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New research grant will support pediatric genomics research
The AGA Research Foundation has partnered with the Rady Children’s Institute of Genomic Medicine to establish the AGA-Rady Children’s Institute of Genomic Medicine Research Scholar Award in Pediatric Genomics. This award will support one promising young investigator conducting research that utilizes genomics to enhance our fundamental understanding of childhood digestive diseases.
This newly established award will provide $90,000 per year for 3 years to one investigator. The funded research must be conducted at Rady Children’s Institute for Genomic Medicine in San Diego starting July 2018.
Stay tuned for additional details and information on how to apply for this grant in summer 2017. More information on this new award is available on the Rady Children’s Hospital website.
The AGA Research Foundation has partnered with the Rady Children’s Institute of Genomic Medicine to establish the AGA-Rady Children’s Institute of Genomic Medicine Research Scholar Award in Pediatric Genomics. This award will support one promising young investigator conducting research that utilizes genomics to enhance our fundamental understanding of childhood digestive diseases.
This newly established award will provide $90,000 per year for 3 years to one investigator. The funded research must be conducted at Rady Children’s Institute for Genomic Medicine in San Diego starting July 2018.
Stay tuned for additional details and information on how to apply for this grant in summer 2017. More information on this new award is available on the Rady Children’s Hospital website.
The AGA Research Foundation has partnered with the Rady Children’s Institute of Genomic Medicine to establish the AGA-Rady Children’s Institute of Genomic Medicine Research Scholar Award in Pediatric Genomics. This award will support one promising young investigator conducting research that utilizes genomics to enhance our fundamental understanding of childhood digestive diseases.
This newly established award will provide $90,000 per year for 3 years to one investigator. The funded research must be conducted at Rady Children’s Institute for Genomic Medicine in San Diego starting July 2018.
Stay tuned for additional details and information on how to apply for this grant in summer 2017. More information on this new award is available on the Rady Children’s Hospital website.
Become an AGA Fellow – AGA’s highest level of membership
AGA recognizes members whose accomplishments demonstrate personal commitment to the field of gastroenterology with the distinction of fellowship. AGA fellowship helps open doors, creates connections, and offers widespread value and recognition. Applicants can choose to apply for fellowship in either clinical practice (private or academic) or in research (basic or clinical).
Gain recognition as a distinguished GI professional and apply today by visiting www.gastro.org/fellowship. This website includes the full list of benefits and criteria for fellowship.
Be honored for your contributions and commitment to the GI field. The deadline for submissions is Monday, July 31, 2017.
AGA recognizes members whose accomplishments demonstrate personal commitment to the field of gastroenterology with the distinction of fellowship. AGA fellowship helps open doors, creates connections, and offers widespread value and recognition. Applicants can choose to apply for fellowship in either clinical practice (private or academic) or in research (basic or clinical).
Gain recognition as a distinguished GI professional and apply today by visiting www.gastro.org/fellowship. This website includes the full list of benefits and criteria for fellowship.
Be honored for your contributions and commitment to the GI field. The deadline for submissions is Monday, July 31, 2017.
AGA recognizes members whose accomplishments demonstrate personal commitment to the field of gastroenterology with the distinction of fellowship. AGA fellowship helps open doors, creates connections, and offers widespread value and recognition. Applicants can choose to apply for fellowship in either clinical practice (private or academic) or in research (basic or clinical).
Gain recognition as a distinguished GI professional and apply today by visiting www.gastro.org/fellowship. This website includes the full list of benefits and criteria for fellowship.
Be honored for your contributions and commitment to the GI field. The deadline for submissions is Monday, July 31, 2017.
AGA makes six recommendations to FDA on interchangeable biosimilars
Gastroenterologists and patients rely on biologics to manage Crohn’s disease and ulcerative colitis. Biosimilar products, which are “highly similar” to the biologic, have begun to be approved by the FDA for such indications. The FDA is now developing a pathway for interchangeable products, which are biosimilars that “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product” according to Section 351(i) of the Public Health Service Act. AGA provided the FDA six recommendations in response to the agency’s draft guidance on demonstrating interchangeability focused on measures to enhance patient safety and ensure that physicians, not insurance companies, drive decisions about switching products. Here is a summary of our comments.
1. Extrapolation of data should not be allowed for any indication where the pathophysiology is known to be different or is yet to be elucidated.
Post-marketing evidence on interchangeability of biosimilar products would alleviate concerns as testing specific products in individual diseases is an important step in determining whether the product is effective and safe for that particular disease. AGA recommends that manufacturers should be required to seek licensure for all the same indications as the reference product to appropriately track adverse events should they arise.
2. The agency should use caution when allowing extrapolation for pediatric indications.
Pediatric patients are recognized as a vulnerable population for which a disease may differ from those of adult patients. In the absence of data specifically ensuring safety and efficacy in children, AGA recommends an exemption of pediatric patients from current FDA positions and guidance documents related to interchangeable products.
3. Sponsors should exclusively use U.S.-licensed reference products in switching studies.
Currently, the FDA’s draft guidance has wording that seems to signal that the agency is willing to entertain use of non-U.S.-licensed products in some cases, casting doubt on the true “interchangeability” of the product. AGA recommends that the guidance be amended to include specific scenarios where this may be acceptable or remove the clause altogether.
4. “Real world” data on biosimilar and interchangeable products must be collected through formal post-marketing observational studies to ensure the longitudinal safety and efficacy for all patient populations being treated with these products.
A central observational registry, like the AGA Fecal Microbiome Transplant National Registry, would ensure the capture of data on the safety and efficacy of interchangeable products for all manufacturers and their adverse effects on patients, if any. Such a registry would also allow the study of outcomes in patients who are switched among multiple products.
5. Gastroenterologists with appropriate disease expertise should be engaged by the FDA when interchangeable products are reviewed for approval.
AGA is part of the FDA’s Network of Experts and hopes that this relationship will continue to be proactively utilized when a proposed product is seeking a gastrointestinal indication.
6. Prescribing physicians must be empowered with the ability to prevent nonmedical switching from a reference product to an interchangeable product.
AGA has concerns over the section of the Public Health Service Act that states that an interchangeable product “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” Health care providers must be empowered to be aware of and prevent nonmedical switching if they believe that the patient’s safety and health is at risk. AGA encourages the FDA to consider making a statement encouraging states to protect physician discretion as it applies to interchangeable biosimilars.
AGA will continue to work with the FDA to ensure that the voice of gastroenterology is heard in relation to biosimilars and interchangeable products.
Gastroenterologists and patients rely on biologics to manage Crohn’s disease and ulcerative colitis. Biosimilar products, which are “highly similar” to the biologic, have begun to be approved by the FDA for such indications. The FDA is now developing a pathway for interchangeable products, which are biosimilars that “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product” according to Section 351(i) of the Public Health Service Act. AGA provided the FDA six recommendations in response to the agency’s draft guidance on demonstrating interchangeability focused on measures to enhance patient safety and ensure that physicians, not insurance companies, drive decisions about switching products. Here is a summary of our comments.
1. Extrapolation of data should not be allowed for any indication where the pathophysiology is known to be different or is yet to be elucidated.
Post-marketing evidence on interchangeability of biosimilar products would alleviate concerns as testing specific products in individual diseases is an important step in determining whether the product is effective and safe for that particular disease. AGA recommends that manufacturers should be required to seek licensure for all the same indications as the reference product to appropriately track adverse events should they arise.
2. The agency should use caution when allowing extrapolation for pediatric indications.
Pediatric patients are recognized as a vulnerable population for which a disease may differ from those of adult patients. In the absence of data specifically ensuring safety and efficacy in children, AGA recommends an exemption of pediatric patients from current FDA positions and guidance documents related to interchangeable products.
3. Sponsors should exclusively use U.S.-licensed reference products in switching studies.
Currently, the FDA’s draft guidance has wording that seems to signal that the agency is willing to entertain use of non-U.S.-licensed products in some cases, casting doubt on the true “interchangeability” of the product. AGA recommends that the guidance be amended to include specific scenarios where this may be acceptable or remove the clause altogether.
4. “Real world” data on biosimilar and interchangeable products must be collected through formal post-marketing observational studies to ensure the longitudinal safety and efficacy for all patient populations being treated with these products.
A central observational registry, like the AGA Fecal Microbiome Transplant National Registry, would ensure the capture of data on the safety and efficacy of interchangeable products for all manufacturers and their adverse effects on patients, if any. Such a registry would also allow the study of outcomes in patients who are switched among multiple products.
5. Gastroenterologists with appropriate disease expertise should be engaged by the FDA when interchangeable products are reviewed for approval.
AGA is part of the FDA’s Network of Experts and hopes that this relationship will continue to be proactively utilized when a proposed product is seeking a gastrointestinal indication.
6. Prescribing physicians must be empowered with the ability to prevent nonmedical switching from a reference product to an interchangeable product.
AGA has concerns over the section of the Public Health Service Act that states that an interchangeable product “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” Health care providers must be empowered to be aware of and prevent nonmedical switching if they believe that the patient’s safety and health is at risk. AGA encourages the FDA to consider making a statement encouraging states to protect physician discretion as it applies to interchangeable biosimilars.
AGA will continue to work with the FDA to ensure that the voice of gastroenterology is heard in relation to biosimilars and interchangeable products.
Gastroenterologists and patients rely on biologics to manage Crohn’s disease and ulcerative colitis. Biosimilar products, which are “highly similar” to the biologic, have begun to be approved by the FDA for such indications. The FDA is now developing a pathway for interchangeable products, which are biosimilars that “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product” according to Section 351(i) of the Public Health Service Act. AGA provided the FDA six recommendations in response to the agency’s draft guidance on demonstrating interchangeability focused on measures to enhance patient safety and ensure that physicians, not insurance companies, drive decisions about switching products. Here is a summary of our comments.
1. Extrapolation of data should not be allowed for any indication where the pathophysiology is known to be different or is yet to be elucidated.
Post-marketing evidence on interchangeability of biosimilar products would alleviate concerns as testing specific products in individual diseases is an important step in determining whether the product is effective and safe for that particular disease. AGA recommends that manufacturers should be required to seek licensure for all the same indications as the reference product to appropriately track adverse events should they arise.
2. The agency should use caution when allowing extrapolation for pediatric indications.
Pediatric patients are recognized as a vulnerable population for which a disease may differ from those of adult patients. In the absence of data specifically ensuring safety and efficacy in children, AGA recommends an exemption of pediatric patients from current FDA positions and guidance documents related to interchangeable products.
3. Sponsors should exclusively use U.S.-licensed reference products in switching studies.
Currently, the FDA’s draft guidance has wording that seems to signal that the agency is willing to entertain use of non-U.S.-licensed products in some cases, casting doubt on the true “interchangeability” of the product. AGA recommends that the guidance be amended to include specific scenarios where this may be acceptable or remove the clause altogether.
4. “Real world” data on biosimilar and interchangeable products must be collected through formal post-marketing observational studies to ensure the longitudinal safety and efficacy for all patient populations being treated with these products.
A central observational registry, like the AGA Fecal Microbiome Transplant National Registry, would ensure the capture of data on the safety and efficacy of interchangeable products for all manufacturers and their adverse effects on patients, if any. Such a registry would also allow the study of outcomes in patients who are switched among multiple products.
5. Gastroenterologists with appropriate disease expertise should be engaged by the FDA when interchangeable products are reviewed for approval.
AGA is part of the FDA’s Network of Experts and hopes that this relationship will continue to be proactively utilized when a proposed product is seeking a gastrointestinal indication.
6. Prescribing physicians must be empowered with the ability to prevent nonmedical switching from a reference product to an interchangeable product.
AGA has concerns over the section of the Public Health Service Act that states that an interchangeable product “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” Health care providers must be empowered to be aware of and prevent nonmedical switching if they believe that the patient’s safety and health is at risk. AGA encourages the FDA to consider making a statement encouraging states to protect physician discretion as it applies to interchangeable biosimilars.
AGA will continue to work with the FDA to ensure that the voice of gastroenterology is heard in relation to biosimilars and interchangeable products.
FDA advisory committee supports new CV liraglutide indication
A Food and Drug Administration advisory committee voted 17-2 in support of a supplemental new drug application for liraglutide (Victoza) injections to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease.
Novo Nordisk, the maker of the glucagon-like peptide-1 (GLP-1) analogue, proposed the additional indication for liraglutide as an adjunct to standard treatment of cardiovascular risk factors in such patients based solely on the results of the randomized, placebo-controlled postmarketing LEADER trial.
If this additional indication for liraglutide is approved by the FDA, the drug would join the antidiabetic drug empagliflozin (Jardiance) in having a second indication for the reduction of the risk of cardiovascular death. The supplemental new drug application for Jardiance was approved by the FDA in December 2016 – also based on the results of a single trial (the EMPA-REG outcomes trial). Of note, the American Diabetes Association in its 2017 Standards of Medical Care has already called for consideration of both liraglutide and empagliflozin to reduce the risk of cardiovascular death in patients with type 2 diabetes and documented cardiovascular disease.
Liraglutide is currently approved for blood glucose lowering in adults with type 2 diabetes and is marketed as Saxenda for the treatment of overweight and obese adults with at least one weight-related comorbidity. It was shown in the LEADER trial to be associated with a significant 13% lower risk vs. placebo for a composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke in patients with type 2 diabetes.
All 19 voting members of the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) agreed that the LEADER results confirm there is no excess cardiovascular risk associated with liraglutide in patients with type 2 diabetes, but, on the question of whether the results provide “the substantial evidence required to establish that liraglutide 1.8 mg reduces cardiovascular risk in patients with type 2 diabetes mellitus and established cardiovascular disease,” almost all voting members expressed concerns about subgroup analyses showing reduced benefit among U.S. patients, compared with those from other countries.
“I think probably the most influential finding for me was the overall cardiovascular mortality finding, followed by the consistency of the results,” said biostatistics expert James D. Neaton, PhD, of the University of Minnesota, Minneapolis. He added that the indication should focus on patients at high cardiovascular event risk, as the LEADER population was a very high risk group.
Similarly, temporary voting member Marvin A. Konstam, MD, of Tufts University, Boston, said “the primary trial results are very robust and substantiated.
“And I think the cardiovascular mortality is the biggest contributor to that, which is obviously a very important finding,” he said, also stressing that the indication should focus on patients with established cardiovascular disease.
“I am concerned about the U.S. population, but at the end of the day, it’s a subgroup, and I just can’t overrate that to diminish the overall finding,” he added.
Peter W.F. Wilson, MD, EMDAC chairperson, said he “wrestles with exactly who benefits the most because of overlapping of some of the groupings.
“But people who really have atherosclerotic cardiovascular disease ... are probably the people who will benefit the most, and I hope those are the people who will get it,” said Dr. Wilson, professor of medicine at Emory University, professor of public health at Rollins School of Public Health, and director of epidemiology and genomic medicine at the Atlanta VA Medical Center.
In explaining his “no” vote, Daniel Budnitz, MD, of the Centers for Disease Control and Prevention, Atlanta, said his was a tough decision, but that ultimately, since the U.S. population is the one the FDA is addressing with its labeling, the subgroup concerns weighed heavily.
“And I do worry about a slippery slope of using single-trial data for new indications, when there are questions and when you do have an interaction term for the U.S. vs. the rest of the world,” he said, adding that he would like to see either another international trial where the United States population does not differ from the rest of the world, or a U.S. trial.
Carmen J. Allegra, MD, of the University of Florida, Gainesville, also voted no, and said he, too, was concerned by the subgroup analysis.
“I was very much concerned and swayed by the subgroup analysis. The U.S. target population is a pretty darn important population for us to consider, and we saw a significant interaction with outcomes vs. the region by the FDA’s analysis,” he said. “I was really swayed by the fact that we really didn’t see evidence of superiority in the U.S. population.”
The LEADER trial, which was designed in accordance with FDA Guidance issued in 2008 to demonstrate that new antidiabetes drugs do not result in unacceptably increased cardiovascular risk, included 9,340 patients who were randomized to receive liraglutide or placebo as add-on to standard of care treatment and who were followed for a median of 3.8 years. Those randomized to receive liraglutide experienced significantly lower risk of the composite primary outcome (hazard ratio, 0.87), Notably, the effect was diminished among U.S. patients, compared with the overall benefit.
However, after hearing LEADER analyses from Novo Nordisk representatives and FDA representatives, and testimony from numerous individuals, including patients, physicians, and patient advocates who spoke overwhelmingly in favor of approval of the supplemental drug application, the committee recommended that approval.
“This was not a slam dunk. I think the subgroup analysis was interesting discussion, but in the end you have to take the data and the primary outcome measure as what you move on,” said temporary voting member David C. Robbins, MD, of the University of Kansas, Kansas City, adding that “the good is outweighing the bad on this.
“I’m glad to see diabetes management moving toward more than lowering blood sugar. It’s a good step in the right direction,” he said.
The FDA, which usually follows the recommendations of its advisory committees, will now consider the supplemental new drug application for liraglutide.
In a statement released after the vote, Todd Hobbs, MD, vice president and U.S. chief medical officer of Novo Nordisk, noted that cardiovascular disease remains the leading cause of death for people with type 2 diabetes. The discussion during the EMDAC meeting is “an important reminder that there is an unmet need to provide benefits beyond HbA1c control” in patients with type 2 diabetes.
EMDAC committee members were screened and found to be in compliance with federal ethics and conflict of interest laws; one (Dr. Konstam) was granted a waiver in accordance with rules allowing such waivers when the need for an individual’s service outweighs any potential financial conflicts of interest. Dr. Konstam reported financial relationships with competing firms.
A Food and Drug Administration advisory committee voted 17-2 in support of a supplemental new drug application for liraglutide (Victoza) injections to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease.
Novo Nordisk, the maker of the glucagon-like peptide-1 (GLP-1) analogue, proposed the additional indication for liraglutide as an adjunct to standard treatment of cardiovascular risk factors in such patients based solely on the results of the randomized, placebo-controlled postmarketing LEADER trial.
If this additional indication for liraglutide is approved by the FDA, the drug would join the antidiabetic drug empagliflozin (Jardiance) in having a second indication for the reduction of the risk of cardiovascular death. The supplemental new drug application for Jardiance was approved by the FDA in December 2016 – also based on the results of a single trial (the EMPA-REG outcomes trial). Of note, the American Diabetes Association in its 2017 Standards of Medical Care has already called for consideration of both liraglutide and empagliflozin to reduce the risk of cardiovascular death in patients with type 2 diabetes and documented cardiovascular disease.
Liraglutide is currently approved for blood glucose lowering in adults with type 2 diabetes and is marketed as Saxenda for the treatment of overweight and obese adults with at least one weight-related comorbidity. It was shown in the LEADER trial to be associated with a significant 13% lower risk vs. placebo for a composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke in patients with type 2 diabetes.
All 19 voting members of the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) agreed that the LEADER results confirm there is no excess cardiovascular risk associated with liraglutide in patients with type 2 diabetes, but, on the question of whether the results provide “the substantial evidence required to establish that liraglutide 1.8 mg reduces cardiovascular risk in patients with type 2 diabetes mellitus and established cardiovascular disease,” almost all voting members expressed concerns about subgroup analyses showing reduced benefit among U.S. patients, compared with those from other countries.
“I think probably the most influential finding for me was the overall cardiovascular mortality finding, followed by the consistency of the results,” said biostatistics expert James D. Neaton, PhD, of the University of Minnesota, Minneapolis. He added that the indication should focus on patients at high cardiovascular event risk, as the LEADER population was a very high risk group.
Similarly, temporary voting member Marvin A. Konstam, MD, of Tufts University, Boston, said “the primary trial results are very robust and substantiated.
“And I think the cardiovascular mortality is the biggest contributor to that, which is obviously a very important finding,” he said, also stressing that the indication should focus on patients with established cardiovascular disease.
“I am concerned about the U.S. population, but at the end of the day, it’s a subgroup, and I just can’t overrate that to diminish the overall finding,” he added.
Peter W.F. Wilson, MD, EMDAC chairperson, said he “wrestles with exactly who benefits the most because of overlapping of some of the groupings.
“But people who really have atherosclerotic cardiovascular disease ... are probably the people who will benefit the most, and I hope those are the people who will get it,” said Dr. Wilson, professor of medicine at Emory University, professor of public health at Rollins School of Public Health, and director of epidemiology and genomic medicine at the Atlanta VA Medical Center.
In explaining his “no” vote, Daniel Budnitz, MD, of the Centers for Disease Control and Prevention, Atlanta, said his was a tough decision, but that ultimately, since the U.S. population is the one the FDA is addressing with its labeling, the subgroup concerns weighed heavily.
“And I do worry about a slippery slope of using single-trial data for new indications, when there are questions and when you do have an interaction term for the U.S. vs. the rest of the world,” he said, adding that he would like to see either another international trial where the United States population does not differ from the rest of the world, or a U.S. trial.
Carmen J. Allegra, MD, of the University of Florida, Gainesville, also voted no, and said he, too, was concerned by the subgroup analysis.
“I was very much concerned and swayed by the subgroup analysis. The U.S. target population is a pretty darn important population for us to consider, and we saw a significant interaction with outcomes vs. the region by the FDA’s analysis,” he said. “I was really swayed by the fact that we really didn’t see evidence of superiority in the U.S. population.”
The LEADER trial, which was designed in accordance with FDA Guidance issued in 2008 to demonstrate that new antidiabetes drugs do not result in unacceptably increased cardiovascular risk, included 9,340 patients who were randomized to receive liraglutide or placebo as add-on to standard of care treatment and who were followed for a median of 3.8 years. Those randomized to receive liraglutide experienced significantly lower risk of the composite primary outcome (hazard ratio, 0.87), Notably, the effect was diminished among U.S. patients, compared with the overall benefit.
However, after hearing LEADER analyses from Novo Nordisk representatives and FDA representatives, and testimony from numerous individuals, including patients, physicians, and patient advocates who spoke overwhelmingly in favor of approval of the supplemental drug application, the committee recommended that approval.
“This was not a slam dunk. I think the subgroup analysis was interesting discussion, but in the end you have to take the data and the primary outcome measure as what you move on,” said temporary voting member David C. Robbins, MD, of the University of Kansas, Kansas City, adding that “the good is outweighing the bad on this.
“I’m glad to see diabetes management moving toward more than lowering blood sugar. It’s a good step in the right direction,” he said.
The FDA, which usually follows the recommendations of its advisory committees, will now consider the supplemental new drug application for liraglutide.
In a statement released after the vote, Todd Hobbs, MD, vice president and U.S. chief medical officer of Novo Nordisk, noted that cardiovascular disease remains the leading cause of death for people with type 2 diabetes. The discussion during the EMDAC meeting is “an important reminder that there is an unmet need to provide benefits beyond HbA1c control” in patients with type 2 diabetes.
EMDAC committee members were screened and found to be in compliance with federal ethics and conflict of interest laws; one (Dr. Konstam) was granted a waiver in accordance with rules allowing such waivers when the need for an individual’s service outweighs any potential financial conflicts of interest. Dr. Konstam reported financial relationships with competing firms.
A Food and Drug Administration advisory committee voted 17-2 in support of a supplemental new drug application for liraglutide (Victoza) injections to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease.
Novo Nordisk, the maker of the glucagon-like peptide-1 (GLP-1) analogue, proposed the additional indication for liraglutide as an adjunct to standard treatment of cardiovascular risk factors in such patients based solely on the results of the randomized, placebo-controlled postmarketing LEADER trial.
If this additional indication for liraglutide is approved by the FDA, the drug would join the antidiabetic drug empagliflozin (Jardiance) in having a second indication for the reduction of the risk of cardiovascular death. The supplemental new drug application for Jardiance was approved by the FDA in December 2016 – also based on the results of a single trial (the EMPA-REG outcomes trial). Of note, the American Diabetes Association in its 2017 Standards of Medical Care has already called for consideration of both liraglutide and empagliflozin to reduce the risk of cardiovascular death in patients with type 2 diabetes and documented cardiovascular disease.
Liraglutide is currently approved for blood glucose lowering in adults with type 2 diabetes and is marketed as Saxenda for the treatment of overweight and obese adults with at least one weight-related comorbidity. It was shown in the LEADER trial to be associated with a significant 13% lower risk vs. placebo for a composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke in patients with type 2 diabetes.
All 19 voting members of the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) agreed that the LEADER results confirm there is no excess cardiovascular risk associated with liraglutide in patients with type 2 diabetes, but, on the question of whether the results provide “the substantial evidence required to establish that liraglutide 1.8 mg reduces cardiovascular risk in patients with type 2 diabetes mellitus and established cardiovascular disease,” almost all voting members expressed concerns about subgroup analyses showing reduced benefit among U.S. patients, compared with those from other countries.
“I think probably the most influential finding for me was the overall cardiovascular mortality finding, followed by the consistency of the results,” said biostatistics expert James D. Neaton, PhD, of the University of Minnesota, Minneapolis. He added that the indication should focus on patients at high cardiovascular event risk, as the LEADER population was a very high risk group.
Similarly, temporary voting member Marvin A. Konstam, MD, of Tufts University, Boston, said “the primary trial results are very robust and substantiated.
“And I think the cardiovascular mortality is the biggest contributor to that, which is obviously a very important finding,” he said, also stressing that the indication should focus on patients with established cardiovascular disease.
“I am concerned about the U.S. population, but at the end of the day, it’s a subgroup, and I just can’t overrate that to diminish the overall finding,” he added.
Peter W.F. Wilson, MD, EMDAC chairperson, said he “wrestles with exactly who benefits the most because of overlapping of some of the groupings.
“But people who really have atherosclerotic cardiovascular disease ... are probably the people who will benefit the most, and I hope those are the people who will get it,” said Dr. Wilson, professor of medicine at Emory University, professor of public health at Rollins School of Public Health, and director of epidemiology and genomic medicine at the Atlanta VA Medical Center.
In explaining his “no” vote, Daniel Budnitz, MD, of the Centers for Disease Control and Prevention, Atlanta, said his was a tough decision, but that ultimately, since the U.S. population is the one the FDA is addressing with its labeling, the subgroup concerns weighed heavily.
“And I do worry about a slippery slope of using single-trial data for new indications, when there are questions and when you do have an interaction term for the U.S. vs. the rest of the world,” he said, adding that he would like to see either another international trial where the United States population does not differ from the rest of the world, or a U.S. trial.
Carmen J. Allegra, MD, of the University of Florida, Gainesville, also voted no, and said he, too, was concerned by the subgroup analysis.
“I was very much concerned and swayed by the subgroup analysis. The U.S. target population is a pretty darn important population for us to consider, and we saw a significant interaction with outcomes vs. the region by the FDA’s analysis,” he said. “I was really swayed by the fact that we really didn’t see evidence of superiority in the U.S. population.”
The LEADER trial, which was designed in accordance with FDA Guidance issued in 2008 to demonstrate that new antidiabetes drugs do not result in unacceptably increased cardiovascular risk, included 9,340 patients who were randomized to receive liraglutide or placebo as add-on to standard of care treatment and who were followed for a median of 3.8 years. Those randomized to receive liraglutide experienced significantly lower risk of the composite primary outcome (hazard ratio, 0.87), Notably, the effect was diminished among U.S. patients, compared with the overall benefit.
However, after hearing LEADER analyses from Novo Nordisk representatives and FDA representatives, and testimony from numerous individuals, including patients, physicians, and patient advocates who spoke overwhelmingly in favor of approval of the supplemental drug application, the committee recommended that approval.
“This was not a slam dunk. I think the subgroup analysis was interesting discussion, but in the end you have to take the data and the primary outcome measure as what you move on,” said temporary voting member David C. Robbins, MD, of the University of Kansas, Kansas City, adding that “the good is outweighing the bad on this.
“I’m glad to see diabetes management moving toward more than lowering blood sugar. It’s a good step in the right direction,” he said.
The FDA, which usually follows the recommendations of its advisory committees, will now consider the supplemental new drug application for liraglutide.
In a statement released after the vote, Todd Hobbs, MD, vice president and U.S. chief medical officer of Novo Nordisk, noted that cardiovascular disease remains the leading cause of death for people with type 2 diabetes. The discussion during the EMDAC meeting is “an important reminder that there is an unmet need to provide benefits beyond HbA1c control” in patients with type 2 diabetes.
EMDAC committee members were screened and found to be in compliance with federal ethics and conflict of interest laws; one (Dr. Konstam) was granted a waiver in accordance with rules allowing such waivers when the need for an individual’s service outweighs any potential financial conflicts of interest. Dr. Konstam reported financial relationships with competing firms.
Mydayis approved for teens, adults with ADHD
The Food and Drug Administration has approved a once-a-day treatment for patients aged 13 years and older with ADHD, Shire announced June 20 in a press release.
The approval of Mydayis was based on results from 16 clinical studies evaluating the medication in more than 1,600 adolescents (aged 13-17 years) and adults with attention-deficit/hyperactivity disorder. In the placebo-controlled clinical studies, Mydayis significantly improved symptoms of ADHD, as measured by the ADHD-RS-IV and the Permanent Product Measure of Performance (PERMP), in adults and adolescents. Improvement on the PERMP reached statistical significance beginning at 2 or 4 hours post dose and lasting up to 16 hours post dose.
The medication, an amphetamine product, consists of three different types of drug-releasing beads.
“With this approval, we hope to help patients who need a once-daily treatment option,” Flemming Ornskov, MD, MPH, said in a press release. Dr. Ornskov is CEO of Shire.
It is estimated that 4.4% of adults have ADHD in the United States, and 50%-66% of children with ADHD may continue to have symptoms of the disorder as adults.
Mydayis will be commercially available in the United States in the third quarter of 2017.
Read the full press release here.
The Food and Drug Administration has approved a once-a-day treatment for patients aged 13 years and older with ADHD, Shire announced June 20 in a press release.
The approval of Mydayis was based on results from 16 clinical studies evaluating the medication in more than 1,600 adolescents (aged 13-17 years) and adults with attention-deficit/hyperactivity disorder. In the placebo-controlled clinical studies, Mydayis significantly improved symptoms of ADHD, as measured by the ADHD-RS-IV and the Permanent Product Measure of Performance (PERMP), in adults and adolescents. Improvement on the PERMP reached statistical significance beginning at 2 or 4 hours post dose and lasting up to 16 hours post dose.
The medication, an amphetamine product, consists of three different types of drug-releasing beads.
“With this approval, we hope to help patients who need a once-daily treatment option,” Flemming Ornskov, MD, MPH, said in a press release. Dr. Ornskov is CEO of Shire.
It is estimated that 4.4% of adults have ADHD in the United States, and 50%-66% of children with ADHD may continue to have symptoms of the disorder as adults.
Mydayis will be commercially available in the United States in the third quarter of 2017.
Read the full press release here.
The Food and Drug Administration has approved a once-a-day treatment for patients aged 13 years and older with ADHD, Shire announced June 20 in a press release.
The approval of Mydayis was based on results from 16 clinical studies evaluating the medication in more than 1,600 adolescents (aged 13-17 years) and adults with attention-deficit/hyperactivity disorder. In the placebo-controlled clinical studies, Mydayis significantly improved symptoms of ADHD, as measured by the ADHD-RS-IV and the Permanent Product Measure of Performance (PERMP), in adults and adolescents. Improvement on the PERMP reached statistical significance beginning at 2 or 4 hours post dose and lasting up to 16 hours post dose.
The medication, an amphetamine product, consists of three different types of drug-releasing beads.
“With this approval, we hope to help patients who need a once-daily treatment option,” Flemming Ornskov, MD, MPH, said in a press release. Dr. Ornskov is CEO of Shire.
It is estimated that 4.4% of adults have ADHD in the United States, and 50%-66% of children with ADHD may continue to have symptoms of the disorder as adults.
Mydayis will be commercially available in the United States in the third quarter of 2017.
Read the full press release here.
How to prevent secondary posttraumatic knee osteoarthritis
LAS VEGAS – A variety of evidence-based strategies are available for preventing posttraumatic knee osteoarthritis (KOA) in patients who have already sustained an anterior cruciate ligament (ACL) injury. And they’re generally ignored, according to May Arna Risberg, PhD.
“We have a lot of knowledge. We can use secondary prevention strategies. And here I think we, as physical therapists, physicians, and orthopedic surgeons, are doing a lousy job because we are sending these ACL-injured patients back to sports before they have normalized knee function and quadriceps strength,” said Dr. Risberg, professor of sports medicine at the Norwegian School of Sport Sciences in Oslo.
With no proven disease-modifying therapy for KOA available to date, secondary prevention of posttraumatic KOA is worthy of high-priority status, she said at the World Congress on Osteoarthritis. An estimated 250,00 ACL injuries occur annually in the United States, and up to one-half of affected patients, most of whom are young, active people, will experience a second ACL rupture within the first few years after undergoing their initial reconstruction. This second ACL injury greatly increases their risk of developing posttraumatic KOA within 15-20 years, while they are still relatively young, she said.
Moreover, if the second ACL injury involves meniscus surgery, the 5-year risk of posttraumatic KOA roughly triples to up to 48%.
She highlighted a few effective strategies for preventing posttraumatic KOA in patients who already have an ACL injury.
Avoid reinjury
Dr. Risberg was senior author of a recent report from the prospective Delaware-Oslo Cohort Study involving 106 athletes who underwent ACL reconstruction following injury in what she termed level I sports. These are sports that entail lots of pivoting, jumping, and hard cutting, such as basketball, soccer, and handball.
In the first 2 years after ACL repair, 30% of patients who returned to participation in a level 1 sport experienced an ACL reinjury, compared with just 8% who opted for a lower-level sport. Athletes who returned to a level 1 sport had an adjusted 4.3 times greater ACL reinjury rate than those who didn’t, Dr. Risberg noted at the congress sponsored by the Osteoarthritis Research Society International.
The good news is that this sharply increased reinjury risk was mitigated if return to a level 1 sport was delayed for at least 9 months post surgery and if the patient had regained quadriceps strength comparable to the uninjured side. For every month that return to sport was delayed out until 9 months post ACL reconstruction, the knee reinjury rate was reduced by 51% (Br J Sports Med. 2016;50:804-8).
In a meta-analysis by other investigators of 12 studies including 5,707 participants, weakness of the knee extensor muscles was independently associated with a 1.65 times increased risk of developing KOA (Osteoarthritis Cartilage. 2015 Feb;23[2]:171-7).
Attend to BMI
A discussion of the importance of maintaining a healthy body weight is an important aspect of patient education for athletes with knee injuries. In a cohort study of 988 patients who underwent primary ACL reconstruction, being overweight or obese was associated with a significantly increased risk of subsequent meniscal tears and chondral lesions (Am J Sports Med. 2015 Dec;43[12]:2966-73).
Also, it’s well established that obesity is a risk factor for knee OA, and Canadian investigators have shown that young athletes with a sports-related intra-articular knee injury were 3.75 times more likely to be overweight or obese 3-10 years post injury, compared with matched uninjured controls (Osteoarthritis Cartilage. 2015 Jul;23[7]:1122-9).
Consider prehabilitative exercise training
Dr. Risberg and coinvestigators have reported that preoperative quadriceps muscle strength deficits are predictive of impaired knee function, as measured by the Cincinnati Knee Score 2 years post surgery. She said she believes ACL reconstruction shouldn’t be done until quadriceps muscle strength is at least 80% of that in the uninjured limb (Br J Sports Med. 2009 May;43[5]:371-6). She and her coinvestigators have published the details of a 5-week progressive exercise therapy program in which they have shown results in significantly improved early postoperative knee function (J Orthop Sports Phys Ther. 2010 Nov;40[11]:705-21). They now try to have patients complete the twice-weekly, 5-week program before final decisions are reached regarding whether to have ACL reconstruction.
Test all before okaying return to sport
It’s important to know if patients who have undergone ACL reconstruction have gotten full knee function back before determining if they’re ready for full-on sports participation. In the Delaware-Oslo Cohort Study, patients who delayed their return until at least 9 months after surgery and passed the return-to-sports test had a 5.6% reinjury rate within 2 years, while those who failed the return-to-sports criteria had a 38.2% ACL reinjury rate.
The return-to-sports testing utilized in this study entailed isokinetic quadriceps strength testing, the single hop leg test, the 14-item self-rated Knee Outcome Survey–Activities of Daily Living Scale, and a self-rated Global Rating Scale of perceived function on a 0-100 scale. To be cleared for return to sports, a patient had to demonstrate having regained at least 90% of quadriceps muscle strength and hop performance along with scoring in the normative range on both of the self-rating instruments.
Surgical vs. nonsurgical treatment of ACL rupture
The evidence on this score is conflicting, according to Dr. Risberg. While most physical therapists believe ACL reconstruction doesn’t protect against later development of KOA, as reflected in a meta-analysis of published studies (J Bone Joint Surg Am. 2014 Feb 19;96[4]:292-300), a more recent retrospective comparison of 964 patients with an isolated ACL tear and an equal number of matched controls concluded that patients treated nonoperatively were six times more likely to have been diagnosed with KOA and 16.7 times more likely to have undergone total knee replacement at a mean follow-up of 13.7 years than were those treated with ACL reconstruction (Am J Sports Med. 2016 Jul;44[7]:1699-707).
Dr. Risberg’s fellow panelist Jackie Whittaker, PhD, said that, as long as quadriceps muscle strengthening is a priority, it makes sense to strengthen the hamstring as well, particularly if the ACL reconstruction utilized the hamstring tendon.
“Also, I would add that it’s important to develop a relationship with these ACL-injured people, who are often very young. Preventing a disease that they’re going to get 20 years later isn’t a priority for them. You need to develop that relationship and build it up over time. Helping them set realistic expectations is very important. And we need to do what we can to help them find some sort of competitive outlet. A lot of these kids were very competitive, and now they’ve had an injury and can’t compete. They don’t want to go back to playing just any sport. They want to be able to be competitive, and if you don’t help them find another way to express that, they sort of give up on physical activity altogether,” according to Dr. Whittaker of the University of Alberta in Edmonton.
Dr. Risberg and Dr. Whittaker reported having no financial conflicts of interest.
LAS VEGAS – A variety of evidence-based strategies are available for preventing posttraumatic knee osteoarthritis (KOA) in patients who have already sustained an anterior cruciate ligament (ACL) injury. And they’re generally ignored, according to May Arna Risberg, PhD.
“We have a lot of knowledge. We can use secondary prevention strategies. And here I think we, as physical therapists, physicians, and orthopedic surgeons, are doing a lousy job because we are sending these ACL-injured patients back to sports before they have normalized knee function and quadriceps strength,” said Dr. Risberg, professor of sports medicine at the Norwegian School of Sport Sciences in Oslo.
With no proven disease-modifying therapy for KOA available to date, secondary prevention of posttraumatic KOA is worthy of high-priority status, she said at the World Congress on Osteoarthritis. An estimated 250,00 ACL injuries occur annually in the United States, and up to one-half of affected patients, most of whom are young, active people, will experience a second ACL rupture within the first few years after undergoing their initial reconstruction. This second ACL injury greatly increases their risk of developing posttraumatic KOA within 15-20 years, while they are still relatively young, she said.
Moreover, if the second ACL injury involves meniscus surgery, the 5-year risk of posttraumatic KOA roughly triples to up to 48%.
She highlighted a few effective strategies for preventing posttraumatic KOA in patients who already have an ACL injury.
Avoid reinjury
Dr. Risberg was senior author of a recent report from the prospective Delaware-Oslo Cohort Study involving 106 athletes who underwent ACL reconstruction following injury in what she termed level I sports. These are sports that entail lots of pivoting, jumping, and hard cutting, such as basketball, soccer, and handball.
In the first 2 years after ACL repair, 30% of patients who returned to participation in a level 1 sport experienced an ACL reinjury, compared with just 8% who opted for a lower-level sport. Athletes who returned to a level 1 sport had an adjusted 4.3 times greater ACL reinjury rate than those who didn’t, Dr. Risberg noted at the congress sponsored by the Osteoarthritis Research Society International.
The good news is that this sharply increased reinjury risk was mitigated if return to a level 1 sport was delayed for at least 9 months post surgery and if the patient had regained quadriceps strength comparable to the uninjured side. For every month that return to sport was delayed out until 9 months post ACL reconstruction, the knee reinjury rate was reduced by 51% (Br J Sports Med. 2016;50:804-8).
In a meta-analysis by other investigators of 12 studies including 5,707 participants, weakness of the knee extensor muscles was independently associated with a 1.65 times increased risk of developing KOA (Osteoarthritis Cartilage. 2015 Feb;23[2]:171-7).
Attend to BMI
A discussion of the importance of maintaining a healthy body weight is an important aspect of patient education for athletes with knee injuries. In a cohort study of 988 patients who underwent primary ACL reconstruction, being overweight or obese was associated with a significantly increased risk of subsequent meniscal tears and chondral lesions (Am J Sports Med. 2015 Dec;43[12]:2966-73).
Also, it’s well established that obesity is a risk factor for knee OA, and Canadian investigators have shown that young athletes with a sports-related intra-articular knee injury were 3.75 times more likely to be overweight or obese 3-10 years post injury, compared with matched uninjured controls (Osteoarthritis Cartilage. 2015 Jul;23[7]:1122-9).
Consider prehabilitative exercise training
Dr. Risberg and coinvestigators have reported that preoperative quadriceps muscle strength deficits are predictive of impaired knee function, as measured by the Cincinnati Knee Score 2 years post surgery. She said she believes ACL reconstruction shouldn’t be done until quadriceps muscle strength is at least 80% of that in the uninjured limb (Br J Sports Med. 2009 May;43[5]:371-6). She and her coinvestigators have published the details of a 5-week progressive exercise therapy program in which they have shown results in significantly improved early postoperative knee function (J Orthop Sports Phys Ther. 2010 Nov;40[11]:705-21). They now try to have patients complete the twice-weekly, 5-week program before final decisions are reached regarding whether to have ACL reconstruction.
Test all before okaying return to sport
It’s important to know if patients who have undergone ACL reconstruction have gotten full knee function back before determining if they’re ready for full-on sports participation. In the Delaware-Oslo Cohort Study, patients who delayed their return until at least 9 months after surgery and passed the return-to-sports test had a 5.6% reinjury rate within 2 years, while those who failed the return-to-sports criteria had a 38.2% ACL reinjury rate.
The return-to-sports testing utilized in this study entailed isokinetic quadriceps strength testing, the single hop leg test, the 14-item self-rated Knee Outcome Survey–Activities of Daily Living Scale, and a self-rated Global Rating Scale of perceived function on a 0-100 scale. To be cleared for return to sports, a patient had to demonstrate having regained at least 90% of quadriceps muscle strength and hop performance along with scoring in the normative range on both of the self-rating instruments.
Surgical vs. nonsurgical treatment of ACL rupture
The evidence on this score is conflicting, according to Dr. Risberg. While most physical therapists believe ACL reconstruction doesn’t protect against later development of KOA, as reflected in a meta-analysis of published studies (J Bone Joint Surg Am. 2014 Feb 19;96[4]:292-300), a more recent retrospective comparison of 964 patients with an isolated ACL tear and an equal number of matched controls concluded that patients treated nonoperatively were six times more likely to have been diagnosed with KOA and 16.7 times more likely to have undergone total knee replacement at a mean follow-up of 13.7 years than were those treated with ACL reconstruction (Am J Sports Med. 2016 Jul;44[7]:1699-707).
Dr. Risberg’s fellow panelist Jackie Whittaker, PhD, said that, as long as quadriceps muscle strengthening is a priority, it makes sense to strengthen the hamstring as well, particularly if the ACL reconstruction utilized the hamstring tendon.
“Also, I would add that it’s important to develop a relationship with these ACL-injured people, who are often very young. Preventing a disease that they’re going to get 20 years later isn’t a priority for them. You need to develop that relationship and build it up over time. Helping them set realistic expectations is very important. And we need to do what we can to help them find some sort of competitive outlet. A lot of these kids were very competitive, and now they’ve had an injury and can’t compete. They don’t want to go back to playing just any sport. They want to be able to be competitive, and if you don’t help them find another way to express that, they sort of give up on physical activity altogether,” according to Dr. Whittaker of the University of Alberta in Edmonton.
Dr. Risberg and Dr. Whittaker reported having no financial conflicts of interest.
LAS VEGAS – A variety of evidence-based strategies are available for preventing posttraumatic knee osteoarthritis (KOA) in patients who have already sustained an anterior cruciate ligament (ACL) injury. And they’re generally ignored, according to May Arna Risberg, PhD.
“We have a lot of knowledge. We can use secondary prevention strategies. And here I think we, as physical therapists, physicians, and orthopedic surgeons, are doing a lousy job because we are sending these ACL-injured patients back to sports before they have normalized knee function and quadriceps strength,” said Dr. Risberg, professor of sports medicine at the Norwegian School of Sport Sciences in Oslo.
With no proven disease-modifying therapy for KOA available to date, secondary prevention of posttraumatic KOA is worthy of high-priority status, she said at the World Congress on Osteoarthritis. An estimated 250,00 ACL injuries occur annually in the United States, and up to one-half of affected patients, most of whom are young, active people, will experience a second ACL rupture within the first few years after undergoing their initial reconstruction. This second ACL injury greatly increases their risk of developing posttraumatic KOA within 15-20 years, while they are still relatively young, she said.
Moreover, if the second ACL injury involves meniscus surgery, the 5-year risk of posttraumatic KOA roughly triples to up to 48%.
She highlighted a few effective strategies for preventing posttraumatic KOA in patients who already have an ACL injury.
Avoid reinjury
Dr. Risberg was senior author of a recent report from the prospective Delaware-Oslo Cohort Study involving 106 athletes who underwent ACL reconstruction following injury in what she termed level I sports. These are sports that entail lots of pivoting, jumping, and hard cutting, such as basketball, soccer, and handball.
In the first 2 years after ACL repair, 30% of patients who returned to participation in a level 1 sport experienced an ACL reinjury, compared with just 8% who opted for a lower-level sport. Athletes who returned to a level 1 sport had an adjusted 4.3 times greater ACL reinjury rate than those who didn’t, Dr. Risberg noted at the congress sponsored by the Osteoarthritis Research Society International.
The good news is that this sharply increased reinjury risk was mitigated if return to a level 1 sport was delayed for at least 9 months post surgery and if the patient had regained quadriceps strength comparable to the uninjured side. For every month that return to sport was delayed out until 9 months post ACL reconstruction, the knee reinjury rate was reduced by 51% (Br J Sports Med. 2016;50:804-8).
In a meta-analysis by other investigators of 12 studies including 5,707 participants, weakness of the knee extensor muscles was independently associated with a 1.65 times increased risk of developing KOA (Osteoarthritis Cartilage. 2015 Feb;23[2]:171-7).
Attend to BMI
A discussion of the importance of maintaining a healthy body weight is an important aspect of patient education for athletes with knee injuries. In a cohort study of 988 patients who underwent primary ACL reconstruction, being overweight or obese was associated with a significantly increased risk of subsequent meniscal tears and chondral lesions (Am J Sports Med. 2015 Dec;43[12]:2966-73).
Also, it’s well established that obesity is a risk factor for knee OA, and Canadian investigators have shown that young athletes with a sports-related intra-articular knee injury were 3.75 times more likely to be overweight or obese 3-10 years post injury, compared with matched uninjured controls (Osteoarthritis Cartilage. 2015 Jul;23[7]:1122-9).
Consider prehabilitative exercise training
Dr. Risberg and coinvestigators have reported that preoperative quadriceps muscle strength deficits are predictive of impaired knee function, as measured by the Cincinnati Knee Score 2 years post surgery. She said she believes ACL reconstruction shouldn’t be done until quadriceps muscle strength is at least 80% of that in the uninjured limb (Br J Sports Med. 2009 May;43[5]:371-6). She and her coinvestigators have published the details of a 5-week progressive exercise therapy program in which they have shown results in significantly improved early postoperative knee function (J Orthop Sports Phys Ther. 2010 Nov;40[11]:705-21). They now try to have patients complete the twice-weekly, 5-week program before final decisions are reached regarding whether to have ACL reconstruction.
Test all before okaying return to sport
It’s important to know if patients who have undergone ACL reconstruction have gotten full knee function back before determining if they’re ready for full-on sports participation. In the Delaware-Oslo Cohort Study, patients who delayed their return until at least 9 months after surgery and passed the return-to-sports test had a 5.6% reinjury rate within 2 years, while those who failed the return-to-sports criteria had a 38.2% ACL reinjury rate.
The return-to-sports testing utilized in this study entailed isokinetic quadriceps strength testing, the single hop leg test, the 14-item self-rated Knee Outcome Survey–Activities of Daily Living Scale, and a self-rated Global Rating Scale of perceived function on a 0-100 scale. To be cleared for return to sports, a patient had to demonstrate having regained at least 90% of quadriceps muscle strength and hop performance along with scoring in the normative range on both of the self-rating instruments.
Surgical vs. nonsurgical treatment of ACL rupture
The evidence on this score is conflicting, according to Dr. Risberg. While most physical therapists believe ACL reconstruction doesn’t protect against later development of KOA, as reflected in a meta-analysis of published studies (J Bone Joint Surg Am. 2014 Feb 19;96[4]:292-300), a more recent retrospective comparison of 964 patients with an isolated ACL tear and an equal number of matched controls concluded that patients treated nonoperatively were six times more likely to have been diagnosed with KOA and 16.7 times more likely to have undergone total knee replacement at a mean follow-up of 13.7 years than were those treated with ACL reconstruction (Am J Sports Med. 2016 Jul;44[7]:1699-707).
Dr. Risberg’s fellow panelist Jackie Whittaker, PhD, said that, as long as quadriceps muscle strengthening is a priority, it makes sense to strengthen the hamstring as well, particularly if the ACL reconstruction utilized the hamstring tendon.
“Also, I would add that it’s important to develop a relationship with these ACL-injured people, who are often very young. Preventing a disease that they’re going to get 20 years later isn’t a priority for them. You need to develop that relationship and build it up over time. Helping them set realistic expectations is very important. And we need to do what we can to help them find some sort of competitive outlet. A lot of these kids were very competitive, and now they’ve had an injury and can’t compete. They don’t want to go back to playing just any sport. They want to be able to be competitive, and if you don’t help them find another way to express that, they sort of give up on physical activity altogether,” according to Dr. Whittaker of the University of Alberta in Edmonton.
Dr. Risberg and Dr. Whittaker reported having no financial conflicts of interest.
EXPERT ANALYSIS FROM OARSI 2017
Newly Diagnosed Patients with Epilepsy Need Psychiatric Evaluation
Every patient who is initially diagnosed with epilepsy should also be evaluated for coexisting psychiatric problems, according to Andres Kanner with the Department of Neurology, University of Miami School of Medicine. Kanner noted that psychiatric comorbidities often existed in patients before they were diagnosed with a seizure. That, coupled with the fact that drug therapy and surgery for epilepsy often cause psychiatric symptoms, is part of the justification for conducting these evaluations.
Kanner AM. Psychiatric comorbidities in new onset epilepsy: Should they be always investigated? Seizure. 2017;49:79-82.
Every patient who is initially diagnosed with epilepsy should also be evaluated for coexisting psychiatric problems, according to Andres Kanner with the Department of Neurology, University of Miami School of Medicine. Kanner noted that psychiatric comorbidities often existed in patients before they were diagnosed with a seizure. That, coupled with the fact that drug therapy and surgery for epilepsy often cause psychiatric symptoms, is part of the justification for conducting these evaluations.
Kanner AM. Psychiatric comorbidities in new onset epilepsy: Should they be always investigated? Seizure. 2017;49:79-82.
Every patient who is initially diagnosed with epilepsy should also be evaluated for coexisting psychiatric problems, according to Andres Kanner with the Department of Neurology, University of Miami School of Medicine. Kanner noted that psychiatric comorbidities often existed in patients before they were diagnosed with a seizure. That, coupled with the fact that drug therapy and surgery for epilepsy often cause psychiatric symptoms, is part of the justification for conducting these evaluations.
Kanner AM. Psychiatric comorbidities in new onset epilepsy: Should they be always investigated? Seizure. 2017;49:79-82.
Similar Adverse Effects Reported in Generic vs Brand AEDs
Although a recent analysis of adverse effects (AEs) found differences between AEs reported for generic versions compared with brand name versions of the 3 common antiepileptic drugs (AEDs), when approved generic formulations were compared to unapproved generics, reporting odds ratios were similar for authorized generic AEDs and generic AEDs. The researchers concluded that the differences were the result of perception biases. There were differences in drug AE reports of suicide and suicide ideation between authorized generic and brand name drugs that could not be explained by bias.
Rahman MM, Alatawi Y, Cheng N, et al. Comparison of brand versus generic antiepileptic drug adverse event reporting rates in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) [published online June 3, 2017]. Epilepsy Res. doi: http://dx.doi.org/10.1016/j.eplepsyres.2017.06.007
Although a recent analysis of adverse effects (AEs) found differences between AEs reported for generic versions compared with brand name versions of the 3 common antiepileptic drugs (AEDs), when approved generic formulations were compared to unapproved generics, reporting odds ratios were similar for authorized generic AEDs and generic AEDs. The researchers concluded that the differences were the result of perception biases. There were differences in drug AE reports of suicide and suicide ideation between authorized generic and brand name drugs that could not be explained by bias.
Rahman MM, Alatawi Y, Cheng N, et al. Comparison of brand versus generic antiepileptic drug adverse event reporting rates in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) [published online June 3, 2017]. Epilepsy Res. doi: http://dx.doi.org/10.1016/j.eplepsyres.2017.06.007
Although a recent analysis of adverse effects (AEs) found differences between AEs reported for generic versions compared with brand name versions of the 3 common antiepileptic drugs (AEDs), when approved generic formulations were compared to unapproved generics, reporting odds ratios were similar for authorized generic AEDs and generic AEDs. The researchers concluded that the differences were the result of perception biases. There were differences in drug AE reports of suicide and suicide ideation between authorized generic and brand name drugs that could not be explained by bias.
Rahman MM, Alatawi Y, Cheng N, et al. Comparison of brand versus generic antiepileptic drug adverse event reporting rates in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) [published online June 3, 2017]. Epilepsy Res. doi: http://dx.doi.org/10.1016/j.eplepsyres.2017.06.007
Stress Linked to Recurrent Seizures in Adults
The likelihood of experiencing a recurrent seizure is closely linked to a person’s stress level, according to a recent study that looked at 52 individuals with a single unprovoked seizure and 29 with newly diagnosed epilepsy. The researchers, who looked at adult residents in low-income areas of Northern Manhattan and Harlem, New York City, found that generalized anxiety disorder increased the risk of a recurrent seizure threefold. In a second analysis, a mood disorder more than doubled the risk of a recurrent seizure.
Baldin E, Hauser WS, Pack A, Hesdorffer DC. Stress is associated with an increased risk of recurrent seizures in adults. Epilepsia. 2017;58:1037-1046.
The likelihood of experiencing a recurrent seizure is closely linked to a person’s stress level, according to a recent study that looked at 52 individuals with a single unprovoked seizure and 29 with newly diagnosed epilepsy. The researchers, who looked at adult residents in low-income areas of Northern Manhattan and Harlem, New York City, found that generalized anxiety disorder increased the risk of a recurrent seizure threefold. In a second analysis, a mood disorder more than doubled the risk of a recurrent seizure.
Baldin E, Hauser WS, Pack A, Hesdorffer DC. Stress is associated with an increased risk of recurrent seizures in adults. Epilepsia. 2017;58:1037-1046.
The likelihood of experiencing a recurrent seizure is closely linked to a person’s stress level, according to a recent study that looked at 52 individuals with a single unprovoked seizure and 29 with newly diagnosed epilepsy. The researchers, who looked at adult residents in low-income areas of Northern Manhattan and Harlem, New York City, found that generalized anxiety disorder increased the risk of a recurrent seizure threefold. In a second analysis, a mood disorder more than doubled the risk of a recurrent seizure.
Baldin E, Hauser WS, Pack A, Hesdorffer DC. Stress is associated with an increased risk of recurrent seizures in adults. Epilepsia. 2017;58:1037-1046.
SPRINT: Intensive BP control cut cardiovascular risk in patients with prediabetes
SAN DIEGO – Treating systolic hypertension to a target of 120 mm Hg instead of 140 mm Hg significantly reduced the rate of cardiovascular events in high-risk patients with prediabetes, according to a post-hoc analysis of the multicenter, randomized, controlled, open-label Systolic Blood Pressure Intervention Trial (SPRINT).
Thus, prediabetes did not undercut the cardiovascular benefits of intensive systolic blood pressure (SBP) control in older, high-risk, hypertensive patients, Adam P. Bress, PharmD, MS, and his associates concluded in a late-breaking poster presented at the annual scientific sessions of the American Diabetes Association.
In contrast, intensive SBP control did not prevent cardiovascular events, compared with standard control among diabetic patients in the randomized, nonblinded ACCORD BP trial (N Engl J Med. 2010; 362:1575-85).
To help clarify SBP targets for prediabetic individuals, Dr. Bress and his associates parsed cardiovascular outcomes in SPRINT based on baseline fasting serum glucose (FSG) levels. More than 5,400 normoglycemic (average FSG, 91 mg per dL) patients and more than 3,800 prediabetic (average FSG, 110 mg per dL) patients were followed for a median of 3.3 years, after which 101 (1.6%) prediabetic intensive control patients and 144 (2.3%) prediabetic standard control patients experienced the combined primary endpoint (HR, 0.7; 95% confidence interval, 0.5-0.9). The hazard ratio for normoglycemic patients was similar (0.9) and approached statistical significance.
Intensive SBP control also was associated with lower rates of individual cardiovascular outcomes and all-cause mortality, compared with standard control in both normoglycemic and prediabetic patients, Dr. Bress and his associates reported. Wide confidence intervals precluded statistical significance for most individual outcomes, but intensive control was associated with a significantly lower risk of all-cause mortality in normoglycemic patients (0.7% vs. 1.4% with standard control; HR, 0.7; 95% CI, 0.5-0.9).
Serious adverse events affected about 37% of patients in all subgroups. Hypotension, syncope, bradycardia, and electrolyte abnormalities were slightly more common in the intensive control groups than the standard control groups, regardless of baseline FPG levels.
SPRINT was sponsored by the National Heart, Lung, and Blood Institute. The National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and Wake Forest University Health Sciences provided additional support. Dr. Bress disclosed research support from Novartis and the National Institutes of Health.
SAN DIEGO – Treating systolic hypertension to a target of 120 mm Hg instead of 140 mm Hg significantly reduced the rate of cardiovascular events in high-risk patients with prediabetes, according to a post-hoc analysis of the multicenter, randomized, controlled, open-label Systolic Blood Pressure Intervention Trial (SPRINT).
Thus, prediabetes did not undercut the cardiovascular benefits of intensive systolic blood pressure (SBP) control in older, high-risk, hypertensive patients, Adam P. Bress, PharmD, MS, and his associates concluded in a late-breaking poster presented at the annual scientific sessions of the American Diabetes Association.
In contrast, intensive SBP control did not prevent cardiovascular events, compared with standard control among diabetic patients in the randomized, nonblinded ACCORD BP trial (N Engl J Med. 2010; 362:1575-85).
To help clarify SBP targets for prediabetic individuals, Dr. Bress and his associates parsed cardiovascular outcomes in SPRINT based on baseline fasting serum glucose (FSG) levels. More than 5,400 normoglycemic (average FSG, 91 mg per dL) patients and more than 3,800 prediabetic (average FSG, 110 mg per dL) patients were followed for a median of 3.3 years, after which 101 (1.6%) prediabetic intensive control patients and 144 (2.3%) prediabetic standard control patients experienced the combined primary endpoint (HR, 0.7; 95% confidence interval, 0.5-0.9). The hazard ratio for normoglycemic patients was similar (0.9) and approached statistical significance.
Intensive SBP control also was associated with lower rates of individual cardiovascular outcomes and all-cause mortality, compared with standard control in both normoglycemic and prediabetic patients, Dr. Bress and his associates reported. Wide confidence intervals precluded statistical significance for most individual outcomes, but intensive control was associated with a significantly lower risk of all-cause mortality in normoglycemic patients (0.7% vs. 1.4% with standard control; HR, 0.7; 95% CI, 0.5-0.9).
Serious adverse events affected about 37% of patients in all subgroups. Hypotension, syncope, bradycardia, and electrolyte abnormalities were slightly more common in the intensive control groups than the standard control groups, regardless of baseline FPG levels.
SPRINT was sponsored by the National Heart, Lung, and Blood Institute. The National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and Wake Forest University Health Sciences provided additional support. Dr. Bress disclosed research support from Novartis and the National Institutes of Health.
SAN DIEGO – Treating systolic hypertension to a target of 120 mm Hg instead of 140 mm Hg significantly reduced the rate of cardiovascular events in high-risk patients with prediabetes, according to a post-hoc analysis of the multicenter, randomized, controlled, open-label Systolic Blood Pressure Intervention Trial (SPRINT).
Thus, prediabetes did not undercut the cardiovascular benefits of intensive systolic blood pressure (SBP) control in older, high-risk, hypertensive patients, Adam P. Bress, PharmD, MS, and his associates concluded in a late-breaking poster presented at the annual scientific sessions of the American Diabetes Association.
In contrast, intensive SBP control did not prevent cardiovascular events, compared with standard control among diabetic patients in the randomized, nonblinded ACCORD BP trial (N Engl J Med. 2010; 362:1575-85).
To help clarify SBP targets for prediabetic individuals, Dr. Bress and his associates parsed cardiovascular outcomes in SPRINT based on baseline fasting serum glucose (FSG) levels. More than 5,400 normoglycemic (average FSG, 91 mg per dL) patients and more than 3,800 prediabetic (average FSG, 110 mg per dL) patients were followed for a median of 3.3 years, after which 101 (1.6%) prediabetic intensive control patients and 144 (2.3%) prediabetic standard control patients experienced the combined primary endpoint (HR, 0.7; 95% confidence interval, 0.5-0.9). The hazard ratio for normoglycemic patients was similar (0.9) and approached statistical significance.
Intensive SBP control also was associated with lower rates of individual cardiovascular outcomes and all-cause mortality, compared with standard control in both normoglycemic and prediabetic patients, Dr. Bress and his associates reported. Wide confidence intervals precluded statistical significance for most individual outcomes, but intensive control was associated with a significantly lower risk of all-cause mortality in normoglycemic patients (0.7% vs. 1.4% with standard control; HR, 0.7; 95% CI, 0.5-0.9).
Serious adverse events affected about 37% of patients in all subgroups. Hypotension, syncope, bradycardia, and electrolyte abnormalities were slightly more common in the intensive control groups than the standard control groups, regardless of baseline FPG levels.
SPRINT was sponsored by the National Heart, Lung, and Blood Institute. The National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and Wake Forest University Health Sciences provided additional support. Dr. Bress disclosed research support from Novartis and the National Institutes of Health.
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: Treating systolic hypertension to a target of 120 mm Hg instead of 140 mm Hg significantly reduced the rate of cardiovascular events in high-risk patients with prediabetes.
Major finding: After a median of 3.3 years, 1.6% of patients with prediabetes in the intensive control group and 2.2% of patients with prediabetes in the standard control group experienced myocardial infarction, acute coronary syndrome without myocardial infarction, stroke, acute decompensated heart failure, or cardiovascular death.
Data source: SPRINT, a randomized, controlled, open-label trial comparing systolic blood pressure targets of less than 140 mm Hg (standard control) and less than 120 mm Hg (intensive control) in hypertensive patients without clinical diabetes who were older than 50 years and at high risk for cardiovascular disease.
Disclosures: SPRINT was sponsored by the National Heart, Lung, and Blood Institute. The National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and Wake Forest University Health Sciences provided additional support. Dr. Bress disclosed research support from Novartis and the National Institutes of Health.