% between 2010 through 2013 (P less than .001). At the same time, treatment with androgen deprivation for intermediate- and high-risk tumors, which had been increasing between 1990 through 2009 (to 10% and 30%, respectively), decreased sharply (to 4% and 24%).

The researchers found that among men aged 75 and older, the rate of surveillance was 54% from 1990 through 1994, decreased to 22% from 2000 through 2004, and increased to 76% from 2010 through 2013. “There was an increase in the use of surgery for men aged 75 years or older with low-risk cancer to 9.5% and intermediate-risk cancer to 15%,” they wrote. “However, these was not an increase in use for those with high-risk cancer, among whom androgen deprivation accounted for 66.7% of treatment.”

Rates of overall surveillance among participating centers ranged widely during the time period studied, from 8% to 64%.

“Given that overtreatment of low-risk disease is a major driver of arguments against prostate cancer screening efforts, these observations may help inform a renewed discussion regarding early detection policy in the United States,” the authors concluded.

CapSURE is currently funded by a grant from the U.S. Department of Defense and by UCSF. Dr. Cooperberg disclosed that he has received grants and personal fees from Myriad Genetics, grants from Genomic Health and GenomeDx, and personal fees from Dendreon, Astellas, and Bayer. Dr. Carroll reported having no financial disclosures.

After years of overtreatment for men with low-risk prostate cancer, the practice of active surveillance/watchful waiting increased sharply in 2010 through 2013. At the same time, high-risk disease was more often treated with potentially curative local treatment rather than with androgen deprivation therapy alone, though not in patients aged 75 and older.

Those are key findings from a snapshot of data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a registry that since 1995 has accrued men with prostate cancer diagnosed at 45 urology practices in the United States.

In a JAMA article published online on July 7, Dr. Matthew R. Cooperberg and Dr. Peter R. Carroll, of the department of urology at the University of California, San Francisco, reported findings from 10,472 men included in the analysis. Their mean age was 66 years and their median Cancer of the Prostate Risk Assessment (CAPRA) score was 2.

Surveillance for low-risk prostate cancer varied between 7% and 14% from 1990 through 2009, but increased to 40% between 2010 through 2013 (P less than .001). At the same time, treatment with androgen deprivation for intermediate- and high-risk tumors, which had been increasing between 1990 through 2009 (to 10% and 30%, respectively), decreased sharply (to 4% and 24%).

The researchers found that among men aged 75 and older, the rate of surveillance was 54% from 1990 through 1994, decreased to 22% from 2000 through 2004, and increased to 76% from 2010 through 2013. “There was an increase in the use of surgery for men aged 75 years or older with low-risk cancer to 9.5% and intermediate-risk cancer to 15%,” they wrote. “However, these was not an increase in use for those with high-risk cancer, among whom androgen deprivation accounted for 66.7% of treatment.”

Rates of overall surveillance among participating centers ranged widely during the time period studied, from 8% to 64%.

“Given that overtreatment of low-risk disease is a major driver of arguments against prostate cancer screening efforts, these observations may help inform a renewed discussion regarding early detection policy in the United States,” the authors concluded.

CapSURE is currently funded by a grant from the U.S. Department of Defense and by UCSF. Dr. Cooperberg disclosed that he has received grants and personal fees from Myriad Genetics, grants from Genomic Health and GenomeDx, and personal fees from Dendreon, Astellas, and Bayer. Dr. Carroll reported having no financial disclosures.

[email protected]

After years of overtreatment for men with low-risk prostate cancer, the practice of active surveillance/watchful waiting increased sharply in 2010 through 2013. At the same time, high-risk disease was more often treated with potentially curative local treatment rather than with androgen deprivation therapy alone, though not in patients aged 75 and older.

Those are key findings from a snapshot of data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a registry that since 1995 has accrued men with prostate cancer diagnosed at 45 urology practices in the United States.

In a JAMA article published online on July 7, Dr. Matthew R. Cooperberg and Dr. Peter R. Carroll, of the department of urology at the University of California, San Francisco, reported findings from 10,472 men included in the analysis. Their mean age was 66 years and their median Cancer of the Prostate Risk Assessment (CAPRA) score was 2.

Surveillance for low-risk prostate cancer varied between 7% and 14% from 1990 through 2009, but increased to 40% between 2010 through 2013 (P less than .001). At the same time, treatment with androgen deprivation for intermediate- and high-risk tumors, which had been increasing between 1990 through 2009 (to 10% and 30%, respectively), decreased sharply (to 4% and 24%).

The researchers found that among men aged 75 and older, the rate of surveillance was 54% from 1990 through 1994, decreased to 22% from 2000 through 2004, and increased to 76% from 2010 through 2013. “There was an increase in the use of surgery for men aged 75 years or older with low-risk cancer to 9.5% and intermediate-risk cancer to 15%,” they wrote. “However, these was not an increase in use for those with high-risk cancer, among whom androgen deprivation accounted for 66.7% of treatment.”

Rates of overall surveillance among participating centers ranged widely during the time period studied, from 8% to 64%.

“Given that overtreatment of low-risk disease is a major driver of arguments against prostate cancer screening efforts, these observations may help inform a renewed discussion regarding early detection policy in the United States,” the authors concluded.

CapSURE is currently funded by a grant from the U.S. Department of Defense and by UCSF. Dr. Cooperberg disclosed that he has received grants and personal fees from Myriad Genetics, grants from Genomic Health and GenomeDx, and personal fees from Dendreon, Astellas, and Bayer. Dr. Carroll reported having no financial disclosures.

[email protected]

After years of overtreatment for men with low-risk prostate cancer, the practice of active surveillance/watchful waiting increased sharply in 2010 through 2013. At the same time, high-risk disease was more often treated with potentially curative local treatment rather than with androgen deprivation therapy alone, though not in patients aged 75 and older.

Those are key findings from a snapshot of data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a registry that since 1995 has accrued men with prostate cancer diagnosed at 45 urology practices in the United States.

In a JAMA article published online on July 7, Dr. Matthew R. Cooperberg and Dr. Peter R. Carroll, of the department of urology at the University of California, San Francisco, reported findings from 10,472 men included in the analysis. Their mean age was 66 years and their median Cancer of the Prostate Risk Assessment (CAPRA) score was 2.

Surveillance for low-risk prostate cancer varied between 7% and 14% from 1990 through 2009, but increased to 40% between 2010 through 2013 (P less than .001). At the same time, treatment with androgen deprivation for intermediate- and high-risk tumors, which had been increasing between 1990 through 2009 (to 10% and 30%, respectively), decreased sharply (to 4% and 24%).

The researchers found that among men aged 75 and older, the rate of surveillance was 54% from 1990 through 1994, decreased to 22% from 2000 through 2004, and increased to 76% from 2010 through 2013. “There was an increase in the use of surgery for men aged 75 years or older with low-risk cancer to 9.5% and intermediate-risk cancer to 15%,” they wrote. “However, these was not an increase in use for those with high-risk cancer, among whom androgen deprivation accounted for 66.7% of treatment.”

Rates of overall surveillance among participating centers ranged widely during the time period studied, from 8% to 64%.

“Given that overtreatment of low-risk disease is a major driver of arguments against prostate cancer screening efforts, these observations may help inform a renewed discussion regarding early detection policy in the United States,” the authors concluded.

CapSURE is currently funded by a grant from the U.S. Department of Defense and by UCSF. Dr. Cooperberg disclosed that he has received grants and personal fees from Myriad Genetics, grants from Genomic Health and GenomeDx, and personal fees from Dendreon, Astellas, and Bayer. Dr. Carroll reported having no financial disclosures.

[email protected]

Mortality among people with a history of diabetes, stroke, or myocardial infarction was similar for each condition, results from a large prospective study suggest. In addition, having two or all three of these conditions was associated with a reduced life expectancy of 12 and 15 years, respectively.

“Valid estimation of the associations of cardiometabolic multimorbidity with mortality requires comparison of people with multimorbidity with participants within the same cohorts who do not have any of the conditions at baseline,” authors of the Emerging Risk Factors Collaboration reported. The study was published online July 7 in JAMA. “Few population cohorts have had sufficient power-detail, and longevity to enable such comparisons,” the researchers wrote. “Our results highlight the need to balance the primary prevention and secondary prevention of cardiovascular disease.”

In an effort to estimate the associations of cardiometabolic multimorbidity with mortality and reductions in life expectancy, the researchers analyzed individual participant data in the Emerging Risk Factors Collaboration (ERFC) from 689,300 participants recruited between 1960 and 2007 into 91 prospective cohorts that have recorded mortality during prolonged follow-up. They compared the ERFC results with those from the UK Biobank, a prospective cohort study of 499,808 patients recruited between 2006 and 2010.

At baseline, the mean age of the ERFC participants was 53 years, 51% were women, and most were enrolled in Europe (69%) or North America (24%). Among ERFC participants without a history of diabetes, stroke, or MI, the all-cause mortality adjusted to the age of 60 years was 6.8 per 1,000 person-years. After adjustment for age and gender, mortality was 15.6 per 1,000 person-years among participants with a history of diabetes, 16.1 among those with stroke, 16.8 among those with an MI, 32 among those with a history of both diabetes and MI, 32.5 among those with both diabetes and stroke, 32.8 among those with both stroke and MI, and 59.5 among those with diabetes, stroke, and MI.

When translated into hazard ratios for mortality, and compared with the reference group, the age- and gender-adjusted HR was 1.9 for participants with a history of diabetes, 2.1 among those with stroke, 2.0 among those with MI, 3.7 among those with a history of both diabetes and MI, 3.8 among those with both diabetes and stroke, 3.5 among those with a both stroke and MI, and 6.9 among those with diabetes, stroke, and MI.

The hazard ratios in all categories were similar to those found in the UK Biobank.

“Our results suggest that the estimated reductions in life expectancy associated with cardiometabolic multimorbidity are of similar magnitude to those previously noted for exposures of major concern to public health, such as lifelong smoking (10 years of reduced life expectancy) and infection with the human immunodeficiency virus (11 years of reduced life expectancy),” the authors wrote. “For example, cardiometabolic multimorbidity at the age of 60 years was associated with an average reduction in life expectancy of about 15 years. We estimated even greater reductions in life expectancy in patients with multimorbidity at younger ages, such as 23 years of life lost in patients with 3 conditions at the age of 40 years.”

The ERFC authors disclosed numerous relevant financial ties to industry.

[email protected]

Mortality among people with a history of diabetes, stroke, or myocardial infarction was similar for each condition, results from a large prospective study suggest. In addition, having two or all three of these conditions was associated with a reduced life expectancy of 12 and 15 years, respectively.

“Valid estimation of the associations of cardiometabolic multimorbidity with mortality requires comparison of people with multimorbidity with participants within the same cohorts who do not have any of the conditions at baseline,” authors of the Emerging Risk Factors Collaboration reported. The study was published online July 7 in JAMA. “Few population cohorts have had sufficient power-detail, and longevity to enable such comparisons,” the researchers wrote. “Our results highlight the need to balance the primary prevention and secondary prevention of cardiovascular disease.”

In an effort to estimate the associations of cardiometabolic multimorbidity with mortality and reductions in life expectancy, the researchers analyzed individual participant data in the Emerging Risk Factors Collaboration (ERFC) from 689,300 participants recruited between 1960 and 2007 into 91 prospective cohorts that have recorded mortality during prolonged follow-up. They compared the ERFC results with those from the UK Biobank, a prospective cohort study of 499,808 patients recruited between 2006 and 2010.

At baseline, the mean age of the ERFC participants was 53 years, 51% were women, and most were enrolled in Europe (69%) or North America (24%). Among ERFC participants without a history of diabetes, stroke, or MI, the all-cause mortality adjusted to the age of 60 years was 6.8 per 1,000 person-years. After adjustment for age and gender, mortality was 15.6 per 1,000 person-years among participants with a history of diabetes, 16.1 among those with stroke, 16.8 among those with an MI, 32 among those with a history of both diabetes and MI, 32.5 among those with both diabetes and stroke, 32.8 among those with both stroke and MI, and 59.5 among those with diabetes, stroke, and MI.

When translated into hazard ratios for mortality, and compared with the reference group, the age- and gender-adjusted HR was 1.9 for participants with a history of diabetes, 2.1 among those with stroke, 2.0 among those with MI, 3.7 among those with a history of both diabetes and MI, 3.8 among those with both diabetes and stroke, 3.5 among those with a both stroke and MI, and 6.9 among those with diabetes, stroke, and MI.

The hazard ratios in all categories were similar to those found in the UK Biobank.

“Our results suggest that the estimated reductions in life expectancy associated with cardiometabolic multimorbidity are of similar magnitude to those previously noted for exposures of major concern to public health, such as lifelong smoking (10 years of reduced life expectancy) and infection with the human immunodeficiency virus (11 years of reduced life expectancy),” the authors wrote. “For example, cardiometabolic multimorbidity at the age of 60 years was associated with an average reduction in life expectancy of about 15 years. We estimated even greater reductions in life expectancy in patients with multimorbidity at younger ages, such as 23 years of life lost in patients with 3 conditions at the age of 40 years.”

The ERFC authors disclosed numerous relevant financial ties to industry.

[email protected]

Mortality among people with a history of diabetes, stroke, or myocardial infarction was similar for each condition, results from a large prospective study suggest. In addition, having two or all three of these conditions was associated with a reduced life expectancy of 12 and 15 years, respectively.

“Valid estimation of the associations of cardiometabolic multimorbidity with mortality requires comparison of people with multimorbidity with participants within the same cohorts who do not have any of the conditions at baseline,” authors of the Emerging Risk Factors Collaboration reported. The study was published online July 7 in JAMA. “Few population cohorts have had sufficient power-detail, and longevity to enable such comparisons,” the researchers wrote. “Our results highlight the need to balance the primary prevention and secondary prevention of cardiovascular disease.”

In an effort to estimate the associations of cardiometabolic multimorbidity with mortality and reductions in life expectancy, the researchers analyzed individual participant data in the Emerging Risk Factors Collaboration (ERFC) from 689,300 participants recruited between 1960 and 2007 into 91 prospective cohorts that have recorded mortality during prolonged follow-up. They compared the ERFC results with those from the UK Biobank, a prospective cohort study of 499,808 patients recruited between 2006 and 2010.

At baseline, the mean age of the ERFC participants was 53 years, 51% were women, and most were enrolled in Europe (69%) or North America (24%). Among ERFC participants without a history of diabetes, stroke, or MI, the all-cause mortality adjusted to the age of 60 years was 6.8 per 1,000 person-years. After adjustment for age and gender, mortality was 15.6 per 1,000 person-years among participants with a history of diabetes, 16.1 among those with stroke, 16.8 among those with an MI, 32 among those with a history of both diabetes and MI, 32.5 among those with both diabetes and stroke, 32.8 among those with both stroke and MI, and 59.5 among those with diabetes, stroke, and MI.

When translated into hazard ratios for mortality, and compared with the reference group, the age- and gender-adjusted HR was 1.9 for participants with a history of diabetes, 2.1 among those with stroke, 2.0 among those with MI, 3.7 among those with a history of both diabetes and MI, 3.8 among those with both diabetes and stroke, 3.5 among those with a both stroke and MI, and 6.9 among those with diabetes, stroke, and MI.

The hazard ratios in all categories were similar to those found in the UK Biobank.

“Our results suggest that the estimated reductions in life expectancy associated with cardiometabolic multimorbidity are of similar magnitude to those previously noted for exposures of major concern to public health, such as lifelong smoking (10 years of reduced life expectancy) and infection with the human immunodeficiency virus (11 years of reduced life expectancy),” the authors wrote. “For example, cardiometabolic multimorbidity at the age of 60 years was associated with an average reduction in life expectancy of about 15 years. We estimated even greater reductions in life expectancy in patients with multimorbidity at younger ages, such as 23 years of life lost in patients with 3 conditions at the age of 40 years.”

The ERFC authors disclosed numerous relevant financial ties to industry.

[email protected]

INDIANAPOLIS – With the emergence of 11 Food and Drug Administration–approved treatments for clinically isolated syndrome and/or relapsing forms of multiple sclerosis since 1993, patients have more choices for disease-modifying therapy than ever before. Dr. Mitzi Joi Williams describes choosing the right disease-modifying therapy as a balancing act that considers efficacy, safety, and tolerability.

“As we have more medications for MS, especially with different mechanisms of action, there may be some side effects that we may not be familiar with,” Dr. Williams, a neurologist at the Multiple Sclerosis Center of Atlanta, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “You want a drug that you and the patient feel comfortable with and find tolerable. In the past when we only had injections, we’d say, ‘you have to tough it out; we don’t have anything else.’ ”

Other considerations, she said, include non–neurologic side effects, sequencing of therapies, and compliance with monitoring. “Some medications require blood work every month for 6 months, others require blood work every month for 4 or 5 years,” Dr. Williams said. “That’s a lot for patients to keep up with.”

The two most recent drugs approved for MS are alemtuzumab and pegylated interferon beta-1a. Alemtuzumab, which is indicated for the treatment of relapsing-remitting MS, is a monoclonal antibody to CD52 and has been previously used in patients with chronic lymphocytic leukemia. Dosing is 12 mg/day delivered intravenously for 3-5 days once a year. Possible adverse effects include profound lymphopenia, autoimmune thyroid disease, immune thrombocytopenic purpura, infusion reaction, and increased susceptibility to infections.

The other newcomer, pegylated interferon beta-1a is a recombinant interferon beta-1a protein attached to a polyethylene glycol molecule that reduces proinflammatory cytokines and inhibits T-cell migration and is indicated for relapsing MS. Dosing is 125 mcg subcutaneously every 2 or 4 weeks. Common adverse events include flulike symptoms, infection-site reactions, fever, and headache.

Another drug that has been submitted to the FDA for approval is daclizumab, a humanized monoclonal antibody that binds to CD25, decreasing activated T cells. It is intended for the treatment of relapsing MS. The dosing schedule would be 150 mg delivered subcutaneously every other week at home. Data from the SELECT trial, a year-long, phase II study of the agent, showed a 50%-54% decrease in annualized relapse rate (ARR), a 43%-57% decrease in confirmed disability, a 79%-86% reduction in new gadolinium (Gd)-enhancing lesions, and a 70%-79% reduction in new or enlarging T2 lesions. A phase II extension trial called SELECTION showed a 59% decrease in ARR, a 54% decrease in confirmed disability, a 86% reduction in new Gd-enhancing lesions, and a 74% reduction in new or enlarging T2 lesions. Potential adverse side effects include increased risk for infection, abnormal liver function tests, diarrhea, constipation, and swelling of the extremities. It has previously been used in rheumatoid arthritis and in kidney transplant patients.

Another promising agent in phase III studies is ocrelizumab, which is being studied in doses of 600 mg or 2,000 mg in patients with relapsing-remitting MS and primary-progressive MS. “It’s an anti-CD20 molecule that is similar to rituximab, which has been used in MS for some time, but it’s a more humanized antibody,” Dr. Williams said. She noted that a multicenter phase II study showed that ARR decreased by 73% with the 2,000-mg dose and by 80% with the 600-mg dose (Lancet 2011;378:1779-87). It also showed that Gd-enhancing lesions decreased by 96% with the 2,000-mg dose and by 89% with the 600-mg dose. “Potential adverse events reported in the trial include infusion-site reactions and increased risk of infection,” she said. “One study participant died from systemic inflammatory response of unknown cause.”

Other drugs for relapsing MS in earlier phases of research included ofatumumab, S1P receptor modulators, Tcelna, statins, antibiotics, and vitamin D3. Agents being investigated for progressive MS include S1P receptor modulators, masitinib, and ibudilast. “The more options we have for our patients, the better, because there’s no one drug that’s right for everyone,” Dr. Williams said.

Potential therapies could eventually come via more studies of drugs and mechanisms for myelin repair, including anti-LINGO-1 and stem cell therapies, as well as hormone therapy in the form of estrogen and testosterone. Other avenues of research include gene and DNA studies, personalized medicine and biomarkers, and monitoring progression of disease.

Dr. Williams disclosed that she is a consultant and speaker for Biogen Idec, Teva Neuroscience, EMD Serono, Mallinckrodt Pharmaceuticals, Novartis, Genzyme, and Acorda Therapeutics.

[email protected]

INDIANAPOLIS – With the emergence of 11 Food and Drug Administration–approved treatments for clinically isolated syndrome and/or relapsing forms of multiple sclerosis since 1993, patients have more choices for disease-modifying therapy than ever before. Dr. Mitzi Joi Williams describes choosing the right disease-modifying therapy as a balancing act that considers efficacy, safety, and tolerability.

“As we have more medications for MS, especially with different mechanisms of action, there may be some side effects that we may not be familiar with,” Dr. Williams, a neurologist at the Multiple Sclerosis Center of Atlanta, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “You want a drug that you and the patient feel comfortable with and find tolerable. In the past when we only had injections, we’d say, ‘you have to tough it out; we don’t have anything else.’ ”

Other considerations, she said, include non–neurologic side effects, sequencing of therapies, and compliance with monitoring. “Some medications require blood work every month for 6 months, others require blood work every month for 4 or 5 years,” Dr. Williams said. “That’s a lot for patients to keep up with.”

The two most recent drugs approved for MS are alemtuzumab and pegylated interferon beta-1a. Alemtuzumab, which is indicated for the treatment of relapsing-remitting MS, is a monoclonal antibody to CD52 and has been previously used in patients with chronic lymphocytic leukemia. Dosing is 12 mg/day delivered intravenously for 3-5 days once a year. Possible adverse effects include profound lymphopenia, autoimmune thyroid disease, immune thrombocytopenic purpura, infusion reaction, and increased susceptibility to infections.

The other newcomer, pegylated interferon beta-1a is a recombinant interferon beta-1a protein attached to a polyethylene glycol molecule that reduces proinflammatory cytokines and inhibits T-cell migration and is indicated for relapsing MS. Dosing is 125 mcg subcutaneously every 2 or 4 weeks. Common adverse events include flulike symptoms, infection-site reactions, fever, and headache.

Another drug that has been submitted to the FDA for approval is daclizumab, a humanized monoclonal antibody that binds to CD25, decreasing activated T cells. It is intended for the treatment of relapsing MS. The dosing schedule would be 150 mg delivered subcutaneously every other week at home. Data from the SELECT trial, a year-long, phase II study of the agent, showed a 50%-54% decrease in annualized relapse rate (ARR), a 43%-57% decrease in confirmed disability, a 79%-86% reduction in new gadolinium (Gd)-enhancing lesions, and a 70%-79% reduction in new or enlarging T2 lesions. A phase II extension trial called SELECTION showed a 59% decrease in ARR, a 54% decrease in confirmed disability, a 86% reduction in new Gd-enhancing lesions, and a 74% reduction in new or enlarging T2 lesions. Potential adverse side effects include increased risk for infection, abnormal liver function tests, diarrhea, constipation, and swelling of the extremities. It has previously been used in rheumatoid arthritis and in kidney transplant patients.

Another promising agent in phase III studies is ocrelizumab, which is being studied in doses of 600 mg or 2,000 mg in patients with relapsing-remitting MS and primary-progressive MS. “It’s an anti-CD20 molecule that is similar to rituximab, which has been used in MS for some time, but it’s a more humanized antibody,” Dr. Williams said. She noted that a multicenter phase II study showed that ARR decreased by 73% with the 2,000-mg dose and by 80% with the 600-mg dose (Lancet 2011;378:1779-87). It also showed that Gd-enhancing lesions decreased by 96% with the 2,000-mg dose and by 89% with the 600-mg dose. “Potential adverse events reported in the trial include infusion-site reactions and increased risk of infection,” she said. “One study participant died from systemic inflammatory response of unknown cause.”

Other drugs for relapsing MS in earlier phases of research included ofatumumab, S1P receptor modulators, Tcelna, statins, antibiotics, and vitamin D3. Agents being investigated for progressive MS include S1P receptor modulators, masitinib, and ibudilast. “The more options we have for our patients, the better, because there’s no one drug that’s right for everyone,” Dr. Williams said.

Potential therapies could eventually come via more studies of drugs and mechanisms for myelin repair, including anti-LINGO-1 and stem cell therapies, as well as hormone therapy in the form of estrogen and testosterone. Other avenues of research include gene and DNA studies, personalized medicine and biomarkers, and monitoring progression of disease.

Dr. Williams disclosed that she is a consultant and speaker for Biogen Idec, Teva Neuroscience, EMD Serono, Mallinckrodt Pharmaceuticals, Novartis, Genzyme, and Acorda Therapeutics.

[email protected]

INDIANAPOLIS – With the emergence of 11 Food and Drug Administration–approved treatments for clinically isolated syndrome and/or relapsing forms of multiple sclerosis since 1993, patients have more choices for disease-modifying therapy than ever before. Dr. Mitzi Joi Williams describes choosing the right disease-modifying therapy as a balancing act that considers efficacy, safety, and tolerability.

“As we have more medications for MS, especially with different mechanisms of action, there may be some side effects that we may not be familiar with,” Dr. Williams, a neurologist at the Multiple Sclerosis Center of Atlanta, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “You want a drug that you and the patient feel comfortable with and find tolerable. In the past when we only had injections, we’d say, ‘you have to tough it out; we don’t have anything else.’ ”

Other considerations, she said, include non–neurologic side effects, sequencing of therapies, and compliance with monitoring. “Some medications require blood work every month for 6 months, others require blood work every month for 4 or 5 years,” Dr. Williams said. “That’s a lot for patients to keep up with.”

The two most recent drugs approved for MS are alemtuzumab and pegylated interferon beta-1a. Alemtuzumab, which is indicated for the treatment of relapsing-remitting MS, is a monoclonal antibody to CD52 and has been previously used in patients with chronic lymphocytic leukemia. Dosing is 12 mg/day delivered intravenously for 3-5 days once a year. Possible adverse effects include profound lymphopenia, autoimmune thyroid disease, immune thrombocytopenic purpura, infusion reaction, and increased susceptibility to infections.

The other newcomer, pegylated interferon beta-1a is a recombinant interferon beta-1a protein attached to a polyethylene glycol molecule that reduces proinflammatory cytokines and inhibits T-cell migration and is indicated for relapsing MS. Dosing is 125 mcg subcutaneously every 2 or 4 weeks. Common adverse events include flulike symptoms, infection-site reactions, fever, and headache.

Another drug that has been submitted to the FDA for approval is daclizumab, a humanized monoclonal antibody that binds to CD25, decreasing activated T cells. It is intended for the treatment of relapsing MS. The dosing schedule would be 150 mg delivered subcutaneously every other week at home. Data from the SELECT trial, a year-long, phase II study of the agent, showed a 50%-54% decrease in annualized relapse rate (ARR), a 43%-57% decrease in confirmed disability, a 79%-86% reduction in new gadolinium (Gd)-enhancing lesions, and a 70%-79% reduction in new or enlarging T2 lesions. A phase II extension trial called SELECTION showed a 59% decrease in ARR, a 54% decrease in confirmed disability, a 86% reduction in new Gd-enhancing lesions, and a 74% reduction in new or enlarging T2 lesions. Potential adverse side effects include increased risk for infection, abnormal liver function tests, diarrhea, constipation, and swelling of the extremities. It has previously been used in rheumatoid arthritis and in kidney transplant patients.

Another promising agent in phase III studies is ocrelizumab, which is being studied in doses of 600 mg or 2,000 mg in patients with relapsing-remitting MS and primary-progressive MS. “It’s an anti-CD20 molecule that is similar to rituximab, which has been used in MS for some time, but it’s a more humanized antibody,” Dr. Williams said. She noted that a multicenter phase II study showed that ARR decreased by 73% with the 2,000-mg dose and by 80% with the 600-mg dose (Lancet 2011;378:1779-87). It also showed that Gd-enhancing lesions decreased by 96% with the 2,000-mg dose and by 89% with the 600-mg dose. “Potential adverse events reported in the trial include infusion-site reactions and increased risk of infection,” she said. “One study participant died from systemic inflammatory response of unknown cause.”

Other drugs for relapsing MS in earlier phases of research included ofatumumab, S1P receptor modulators, Tcelna, statins, antibiotics, and vitamin D3. Agents being investigated for progressive MS include S1P receptor modulators, masitinib, and ibudilast. “The more options we have for our patients, the better, because there’s no one drug that’s right for everyone,” Dr. Williams said.

Potential therapies could eventually come via more studies of drugs and mechanisms for myelin repair, including anti-LINGO-1 and stem cell therapies, as well as hormone therapy in the form of estrogen and testosterone. Other avenues of research include gene and DNA studies, personalized medicine and biomarkers, and monitoring progression of disease.

Dr. Williams disclosed that she is a consultant and speaker for Biogen Idec, Teva Neuroscience, EMD Serono, Mallinckrodt Pharmaceuticals, Novartis, Genzyme, and Acorda Therapeutics.

[email protected]

Between 1997 and 2006, the proportion of hospitalizations in the United States for pediatric pulmonary hypertension doubled, from 1 in 1,000 discharges for the condition in 1997 to 1 in 500 in 2006, a national retrospective cohort study found.

“These results have practice and policy implications at the institutional, state, and national levels, particularly in the face of increasing pressure to restrain costs while caring for a population with increasingly complex medical needs,” researchers led by Dr. Bryan G. Maxwell reported online June 6, 2015 in Pediatrics (doi/10.1542/peds.2014-3834).

Dr. Maxwell of the departments of anesthesiology and critical care medicine at Johns Hopkins University, Baltimore, Md., and his associates examined data on pediatric pulmonary hypertension (PH) hospitalizations between 1997 and 2006 from the Kids’ Inpatient Database, which is part of the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality.

Of the estimated 43 million pediatric discharges that occurred between 1997 and 2006, 0.13% were for PH, and discharges for the condition increased over the study period, from 1 in 500 in 1997 to 1 in 1,000 in 2006 (P less than .0001). During the same time period, inflation-adjusted national hospital charges for PH hospitalizations increased from $926 million to 3.12 billion (P = .0003).

The researchers also found that the increase in PH discharges was most pronounced between 2006 and 2012, and that most PH hospitalizations did not occur in dedicated children’s hospitals. The overall mortality of patients discharged with PH was 5.9%, and steadily improved between 1997 and 2012 (P less than .0001).

Dr. Maxwell and his associates acknowledged certain limitations of the study, including the fact that the Kids’ Inpatient Database does not provide longitudinal data on patients with PH over time or on outpatient care, and that ICD-9-CM codes “do not permit accurate identification of subgroups of patients with PH in a way that is consistent with the most current schemata for categorizing PH.”

Despite such limitations, they concluded that the current study “is useful in demonstrating the burgeoning number and nature of pediatric PH hospitalizations and the implications of these trends for resource utilization and public policy.”

The researchers reported having no relevant financial disclosures.

[email protected]

Between 1997 and 2006, the proportion of hospitalizations in the United States for pediatric pulmonary hypertension doubled, from 1 in 1,000 discharges for the condition in 1997 to 1 in 500 in 2006, a national retrospective cohort study found.

“These results have practice and policy implications at the institutional, state, and national levels, particularly in the face of increasing pressure to restrain costs while caring for a population with increasingly complex medical needs,” researchers led by Dr. Bryan G. Maxwell reported online June 6, 2015 in Pediatrics (doi/10.1542/peds.2014-3834).

Dr. Maxwell of the departments of anesthesiology and critical care medicine at Johns Hopkins University, Baltimore, Md., and his associates examined data on pediatric pulmonary hypertension (PH) hospitalizations between 1997 and 2006 from the Kids’ Inpatient Database, which is part of the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality.

Of the estimated 43 million pediatric discharges that occurred between 1997 and 2006, 0.13% were for PH, and discharges for the condition increased over the study period, from 1 in 500 in 1997 to 1 in 1,000 in 2006 (P less than .0001). During the same time period, inflation-adjusted national hospital charges for PH hospitalizations increased from $926 million to 3.12 billion (P = .0003).

The researchers also found that the increase in PH discharges was most pronounced between 2006 and 2012, and that most PH hospitalizations did not occur in dedicated children’s hospitals. The overall mortality of patients discharged with PH was 5.9%, and steadily improved between 1997 and 2012 (P less than .0001).

Dr. Maxwell and his associates acknowledged certain limitations of the study, including the fact that the Kids’ Inpatient Database does not provide longitudinal data on patients with PH over time or on outpatient care, and that ICD-9-CM codes “do not permit accurate identification of subgroups of patients with PH in a way that is consistent with the most current schemata for categorizing PH.”

Despite such limitations, they concluded that the current study “is useful in demonstrating the burgeoning number and nature of pediatric PH hospitalizations and the implications of these trends for resource utilization and public policy.”

The researchers reported having no relevant financial disclosures.

[email protected]

Between 1997 and 2006, the proportion of hospitalizations in the United States for pediatric pulmonary hypertension doubled, from 1 in 1,000 discharges for the condition in 1997 to 1 in 500 in 2006, a national retrospective cohort study found.

“These results have practice and policy implications at the institutional, state, and national levels, particularly in the face of increasing pressure to restrain costs while caring for a population with increasingly complex medical needs,” researchers led by Dr. Bryan G. Maxwell reported online June 6, 2015 in Pediatrics (doi/10.1542/peds.2014-3834).

Dr. Maxwell of the departments of anesthesiology and critical care medicine at Johns Hopkins University, Baltimore, Md., and his associates examined data on pediatric pulmonary hypertension (PH) hospitalizations between 1997 and 2006 from the Kids’ Inpatient Database, which is part of the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality.

Of the estimated 43 million pediatric discharges that occurred between 1997 and 2006, 0.13% were for PH, and discharges for the condition increased over the study period, from 1 in 500 in 1997 to 1 in 1,000 in 2006 (P less than .0001). During the same time period, inflation-adjusted national hospital charges for PH hospitalizations increased from $926 million to 3.12 billion (P = .0003).

The researchers also found that the increase in PH discharges was most pronounced between 2006 and 2012, and that most PH hospitalizations did not occur in dedicated children’s hospitals. The overall mortality of patients discharged with PH was 5.9%, and steadily improved between 1997 and 2012 (P less than .0001).

Dr. Maxwell and his associates acknowledged certain limitations of the study, including the fact that the Kids’ Inpatient Database does not provide longitudinal data on patients with PH over time or on outpatient care, and that ICD-9-CM codes “do not permit accurate identification of subgroups of patients with PH in a way that is consistent with the most current schemata for categorizing PH.”

Despite such limitations, they concluded that the current study “is useful in demonstrating the burgeoning number and nature of pediatric PH hospitalizations and the implications of these trends for resource utilization and public policy.”

The researchers reported having no relevant financial disclosures.

[email protected]

Health professionals from two cohort studies who consumed citrus products more than 1.6 times a day had a 36% higher risk of developing cutaneous malignant melanoma, compared with those who consumed citrus less than twice a week, a large prospective study showed.

Among citrus products studied, consumption of whole grapefruit, but not grapefruit juice, showed the most apparent association with melanoma risk, Shaowei Wu, Ph.D., of Brigham and Women’s Hospital, Boston, and associates reported online June 29 (J. Clin. Oncol. 2015 [doi:10.1200/JCO.2014.57.4111]).

“These findings provide evidence for the potential photocarcinogenic effect of psoralen-rich foods,” the researchers wrote. “However, previous studies have also suggested that fruit intake may have potential beneficial effects for the prevention of chronic diseases, such as breast cancer and type 2 diabetes. Although our findings are consistent with evidence from animal experiments, which revealed a potential synergistic effect between psoralens and UV radiation, further investigation is needed to confirm our findings and guide sun exposure behaviors among individuals with high citrus consumption.”

©Ls9907/Thinkstockphotos.com

For the analysis, the researchers evaluated dietary information from 63,810 women in the Nurses’ Health Study (1984-2010) and 41,622 men in the Health Professionals Follow-up Study (1986-2010). In these studies, dietary information was assessed every 2-4 years during follow-up, while incident melanoma cases were identified through self-report and confirmed by pathology.

During a follow-up period of 24-26 years, the researchers documented 1,840 incident melanomas. After adjusting for risk factors, the pooled multivariable hazard ratios for melanoma were 1.00 for overall citrus consumption less than twice per week (reference), 1.10 for two to four times per week, 1.26 for five to six times per week, 1.27 for 1-1.5 times per day, and 1.36 for 1.6 times per day or more.

“Interestingly, fresh grapefruit showed the most apparent association with melanoma among individual citrus products, which may be explained by its higher levels of psoralens and furocoumarins when compared with oranges,” wrote the researchers, who found that the pooled multivariable HR for melanoma was 1.41 for the highest consumption of grapefruit (defined as three or more times per week, versus none).

“The significant but less apparent association between [consumption of] orange juice with melanoma risk may be partly explained by its much higher consumption levels, which contributed to greater than 50% of overall citrus consumption, whereas the null association of grapefruit juice with melanoma risk may be a result of its much lower consumption levels and a large number of nonconsumers, as compared with the other individual citrus products,” they said.

In addition, Dr. Wu and associates found that the association between grapefruit consumption and melanoma was more apparent among those with a history of sunburn and higher exposure to UV radiation. The association also appeared to be stronger “for melanomas on body sites with higher continuous sun exposure (e.g., head, neck, and extremities) than for melanomas on body sites with lower continuous sun exposure (e.g., truncal sites), which may suggest a potential synergistic effect between dietary consumption and solar UV radiation.”

They acknowledged certain limitations of the study, including the fact that the dietary data were self-reported and that the two cohorts were “mostly comprised [of] white, educated U.S. health professionals, which potentially limits the generalizability of the findings.”

Dr. Wu and five coauthors reported having no financial disclosures. A seventh coauthor, Dr. Abrar A. Qureshi, disclosed that he has a consulting or advisory role with Abbvie, Novartis, Janssen Pharmaceuticals, and Pfizer. He also has received research funding from Regeneron.

[email protected]

Health professionals from two cohort studies who consumed citrus products more than 1.6 times a day had a 36% higher risk of developing cutaneous malignant melanoma, compared with those who consumed citrus less than twice a week, a large prospective study showed.

Among citrus products studied, consumption of whole grapefruit, but not grapefruit juice, showed the most apparent association with melanoma risk, Shaowei Wu, Ph.D., of Brigham and Women’s Hospital, Boston, and associates reported online June 29 (J. Clin. Oncol. 2015 [doi:10.1200/JCO.2014.57.4111]).

“These findings provide evidence for the potential photocarcinogenic effect of psoralen-rich foods,” the researchers wrote. “However, previous studies have also suggested that fruit intake may have potential beneficial effects for the prevention of chronic diseases, such as breast cancer and type 2 diabetes. Although our findings are consistent with evidence from animal experiments, which revealed a potential synergistic effect between psoralens and UV radiation, further investigation is needed to confirm our findings and guide sun exposure behaviors among individuals with high citrus consumption.”

©Ls9907/Thinkstockphotos.com

For the analysis, the researchers evaluated dietary information from 63,810 women in the Nurses’ Health Study (1984-2010) and 41,622 men in the Health Professionals Follow-up Study (1986-2010). In these studies, dietary information was assessed every 2-4 years during follow-up, while incident melanoma cases were identified through self-report and confirmed by pathology.

During a follow-up period of 24-26 years, the researchers documented 1,840 incident melanomas. After adjusting for risk factors, the pooled multivariable hazard ratios for melanoma were 1.00 for overall citrus consumption less than twice per week (reference), 1.10 for two to four times per week, 1.26 for five to six times per week, 1.27 for 1-1.5 times per day, and 1.36 for 1.6 times per day or more.

“Interestingly, fresh grapefruit showed the most apparent association with melanoma among individual citrus products, which may be explained by its higher levels of psoralens and furocoumarins when compared with oranges,” wrote the researchers, who found that the pooled multivariable HR for melanoma was 1.41 for the highest consumption of grapefruit (defined as three or more times per week, versus none).

“The significant but less apparent association between [consumption of] orange juice with melanoma risk may be partly explained by its much higher consumption levels, which contributed to greater than 50% of overall citrus consumption, whereas the null association of grapefruit juice with melanoma risk may be a result of its much lower consumption levels and a large number of nonconsumers, as compared with the other individual citrus products,” they said.

In addition, Dr. Wu and associates found that the association between grapefruit consumption and melanoma was more apparent among those with a history of sunburn and higher exposure to UV radiation. The association also appeared to be stronger “for melanomas on body sites with higher continuous sun exposure (e.g., head, neck, and extremities) than for melanomas on body sites with lower continuous sun exposure (e.g., truncal sites), which may suggest a potential synergistic effect between dietary consumption and solar UV radiation.”

They acknowledged certain limitations of the study, including the fact that the dietary data were self-reported and that the two cohorts were “mostly comprised [of] white, educated U.S. health professionals, which potentially limits the generalizability of the findings.”

Dr. Wu and five coauthors reported having no financial disclosures. A seventh coauthor, Dr. Abrar A. Qureshi, disclosed that he has a consulting or advisory role with Abbvie, Novartis, Janssen Pharmaceuticals, and Pfizer. He also has received research funding from Regeneron.

[email protected]

Health professionals from two cohort studies who consumed citrus products more than 1.6 times a day had a 36% higher risk of developing cutaneous malignant melanoma, compared with those who consumed citrus less than twice a week, a large prospective study showed.

Among citrus products studied, consumption of whole grapefruit, but not grapefruit juice, showed the most apparent association with melanoma risk, Shaowei Wu, Ph.D., of Brigham and Women’s Hospital, Boston, and associates reported online June 29 (J. Clin. Oncol. 2015 [doi:10.1200/JCO.2014.57.4111]).

“These findings provide evidence for the potential photocarcinogenic effect of psoralen-rich foods,” the researchers wrote. “However, previous studies have also suggested that fruit intake may have potential beneficial effects for the prevention of chronic diseases, such as breast cancer and type 2 diabetes. Although our findings are consistent with evidence from animal experiments, which revealed a potential synergistic effect between psoralens and UV radiation, further investigation is needed to confirm our findings and guide sun exposure behaviors among individuals with high citrus consumption.”

©Ls9907/Thinkstockphotos.com

For the analysis, the researchers evaluated dietary information from 63,810 women in the Nurses’ Health Study (1984-2010) and 41,622 men in the Health Professionals Follow-up Study (1986-2010). In these studies, dietary information was assessed every 2-4 years during follow-up, while incident melanoma cases were identified through self-report and confirmed by pathology.

During a follow-up period of 24-26 years, the researchers documented 1,840 incident melanomas. After adjusting for risk factors, the pooled multivariable hazard ratios for melanoma were 1.00 for overall citrus consumption less than twice per week (reference), 1.10 for two to four times per week, 1.26 for five to six times per week, 1.27 for 1-1.5 times per day, and 1.36 for 1.6 times per day or more.

“Interestingly, fresh grapefruit showed the most apparent association with melanoma among individual citrus products, which may be explained by its higher levels of psoralens and furocoumarins when compared with oranges,” wrote the researchers, who found that the pooled multivariable HR for melanoma was 1.41 for the highest consumption of grapefruit (defined as three or more times per week, versus none).

“The significant but less apparent association between [consumption of] orange juice with melanoma risk may be partly explained by its much higher consumption levels, which contributed to greater than 50% of overall citrus consumption, whereas the null association of grapefruit juice with melanoma risk may be a result of its much lower consumption levels and a large number of nonconsumers, as compared with the other individual citrus products,” they said.

In addition, Dr. Wu and associates found that the association between grapefruit consumption and melanoma was more apparent among those with a history of sunburn and higher exposure to UV radiation. The association also appeared to be stronger “for melanomas on body sites with higher continuous sun exposure (e.g., head, neck, and extremities) than for melanomas on body sites with lower continuous sun exposure (e.g., truncal sites), which may suggest a potential synergistic effect between dietary consumption and solar UV radiation.”

They acknowledged certain limitations of the study, including the fact that the dietary data were self-reported and that the two cohorts were “mostly comprised [of] white, educated U.S. health professionals, which potentially limits the generalizability of the findings.”

Dr. Wu and five coauthors reported having no financial disclosures. A seventh coauthor, Dr. Abrar A. Qureshi, disclosed that he has a consulting or advisory role with Abbvie, Novartis, Janssen Pharmaceuticals, and Pfizer. He also has received research funding from Regeneron.

[email protected]

INDIANAPOLIS – Consider disease activity, patient comorbidities, treatment tolerability, and patient or physician preference when prescribing disease-modifying therapy for multiple sclerosis patients.

“Where I practice, patient preference can sound something like, ‘My sister-in-law’s cousin’s friend at church takes drug X, and that’s the one I’m interested in,’ ” said Dr. Myla D. Goldman, a neurologist who directs the James Q. Miller Multiple Sclerosis Clinic at the University of Virginia, Charlottesville. “It’s sometimes guided by just familiarity or word of mouth, or something that they’ve read or someone that they know. In terms of our own preferences as clinicians, those are much harder to characterize. I think they become shaped over time and our own experiences, as well as being guided by evidence-based medicine.”

In a survey, 102 neurologists were asked about how they made decisions regarding the prescription of disease-modifying therapies (DMTs) for patients with MS (Patient Prefer. Adherence 2014;8:415-22). More than 80% ranked efficacy as the most important attribute of DMT medication selection, followed by safety, tolerability, patient preference, and convenience (including dosing frequency and administration method). In a separate study presented at the 2014 meeting of the American Academy of Neurology, 1,628 MS patients in Germany were asked about the importance of different DMT features (Neurology 2014;82[10 Suppl.]:P3.137). They ranked oral administration as the most important attribute in guiding their DMT preference, while the second most relevant attribute was frequency of administration.

In a more recent study, 50 patients with relapsing-remitting MS were asked about their preferences for attributes of DMTs (Int. J. MS Care 2015;17:74-82). Survey respondents showed the highest preference for medications that would improve their symptoms, which is not a proven DMT outcome. Preventing relapses, which is a key clinical trial outcome, was not associated with significant preferences.

“This is important to know but adds another layer of challenge and complication [because] what we understand most about many of these agents is their effect on relapse rates,” Dr. Goldman said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “It’s another disconnect in terms of what we’re thinking about, the tools that we have, and where our patients are coming from.”

Other factors to consider when selecting a DMT include disease activity/burden, risk/prognostic factors, treatment safety/tolerability, comorbidity, and treatment access/logistics. “As we’ve had more and more [DMT] choices available to us, we’ve become more restricted in how we make choices – which patients can have what choices in what order,” she said. “This is a reality that we all have to face but is something that varies from third-party payers and region, and can be really complicated to navigate.”

In general, Dr. Goldman continued, it’s recognized that more active disease requires more effective therapies with greater tolerance for risk. However, evidence suggesting that early disease activity predicts long-term outcome is poor, “not because it may not be true but because we don’t have as robust data as we would like,” she said. “We also have few [clinical] trials focused on this group. So when we look at high disease activity, it’s typically in a subgroup analysis. There are risks for underpowering and a lack of direct comparisons among therapies. I have found that my idea of disease activity and my individual patient’s idea of disease activity sometimes differ. Perhaps I think we need to make a change, and they feel comfortable with what they’re taking, or vice versa.”

There are various predictors of disease activity and outcomes based on early signs and symptoms, “but these outcomes are variable when we are comparing across studies,” she noted. These predictors and outcomes include:

• Early disease activity predicts relapse disease activity early, especially with posterior fossa lesions and enhancing lesions.

• Early MRI activity predicts long-term disability.

• A baseline T2 lesion burden predicts change in the Kurtzke Expanded Disability Status Scale (EDSS) and progression to secondary-progressive MS.

• A T2 lesion change at 1 year predicts EDSS change.

• Brain atrophy over 2 years predicts EDSS at 8 years.

Favorable prognostic factors include monofocal onset, onset with optic neuritis or isolated sensory symptoms, younger age at onset, being white, being female, having a low relapse rate in the first 2-5 years, and a long interval between the first and second relapse. “That’s where early treatment and impact on relapse rate has a really important role,” she said.

Unfavorable factors in relapsing-remitting MS include multifocal onset, being black, older age at onset, being male, high relapse rate in the first 2-5 years, disability at 5 years, cognitive impairment, high MRI lesion load at baseline, atrophy and T1 holes on MRI, and being a smoker.

Dr. Goldman pointed out that efficacy, safety, and tolerability of most DMTs are unknown in patients with comorbidities such as obesity or cardiovascular disease. “It’s important to remember that for many patients with comorbidity, these are exclusion criteria in the clinical trials program,” she said. “So while we know that having comorbidities in an MS population does affect quality of life and increase disability progression, what we are lacking understanding [about] is how these may affect treatment response.”

Dr. Goldman disclosed that she is a consultant and advisory board member for Questcor Pharmaceuticals.

The session was sponsored by an educational grant from Biogen.

[email protected]

On Twitter @dougbrunk

INDIANAPOLIS – Consider disease activity, patient comorbidities, treatment tolerability, and patient or physician preference when prescribing disease-modifying therapy for multiple sclerosis patients.

“Where I practice, patient preference can sound something like, ‘My sister-in-law’s cousin’s friend at church takes drug X, and that’s the one I’m interested in,’ ” said Dr. Myla D. Goldman, a neurologist who directs the James Q. Miller Multiple Sclerosis Clinic at the University of Virginia, Charlottesville. “It’s sometimes guided by just familiarity or word of mouth, or something that they’ve read or someone that they know. In terms of our own preferences as clinicians, those are much harder to characterize. I think they become shaped over time and our own experiences, as well as being guided by evidence-based medicine.”

In a survey, 102 neurologists were asked about how they made decisions regarding the prescription of disease-modifying therapies (DMTs) for patients with MS (Patient Prefer. Adherence 2014;8:415-22). More than 80% ranked efficacy as the most important attribute of DMT medication selection, followed by safety, tolerability, patient preference, and convenience (including dosing frequency and administration method). In a separate study presented at the 2014 meeting of the American Academy of Neurology, 1,628 MS patients in Germany were asked about the importance of different DMT features (Neurology 2014;82[10 Suppl.]:P3.137). They ranked oral administration as the most important attribute in guiding their DMT preference, while the second most relevant attribute was frequency of administration.

In a more recent study, 50 patients with relapsing-remitting MS were asked about their preferences for attributes of DMTs (Int. J. MS Care 2015;17:74-82). Survey respondents showed the highest preference for medications that would improve their symptoms, which is not a proven DMT outcome. Preventing relapses, which is a key clinical trial outcome, was not associated with significant preferences.

“This is important to know but adds another layer of challenge and complication [because] what we understand most about many of these agents is their effect on relapse rates,” Dr. Goldman said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “It’s another disconnect in terms of what we’re thinking about, the tools that we have, and where our patients are coming from.”

Other factors to consider when selecting a DMT include disease activity/burden, risk/prognostic factors, treatment safety/tolerability, comorbidity, and treatment access/logistics. “As we’ve had more and more [DMT] choices available to us, we’ve become more restricted in how we make choices – which patients can have what choices in what order,” she said. “This is a reality that we all have to face but is something that varies from third-party payers and region, and can be really complicated to navigate.”

In general, Dr. Goldman continued, it’s recognized that more active disease requires more effective therapies with greater tolerance for risk. However, evidence suggesting that early disease activity predicts long-term outcome is poor, “not because it may not be true but because we don’t have as robust data as we would like,” she said. “We also have few [clinical] trials focused on this group. So when we look at high disease activity, it’s typically in a subgroup analysis. There are risks for underpowering and a lack of direct comparisons among therapies. I have found that my idea of disease activity and my individual patient’s idea of disease activity sometimes differ. Perhaps I think we need to make a change, and they feel comfortable with what they’re taking, or vice versa.”

There are various predictors of disease activity and outcomes based on early signs and symptoms, “but these outcomes are variable when we are comparing across studies,” she noted. These predictors and outcomes include:

• Early disease activity predicts relapse disease activity early, especially with posterior fossa lesions and enhancing lesions.

• Early MRI activity predicts long-term disability.

• A baseline T2 lesion burden predicts change in the Kurtzke Expanded Disability Status Scale (EDSS) and progression to secondary-progressive MS.

• A T2 lesion change at 1 year predicts EDSS change.

• Brain atrophy over 2 years predicts EDSS at 8 years.

Favorable prognostic factors include monofocal onset, onset with optic neuritis or isolated sensory symptoms, younger age at onset, being white, being female, having a low relapse rate in the first 2-5 years, and a long interval between the first and second relapse. “That’s where early treatment and impact on relapse rate has a really important role,” she said.

Unfavorable factors in relapsing-remitting MS include multifocal onset, being black, older age at onset, being male, high relapse rate in the first 2-5 years, disability at 5 years, cognitive impairment, high MRI lesion load at baseline, atrophy and T1 holes on MRI, and being a smoker.

Dr. Goldman pointed out that efficacy, safety, and tolerability of most DMTs are unknown in patients with comorbidities such as obesity or cardiovascular disease. “It’s important to remember that for many patients with comorbidity, these are exclusion criteria in the clinical trials program,” she said. “So while we know that having comorbidities in an MS population does affect quality of life and increase disability progression, what we are lacking understanding [about] is how these may affect treatment response.”

Dr. Goldman disclosed that she is a consultant and advisory board member for Questcor Pharmaceuticals.

The session was sponsored by an educational grant from Biogen.

[email protected]

On Twitter @dougbrunk

INDIANAPOLIS – Consider disease activity, patient comorbidities, treatment tolerability, and patient or physician preference when prescribing disease-modifying therapy for multiple sclerosis patients.

“Where I practice, patient preference can sound something like, ‘My sister-in-law’s cousin’s friend at church takes drug X, and that’s the one I’m interested in,’ ” said Dr. Myla D. Goldman, a neurologist who directs the James Q. Miller Multiple Sclerosis Clinic at the University of Virginia, Charlottesville. “It’s sometimes guided by just familiarity or word of mouth, or something that they’ve read or someone that they know. In terms of our own preferences as clinicians, those are much harder to characterize. I think they become shaped over time and our own experiences, as well as being guided by evidence-based medicine.”

In a survey, 102 neurologists were asked about how they made decisions regarding the prescription of disease-modifying therapies (DMTs) for patients with MS (Patient Prefer. Adherence 2014;8:415-22). More than 80% ranked efficacy as the most important attribute of DMT medication selection, followed by safety, tolerability, patient preference, and convenience (including dosing frequency and administration method). In a separate study presented at the 2014 meeting of the American Academy of Neurology, 1,628 MS patients in Germany were asked about the importance of different DMT features (Neurology 2014;82[10 Suppl.]:P3.137). They ranked oral administration as the most important attribute in guiding their DMT preference, while the second most relevant attribute was frequency of administration.

In a more recent study, 50 patients with relapsing-remitting MS were asked about their preferences for attributes of DMTs (Int. J. MS Care 2015;17:74-82). Survey respondents showed the highest preference for medications that would improve their symptoms, which is not a proven DMT outcome. Preventing relapses, which is a key clinical trial outcome, was not associated with significant preferences.

“This is important to know but adds another layer of challenge and complication [because] what we understand most about many of these agents is their effect on relapse rates,” Dr. Goldman said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “It’s another disconnect in terms of what we’re thinking about, the tools that we have, and where our patients are coming from.”

Other factors to consider when selecting a DMT include disease activity/burden, risk/prognostic factors, treatment safety/tolerability, comorbidity, and treatment access/logistics. “As we’ve had more and more [DMT] choices available to us, we’ve become more restricted in how we make choices – which patients can have what choices in what order,” she said. “This is a reality that we all have to face but is something that varies from third-party payers and region, and can be really complicated to navigate.”

In general, Dr. Goldman continued, it’s recognized that more active disease requires more effective therapies with greater tolerance for risk. However, evidence suggesting that early disease activity predicts long-term outcome is poor, “not because it may not be true but because we don’t have as robust data as we would like,” she said. “We also have few [clinical] trials focused on this group. So when we look at high disease activity, it’s typically in a subgroup analysis. There are risks for underpowering and a lack of direct comparisons among therapies. I have found that my idea of disease activity and my individual patient’s idea of disease activity sometimes differ. Perhaps I think we need to make a change, and they feel comfortable with what they’re taking, or vice versa.”

There are various predictors of disease activity and outcomes based on early signs and symptoms, “but these outcomes are variable when we are comparing across studies,” she noted. These predictors and outcomes include:

• Early disease activity predicts relapse disease activity early, especially with posterior fossa lesions and enhancing lesions.

• Early MRI activity predicts long-term disability.

• A baseline T2 lesion burden predicts change in the Kurtzke Expanded Disability Status Scale (EDSS) and progression to secondary-progressive MS.

• A T2 lesion change at 1 year predicts EDSS change.

• Brain atrophy over 2 years predicts EDSS at 8 years.

Favorable prognostic factors include monofocal onset, onset with optic neuritis or isolated sensory symptoms, younger age at onset, being white, being female, having a low relapse rate in the first 2-5 years, and a long interval between the first and second relapse. “That’s where early treatment and impact on relapse rate has a really important role,” she said.

Unfavorable factors in relapsing-remitting MS include multifocal onset, being black, older age at onset, being male, high relapse rate in the first 2-5 years, disability at 5 years, cognitive impairment, high MRI lesion load at baseline, atrophy and T1 holes on MRI, and being a smoker.

Dr. Goldman pointed out that efficacy, safety, and tolerability of most DMTs are unknown in patients with comorbidities such as obesity or cardiovascular disease. “It’s important to remember that for many patients with comorbidity, these are exclusion criteria in the clinical trials program,” she said. “So while we know that having comorbidities in an MS population does affect quality of life and increase disability progression, what we are lacking understanding [about] is how these may affect treatment response.”

Dr. Goldman disclosed that she is a consultant and advisory board member for Questcor Pharmaceuticals.

The session was sponsored by an educational grant from Biogen.

[email protected]

On Twitter @dougbrunk