Elizabeth Mechcatie

A new website has been launched that provides the latest information to help guide clinicians on treating patients with chronic hepatitis C and will be updated regularly with developments in this rapidly changing area of medicine.

A collaboration of the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) with the International Antiviral Society-USA (IAS-USA), the website – HCVguidelines.org – provides evidence-based consensus recommendations for screening and treating people with hepatitis C virus (HCV).

The recommendations were developed by a panel of 27 liver disease and infectious diseases specialists and a patient advocate and are intended for "health care providers who treat the disease and others who need updated information on the best practices," according to a statement issued by IDSA and AASLD announcing the launch of the website, which became available on Jan. 29. Examples of the information provided include guidance on the use of direct-acting HCV antivirals, with and without interferon for the most common type of HCV, genotype 1; treatment of different subgroups, such as those coinfected with HIV, those with decompensated liver disease, and liver transplant recipients; and regimens for treatment of interferon-ineligible and interferon-eligible patients.

The website is a living document and will be updated regularly with new recommendations that reflect new research, Food and Drug Administration (FDA) approvals of new drugs, changing recommendations for monitoring patients, and other developments. This aspect is "absolutely necessary in this field" because of the many recent developments and multiple drugs that are in development and approaching approval, Dr. Michael Saag, the panel cochair for IAS-USA, said during a telephone briefing held to announce the launch.

Changes can be made weekly or monthly, "so that clinicians can have confidence that, when they go to this website, they will get the most accurate and up-to-date guidance on the treatment of hepatitis C," added Dr. Saag, professor of medicine and director of the division of infectious diseases at the University of Alabama at Birmingham.

During the briefing, Dr. Henry Masur of the National Institutes of Health, Bethesda, Md., pointed out that, for the first time, treatments that cure hepatitis C are available, which are more effective than previous treatments and easier to tolerate. "What we’re eager to see is that these drugs are used by practitioners to treat the millions of patients who have hepatitis C both in North America and elsewhere ... and it’s important that clinicians have access to guidance on how best to use these drugs as new trials are quickly done and new information becomes available."

An estimated 3-4 million people in the United States are infected with HCV and could develop chronic liver disease; the cure rate for chronic HCV is now close to 95% with currently available treatments.

Noting that the next-generation antivirals have the potential to cure most patients with hepatitis C, Dr. David Thomas, professor of medicine and chair of the division of infectious diseases at Johns Hopkins University, Baltimore, said that the website is expected to be used not only by clinicians who are well versed in prescribing antiviral drugs, "but also by many who are inexperienced or even new to the treatment of hepatitis C." This includes gastroenterologists and infectious disease clinicians who have not been treating patients with hepatitis C and may include primary care physicians as well, he added. Dr. Thomas was the panel cochair for IDSA.

Recent developments in the treatment of hepatitis C include the FDA approvals of sofosbuvir and simeprevir late last year for treating chronic HCV, considered major advances in treatment.

The website is HCVguidelines.org. More information on hepatitis C is available at www.idsociety.org/HCV.

[email protected]

A new website has been launched that provides the latest information to help guide clinicians on treating patients with chronic hepatitis C and will be updated regularly with developments in this rapidly changing area of medicine.

A collaboration of the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) with the International Antiviral Society-USA (IAS-USA), the website – HCVguidelines.org – provides evidence-based consensus recommendations for screening and treating people with hepatitis C virus (HCV).

The recommendations were developed by a panel of 27 liver disease and infectious diseases specialists and a patient advocate and are intended for "health care providers who treat the disease and others who need updated information on the best practices," according to a statement issued by IDSA and AASLD announcing the launch of the website, which became available on Jan. 29. Examples of the information provided include guidance on the use of direct-acting HCV antivirals, with and without interferon for the most common type of HCV, genotype 1; treatment of different subgroups, such as those coinfected with HIV, those with decompensated liver disease, and liver transplant recipients; and regimens for treatment of interferon-ineligible and interferon-eligible patients.

The website is a living document and will be updated regularly with new recommendations that reflect new research, Food and Drug Administration (FDA) approvals of new drugs, changing recommendations for monitoring patients, and other developments. This aspect is "absolutely necessary in this field" because of the many recent developments and multiple drugs that are in development and approaching approval, Dr. Michael Saag, the panel cochair for IAS-USA, said during a telephone briefing held to announce the launch.

Changes can be made weekly or monthly, "so that clinicians can have confidence that, when they go to this website, they will get the most accurate and up-to-date guidance on the treatment of hepatitis C," added Dr. Saag, professor of medicine and director of the division of infectious diseases at the University of Alabama at Birmingham.

During the briefing, Dr. Henry Masur of the National Institutes of Health, Bethesda, Md., pointed out that, for the first time, treatments that cure hepatitis C are available, which are more effective than previous treatments and easier to tolerate. "What we’re eager to see is that these drugs are used by practitioners to treat the millions of patients who have hepatitis C both in North America and elsewhere ... and it’s important that clinicians have access to guidance on how best to use these drugs as new trials are quickly done and new information becomes available."

An estimated 3-4 million people in the United States are infected with HCV and could develop chronic liver disease; the cure rate for chronic HCV is now close to 95% with currently available treatments.

Noting that the next-generation antivirals have the potential to cure most patients with hepatitis C, Dr. David Thomas, professor of medicine and chair of the division of infectious diseases at Johns Hopkins University, Baltimore, said that the website is expected to be used not only by clinicians who are well versed in prescribing antiviral drugs, "but also by many who are inexperienced or even new to the treatment of hepatitis C." This includes gastroenterologists and infectious disease clinicians who have not been treating patients with hepatitis C and may include primary care physicians as well, he added. Dr. Thomas was the panel cochair for IDSA.

Recent developments in the treatment of hepatitis C include the FDA approvals of sofosbuvir and simeprevir late last year for treating chronic HCV, considered major advances in treatment.

The website is HCVguidelines.org. More information on hepatitis C is available at www.idsociety.org/HCV.

[email protected]

A new website has been launched that provides the latest information to help guide clinicians on treating patients with chronic hepatitis C and will be updated regularly with developments in this rapidly changing area of medicine.

A collaboration of the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) with the International Antiviral Society-USA (IAS-USA), the website – HCVguidelines.org – provides evidence-based consensus recommendations for screening and treating people with hepatitis C virus (HCV).

The recommendations were developed by a panel of 27 liver disease and infectious diseases specialists and a patient advocate and are intended for "health care providers who treat the disease and others who need updated information on the best practices," according to a statement issued by IDSA and AASLD announcing the launch of the website, which became available on Jan. 29. Examples of the information provided include guidance on the use of direct-acting HCV antivirals, with and without interferon for the most common type of HCV, genotype 1; treatment of different subgroups, such as those coinfected with HIV, those with decompensated liver disease, and liver transplant recipients; and regimens for treatment of interferon-ineligible and interferon-eligible patients.

The website is a living document and will be updated regularly with new recommendations that reflect new research, Food and Drug Administration (FDA) approvals of new drugs, changing recommendations for monitoring patients, and other developments. This aspect is "absolutely necessary in this field" because of the many recent developments and multiple drugs that are in development and approaching approval, Dr. Michael Saag, the panel cochair for IAS-USA, said during a telephone briefing held to announce the launch.

Changes can be made weekly or monthly, "so that clinicians can have confidence that, when they go to this website, they will get the most accurate and up-to-date guidance on the treatment of hepatitis C," added Dr. Saag, professor of medicine and director of the division of infectious diseases at the University of Alabama at Birmingham.

During the briefing, Dr. Henry Masur of the National Institutes of Health, Bethesda, Md., pointed out that, for the first time, treatments that cure hepatitis C are available, which are more effective than previous treatments and easier to tolerate. "What we’re eager to see is that these drugs are used by practitioners to treat the millions of patients who have hepatitis C both in North America and elsewhere ... and it’s important that clinicians have access to guidance on how best to use these drugs as new trials are quickly done and new information becomes available."

An estimated 3-4 million people in the United States are infected with HCV and could develop chronic liver disease; the cure rate for chronic HCV is now close to 95% with currently available treatments.

Noting that the next-generation antivirals have the potential to cure most patients with hepatitis C, Dr. David Thomas, professor of medicine and chair of the division of infectious diseases at Johns Hopkins University, Baltimore, said that the website is expected to be used not only by clinicians who are well versed in prescribing antiviral drugs, "but also by many who are inexperienced or even new to the treatment of hepatitis C." This includes gastroenterologists and infectious disease clinicians who have not been treating patients with hepatitis C and may include primary care physicians as well, he added. Dr. Thomas was the panel cochair for IDSA.

Recent developments in the treatment of hepatitis C include the FDA approvals of sofosbuvir and simeprevir late last year for treating chronic HCV, considered major advances in treatment.

The website is HCVguidelines.org. More information on hepatitis C is available at www.idsociety.org/HCV.

[email protected]

Almost 7,400 children and adolescents were hospitalized for firearm-related injuries in 2009, and more than half were due to assaults, in what the authors say is the first study to highlight "the substantial morbidity" experienced by children and adolescents in the United States who survive a firearm injury and are hospitalized.

The rates of hospitalizations were highest in teenagers aged 15-19 years and among black males, reported Dr. John M. Leventhal, of the pediatrics department at Yale University, New Haven, Conn., and his associates. In 6% of the cases, the child or adolescent died while hospitalized. For black males aged 15-19 years, the estimated annual risk of hospitalization for a firearm injury was 1 per 672.

"Public health efforts should be dedicated to reducing this common source of childhood injuries," the authors concluded, noting that the results "underscore the important role that pediatricians and other health care providers who care for children can play in the primary prevention of firearm injuries." The study appeared in the February 2014 issue of Pediatrics (2014;133:219-25).

Using data from the 2009 Kids’ Inpatient Database, a nationally representative sample of discharge data from more than 4,000 acute care hospitals in 44 states, representing 96% of the U.S. population, they calculated hospitalizations for nonfatal injuries caused by firearms in children and adolescents under age 20, which included injuries due to BB and air guns but not paintball guns.

There were 7,391 such hospitalizations. Most – almost 62% – of the injuries were related to assaults, and the least amount – almost 4% – were due to suicide attempts. The injuries were categorized as unintentional in two-thirds of children under age 10, 54% in those aged 10-14 years, and 24% among those aged 15-19 years.

Almost 90% of the hospitalizations were in males; and the gender difference was present, no matter the cause of the injury.

The authors also identified significant racial differences: 47% of the hospitalizations were in black children and adolescents vs. 16% in whites and 19% in Hispanics; 54% of the hospitalizations due to assaults were in black children and adolescents vs. almost 9% in whites and 21% in Hispanics (the rest were in unknown or other categories of race or ethnicity). Almost 14% of the suicide attempts were in black children, compared with 50% in white children and adolescents, a significant difference (14% of the suicide attempts were in Hispanics).

Compared with those aged 4 years and younger, those in the 15- to 19-year age group were about 121 times more likely to be hospitalized for a firearms-related assault and almost 146 times more likely to be hospitalized for an unintentional injury.

The overall hospitalization rate due to firearm injuries was 8.87 per 100,000 persons under age 20, with markedly higher rates among those aged 15-19 years. When the investigators calculated rates based on race and gender, they found the highest rates among black children and adolescents – about 25 per 100,000 persons – compared with 7.93 among Hispanics, 6.56 for other races, and 2.6 among whites.

The rate among males was about 15 per 100,000 persons, compared with almost 2 per 100,000 persons for females. The rate for black males was almost 45 per 100,000 persons, compared with about 4 per 100,000 persons among white males. And among those aged 15-19 years, the rate among black males was almost 149 per 100,000 persons, vs. about 11 per 100,000 persons for white males in this age group. There were similar differences among females, but the differences "were not as dramatic," the authors said.

The most common injuries were open wounds, in about half of the cases, and fractures in about half of cases, and internal injuries of the thorax, abdomen, or pelvis in about 34%. Almost 62% of the those hospitalized had a major procedure in the operating room. Almost half the hospitalizations were covered by Medicaid, followed by private health insurance in 25%, almost 17% self-pay (uninsured), and 8.5% by other types of health insurance – with a similar distribution of payment type for undetermined and unintentional assaults. However, almost half of the hospitalizations for suicide attempts were paid by private insurance, while only about 25% were covered by Medicaid.

The authors had no relevant financial disclosures or potential conflicts of interest.

[email protected]

Almost 7,400 children and adolescents were hospitalized for firearm-related injuries in 2009, and more than half were due to assaults, in what the authors say is the first study to highlight "the substantial morbidity" experienced by children and adolescents in the United States who survive a firearm injury and are hospitalized.

The rates of hospitalizations were highest in teenagers aged 15-19 years and among black males, reported Dr. John M. Leventhal, of the pediatrics department at Yale University, New Haven, Conn., and his associates. In 6% of the cases, the child or adolescent died while hospitalized. For black males aged 15-19 years, the estimated annual risk of hospitalization for a firearm injury was 1 per 672.

"Public health efforts should be dedicated to reducing this common source of childhood injuries," the authors concluded, noting that the results "underscore the important role that pediatricians and other health care providers who care for children can play in the primary prevention of firearm injuries." The study appeared in the February 2014 issue of Pediatrics (2014;133:219-25).

Using data from the 2009 Kids’ Inpatient Database, a nationally representative sample of discharge data from more than 4,000 acute care hospitals in 44 states, representing 96% of the U.S. population, they calculated hospitalizations for nonfatal injuries caused by firearms in children and adolescents under age 20, which included injuries due to BB and air guns but not paintball guns.

There were 7,391 such hospitalizations. Most – almost 62% – of the injuries were related to assaults, and the least amount – almost 4% – were due to suicide attempts. The injuries were categorized as unintentional in two-thirds of children under age 10, 54% in those aged 10-14 years, and 24% among those aged 15-19 years.

Almost 90% of the hospitalizations were in males; and the gender difference was present, no matter the cause of the injury.

The authors also identified significant racial differences: 47% of the hospitalizations were in black children and adolescents vs. 16% in whites and 19% in Hispanics; 54% of the hospitalizations due to assaults were in black children and adolescents vs. almost 9% in whites and 21% in Hispanics (the rest were in unknown or other categories of race or ethnicity). Almost 14% of the suicide attempts were in black children, compared with 50% in white children and adolescents, a significant difference (14% of the suicide attempts were in Hispanics).

Compared with those aged 4 years and younger, those in the 15- to 19-year age group were about 121 times more likely to be hospitalized for a firearms-related assault and almost 146 times more likely to be hospitalized for an unintentional injury.

The overall hospitalization rate due to firearm injuries was 8.87 per 100,000 persons under age 20, with markedly higher rates among those aged 15-19 years. When the investigators calculated rates based on race and gender, they found the highest rates among black children and adolescents – about 25 per 100,000 persons – compared with 7.93 among Hispanics, 6.56 for other races, and 2.6 among whites.

The rate among males was about 15 per 100,000 persons, compared with almost 2 per 100,000 persons for females. The rate for black males was almost 45 per 100,000 persons, compared with about 4 per 100,000 persons among white males. And among those aged 15-19 years, the rate among black males was almost 149 per 100,000 persons, vs. about 11 per 100,000 persons for white males in this age group. There were similar differences among females, but the differences "were not as dramatic," the authors said.

The most common injuries were open wounds, in about half of the cases, and fractures in about half of cases, and internal injuries of the thorax, abdomen, or pelvis in about 34%. Almost 62% of the those hospitalized had a major procedure in the operating room. Almost half the hospitalizations were covered by Medicaid, followed by private health insurance in 25%, almost 17% self-pay (uninsured), and 8.5% by other types of health insurance – with a similar distribution of payment type for undetermined and unintentional assaults. However, almost half of the hospitalizations for suicide attempts were paid by private insurance, while only about 25% were covered by Medicaid.

The authors had no relevant financial disclosures or potential conflicts of interest.

[email protected]

Almost 7,400 children and adolescents were hospitalized for firearm-related injuries in 2009, and more than half were due to assaults, in what the authors say is the first study to highlight "the substantial morbidity" experienced by children and adolescents in the United States who survive a firearm injury and are hospitalized.

The rates of hospitalizations were highest in teenagers aged 15-19 years and among black males, reported Dr. John M. Leventhal, of the pediatrics department at Yale University, New Haven, Conn., and his associates. In 6% of the cases, the child or adolescent died while hospitalized. For black males aged 15-19 years, the estimated annual risk of hospitalization for a firearm injury was 1 per 672.

"Public health efforts should be dedicated to reducing this common source of childhood injuries," the authors concluded, noting that the results "underscore the important role that pediatricians and other health care providers who care for children can play in the primary prevention of firearm injuries." The study appeared in the February 2014 issue of Pediatrics (2014;133:219-25).

Using data from the 2009 Kids’ Inpatient Database, a nationally representative sample of discharge data from more than 4,000 acute care hospitals in 44 states, representing 96% of the U.S. population, they calculated hospitalizations for nonfatal injuries caused by firearms in children and adolescents under age 20, which included injuries due to BB and air guns but not paintball guns.

There were 7,391 such hospitalizations. Most – almost 62% – of the injuries were related to assaults, and the least amount – almost 4% – were due to suicide attempts. The injuries were categorized as unintentional in two-thirds of children under age 10, 54% in those aged 10-14 years, and 24% among those aged 15-19 years.

Almost 90% of the hospitalizations were in males; and the gender difference was present, no matter the cause of the injury.

The authors also identified significant racial differences: 47% of the hospitalizations were in black children and adolescents vs. 16% in whites and 19% in Hispanics; 54% of the hospitalizations due to assaults were in black children and adolescents vs. almost 9% in whites and 21% in Hispanics (the rest were in unknown or other categories of race or ethnicity). Almost 14% of the suicide attempts were in black children, compared with 50% in white children and adolescents, a significant difference (14% of the suicide attempts were in Hispanics).

Compared with those aged 4 years and younger, those in the 15- to 19-year age group were about 121 times more likely to be hospitalized for a firearms-related assault and almost 146 times more likely to be hospitalized for an unintentional injury.

The overall hospitalization rate due to firearm injuries was 8.87 per 100,000 persons under age 20, with markedly higher rates among those aged 15-19 years. When the investigators calculated rates based on race and gender, they found the highest rates among black children and adolescents – about 25 per 100,000 persons – compared with 7.93 among Hispanics, 6.56 for other races, and 2.6 among whites.

The rate among males was about 15 per 100,000 persons, compared with almost 2 per 100,000 persons for females. The rate for black males was almost 45 per 100,000 persons, compared with about 4 per 100,000 persons among white males. And among those aged 15-19 years, the rate among black males was almost 149 per 100,000 persons, vs. about 11 per 100,000 persons for white males in this age group. There were similar differences among females, but the differences "were not as dramatic," the authors said.

The most common injuries were open wounds, in about half of the cases, and fractures in about half of cases, and internal injuries of the thorax, abdomen, or pelvis in about 34%. Almost 62% of the those hospitalized had a major procedure in the operating room. Almost half the hospitalizations were covered by Medicaid, followed by private health insurance in 25%, almost 17% self-pay (uninsured), and 8.5% by other types of health insurance – with a similar distribution of payment type for undetermined and unintentional assaults. However, almost half of the hospitalizations for suicide attempts were paid by private insurance, while only about 25% were covered by Medicaid.

The authors had no relevant financial disclosures or potential conflicts of interest.

[email protected]

WASHINGTON – Stereotactic laser ablation resulted in better cognitive outcomes in patients with temporal lobe epilepsy than did treatment with standard open surgical approaches, Daniel Drane, Ph.D., reported at the annual meeting of the American Epilepsy Society.

In a study comparing pre- and posttreatment cognitive outcomes in 17 people with temporal lobe epilepsy, those treated with MRI-guided laser ablation had better outcomes on episodic memory measures 6 months after surgery than did the patients treated with standard surgical treatments, said Dr. Drane of the departments of neurology and pediatrics at Emory University, Atlanta. The results suggest that "memory decline requires broader damage to mesial temporal lobe structures or that epilepsy patients are able to reorganize memory more efficiently if structural damage is more selective," he concluded.

Elizabeth Mechcatie/Frontline Medical News

The study compared neuropsychological data before surgery and 6 months after surgery in 7 people who were treated with hippocampal laser ablation (5 left and 2 right resections) and 10 people who underwent surgery with standard or selective surgical approaches, including selective amygdalohippocampectomy (5 left and 5 right resections). Patients in both groups were similar in age (mean 36-39 years) and were on a mean of two antiepileptic drugs. Two patients in the surgery group and three in the laser ablation group had had seizures since they were 5 years or younger.

The investigators evaluated episodic memory with measures that included tasks of visual and verbal memory.

After treatment, there was evidence of a significant decline in one or both of the memory tasks in only 1 of the 7 patients treated with laser ablation, compared with 9 of the 10 surgical patients, a statistically significant difference, Dr. Drane said. In addition, six patients who had laser ablation showed a significant improvement in one or more memory measures after treatment, compared with four standard surgery patients.

In a statement issued during the meeting, Dr. Drane said that considering "the presumed importance of the hippocampus in episodic memory, we were surprised by the absence of any decline" in the laser ablation group. The results suggest that the function of the hippocampus may not be completely understood "and that being able to perform such a precise resection may help us learn more about brain regions in a manner that was never before possible in humans," he added.

During a press briefing held during the meeting, Dr. Drane pointed out that laser ablation benefits patients with less pain and a short hospital stay lasting a median of 1 day with no time spent in the intensive care unit.

Another possible benefit of the less invasive procedure is a positive effect on mood, he said. He described a patient in her early 60s with chronic epilepsy and chronic depression who was completely seizure free after laser ablation. But the most striking result of treatment was that she was no longer depressed and was off all antidepressants for the first time since she was a teenager.

This is just one case, but mood may benefit "from not cutting so many regions," he noted.

Dr. Drane said he received funding from the National Institutes of Health to conduct the study.

[email protected]

WASHINGTON – Stereotactic laser ablation resulted in better cognitive outcomes in patients with temporal lobe epilepsy than did treatment with standard open surgical approaches, Daniel Drane, Ph.D., reported at the annual meeting of the American Epilepsy Society.

In a study comparing pre- and posttreatment cognitive outcomes in 17 people with temporal lobe epilepsy, those treated with MRI-guided laser ablation had better outcomes on episodic memory measures 6 months after surgery than did the patients treated with standard surgical treatments, said Dr. Drane of the departments of neurology and pediatrics at Emory University, Atlanta. The results suggest that "memory decline requires broader damage to mesial temporal lobe structures or that epilepsy patients are able to reorganize memory more efficiently if structural damage is more selective," he concluded.

Elizabeth Mechcatie/Frontline Medical News

The study compared neuropsychological data before surgery and 6 months after surgery in 7 people who were treated with hippocampal laser ablation (5 left and 2 right resections) and 10 people who underwent surgery with standard or selective surgical approaches, including selective amygdalohippocampectomy (5 left and 5 right resections). Patients in both groups were similar in age (mean 36-39 years) and were on a mean of two antiepileptic drugs. Two patients in the surgery group and three in the laser ablation group had had seizures since they were 5 years or younger.

The investigators evaluated episodic memory with measures that included tasks of visual and verbal memory.

After treatment, there was evidence of a significant decline in one or both of the memory tasks in only 1 of the 7 patients treated with laser ablation, compared with 9 of the 10 surgical patients, a statistically significant difference, Dr. Drane said. In addition, six patients who had laser ablation showed a significant improvement in one or more memory measures after treatment, compared with four standard surgery patients.

In a statement issued during the meeting, Dr. Drane said that considering "the presumed importance of the hippocampus in episodic memory, we were surprised by the absence of any decline" in the laser ablation group. The results suggest that the function of the hippocampus may not be completely understood "and that being able to perform such a precise resection may help us learn more about brain regions in a manner that was never before possible in humans," he added.

During a press briefing held during the meeting, Dr. Drane pointed out that laser ablation benefits patients with less pain and a short hospital stay lasting a median of 1 day with no time spent in the intensive care unit.

Another possible benefit of the less invasive procedure is a positive effect on mood, he said. He described a patient in her early 60s with chronic epilepsy and chronic depression who was completely seizure free after laser ablation. But the most striking result of treatment was that she was no longer depressed and was off all antidepressants for the first time since she was a teenager.

This is just one case, but mood may benefit "from not cutting so many regions," he noted.

Dr. Drane said he received funding from the National Institutes of Health to conduct the study.

[email protected]

WASHINGTON – Stereotactic laser ablation resulted in better cognitive outcomes in patients with temporal lobe epilepsy than did treatment with standard open surgical approaches, Daniel Drane, Ph.D., reported at the annual meeting of the American Epilepsy Society.

In a study comparing pre- and posttreatment cognitive outcomes in 17 people with temporal lobe epilepsy, those treated with MRI-guided laser ablation had better outcomes on episodic memory measures 6 months after surgery than did the patients treated with standard surgical treatments, said Dr. Drane of the departments of neurology and pediatrics at Emory University, Atlanta. The results suggest that "memory decline requires broader damage to mesial temporal lobe structures or that epilepsy patients are able to reorganize memory more efficiently if structural damage is more selective," he concluded.

Elizabeth Mechcatie/Frontline Medical News

The study compared neuropsychological data before surgery and 6 months after surgery in 7 people who were treated with hippocampal laser ablation (5 left and 2 right resections) and 10 people who underwent surgery with standard or selective surgical approaches, including selective amygdalohippocampectomy (5 left and 5 right resections). Patients in both groups were similar in age (mean 36-39 years) and were on a mean of two antiepileptic drugs. Two patients in the surgery group and three in the laser ablation group had had seizures since they were 5 years or younger.

The investigators evaluated episodic memory with measures that included tasks of visual and verbal memory.

After treatment, there was evidence of a significant decline in one or both of the memory tasks in only 1 of the 7 patients treated with laser ablation, compared with 9 of the 10 surgical patients, a statistically significant difference, Dr. Drane said. In addition, six patients who had laser ablation showed a significant improvement in one or more memory measures after treatment, compared with four standard surgery patients.

In a statement issued during the meeting, Dr. Drane said that considering "the presumed importance of the hippocampus in episodic memory, we were surprised by the absence of any decline" in the laser ablation group. The results suggest that the function of the hippocampus may not be completely understood "and that being able to perform such a precise resection may help us learn more about brain regions in a manner that was never before possible in humans," he added.

During a press briefing held during the meeting, Dr. Drane pointed out that laser ablation benefits patients with less pain and a short hospital stay lasting a median of 1 day with no time spent in the intensive care unit.

Another possible benefit of the less invasive procedure is a positive effect on mood, he said. He described a patient in her early 60s with chronic epilepsy and chronic depression who was completely seizure free after laser ablation. But the most striking result of treatment was that she was no longer depressed and was off all antidepressants for the first time since she was a teenager.

This is just one case, but mood may benefit "from not cutting so many regions," he noted.

Dr. Drane said he received funding from the National Institutes of Health to conduct the study.

[email protected]

The Food and Drug Administration authorized for marketing a postnatal diagnostic test that helps detect genetic causes of developmental delay or intellectual disabilities in children, but it is not intended to be used as a stand-alone test, the agency announced on Jan 17.

With a blood sample, the CytoScan Dx Assay analyzes the entire genome and detects chromosomal variations in regions of the genome that are associated with intellectual and developmental disabilities, such as DiGeorge syndrome, according to the FDA statement. The statement emphasized that is should not be used as a stand-alone diagnostic test, or for preimplantation or prenatal testing or screening; population screening; "or for the detection of, or screening for acquired or genetic aberrations occurring after birth, such as cancer."

Moreover, test results "should only be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, evaluation of parental samples, clinical genetic evaluation, and counseling as appropriate," the statement said. Results should only be interpreted by health care professionals who are board certified in clinical cytogenetics or molecular genetics.

Evaluation of the test included a comparison of results of almost 1,000 blood samples, which found the test was better at detecting certain chromosomal abnormalities than karyotyping and fluorescence in situ hybridization (FISH) chromosomal tests.

"This new tool may help in the identification of possible causes of a child’s developmental delay or intellectual disability, allowing health care providers and parents to intervene with appropriate care and support for the child," Alberto Gutierrez, Ph.D., director of the office of in vitro diagnostics and radiological health in the FDA’s Center for Devices and Radiological Health, said in the statement.

The test is manufactured by Affymetrix.

[email protected]

The Food and Drug Administration authorized for marketing a postnatal diagnostic test that helps detect genetic causes of developmental delay or intellectual disabilities in children, but it is not intended to be used as a stand-alone test, the agency announced on Jan 17.

With a blood sample, the CytoScan Dx Assay analyzes the entire genome and detects chromosomal variations in regions of the genome that are associated with intellectual and developmental disabilities, such as DiGeorge syndrome, according to the FDA statement. The statement emphasized that is should not be used as a stand-alone diagnostic test, or for preimplantation or prenatal testing or screening; population screening; "or for the detection of, or screening for acquired or genetic aberrations occurring after birth, such as cancer."

Moreover, test results "should only be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, evaluation of parental samples, clinical genetic evaluation, and counseling as appropriate," the statement said. Results should only be interpreted by health care professionals who are board certified in clinical cytogenetics or molecular genetics.

Evaluation of the test included a comparison of results of almost 1,000 blood samples, which found the test was better at detecting certain chromosomal abnormalities than karyotyping and fluorescence in situ hybridization (FISH) chromosomal tests.

"This new tool may help in the identification of possible causes of a child’s developmental delay or intellectual disability, allowing health care providers and parents to intervene with appropriate care and support for the child," Alberto Gutierrez, Ph.D., director of the office of in vitro diagnostics and radiological health in the FDA’s Center for Devices and Radiological Health, said in the statement.

The test is manufactured by Affymetrix.

[email protected]

The Food and Drug Administration authorized for marketing a postnatal diagnostic test that helps detect genetic causes of developmental delay or intellectual disabilities in children, but it is not intended to be used as a stand-alone test, the agency announced on Jan 17.

With a blood sample, the CytoScan Dx Assay analyzes the entire genome and detects chromosomal variations in regions of the genome that are associated with intellectual and developmental disabilities, such as DiGeorge syndrome, according to the FDA statement. The statement emphasized that is should not be used as a stand-alone diagnostic test, or for preimplantation or prenatal testing or screening; population screening; "or for the detection of, or screening for acquired or genetic aberrations occurring after birth, such as cancer."

Moreover, test results "should only be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, evaluation of parental samples, clinical genetic evaluation, and counseling as appropriate," the statement said. Results should only be interpreted by health care professionals who are board certified in clinical cytogenetics or molecular genetics.

Evaluation of the test included a comparison of results of almost 1,000 blood samples, which found the test was better at detecting certain chromosomal abnormalities than karyotyping and fluorescence in situ hybridization (FISH) chromosomal tests.

"This new tool may help in the identification of possible causes of a child’s developmental delay or intellectual disability, allowing health care providers and parents to intervene with appropriate care and support for the child," Alberto Gutierrez, Ph.D., director of the office of in vitro diagnostics and radiological health in the FDA’s Center for Devices and Radiological Health, said in the statement.

The test is manufactured by Affymetrix.

[email protected]

SILVER SPRING, MD. – Collection of missing data and additional analyses from a large study on rivaroxaban failed to convince a Food and Drug Administration advisory panel to recommend approval of the anticoagulant drug for acute coronary syndrome.

At a meeting Jan. 16, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 10 to 0, with 1 abstention, that the factor Xa inhibitor rivaroxaban (Xarelto) should not be approved as a treatment for acute coronary syndromes (ACS). Rivaroxaban maker Janssen Pharmaceuticals had proposed an indication to reduce the risk of thrombotic cardiovascular events in patients with ACS, based on the results of the ATLAS ACS 2 TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Aspirin With/Without Thienopyridine Therapy in Subjects With Acute Coronary Syndrome) trial.

That study compared two doses of rivaroxaban (2.5 mg twice a day, the proposed dose, and 5 mg twice a day) plus standard antiplatelet therapy (aspirin and a thienopyridine) to placebo plus standard therapy in more than 15,000 people with recent ACS. The primary endpoint – the risk of a composite of cardiovascular death, MI, or stroke – was significantly reduced (P = .039) by 15% among patients on the 2.5-mg twice-daily dose, compared with patients on placebo. The difference was primarily driven by a reduction in cardiovascular deaths among rivaroxaban patients.

But in May 2012, the FDA panel voted 4 to 6 against approval of rivaroxaban for the ACS indication, citing safety concerns and the large amount of missing data from the study. In June 2012, the FDA declined to approve the indication, and the agency refused again in March 2013, after Janssen provided more information. The company disputed the decision and continued to pursue approval. Janssen submitted new analyses and proposed that treatment be limited to 90 days.

At the Jan. 16 advisory committee meeting, panel members commended the study investigators and Janssen for that new work. But they still voted against approval, noting that the missing data remained a problem, the P value for the primary endpoint was not low enough to support approval based on a single trial, and concerns continued about bleeding risk.

The additional work "didn’t really add in a substantial way to the primary endpoint analysis," explained advisory panel member Dr. Philip Sager. Overall, the study "wasn’t robust enough in terms of statistical significance to be considered as a positive study," added Dr. Sager, chair of the scientific programs committee at the Cardiac Safety Research Consortium, San Francisco.

The FDA has approved rivaroxaban for several indications, including reduction of the risk of stroke and systemic embolism in nonvalvular atrial fibrillation, treatment of deep vein thrombosis, and prevention of deep vein thrombosis after hip or knee replacement surgery.

Janssen will work with the FDA to address the questions raised at the meeting, according to a statement issued by the Johnson & Johnson subsidiary.

In May 2013, European Union drug regulators approved an ACS indication for rivaroxaban, to prevent atherothrombotic events (cardiovascular death, myocardial infarction, or stroke) after an ACS in adults with elevated cardiac biomarkers, at a dose of 2.5 mg twice a day, co-administered with acetylsalicylic acid alone or with acetylsalicylic acid plus clopidogrel or ticlopidine.

The FDA usually follows the recommendations of its advisory panels. Advisory panel members have been cleared of potential conflicts related to the meeting topic. Occasionally, a panelist is given a waiver, but no waivers were given at this meeting.

[email protected]

SILVER SPRING, MD. – Collection of missing data and additional analyses from a large study on rivaroxaban failed to convince a Food and Drug Administration advisory panel to recommend approval of the anticoagulant drug for acute coronary syndrome.

At a meeting Jan. 16, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 10 to 0, with 1 abstention, that the factor Xa inhibitor rivaroxaban (Xarelto) should not be approved as a treatment for acute coronary syndromes (ACS). Rivaroxaban maker Janssen Pharmaceuticals had proposed an indication to reduce the risk of thrombotic cardiovascular events in patients with ACS, based on the results of the ATLAS ACS 2 TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Aspirin With/Without Thienopyridine Therapy in Subjects With Acute Coronary Syndrome) trial.

That study compared two doses of rivaroxaban (2.5 mg twice a day, the proposed dose, and 5 mg twice a day) plus standard antiplatelet therapy (aspirin and a thienopyridine) to placebo plus standard therapy in more than 15,000 people with recent ACS. The primary endpoint – the risk of a composite of cardiovascular death, MI, or stroke – was significantly reduced (P = .039) by 15% among patients on the 2.5-mg twice-daily dose, compared with patients on placebo. The difference was primarily driven by a reduction in cardiovascular deaths among rivaroxaban patients.

But in May 2012, the FDA panel voted 4 to 6 against approval of rivaroxaban for the ACS indication, citing safety concerns and the large amount of missing data from the study. In June 2012, the FDA declined to approve the indication, and the agency refused again in March 2013, after Janssen provided more information. The company disputed the decision and continued to pursue approval. Janssen submitted new analyses and proposed that treatment be limited to 90 days.

At the Jan. 16 advisory committee meeting, panel members commended the study investigators and Janssen for that new work. But they still voted against approval, noting that the missing data remained a problem, the P value for the primary endpoint was not low enough to support approval based on a single trial, and concerns continued about bleeding risk.

The additional work "didn’t really add in a substantial way to the primary endpoint analysis," explained advisory panel member Dr. Philip Sager. Overall, the study "wasn’t robust enough in terms of statistical significance to be considered as a positive study," added Dr. Sager, chair of the scientific programs committee at the Cardiac Safety Research Consortium, San Francisco.

The FDA has approved rivaroxaban for several indications, including reduction of the risk of stroke and systemic embolism in nonvalvular atrial fibrillation, treatment of deep vein thrombosis, and prevention of deep vein thrombosis after hip or knee replacement surgery.

Janssen will work with the FDA to address the questions raised at the meeting, according to a statement issued by the Johnson & Johnson subsidiary.

In May 2013, European Union drug regulators approved an ACS indication for rivaroxaban, to prevent atherothrombotic events (cardiovascular death, myocardial infarction, or stroke) after an ACS in adults with elevated cardiac biomarkers, at a dose of 2.5 mg twice a day, co-administered with acetylsalicylic acid alone or with acetylsalicylic acid plus clopidogrel or ticlopidine.

The FDA usually follows the recommendations of its advisory panels. Advisory panel members have been cleared of potential conflicts related to the meeting topic. Occasionally, a panelist is given a waiver, but no waivers were given at this meeting.

[email protected]

SILVER SPRING, MD. – Collection of missing data and additional analyses from a large study on rivaroxaban failed to convince a Food and Drug Administration advisory panel to recommend approval of the anticoagulant drug for acute coronary syndrome.

At a meeting Jan. 16, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 10 to 0, with 1 abstention, that the factor Xa inhibitor rivaroxaban (Xarelto) should not be approved as a treatment for acute coronary syndromes (ACS). Rivaroxaban maker Janssen Pharmaceuticals had proposed an indication to reduce the risk of thrombotic cardiovascular events in patients with ACS, based on the results of the ATLAS ACS 2 TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Aspirin With/Without Thienopyridine Therapy in Subjects With Acute Coronary Syndrome) trial.

That study compared two doses of rivaroxaban (2.5 mg twice a day, the proposed dose, and 5 mg twice a day) plus standard antiplatelet therapy (aspirin and a thienopyridine) to placebo plus standard therapy in more than 15,000 people with recent ACS. The primary endpoint – the risk of a composite of cardiovascular death, MI, or stroke – was significantly reduced (P = .039) by 15% among patients on the 2.5-mg twice-daily dose, compared with patients on placebo. The difference was primarily driven by a reduction in cardiovascular deaths among rivaroxaban patients.

But in May 2012, the FDA panel voted 4 to 6 against approval of rivaroxaban for the ACS indication, citing safety concerns and the large amount of missing data from the study. In June 2012, the FDA declined to approve the indication, and the agency refused again in March 2013, after Janssen provided more information. The company disputed the decision and continued to pursue approval. Janssen submitted new analyses and proposed that treatment be limited to 90 days.

At the Jan. 16 advisory committee meeting, panel members commended the study investigators and Janssen for that new work. But they still voted against approval, noting that the missing data remained a problem, the P value for the primary endpoint was not low enough to support approval based on a single trial, and concerns continued about bleeding risk.

The additional work "didn’t really add in a substantial way to the primary endpoint analysis," explained advisory panel member Dr. Philip Sager. Overall, the study "wasn’t robust enough in terms of statistical significance to be considered as a positive study," added Dr. Sager, chair of the scientific programs committee at the Cardiac Safety Research Consortium, San Francisco.

The FDA has approved rivaroxaban for several indications, including reduction of the risk of stroke and systemic embolism in nonvalvular atrial fibrillation, treatment of deep vein thrombosis, and prevention of deep vein thrombosis after hip or knee replacement surgery.

Janssen will work with the FDA to address the questions raised at the meeting, according to a statement issued by the Johnson & Johnson subsidiary.

In May 2013, European Union drug regulators approved an ACS indication for rivaroxaban, to prevent atherothrombotic events (cardiovascular death, myocardial infarction, or stroke) after an ACS in adults with elevated cardiac biomarkers, at a dose of 2.5 mg twice a day, co-administered with acetylsalicylic acid alone or with acetylsalicylic acid plus clopidogrel or ticlopidine.

The FDA usually follows the recommendations of its advisory panels. Advisory panel members have been cleared of potential conflicts related to the meeting topic. Occasionally, a panelist is given a waiver, but no waivers were given at this meeting.

[email protected]

SILVER SPRING, MD. – Vorapaxar has won the backing of a Food and Drug Administration advisory panel for secondary prevention of atherothrombotic events.

At a meeting on Jan. 15, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 10-1 to recommend approval of the novel antiplatelet drug for reducing atherothrombotic events in patients with a history of MI – the indication proposed by Merck. The recommended dose is one 2.5-mg tablet per day.

The indication also includes the statement that treatment with vorapaxar has been shown to reduce the rate of the combined endpoint of cardiovascular death, MI, stroke, and urgent coronary revascularization; it is contraindicated in patients with a history of stroke or transient ischemic attack and a history of intracranial hemorrhage (ICH).

Vorapaxar is an antagonist of protease-activated receptor-1, which inhibits the action of thrombin on the platelet, according to the company. If approved, it will be the first marketed drug of that class.

The company conducted two phase III studies in two different groups of patients. In the TRACER (The Thrombin Receptor Antagonist for Clinical Event Reduction in ACS) study, which compared vorapaxar with placebo, added to standard therapy, as acute therapy (2.5 mg per day after a 40-mg loading dose, or placebo) in almost 13,000 hospitalized patients randomized within 24 hours of presenting with ACS (with non-ST elevation), it reduced the risk of atherothrombotic events (N. Engl. J. Med. 2012;366:20-33).

The study, however, was terminated early after an increased risk of major bleeding, including ICH, was detected and the company stopped the treatment in patients with a history of stroke or new stroke in the other phase III trial, the TRA 2P–TIMI 50 (Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Events) study. The company dropped plans to pursue the acute ACS indication.

The proposed indication is based on the results of the TRA 2P–TIMI 50 study, which randomized 26,449 patients to placebo or 2.5 mg of vorapaxar a day, added to standard therapy (including other antiplatelet agents) in 26,449 outpatients with a previous MI, previous ischemic stroke, or peripheral arterial disease (N. Engl. J. Med. 2012;366:1404-13). (Almost 80% of the patients in the study who met the criteria in the proposed indication were on dual antiplatelet therapy with aspirin and a thienopyridine.)

In the overall cohort, including those who had to stop treatment early, compared with placebo, the risk of the primary composite endpoint of cardiovascular death, MI, stroke, or urgent coronary revascularization was reduced by 12%, and the risk of a secondary efficacy endpoint (CV death, MI, stroke) was reduced by 13% over 3 years among those treated with vorapaxar – effects that were statistically significant, Merck said.

The risk of severe or moderate bleeding was increased by 51% among those on vorapaxar over placebo. The ICH rate over 3 years was 1% among those on vorapaxar, compared with 0.6% among those on placebo, but the absolute risk was higher in those with a history of stroke, according to Merck.

There is "clearly an unmet need" in this group of patients with a history of MI, "and a lack of therapies that have been shown to really be beneficial long term in this population," said the panel chair, Dr. Philip Sager, chair of the scientific programs committee, Cardiac Safety Research Consortium, San Francisco. "While there certainly is some bleeding risk, the benefits on the primary endpoint and secondary endpoint clearly outweigh those risks, and the benefit-risk relationship is positive," he added.

The panelist who voted against approval, Dr. Mori Krantz, director of the Colorado Prevention Center, Denver Health Medical Center, agreed that the primary efficacy endpoint had been met but was concerned about the size of the benefit and the large number of people needed to treat to benefit one patient. "Although the intracranial hemorrhages and the major bleeds were potentially manageable, I worry about the amplification of that signal," because triple antiplatelet therapy is "unprecedented," he added.

Other safety concerns cited by panelists included a lack of an antidote and the lack of an effect in people weighing less than 60 kg (132 lb), an unresolved issue.

If approved, Merck plans to market vorapaxar as Zontivity. The FDA usually follows the recommendations of its advisory panels. Members of advisory panels have been cleared of potential conflicts of interest, although occasionally they are given a waiver, but not at this meeting.

The FDA is due to make a decision on approval during the first half of this year, Merck said.

[email protected]

SILVER SPRING, MD. – Vorapaxar has won the backing of a Food and Drug Administration advisory panel for secondary prevention of atherothrombotic events.

At a meeting on Jan. 15, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 10-1 to recommend approval of the novel antiplatelet drug for reducing atherothrombotic events in patients with a history of MI – the indication proposed by Merck. The recommended dose is one 2.5-mg tablet per day.

The indication also includes the statement that treatment with vorapaxar has been shown to reduce the rate of the combined endpoint of cardiovascular death, MI, stroke, and urgent coronary revascularization; it is contraindicated in patients with a history of stroke or transient ischemic attack and a history of intracranial hemorrhage (ICH).

Vorapaxar is an antagonist of protease-activated receptor-1, which inhibits the action of thrombin on the platelet, according to the company. If approved, it will be the first marketed drug of that class.

The company conducted two phase III studies in two different groups of patients. In the TRACER (The Thrombin Receptor Antagonist for Clinical Event Reduction in ACS) study, which compared vorapaxar with placebo, added to standard therapy, as acute therapy (2.5 mg per day after a 40-mg loading dose, or placebo) in almost 13,000 hospitalized patients randomized within 24 hours of presenting with ACS (with non-ST elevation), it reduced the risk of atherothrombotic events (N. Engl. J. Med. 2012;366:20-33).

The study, however, was terminated early after an increased risk of major bleeding, including ICH, was detected and the company stopped the treatment in patients with a history of stroke or new stroke in the other phase III trial, the TRA 2P–TIMI 50 (Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Events) study. The company dropped plans to pursue the acute ACS indication.

The proposed indication is based on the results of the TRA 2P–TIMI 50 study, which randomized 26,449 patients to placebo or 2.5 mg of vorapaxar a day, added to standard therapy (including other antiplatelet agents) in 26,449 outpatients with a previous MI, previous ischemic stroke, or peripheral arterial disease (N. Engl. J. Med. 2012;366:1404-13). (Almost 80% of the patients in the study who met the criteria in the proposed indication were on dual antiplatelet therapy with aspirin and a thienopyridine.)

In the overall cohort, including those who had to stop treatment early, compared with placebo, the risk of the primary composite endpoint of cardiovascular death, MI, stroke, or urgent coronary revascularization was reduced by 12%, and the risk of a secondary efficacy endpoint (CV death, MI, stroke) was reduced by 13% over 3 years among those treated with vorapaxar – effects that were statistically significant, Merck said.

The risk of severe or moderate bleeding was increased by 51% among those on vorapaxar over placebo. The ICH rate over 3 years was 1% among those on vorapaxar, compared with 0.6% among those on placebo, but the absolute risk was higher in those with a history of stroke, according to Merck.

There is "clearly an unmet need" in this group of patients with a history of MI, "and a lack of therapies that have been shown to really be beneficial long term in this population," said the panel chair, Dr. Philip Sager, chair of the scientific programs committee, Cardiac Safety Research Consortium, San Francisco. "While there certainly is some bleeding risk, the benefits on the primary endpoint and secondary endpoint clearly outweigh those risks, and the benefit-risk relationship is positive," he added.

The panelist who voted against approval, Dr. Mori Krantz, director of the Colorado Prevention Center, Denver Health Medical Center, agreed that the primary efficacy endpoint had been met but was concerned about the size of the benefit and the large number of people needed to treat to benefit one patient. "Although the intracranial hemorrhages and the major bleeds were potentially manageable, I worry about the amplification of that signal," because triple antiplatelet therapy is "unprecedented," he added.

Other safety concerns cited by panelists included a lack of an antidote and the lack of an effect in people weighing less than 60 kg (132 lb), an unresolved issue.

If approved, Merck plans to market vorapaxar as Zontivity. The FDA usually follows the recommendations of its advisory panels. Members of advisory panels have been cleared of potential conflicts of interest, although occasionally they are given a waiver, but not at this meeting.

The FDA is due to make a decision on approval during the first half of this year, Merck said.

[email protected]

SILVER SPRING, MD. – Vorapaxar has won the backing of a Food and Drug Administration advisory panel for secondary prevention of atherothrombotic events.

At a meeting on Jan. 15, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 10-1 to recommend approval of the novel antiplatelet drug for reducing atherothrombotic events in patients with a history of MI – the indication proposed by Merck. The recommended dose is one 2.5-mg tablet per day.

The indication also includes the statement that treatment with vorapaxar has been shown to reduce the rate of the combined endpoint of cardiovascular death, MI, stroke, and urgent coronary revascularization; it is contraindicated in patients with a history of stroke or transient ischemic attack and a history of intracranial hemorrhage (ICH).

Vorapaxar is an antagonist of protease-activated receptor-1, which inhibits the action of thrombin on the platelet, according to the company. If approved, it will be the first marketed drug of that class.

The company conducted two phase III studies in two different groups of patients. In the TRACER (The Thrombin Receptor Antagonist for Clinical Event Reduction in ACS) study, which compared vorapaxar with placebo, added to standard therapy, as acute therapy (2.5 mg per day after a 40-mg loading dose, or placebo) in almost 13,000 hospitalized patients randomized within 24 hours of presenting with ACS (with non-ST elevation), it reduced the risk of atherothrombotic events (N. Engl. J. Med. 2012;366:20-33).

The study, however, was terminated early after an increased risk of major bleeding, including ICH, was detected and the company stopped the treatment in patients with a history of stroke or new stroke in the other phase III trial, the TRA 2P–TIMI 50 (Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Events) study. The company dropped plans to pursue the acute ACS indication.

The proposed indication is based on the results of the TRA 2P–TIMI 50 study, which randomized 26,449 patients to placebo or 2.5 mg of vorapaxar a day, added to standard therapy (including other antiplatelet agents) in 26,449 outpatients with a previous MI, previous ischemic stroke, or peripheral arterial disease (N. Engl. J. Med. 2012;366:1404-13). (Almost 80% of the patients in the study who met the criteria in the proposed indication were on dual antiplatelet therapy with aspirin and a thienopyridine.)

In the overall cohort, including those who had to stop treatment early, compared with placebo, the risk of the primary composite endpoint of cardiovascular death, MI, stroke, or urgent coronary revascularization was reduced by 12%, and the risk of a secondary efficacy endpoint (CV death, MI, stroke) was reduced by 13% over 3 years among those treated with vorapaxar – effects that were statistically significant, Merck said.

The risk of severe or moderate bleeding was increased by 51% among those on vorapaxar over placebo. The ICH rate over 3 years was 1% among those on vorapaxar, compared with 0.6% among those on placebo, but the absolute risk was higher in those with a history of stroke, according to Merck.

There is "clearly an unmet need" in this group of patients with a history of MI, "and a lack of therapies that have been shown to really be beneficial long term in this population," said the panel chair, Dr. Philip Sager, chair of the scientific programs committee, Cardiac Safety Research Consortium, San Francisco. "While there certainly is some bleeding risk, the benefits on the primary endpoint and secondary endpoint clearly outweigh those risks, and the benefit-risk relationship is positive," he added.

The panelist who voted against approval, Dr. Mori Krantz, director of the Colorado Prevention Center, Denver Health Medical Center, agreed that the primary efficacy endpoint had been met but was concerned about the size of the benefit and the large number of people needed to treat to benefit one patient. "Although the intracranial hemorrhages and the major bleeds were potentially manageable, I worry about the amplification of that signal," because triple antiplatelet therapy is "unprecedented," he added.

Other safety concerns cited by panelists included a lack of an antidote and the lack of an effect in people weighing less than 60 kg (132 lb), an unresolved issue.

If approved, Merck plans to market vorapaxar as Zontivity. The FDA usually follows the recommendations of its advisory panels. Members of advisory panels have been cleared of potential conflicts of interest, although occasionally they are given a waiver, but not at this meeting.

The FDA is due to make a decision on approval during the first half of this year, Merck said.

[email protected]

WASHINGTON – Despite the recent attention given to considering obesity a disease, there are still many limitations to providing treatments for obesity and receiving adequate reimbursement for those treatments, Dr. Lee Kaplan said at a public workshop cosponsored by the Food and Drug Administration and the American Gastroenterological Association.

The American Medical Association resolution to recognize obesity as a disease in 2013 has no legal authority, and therefore does not represent as much progress as suggested by the media attention surrounding the announcement, said Dr. Kaplan, director of the Massachusetts General Hospital Weight Center, Boston.

The AMA resolution was preceded by the Internal Revenue Service’s determination that obesity could qualify as a medical deduction in 2007, and in 2008, the Obesity Society provided support for considering obesity as a medical disorder.

But despite these apparent signs of progress, limitations remain. Weight loss drugs are excluded under Medicare Part D coverage, and while Medicare has started coverage for nutritional counseling, only services provided in a primary care setting are covered, he pointed out. An estimated 1 of every 400 people with obesity in the United States has bariatric surgery every year, but 1 in 100-150 of every 400 meets the criteria for surgery, which "doesn’t sound like we are addressing the problem very seriously," he said.

One problem is that obesity, which has many causes, is lumped together "into one big group," raising the issue of whether treating obesity would require an investment that is so huge, "that even as a society we cannot make it."

A critical issue is how to define obesity, Dr. Kaplan said. A simple definition is excess fat accumulation that presents a risk to health, but this definition does not include ways of measuring excess fat. One measurement, body mass index, is a marker, not a definition of obesity.

A major barrier is the development of an effective therapy, he said, noting that other than gastric bands, there are no devices on the market to treat obesity, and the four drugs approved by the FDA have modest efficacy overall and are not widely used. Another major barrier is "provider utilization," getting the provider to prescribe treatments and obtain reimbursement for the costs of treatment.

"There is also a large gap between the relatively noninvasive treatments and the invasive, more effective therapies, which needs to be filled by midlevel therapies," he said. Those therapies should be gastrointestinal therapies almost exclusively, he added. The current treatment strategy is fairly simplistic: Patients are asked to change their lifestyle and when that does not work, the next step is to see a dietician, psychologist, or another professional to help with their lifestyle changes, followed by the addition of medication if that does not work. Surgery is broached in a small number of patients.

"Obesity is a disease whether we call it one or not, because it behaves like a disease," and there are implications to viewing it as a disease, he said. Therapy should be physiologically based, and the heterogeneity in the underlying causes of obesity, which explains the variable treatment responses, provides an opportunity to benefit selected subpopulations.

Considering the number of disorders that are associated with obesity, it is not surprising that treatment responses vary widely, Dr. Kaplan said. People with one defect may do better than others with gastric bypass, and some people may respond better than others to the approved combination of phentermine and topiramate (Qsymia) – as reflected in the ranges of response rates associated with these therapies, he pointed out.

The average excess weight loss with gastric bypass, the most effective therapy for obesity, is about 65%, but it can be as low as 20% in some people. With banding, some patients lose all or most of their excess weight, but most lose about 25%-30%, he said. Similarly, Dr. Kaplan found some patients responded well to treatment with sibutramine (which is no longer marketed), while others did not respond well; the same pattern was seen with lorcaserin.

"Whether you’re talking about a drug, a device, surgery, or lifestyle modifications, ... you see this very broad response," because there are subtypes of obesity, he said. Identifying the subgroups of patients that are highly responsive to any of these treatments could increase the success rate of the treatment, he noted.

[email protected]

WASHINGTON – Despite the recent attention given to considering obesity a disease, there are still many limitations to providing treatments for obesity and receiving adequate reimbursement for those treatments, Dr. Lee Kaplan said at a public workshop cosponsored by the Food and Drug Administration and the American Gastroenterological Association.

The American Medical Association resolution to recognize obesity as a disease in 2013 has no legal authority, and therefore does not represent as much progress as suggested by the media attention surrounding the announcement, said Dr. Kaplan, director of the Massachusetts General Hospital Weight Center, Boston.

The AMA resolution was preceded by the Internal Revenue Service’s determination that obesity could qualify as a medical deduction in 2007, and in 2008, the Obesity Society provided support for considering obesity as a medical disorder.

But despite these apparent signs of progress, limitations remain. Weight loss drugs are excluded under Medicare Part D coverage, and while Medicare has started coverage for nutritional counseling, only services provided in a primary care setting are covered, he pointed out. An estimated 1 of every 400 people with obesity in the United States has bariatric surgery every year, but 1 in 100-150 of every 400 meets the criteria for surgery, which "doesn’t sound like we are addressing the problem very seriously," he said.

One problem is that obesity, which has many causes, is lumped together "into one big group," raising the issue of whether treating obesity would require an investment that is so huge, "that even as a society we cannot make it."

A critical issue is how to define obesity, Dr. Kaplan said. A simple definition is excess fat accumulation that presents a risk to health, but this definition does not include ways of measuring excess fat. One measurement, body mass index, is a marker, not a definition of obesity.

A major barrier is the development of an effective therapy, he said, noting that other than gastric bands, there are no devices on the market to treat obesity, and the four drugs approved by the FDA have modest efficacy overall and are not widely used. Another major barrier is "provider utilization," getting the provider to prescribe treatments and obtain reimbursement for the costs of treatment.

"There is also a large gap between the relatively noninvasive treatments and the invasive, more effective therapies, which needs to be filled by midlevel therapies," he said. Those therapies should be gastrointestinal therapies almost exclusively, he added. The current treatment strategy is fairly simplistic: Patients are asked to change their lifestyle and when that does not work, the next step is to see a dietician, psychologist, or another professional to help with their lifestyle changes, followed by the addition of medication if that does not work. Surgery is broached in a small number of patients.

"Obesity is a disease whether we call it one or not, because it behaves like a disease," and there are implications to viewing it as a disease, he said. Therapy should be physiologically based, and the heterogeneity in the underlying causes of obesity, which explains the variable treatment responses, provides an opportunity to benefit selected subpopulations.

Considering the number of disorders that are associated with obesity, it is not surprising that treatment responses vary widely, Dr. Kaplan said. People with one defect may do better than others with gastric bypass, and some people may respond better than others to the approved combination of phentermine and topiramate (Qsymia) – as reflected in the ranges of response rates associated with these therapies, he pointed out.

The average excess weight loss with gastric bypass, the most effective therapy for obesity, is about 65%, but it can be as low as 20% in some people. With banding, some patients lose all or most of their excess weight, but most lose about 25%-30%, he said. Similarly, Dr. Kaplan found some patients responded well to treatment with sibutramine (which is no longer marketed), while others did not respond well; the same pattern was seen with lorcaserin.

"Whether you’re talking about a drug, a device, surgery, or lifestyle modifications, ... you see this very broad response," because there are subtypes of obesity, he said. Identifying the subgroups of patients that are highly responsive to any of these treatments could increase the success rate of the treatment, he noted.

[email protected]

WASHINGTON – Despite the recent attention given to considering obesity a disease, there are still many limitations to providing treatments for obesity and receiving adequate reimbursement for those treatments, Dr. Lee Kaplan said at a public workshop cosponsored by the Food and Drug Administration and the American Gastroenterological Association.

The American Medical Association resolution to recognize obesity as a disease in 2013 has no legal authority, and therefore does not represent as much progress as suggested by the media attention surrounding the announcement, said Dr. Kaplan, director of the Massachusetts General Hospital Weight Center, Boston.

The AMA resolution was preceded by the Internal Revenue Service’s determination that obesity could qualify as a medical deduction in 2007, and in 2008, the Obesity Society provided support for considering obesity as a medical disorder.

But despite these apparent signs of progress, limitations remain. Weight loss drugs are excluded under Medicare Part D coverage, and while Medicare has started coverage for nutritional counseling, only services provided in a primary care setting are covered, he pointed out. An estimated 1 of every 400 people with obesity in the United States has bariatric surgery every year, but 1 in 100-150 of every 400 meets the criteria for surgery, which "doesn’t sound like we are addressing the problem very seriously," he said.

One problem is that obesity, which has many causes, is lumped together "into one big group," raising the issue of whether treating obesity would require an investment that is so huge, "that even as a society we cannot make it."

A critical issue is how to define obesity, Dr. Kaplan said. A simple definition is excess fat accumulation that presents a risk to health, but this definition does not include ways of measuring excess fat. One measurement, body mass index, is a marker, not a definition of obesity.

A major barrier is the development of an effective therapy, he said, noting that other than gastric bands, there are no devices on the market to treat obesity, and the four drugs approved by the FDA have modest efficacy overall and are not widely used. Another major barrier is "provider utilization," getting the provider to prescribe treatments and obtain reimbursement for the costs of treatment.

"There is also a large gap between the relatively noninvasive treatments and the invasive, more effective therapies, which needs to be filled by midlevel therapies," he said. Those therapies should be gastrointestinal therapies almost exclusively, he added. The current treatment strategy is fairly simplistic: Patients are asked to change their lifestyle and when that does not work, the next step is to see a dietician, psychologist, or another professional to help with their lifestyle changes, followed by the addition of medication if that does not work. Surgery is broached in a small number of patients.

"Obesity is a disease whether we call it one or not, because it behaves like a disease," and there are implications to viewing it as a disease, he said. Therapy should be physiologically based, and the heterogeneity in the underlying causes of obesity, which explains the variable treatment responses, provides an opportunity to benefit selected subpopulations.

Considering the number of disorders that are associated with obesity, it is not surprising that treatment responses vary widely, Dr. Kaplan said. People with one defect may do better than others with gastric bypass, and some people may respond better than others to the approved combination of phentermine and topiramate (Qsymia) – as reflected in the ranges of response rates associated with these therapies, he pointed out.

The average excess weight loss with gastric bypass, the most effective therapy for obesity, is about 65%, but it can be as low as 20% in some people. With banding, some patients lose all or most of their excess weight, but most lose about 25%-30%, he said. Similarly, Dr. Kaplan found some patients responded well to treatment with sibutramine (which is no longer marketed), while others did not respond well; the same pattern was seen with lorcaserin.

"Whether you’re talking about a drug, a device, surgery, or lifestyle modifications, ... you see this very broad response," because there are subtypes of obesity, he said. Identifying the subgroups of patients that are highly responsive to any of these treatments could increase the success rate of the treatment, he noted.

[email protected]

WASHINGTON – Advances in dietary therapy for nonlesional epilepsy have made it a more feasible approach for many patients because of options that now include a "smarter and gentler" ketogenic diet and a modified Atkins diet, Dr. Eric Kossoff said at the annual meeting of the American Epilepsy Society.

"We’ve come a long way ... in making diets easier, safer [and] more palatable, and that’s really opened up many different options for patients who didn’t have diet as an option before," said Dr. Kossoff, a pediatric neurologist at Johns Hopkins Children’s Center, Baltimore. For patients with nonlesional epilepsy, diets can be helpful – sometimes even resulting in seizure freedom – and should be considered earlier in the course of treatment, he added.

Most of his discussion focused on pediatric patients, but he said that some children continue the diet into adulthood, and there is increasing interest in the potential of dietary approaches, particularly a modified Atkins diet, for adults with nonlesional epilepsy. Adult epilepsy diet centers also are starting to appear in large U.S. cities and internationally.

The currently recommended ketogenic diet (high fat, moderate protein, and low carbohydrate) is far less rigid and restrictive than the traditional ketogenic diet used for more than 80 years, which entailed starting the diet in the hospital with intensive dietician involvement, precisely weighing food with a gram scale, and following the diet for 6 months to 2 years, he pointed out. Dieticians have more leeway in making the diet more palatable, with resources like the online KetoCalculator program that helps families plan and create meals.

There is now more information that health care practitioners can use to predict the type of patient more likely to respond to diet. Fasting and hospital admission are no longer needed, and adverse events are anticipated and prevented, not treated, said Dr. Kossoff, who is also medical director of the Ketogenic Diet Center at the John M. Freeman Pediatric Epilepsy Center at Johns Hopkins. In a 2007 study of diet in 45 children with lesional epilepsy, there was some response to diet, but none of the children were seizure free (Seizure 2007;16:615-9). At Johns Hopkins and other epilepsy centers in the United States and elsewhere, the ketogenic diet is mostly recommended as a treatment for nonlesional epilepsy, based on this study and anecdotal experience, with the exception of tuberous sclerosis, he added.

In addition, clinical data from multiple prospective and retrospective studies have provided solid evidence that the diet can be effective, he said. These include "dramatic" results of a randomized controlled study, which found that 38% of the children on the ketogenic diet had more than a 50% reduction in baseline seizures after 3 months, compared with 6% of controls (Lancet Neurol. 2008;7:500-6). "This really did change a lot of mind-sets that diet had not been proven," he said. Based on the results of the available studies combined, there is about a 50%-55% likelihood of a response with diet and about a 15% likelihood of being seizure free, he noted.

The need to fast is now being reconsidered by most centers, Dr. Kossoff said. A 2005 randomized controlled study that compared the effects of starting the diet with fasting to gradually introducing the diet without a fasting period found that while fasting resulted in a more rapid rise in serum ketones, seizure-free and seizure-reduction rates at 3 months were similar in both groups. Fasting can be viewed as "an IV load of a ketogenic diet," he added. "It gets the seizure improvement to occur quicker, but long term, it doesn’t seem to make much of a difference."

Improvements in addressing weight loss, vomiting, constipation, and other potential side effects of the ketogenic diet include the use of supplements such as multivitamins, vitamin D, and selenium, as well as laxatives. At Johns Hopkins, Dr. Kossoff and his associates have found that the use of oral citrates reduces the risk of kidney stones associated with the diet to less than 1% (from about 5%-6%).

Traditionally, the ketogenic diet has been recommended for up to 2 years, but most studies indicate that patients who will benefit will start to respond within 2-4 weeks, and it is not necessary to wait for 6 months to see if they respond. He and his associates recommend waiting for at least 3 months to see if a patient responds.

Traditionally, 2 years on the diet has been recommended, but there are studies indicating a shorter period of time may be adequate. Some patients, however, have a recurrence when they stop the diet and need to continue the diet into adulthood for as long as 20-30 years, if necessary.

In addition to the classic ketogenic diet, Dr. Kossoff described several other less restrictive dietary treatment options. The modified Atkins diet falls between a regular diet and a classic ketogenic diet, with high fat (about 65% vs. about 90% with the classic ketogenic diet) and low carbohydrates. Also with the modified Atkins diet, there is no need to fast, restrict calories or fluids, hospitalize the patient, or weigh food on a gram scale. Over a decade, 32 studies involving 400 patients treated with this approach, including 17 prospective studies, have provided evidence that the diet is effective, with almost a 50% responder rate and a 13% seizure-free rate, "remarkably similar to what we see with a classic ketogenic diet," he noted.

This is the dietary approach most likely to be used in adults, he added.

The Low Glycemic Index diet is also a high-fat, low-carbohydrate diet, but it primarily targets the type of carbohydrates in the diet, aiming for a glycemic index of less than 50. Interestingly, this diet does induce urinary ketosis but is effective, "suggesting that these diets may work by mechanisms we are not completely sure of, not necessarily ketosis," Dr. Kossoff said.

Dr. Kossoff declared that he had no relevant disclosures. He was the lead author of the International Ketogenic Diet Study Group’s recommendations on the ketogenic diet in children (Epilepsia 2009;50:304-17).

[email protected]

WASHINGTON – Advances in dietary therapy for nonlesional epilepsy have made it a more feasible approach for many patients because of options that now include a "smarter and gentler" ketogenic diet and a modified Atkins diet, Dr. Eric Kossoff said at the annual meeting of the American Epilepsy Society.

"We’ve come a long way ... in making diets easier, safer [and] more palatable, and that’s really opened up many different options for patients who didn’t have diet as an option before," said Dr. Kossoff, a pediatric neurologist at Johns Hopkins Children’s Center, Baltimore. For patients with nonlesional epilepsy, diets can be helpful – sometimes even resulting in seizure freedom – and should be considered earlier in the course of treatment, he added.

Most of his discussion focused on pediatric patients, but he said that some children continue the diet into adulthood, and there is increasing interest in the potential of dietary approaches, particularly a modified Atkins diet, for adults with nonlesional epilepsy. Adult epilepsy diet centers also are starting to appear in large U.S. cities and internationally.

The currently recommended ketogenic diet (high fat, moderate protein, and low carbohydrate) is far less rigid and restrictive than the traditional ketogenic diet used for more than 80 years, which entailed starting the diet in the hospital with intensive dietician involvement, precisely weighing food with a gram scale, and following the diet for 6 months to 2 years, he pointed out. Dieticians have more leeway in making the diet more palatable, with resources like the online KetoCalculator program that helps families plan and create meals.

There is now more information that health care practitioners can use to predict the type of patient more likely to respond to diet. Fasting and hospital admission are no longer needed, and adverse events are anticipated and prevented, not treated, said Dr. Kossoff, who is also medical director of the Ketogenic Diet Center at the John M. Freeman Pediatric Epilepsy Center at Johns Hopkins. In a 2007 study of diet in 45 children with lesional epilepsy, there was some response to diet, but none of the children were seizure free (Seizure 2007;16:615-9). At Johns Hopkins and other epilepsy centers in the United States and elsewhere, the ketogenic diet is mostly recommended as a treatment for nonlesional epilepsy, based on this study and anecdotal experience, with the exception of tuberous sclerosis, he added.

In addition, clinical data from multiple prospective and retrospective studies have provided solid evidence that the diet can be effective, he said. These include "dramatic" results of a randomized controlled study, which found that 38% of the children on the ketogenic diet had more than a 50% reduction in baseline seizures after 3 months, compared with 6% of controls (Lancet Neurol. 2008;7:500-6). "This really did change a lot of mind-sets that diet had not been proven," he said. Based on the results of the available studies combined, there is about a 50%-55% likelihood of a response with diet and about a 15% likelihood of being seizure free, he noted.

The need to fast is now being reconsidered by most centers, Dr. Kossoff said. A 2005 randomized controlled study that compared the effects of starting the diet with fasting to gradually introducing the diet without a fasting period found that while fasting resulted in a more rapid rise in serum ketones, seizure-free and seizure-reduction rates at 3 months were similar in both groups. Fasting can be viewed as "an IV load of a ketogenic diet," he added. "It gets the seizure improvement to occur quicker, but long term, it doesn’t seem to make much of a difference."

Improvements in addressing weight loss, vomiting, constipation, and other potential side effects of the ketogenic diet include the use of supplements such as multivitamins, vitamin D, and selenium, as well as laxatives. At Johns Hopkins, Dr. Kossoff and his associates have found that the use of oral citrates reduces the risk of kidney stones associated with the diet to less than 1% (from about 5%-6%).

Traditionally, the ketogenic diet has been recommended for up to 2 years, but most studies indicate that patients who will benefit will start to respond within 2-4 weeks, and it is not necessary to wait for 6 months to see if they respond. He and his associates recommend waiting for at least 3 months to see if a patient responds.

Traditionally, 2 years on the diet has been recommended, but there are studies indicating a shorter period of time may be adequate. Some patients, however, have a recurrence when they stop the diet and need to continue the diet into adulthood for as long as 20-30 years, if necessary.

In addition to the classic ketogenic diet, Dr. Kossoff described several other less restrictive dietary treatment options. The modified Atkins diet falls between a regular diet and a classic ketogenic diet, with high fat (about 65% vs. about 90% with the classic ketogenic diet) and low carbohydrates. Also with the modified Atkins diet, there is no need to fast, restrict calories or fluids, hospitalize the patient, or weigh food on a gram scale. Over a decade, 32 studies involving 400 patients treated with this approach, including 17 prospective studies, have provided evidence that the diet is effective, with almost a 50% responder rate and a 13% seizure-free rate, "remarkably similar to what we see with a classic ketogenic diet," he noted.

This is the dietary approach most likely to be used in adults, he added.

The Low Glycemic Index diet is also a high-fat, low-carbohydrate diet, but it primarily targets the type of carbohydrates in the diet, aiming for a glycemic index of less than 50. Interestingly, this diet does induce urinary ketosis but is effective, "suggesting that these diets may work by mechanisms we are not completely sure of, not necessarily ketosis," Dr. Kossoff said.

Dr. Kossoff declared that he had no relevant disclosures. He was the lead author of the International Ketogenic Diet Study Group’s recommendations on the ketogenic diet in children (Epilepsia 2009;50:304-17).

[email protected]

WASHINGTON – Advances in dietary therapy for nonlesional epilepsy have made it a more feasible approach for many patients because of options that now include a "smarter and gentler" ketogenic diet and a modified Atkins diet, Dr. Eric Kossoff said at the annual meeting of the American Epilepsy Society.

"We’ve come a long way ... in making diets easier, safer [and] more palatable, and that’s really opened up many different options for patients who didn’t have diet as an option before," said Dr. Kossoff, a pediatric neurologist at Johns Hopkins Children’s Center, Baltimore. For patients with nonlesional epilepsy, diets can be helpful – sometimes even resulting in seizure freedom – and should be considered earlier in the course of treatment, he added.

Most of his discussion focused on pediatric patients, but he said that some children continue the diet into adulthood, and there is increasing interest in the potential of dietary approaches, particularly a modified Atkins diet, for adults with nonlesional epilepsy. Adult epilepsy diet centers also are starting to appear in large U.S. cities and internationally.

The currently recommended ketogenic diet (high fat, moderate protein, and low carbohydrate) is far less rigid and restrictive than the traditional ketogenic diet used for more than 80 years, which entailed starting the diet in the hospital with intensive dietician involvement, precisely weighing food with a gram scale, and following the diet for 6 months to 2 years, he pointed out. Dieticians have more leeway in making the diet more palatable, with resources like the online KetoCalculator program that helps families plan and create meals.

There is now more information that health care practitioners can use to predict the type of patient more likely to respond to diet. Fasting and hospital admission are no longer needed, and adverse events are anticipated and prevented, not treated, said Dr. Kossoff, who is also medical director of the Ketogenic Diet Center at the John M. Freeman Pediatric Epilepsy Center at Johns Hopkins. In a 2007 study of diet in 45 children with lesional epilepsy, there was some response to diet, but none of the children were seizure free (Seizure 2007;16:615-9). At Johns Hopkins and other epilepsy centers in the United States and elsewhere, the ketogenic diet is mostly recommended as a treatment for nonlesional epilepsy, based on this study and anecdotal experience, with the exception of tuberous sclerosis, he added.

In addition, clinical data from multiple prospective and retrospective studies have provided solid evidence that the diet can be effective, he said. These include "dramatic" results of a randomized controlled study, which found that 38% of the children on the ketogenic diet had more than a 50% reduction in baseline seizures after 3 months, compared with 6% of controls (Lancet Neurol. 2008;7:500-6). "This really did change a lot of mind-sets that diet had not been proven," he said. Based on the results of the available studies combined, there is about a 50%-55% likelihood of a response with diet and about a 15% likelihood of being seizure free, he noted.

The need to fast is now being reconsidered by most centers, Dr. Kossoff said. A 2005 randomized controlled study that compared the effects of starting the diet with fasting to gradually introducing the diet without a fasting period found that while fasting resulted in a more rapid rise in serum ketones, seizure-free and seizure-reduction rates at 3 months were similar in both groups. Fasting can be viewed as "an IV load of a ketogenic diet," he added. "It gets the seizure improvement to occur quicker, but long term, it doesn’t seem to make much of a difference."

Improvements in addressing weight loss, vomiting, constipation, and other potential side effects of the ketogenic diet include the use of supplements such as multivitamins, vitamin D, and selenium, as well as laxatives. At Johns Hopkins, Dr. Kossoff and his associates have found that the use of oral citrates reduces the risk of kidney stones associated with the diet to less than 1% (from about 5%-6%).

Traditionally, the ketogenic diet has been recommended for up to 2 years, but most studies indicate that patients who will benefit will start to respond within 2-4 weeks, and it is not necessary to wait for 6 months to see if they respond. He and his associates recommend waiting for at least 3 months to see if a patient responds.

Traditionally, 2 years on the diet has been recommended, but there are studies indicating a shorter period of time may be adequate. Some patients, however, have a recurrence when they stop the diet and need to continue the diet into adulthood for as long as 20-30 years, if necessary.

In addition to the classic ketogenic diet, Dr. Kossoff described several other less restrictive dietary treatment options. The modified Atkins diet falls between a regular diet and a classic ketogenic diet, with high fat (about 65% vs. about 90% with the classic ketogenic diet) and low carbohydrates. Also with the modified Atkins diet, there is no need to fast, restrict calories or fluids, hospitalize the patient, or weigh food on a gram scale. Over a decade, 32 studies involving 400 patients treated with this approach, including 17 prospective studies, have provided evidence that the diet is effective, with almost a 50% responder rate and a 13% seizure-free rate, "remarkably similar to what we see with a classic ketogenic diet," he noted.

This is the dietary approach most likely to be used in adults, he added.

The Low Glycemic Index diet is also a high-fat, low-carbohydrate diet, but it primarily targets the type of carbohydrates in the diet, aiming for a glycemic index of less than 50. Interestingly, this diet does induce urinary ketosis but is effective, "suggesting that these diets may work by mechanisms we are not completely sure of, not necessarily ketosis," Dr. Kossoff said.

Dr. Kossoff declared that he had no relevant disclosures. He was the lead author of the International Ketogenic Diet Study Group’s recommendations on the ketogenic diet in children (Epilepsia 2009;50:304-17).

[email protected]

WASHINGTON – People with epilepsy who were considered to be in intermediate control of their seizures were hospitalized for similar lengths of time and went to the emergency room as often as those with uncontrolled epilepsy in a large retrospective study of commercially insured adults with epilepsy, Dr. Fulton Velez reported at the annual meeting of the American Epilepsy Society.

The results suggest that the use of health care resources may be greater among patients whose seizures are less than optimally controlled, which "may have important health care utilization implications for patients and payers," said Dr. Velez, director of health economics and outcomes research at Sunovion Pharmaceuticals, a manufacturer of antiepileptic drugs (AEDs).

The investigators reviewed the use of health care resources in 26,625 adults with epilepsy who were enrolled in the MarketScan database, a national database that contains data on over 180 million patients since 1995, according to its website. The patients were treated with at least one add-on AED within 60 days of being diagnosed and were followed for at least 1 year (the average follow-up time was 3.25 years).

Dr. Velez and his colleagues fit the patients into three categories:

• Uncontrolled, defined as one emergency room or inpatient stay preceded by two or more changes in drug therapy, either an additional drug or a switch in drugs in the preceding 6 months.

• Well controlled, meaning no change in AED therapy and no epilepsy-related emergency room or inpatient visits.

• Intermediate controlled, which meant that the patient was not classified as uncontrolled or well controlled.

Most (83%) fell into the intermediate-control category, 2% were uncontrolled, and 15% were well controlled. Their mean age was 49 years and almost 60% were women.

As expected, the use of health care resources was markedly higher among the uncontrolled patients, Dr. Velez said. Patients in the uncontrolled category used significantly more AEDs and had significantly more outpatient and neurologist visits than did those in the well-controlled and intermediate-control categories.

The uncontrolled patients used 1.6 times more AEDs than did those who were well controlled and those who were in the intermediate-control category. The rate of outpatient visits was 20% higher among uncontrolled patients than in those who were well controlled. In addition, the rate of neurologist visits among those who were uncontrolled was about 40% higher than in those who were well controlled and 19% higher than those who were in the intermediate-control category, Dr. Velez said.

Not surprisingly, patients with uncontrolled epilepsy visited the emergency room 12 times as often and stayed in the hospital more than 7 times as often as did those with well-controlled epilepsy. Their duration of hospitalizations also was nine times as long.

There were, however, no differences in the rate of emergency room visits or length of hospital stays between the intermediate control and uncontrolled patients, Dr. Velez said. In addition, the rate of inpatient hospitalizations was about 12% higher among the intermediate-control group. "The findings of this study suggest that even small departures from optimal seizure control are associated with a marked increase in health resource utilization among epilepsy patients," he said in a statement issued by the American Epilepsy Society during the meeting.

The study was performed by HERON Evidence Development AB, Stockholm, and the data analysis was funded by Sunovion.

[email protected]

WASHINGTON – People with epilepsy who were considered to be in intermediate control of their seizures were hospitalized for similar lengths of time and went to the emergency room as often as those with uncontrolled epilepsy in a large retrospective study of commercially insured adults with epilepsy, Dr. Fulton Velez reported at the annual meeting of the American Epilepsy Society.

The results suggest that the use of health care resources may be greater among patients whose seizures are less than optimally controlled, which "may have important health care utilization implications for patients and payers," said Dr. Velez, director of health economics and outcomes research at Sunovion Pharmaceuticals, a manufacturer of antiepileptic drugs (AEDs).

The investigators reviewed the use of health care resources in 26,625 adults with epilepsy who were enrolled in the MarketScan database, a national database that contains data on over 180 million patients since 1995, according to its website. The patients were treated with at least one add-on AED within 60 days of being diagnosed and were followed for at least 1 year (the average follow-up time was 3.25 years).

Dr. Velez and his colleagues fit the patients into three categories:

• Uncontrolled, defined as one emergency room or inpatient stay preceded by two or more changes in drug therapy, either an additional drug or a switch in drugs in the preceding 6 months.

• Well controlled, meaning no change in AED therapy and no epilepsy-related emergency room or inpatient visits.

• Intermediate controlled, which meant that the patient was not classified as uncontrolled or well controlled.

Most (83%) fell into the intermediate-control category, 2% were uncontrolled, and 15% were well controlled. Their mean age was 49 years and almost 60% were women.

As expected, the use of health care resources was markedly higher among the uncontrolled patients, Dr. Velez said. Patients in the uncontrolled category used significantly more AEDs and had significantly more outpatient and neurologist visits than did those in the well-controlled and intermediate-control categories.

The uncontrolled patients used 1.6 times more AEDs than did those who were well controlled and those who were in the intermediate-control category. The rate of outpatient visits was 20% higher among uncontrolled patients than in those who were well controlled. In addition, the rate of neurologist visits among those who were uncontrolled was about 40% higher than in those who were well controlled and 19% higher than those who were in the intermediate-control category, Dr. Velez said.

Not surprisingly, patients with uncontrolled epilepsy visited the emergency room 12 times as often and stayed in the hospital more than 7 times as often as did those with well-controlled epilepsy. Their duration of hospitalizations also was nine times as long.

There were, however, no differences in the rate of emergency room visits or length of hospital stays between the intermediate control and uncontrolled patients, Dr. Velez said. In addition, the rate of inpatient hospitalizations was about 12% higher among the intermediate-control group. "The findings of this study suggest that even small departures from optimal seizure control are associated with a marked increase in health resource utilization among epilepsy patients," he said in a statement issued by the American Epilepsy Society during the meeting.

The study was performed by HERON Evidence Development AB, Stockholm, and the data analysis was funded by Sunovion.

[email protected]

WASHINGTON – People with epilepsy who were considered to be in intermediate control of their seizures were hospitalized for similar lengths of time and went to the emergency room as often as those with uncontrolled epilepsy in a large retrospective study of commercially insured adults with epilepsy, Dr. Fulton Velez reported at the annual meeting of the American Epilepsy Society.

The results suggest that the use of health care resources may be greater among patients whose seizures are less than optimally controlled, which "may have important health care utilization implications for patients and payers," said Dr. Velez, director of health economics and outcomes research at Sunovion Pharmaceuticals, a manufacturer of antiepileptic drugs (AEDs).

The investigators reviewed the use of health care resources in 26,625 adults with epilepsy who were enrolled in the MarketScan database, a national database that contains data on over 180 million patients since 1995, according to its website. The patients were treated with at least one add-on AED within 60 days of being diagnosed and were followed for at least 1 year (the average follow-up time was 3.25 years).

Dr. Velez and his colleagues fit the patients into three categories:

• Uncontrolled, defined as one emergency room or inpatient stay preceded by two or more changes in drug therapy, either an additional drug or a switch in drugs in the preceding 6 months.

• Well controlled, meaning no change in AED therapy and no epilepsy-related emergency room or inpatient visits.

• Intermediate controlled, which meant that the patient was not classified as uncontrolled or well controlled.

Most (83%) fell into the intermediate-control category, 2% were uncontrolled, and 15% were well controlled. Their mean age was 49 years and almost 60% were women.

As expected, the use of health care resources was markedly higher among the uncontrolled patients, Dr. Velez said. Patients in the uncontrolled category used significantly more AEDs and had significantly more outpatient and neurologist visits than did those in the well-controlled and intermediate-control categories.

The uncontrolled patients used 1.6 times more AEDs than did those who were well controlled and those who were in the intermediate-control category. The rate of outpatient visits was 20% higher among uncontrolled patients than in those who were well controlled. In addition, the rate of neurologist visits among those who were uncontrolled was about 40% higher than in those who were well controlled and 19% higher than those who were in the intermediate-control category, Dr. Velez said.

Not surprisingly, patients with uncontrolled epilepsy visited the emergency room 12 times as often and stayed in the hospital more than 7 times as often as did those with well-controlled epilepsy. Their duration of hospitalizations also was nine times as long.

There were, however, no differences in the rate of emergency room visits or length of hospital stays between the intermediate control and uncontrolled patients, Dr. Velez said. In addition, the rate of inpatient hospitalizations was about 12% higher among the intermediate-control group. "The findings of this study suggest that even small departures from optimal seizure control are associated with a marked increase in health resource utilization among epilepsy patients," he said in a statement issued by the American Epilepsy Society during the meeting.

The study was performed by HERON Evidence Development AB, Stockholm, and the data analysis was funded by Sunovion.

[email protected]

A combination of two targeted, orally administered drug therapies – trametinib and dabrafenib – has been approved by the Food and Drug Administration for treating patients with unresectable melanoma or metastatic melanoma with BRAF V600E or V600K mutations, manufacturer GlaxoSmithKline announced on Jan. 9.

An FDA-approved test is used to detect the mutations, according to the company statement.

Trametinib, marketed as Mekinist, and dabrafenib, marketed as Tafinlar, were each approved in May 2013 as separate treatments for metastatic or unresectable melanomas that express the mutations – along with a companion test to detect the mutations. Both are kinase inhibitors.

The GSK statement noted that the accelerated approval of the combination therapy is based on the response rate and median duration of response results in a phase I/II study of 108 patients, which compared the combination (150 mg of dabrafenib twice a day and 2 mg of trametinib once a day) to treatment with dabrafenib alone. The overall response rates, as assessed by the investigators, were 76% among those on the combination and 54% for those on dabrafenib alone. The median duration of response was 10.5 months among those on the combination, vs. 5.6 months among those on dabrafenib alone.

The most common adverse events associated with the combination treatment included fever in 71% of patients, chills in 58%, fatigue in 52%, rash in 45%, nausea in 44%, vomiting in 40%, and diarrhea in 36%. Renal failure, pyrexia, back pain, and hemorrhage were among the most common grade-3 or -4 adverse events among those on the combination.

Serious adverse effects associated with treatment, including some potentially fatal effects, are new primary cutaneous skin cancers, tumor promotion in wild-type BRAF melanoma, and hemorrhagic events, according to GSK.

The FDA approval occurred through an accelerated process based on clinical evidence that the treatment has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. As a condition of accelerated approval, manufacturers are required to provide more clinical data confirming benefit, and if the follow-up studies fail to confirm benefit, the FDA can withdraw approval.

Full approval is dependent on the results of an ongoing phase III study, GSK said.

The updated trametinib label states that "improvement in disease-related symptoms or overall survival has not been demonstrated" for the combination treatment.

The prescribing information for Mekinist is available at http://us.gsk.com/products/assets/us_mekinist.pdf. The prescribing information for Tafinlar (which does not yet include the updated information on the combination therapy approval) is available at http://us.gsk.com/products/assets/us_tafinlar.pdf.

[email protected]

A combination of two targeted, orally administered drug therapies – trametinib and dabrafenib – has been approved by the Food and Drug Administration for treating patients with unresectable melanoma or metastatic melanoma with BRAF V600E or V600K mutations, manufacturer GlaxoSmithKline announced on Jan. 9.

An FDA-approved test is used to detect the mutations, according to the company statement.

Trametinib, marketed as Mekinist, and dabrafenib, marketed as Tafinlar, were each approved in May 2013 as separate treatments for metastatic or unresectable melanomas that express the mutations – along with a companion test to detect the mutations. Both are kinase inhibitors.

The GSK statement noted that the accelerated approval of the combination therapy is based on the response rate and median duration of response results in a phase I/II study of 108 patients, which compared the combination (150 mg of dabrafenib twice a day and 2 mg of trametinib once a day) to treatment with dabrafenib alone. The overall response rates, as assessed by the investigators, were 76% among those on the combination and 54% for those on dabrafenib alone. The median duration of response was 10.5 months among those on the combination, vs. 5.6 months among those on dabrafenib alone.

The most common adverse events associated with the combination treatment included fever in 71% of patients, chills in 58%, fatigue in 52%, rash in 45%, nausea in 44%, vomiting in 40%, and diarrhea in 36%. Renal failure, pyrexia, back pain, and hemorrhage were among the most common grade-3 or -4 adverse events among those on the combination.

Serious adverse effects associated with treatment, including some potentially fatal effects, are new primary cutaneous skin cancers, tumor promotion in wild-type BRAF melanoma, and hemorrhagic events, according to GSK.

The FDA approval occurred through an accelerated process based on clinical evidence that the treatment has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. As a condition of accelerated approval, manufacturers are required to provide more clinical data confirming benefit, and if the follow-up studies fail to confirm benefit, the FDA can withdraw approval.

Full approval is dependent on the results of an ongoing phase III study, GSK said.

The updated trametinib label states that "improvement in disease-related symptoms or overall survival has not been demonstrated" for the combination treatment.

The prescribing information for Mekinist is available at http://us.gsk.com/products/assets/us_mekinist.pdf. The prescribing information for Tafinlar (which does not yet include the updated information on the combination therapy approval) is available at http://us.gsk.com/products/assets/us_tafinlar.pdf.

[email protected]

A combination of two targeted, orally administered drug therapies – trametinib and dabrafenib – has been approved by the Food and Drug Administration for treating patients with unresectable melanoma or metastatic melanoma with BRAF V600E or V600K mutations, manufacturer GlaxoSmithKline announced on Jan. 9.

An FDA-approved test is used to detect the mutations, according to the company statement.

Trametinib, marketed as Mekinist, and dabrafenib, marketed as Tafinlar, were each approved in May 2013 as separate treatments for metastatic or unresectable melanomas that express the mutations – along with a companion test to detect the mutations. Both are kinase inhibitors.

The GSK statement noted that the accelerated approval of the combination therapy is based on the response rate and median duration of response results in a phase I/II study of 108 patients, which compared the combination (150 mg of dabrafenib twice a day and 2 mg of trametinib once a day) to treatment with dabrafenib alone. The overall response rates, as assessed by the investigators, were 76% among those on the combination and 54% for those on dabrafenib alone. The median duration of response was 10.5 months among those on the combination, vs. 5.6 months among those on dabrafenib alone.

The most common adverse events associated with the combination treatment included fever in 71% of patients, chills in 58%, fatigue in 52%, rash in 45%, nausea in 44%, vomiting in 40%, and diarrhea in 36%. Renal failure, pyrexia, back pain, and hemorrhage were among the most common grade-3 or -4 adverse events among those on the combination.

Serious adverse effects associated with treatment, including some potentially fatal effects, are new primary cutaneous skin cancers, tumor promotion in wild-type BRAF melanoma, and hemorrhagic events, according to GSK.

The FDA approval occurred through an accelerated process based on clinical evidence that the treatment has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. As a condition of accelerated approval, manufacturers are required to provide more clinical data confirming benefit, and if the follow-up studies fail to confirm benefit, the FDA can withdraw approval.

Full approval is dependent on the results of an ongoing phase III study, GSK said.

The updated trametinib label states that "improvement in disease-related symptoms or overall survival has not been demonstrated" for the combination treatment.

The prescribing information for Mekinist is available at http://us.gsk.com/products/assets/us_mekinist.pdf. The prescribing information for Tafinlar (which does not yet include the updated information on the combination therapy approval) is available at http://us.gsk.com/products/assets/us_tafinlar.pdf.

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