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A New, Easily Identifiable Sign of Concussion?
Spontaneous Headshake After a Kinematic Event (SHAAKE) refers to the rapid, back-and-forth head movement athletes exhibit following a blow to the head. This voluntary motion typically occurs within seconds to minutes after impact and is a familiar response in athletes.
In a recent survey, 7 out of 10 adult athletes recalled making this movement after a collision, and three out of four times they attributed this back-and-forth head movement to a concussion. The association was strongest among football players, who reported that over 90% of SHAAKE episodes were associated with a concussion.
The results were published online in Diagnostics.
Call to Action
“Everyone” — including sports and medical organizations — “should be adding this to their list of potential concussion signs and their protocol immediately,” study investigator Chris Nowinski, PhD, CEO and co-founder of the Concussion Legacy Foundation, told this news organization.
Nowinski said it’s “fascinating” that this concussion sign hasn’t been formally studied or added to formal concussion screening metrics before now, given that it’s been depicted in movies, television, and cartoons for decades.
Coaches, medical professionals, and concussion spotters should be trained to recognize when a SHAAKE happens, he said.
“The interesting thing is, I don’t think coaches or parents need much training other than to officially tie this to suspicion of a concussion,” Nowinski added.
The Case of Miami Dolphins QB Tua Tagovailoa
Nowinski said he was tipped off to SHAAKE as a concussion sign after Miami Dolphins quarterback Tua Tagovailoa’s controversial undiagnosed concussion during a National Football League (NFL) game in 2022.
After Tagovailoa’s head hit the ground, he rapidly shook his head side to side, indicating displaying SHAAKE, before stumbling and collapsing. At the time, a sideline doctor attributed his collapse to a prior back injury.
If Tagovailoa had been diagnosed with a concussion, he likely would not have been playing in a game just 4 days later, where he lost consciousness after suffering a suspected second concussion and was removed from the field on a stretcher.
For the survey, Nowinski and colleagues showed 347 current and former athletes, including 109 football players, video examples of SHAAKE and them asked about their experiences with this potential indicator of concussion.
Nearly 69% of athletes reported exhibiting a SHAAKE during their career, and 93% of those reported a SHAAKE in association with concussion at least once. Athletes reported SHAAKE a median of five times in their lives.
Of the athletes who reported SHAAKE, 85% linked this head-shaking movement to concussion symptoms such as disorientation (71%) and dizziness (54%).
Across all sports, SHAAKE showed a sensitivity of 49.6% and a positive predictive value (PPV) of 72.4% for diagnosing concussions.
Among football players, sensitivity improved to 52.3%, with an estimated specificity of 99.9%, a PPV of 91.9%, and an estimated negative predictive value of 99.5%.
The main limitation of the survey was the potential for recall bias due to survey participants self-reporting prior concussions. The researchers called for future prospective studies to validate SHAAKE as a sign of concussion.
Instant Replay for Brain Injury?
Experts echoed the need for validation. SHAAKE represents a “promising advance” in objective TBI assessment, particularly for sideline evaluation, said Shaheen Lakhan, MD, PhD, neurologist, and researcher based in Miami, Florida, who wasn’t involved in the research.
The potential value of SHAAKE is “particularly notable given the well-documented tendency for athletes to minimize or conceal symptoms to maintain play eligibility, a limitation that has historically challenged our reliance on subjective reporting and observational assessments,” Lakhan said.
“Moving forward, validation through prospective studies incorporating real-time video analysis, helmet sensor data, and clinician-confirmed TBI diagnoses will be essential. With appropriate validation, SHAAKE could emerge as a valuable component of our sideline assessment arsenal, complementing rather than replacing existing diagnostic approaches,” Lakhan said.
“SHAAKE could be the ‘instant replay’ for brain injuries that sports medicine has been waiting for — but like any new technology, we need to make sure it works for every player, not just some,” Lakhan added.
Also weighing in, Richard Figler, MD, director of the Concussion Center, Cleveland Clinic Sports Medicine Center, Cleveland, cautioned that the survey participants were recruited from a concussion registry and self-reported an average of 23 concussions — more than one third of which happened 5-10 years prior — which begs the question, “How much are they actually remembering?”
“Our goal is to make sure that the athletes are safe and that we’re not missing concussions, and we don’t have great tools to start off with. This study opens up the door for some prospective studies [of SHAAKE] moving forward. I think we need more data before this should be listed as a definitive marker,” said Figler, who also wasn’t involved in the study.
In any case, he said, when it comes to suspected concussion in sports, “when in doubt, you sit them out,” Figler said.
This research received no external funding. Nowinski has received travel reimbursement from the NFL Players Association (NFLPA), NFL, World Rugby, WWE, and All Elite Wrestling; served as an expert witness in cases related to concussion and chronic traumatic encephalopathy; and is compensated for speaking appearances and serving on the NFL Concussion Settlement Player Advocacy Committee. Daniel H. Daneshvar served as an expert witness in legal cases involving brain injury and concussion and received funding from the Football Players Health Study at Harvard University, which is funded by the NFLPA and evaluates patients for the MGH Brain and Body TRUST Center, sponsored in part by the NFLPA. Lakhan and Figler had no relevant disclosures.
A version of this article appeared on Medscape.com.
Spontaneous Headshake After a Kinematic Event (SHAAKE) refers to the rapid, back-and-forth head movement athletes exhibit following a blow to the head. This voluntary motion typically occurs within seconds to minutes after impact and is a familiar response in athletes.
In a recent survey, 7 out of 10 adult athletes recalled making this movement after a collision, and three out of four times they attributed this back-and-forth head movement to a concussion. The association was strongest among football players, who reported that over 90% of SHAAKE episodes were associated with a concussion.
The results were published online in Diagnostics.
Call to Action
“Everyone” — including sports and medical organizations — “should be adding this to their list of potential concussion signs and their protocol immediately,” study investigator Chris Nowinski, PhD, CEO and co-founder of the Concussion Legacy Foundation, told this news organization.
Nowinski said it’s “fascinating” that this concussion sign hasn’t been formally studied or added to formal concussion screening metrics before now, given that it’s been depicted in movies, television, and cartoons for decades.
Coaches, medical professionals, and concussion spotters should be trained to recognize when a SHAAKE happens, he said.
“The interesting thing is, I don’t think coaches or parents need much training other than to officially tie this to suspicion of a concussion,” Nowinski added.
The Case of Miami Dolphins QB Tua Tagovailoa
Nowinski said he was tipped off to SHAAKE as a concussion sign after Miami Dolphins quarterback Tua Tagovailoa’s controversial undiagnosed concussion during a National Football League (NFL) game in 2022.
After Tagovailoa’s head hit the ground, he rapidly shook his head side to side, indicating displaying SHAAKE, before stumbling and collapsing. At the time, a sideline doctor attributed his collapse to a prior back injury.
If Tagovailoa had been diagnosed with a concussion, he likely would not have been playing in a game just 4 days later, where he lost consciousness after suffering a suspected second concussion and was removed from the field on a stretcher.
For the survey, Nowinski and colleagues showed 347 current and former athletes, including 109 football players, video examples of SHAAKE and them asked about their experiences with this potential indicator of concussion.
Nearly 69% of athletes reported exhibiting a SHAAKE during their career, and 93% of those reported a SHAAKE in association with concussion at least once. Athletes reported SHAAKE a median of five times in their lives.
Of the athletes who reported SHAAKE, 85% linked this head-shaking movement to concussion symptoms such as disorientation (71%) and dizziness (54%).
Across all sports, SHAAKE showed a sensitivity of 49.6% and a positive predictive value (PPV) of 72.4% for diagnosing concussions.
Among football players, sensitivity improved to 52.3%, with an estimated specificity of 99.9%, a PPV of 91.9%, and an estimated negative predictive value of 99.5%.
The main limitation of the survey was the potential for recall bias due to survey participants self-reporting prior concussions. The researchers called for future prospective studies to validate SHAAKE as a sign of concussion.
Instant Replay for Brain Injury?
Experts echoed the need for validation. SHAAKE represents a “promising advance” in objective TBI assessment, particularly for sideline evaluation, said Shaheen Lakhan, MD, PhD, neurologist, and researcher based in Miami, Florida, who wasn’t involved in the research.
The potential value of SHAAKE is “particularly notable given the well-documented tendency for athletes to minimize or conceal symptoms to maintain play eligibility, a limitation that has historically challenged our reliance on subjective reporting and observational assessments,” Lakhan said.
“Moving forward, validation through prospective studies incorporating real-time video analysis, helmet sensor data, and clinician-confirmed TBI diagnoses will be essential. With appropriate validation, SHAAKE could emerge as a valuable component of our sideline assessment arsenal, complementing rather than replacing existing diagnostic approaches,” Lakhan said.
“SHAAKE could be the ‘instant replay’ for brain injuries that sports medicine has been waiting for — but like any new technology, we need to make sure it works for every player, not just some,” Lakhan added.
Also weighing in, Richard Figler, MD, director of the Concussion Center, Cleveland Clinic Sports Medicine Center, Cleveland, cautioned that the survey participants were recruited from a concussion registry and self-reported an average of 23 concussions — more than one third of which happened 5-10 years prior — which begs the question, “How much are they actually remembering?”
“Our goal is to make sure that the athletes are safe and that we’re not missing concussions, and we don’t have great tools to start off with. This study opens up the door for some prospective studies [of SHAAKE] moving forward. I think we need more data before this should be listed as a definitive marker,” said Figler, who also wasn’t involved in the study.
In any case, he said, when it comes to suspected concussion in sports, “when in doubt, you sit them out,” Figler said.
This research received no external funding. Nowinski has received travel reimbursement from the NFL Players Association (NFLPA), NFL, World Rugby, WWE, and All Elite Wrestling; served as an expert witness in cases related to concussion and chronic traumatic encephalopathy; and is compensated for speaking appearances and serving on the NFL Concussion Settlement Player Advocacy Committee. Daniel H. Daneshvar served as an expert witness in legal cases involving brain injury and concussion and received funding from the Football Players Health Study at Harvard University, which is funded by the NFLPA and evaluates patients for the MGH Brain and Body TRUST Center, sponsored in part by the NFLPA. Lakhan and Figler had no relevant disclosures.
A version of this article appeared on Medscape.com.
Spontaneous Headshake After a Kinematic Event (SHAAKE) refers to the rapid, back-and-forth head movement athletes exhibit following a blow to the head. This voluntary motion typically occurs within seconds to minutes after impact and is a familiar response in athletes.
In a recent survey, 7 out of 10 adult athletes recalled making this movement after a collision, and three out of four times they attributed this back-and-forth head movement to a concussion. The association was strongest among football players, who reported that over 90% of SHAAKE episodes were associated with a concussion.
The results were published online in Diagnostics.
Call to Action
“Everyone” — including sports and medical organizations — “should be adding this to their list of potential concussion signs and their protocol immediately,” study investigator Chris Nowinski, PhD, CEO and co-founder of the Concussion Legacy Foundation, told this news organization.
Nowinski said it’s “fascinating” that this concussion sign hasn’t been formally studied or added to formal concussion screening metrics before now, given that it’s been depicted in movies, television, and cartoons for decades.
Coaches, medical professionals, and concussion spotters should be trained to recognize when a SHAAKE happens, he said.
“The interesting thing is, I don’t think coaches or parents need much training other than to officially tie this to suspicion of a concussion,” Nowinski added.
The Case of Miami Dolphins QB Tua Tagovailoa
Nowinski said he was tipped off to SHAAKE as a concussion sign after Miami Dolphins quarterback Tua Tagovailoa’s controversial undiagnosed concussion during a National Football League (NFL) game in 2022.
After Tagovailoa’s head hit the ground, he rapidly shook his head side to side, indicating displaying SHAAKE, before stumbling and collapsing. At the time, a sideline doctor attributed his collapse to a prior back injury.
If Tagovailoa had been diagnosed with a concussion, he likely would not have been playing in a game just 4 days later, where he lost consciousness after suffering a suspected second concussion and was removed from the field on a stretcher.
For the survey, Nowinski and colleagues showed 347 current and former athletes, including 109 football players, video examples of SHAAKE and them asked about their experiences with this potential indicator of concussion.
Nearly 69% of athletes reported exhibiting a SHAAKE during their career, and 93% of those reported a SHAAKE in association with concussion at least once. Athletes reported SHAAKE a median of five times in their lives.
Of the athletes who reported SHAAKE, 85% linked this head-shaking movement to concussion symptoms such as disorientation (71%) and dizziness (54%).
Across all sports, SHAAKE showed a sensitivity of 49.6% and a positive predictive value (PPV) of 72.4% for diagnosing concussions.
Among football players, sensitivity improved to 52.3%, with an estimated specificity of 99.9%, a PPV of 91.9%, and an estimated negative predictive value of 99.5%.
The main limitation of the survey was the potential for recall bias due to survey participants self-reporting prior concussions. The researchers called for future prospective studies to validate SHAAKE as a sign of concussion.
Instant Replay for Brain Injury?
Experts echoed the need for validation. SHAAKE represents a “promising advance” in objective TBI assessment, particularly for sideline evaluation, said Shaheen Lakhan, MD, PhD, neurologist, and researcher based in Miami, Florida, who wasn’t involved in the research.
The potential value of SHAAKE is “particularly notable given the well-documented tendency for athletes to minimize or conceal symptoms to maintain play eligibility, a limitation that has historically challenged our reliance on subjective reporting and observational assessments,” Lakhan said.
“Moving forward, validation through prospective studies incorporating real-time video analysis, helmet sensor data, and clinician-confirmed TBI diagnoses will be essential. With appropriate validation, SHAAKE could emerge as a valuable component of our sideline assessment arsenal, complementing rather than replacing existing diagnostic approaches,” Lakhan said.
“SHAAKE could be the ‘instant replay’ for brain injuries that sports medicine has been waiting for — but like any new technology, we need to make sure it works for every player, not just some,” Lakhan added.
Also weighing in, Richard Figler, MD, director of the Concussion Center, Cleveland Clinic Sports Medicine Center, Cleveland, cautioned that the survey participants were recruited from a concussion registry and self-reported an average of 23 concussions — more than one third of which happened 5-10 years prior — which begs the question, “How much are they actually remembering?”
“Our goal is to make sure that the athletes are safe and that we’re not missing concussions, and we don’t have great tools to start off with. This study opens up the door for some prospective studies [of SHAAKE] moving forward. I think we need more data before this should be listed as a definitive marker,” said Figler, who also wasn’t involved in the study.
In any case, he said, when it comes to suspected concussion in sports, “when in doubt, you sit them out,” Figler said.
This research received no external funding. Nowinski has received travel reimbursement from the NFL Players Association (NFLPA), NFL, World Rugby, WWE, and All Elite Wrestling; served as an expert witness in cases related to concussion and chronic traumatic encephalopathy; and is compensated for speaking appearances and serving on the NFL Concussion Settlement Player Advocacy Committee. Daniel H. Daneshvar served as an expert witness in legal cases involving brain injury and concussion and received funding from the Football Players Health Study at Harvard University, which is funded by the NFLPA and evaluates patients for the MGH Brain and Body TRUST Center, sponsored in part by the NFLPA. Lakhan and Figler had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM DIAGNOSTICS
Blood Tests for Alzheimer’s Are Here... Are Clinicians Ready?
With the approval of anti-amyloid monoclonal antibodies to treat early-stage Alzheimer’s disease, the need for accurate and early diagnosis is crucial.
Recently, an expert workgroup convened by the Global CEO Initiative on Alzheimer’s Disease published recommendations for the clinical implementation of Alzheimer’s disease blood-based biomarkers.
“Our hope was to provide some recommendations that clinicians could use to develop the best pathways for their clinical practice,” said workgroup co-chair Michelle M. Mielke, PhD, with Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Triage and Confirmatory Pathways
The group recommends two implementation pathways for Alzheimer’s disease blood biomarkers — one for current use for triaging and another for future use to confirm amyloid pathology once blood biomarker tests have reached sufficient performance for this purpose.
In the triage pathway, a negative blood biomarker test would flag individuals unlikely to have detectable brain amyloid pathology. This outcome would prompt clinicians to focus on evaluating non–Alzheimer’s disease-related causes of cognitive impairment, which may streamline the diagnosis of other causes of cognitive impairment, the authors said.
A positive triage blood test would suggest a higher likelihood of amyloid pathology and prompt referral to secondary care for further assessment and consideration for a second, more accurate test, such as amyloid PET or CSF for amyloid confirmation.
In the confirmatory pathway, a positive blood biomarker test result would identify amyloid pathology without the need for a second test, providing a faster route to diagnosis, the authors noted.
Mielke emphasized that these recommendations represent a “first step” and will need to be updated as experiences with the Alzheimer’s disease blood biomarkers in clinical care increase and additional barriers and facilitators are identified.
“These updates will likely include community-informed approaches that incorporate feedback from patients as well as healthcare providers, alongside results from validation in diverse real-world settings,” said workgroup co-chair Chi Udeh-Momoh, PhD, MSc, with Wake Forest University School of Medicine and the Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.
The Alzheimer’s Association published “appropriate use” recommendations for blood biomarkers in 2022.
“Currently, the Alzheimer’s Association is building an updated library of clinical guidance that distills the scientific evidence using de novo systematic reviews and translates them into clear and actionable recommendations for clinical practice,” said Rebecca M. Edelmayer, PhD, vice president of scientific engagement, Alzheimer’s Association.
“The first major effort with our new process will be the upcoming Evidence-based Clinical Practice Guideline on the Use of Blood-based Biomarkers (BBMs) in Specialty Care Settings. This guideline’s recommendations will be published in early 2025,” Edelmayer said.
Availability and Accuracy
Research has shown that amyloid beta and tau protein blood biomarkers — especially a high plasma phosphorylated (p)–tau217 levels — are highly accurate in identifying Alzheimer’s disease in patients with cognitive symptoms attending primary and secondary care clinics.
Several tests targeting plasma p-tau217 are now available for use. They include the PrecivityAD2 blood test from C2N Diagnostics and the Simoa p-Tau 217 Planar Kit and LucentAD p-Tau 217 — both from Quanterix.
In a recent head-to-head comparison of seven leading blood tests for AD pathology, measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with Alzheimer’s disease outcomes.
A recent Swedish study showed that the PrecivityAD2 test had an accuracy of 91% for correctly classifying clinical, biomarker-verified Alzheimer’s disease.
“We’ve been using these blood biomarkers in research for a long time and we’re now taking the jump to start using them in clinic to risk stratify patients,” said Fanny Elahi, MD, PhD, director of fluid biomarker research for the Barbara and Maurice Deane Center for Wellness and Cognitive Health at Icahn Mount Sinai in New York City.
New York’s Mount Sinai Health System is among the first in the northeast to offer blood tests across primary and specialty care settings for early diagnosis of AD and related dementias.
Edelmayer cautioned, “There is no single, stand-alone test to diagnose Alzheimer’s disease today. Blood testing is one piece of the diagnostic process.”
“Currently, physicians use well-established diagnostic tools combined with medical history and other information, including neurological exams, cognitive and functional assessments as well as brain imaging and spinal fluid analysis and blood to make an accurate diagnosis and to understand which patients are eligible for approved treatments,” she said.
There are also emerging biomarkers in the research pipeline, Edelmayer said.
“For example, some researchers think retinal imaging has the potential to detect biological signs of Alzheimer’s disease within certain areas of the eye,” she explained.
“Other emerging biomarkers include examining components in saliva and the skin for signals that may indicate early biological changes in the brain. These biomarkers are still very exploratory, and more research is needed before these tests or biomarkers can be used more routinely to study risk or aid in diagnosis,” Edelmayer said.
Ideal Candidates for Alzheimer’s Disease Blood Testing?
Experts agree that blood tests represent a convenient and scalable option to address the anticipated surge in demand for biomarker testing with the availability of disease-modifying treatments. For now, however, they are not for all older adults worried about their memory.
“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid,” the authors of a recent JAMA editorial noted.
At Mount Sinai, “we’re not starting with stone-cold asymptomatic individuals. But ultimately, this is what the blood tests are intended for — screening,” Elahi noted.
She also noted that Mount Sinai has a “very diverse population” — some with young onset cognitive symptoms, so the entry criteria for testing are “very wide.”
“Anyone above age 40 with symptoms can qualify to get a blood test. We do ask at this stage that either the individual report symptoms or someone in their life or their clinician be worried about their cognition or their brain function,” Elahi said.
Ethical Considerations, Counseling
Elahi emphasized the importance of counseling patients who come to the clinic seeking an Alzheimer’s disease blood test. This should include how the diagnostic process will unfold and what the next steps are with a given result.
Elahi said patients need to be informed that Alzheimer’s disease blood biomarkers are still “relatively new,” and a test can help a patient “know the likelihood of having the disease, but it won’t be 100% definitive.”
To ensure the ethical principle of “do no harm,” counseling should ensure that patients are fully prepared for the implications of the test results and ensure that the decision to test aligns with the patient’s readiness and well-being, Elahi said.
Edelmayer said the forthcoming clinical practice guidelines will provide “evidence-based recommendations for physicians to help guide them through the decision-making process around who should be tested and when. In the meantime, the Alzheimer’s Association urges providers to refer to the 2022 appropriate use recommendations for blood tests in clinical practice and trial settings.”
Mielke has served on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio. Edelmayer and Elahi had no relevant disclosures.
A version of this article appeared on Medscape.com.
With the approval of anti-amyloid monoclonal antibodies to treat early-stage Alzheimer’s disease, the need for accurate and early diagnosis is crucial.
Recently, an expert workgroup convened by the Global CEO Initiative on Alzheimer’s Disease published recommendations for the clinical implementation of Alzheimer’s disease blood-based biomarkers.
“Our hope was to provide some recommendations that clinicians could use to develop the best pathways for their clinical practice,” said workgroup co-chair Michelle M. Mielke, PhD, with Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Triage and Confirmatory Pathways
The group recommends two implementation pathways for Alzheimer’s disease blood biomarkers — one for current use for triaging and another for future use to confirm amyloid pathology once blood biomarker tests have reached sufficient performance for this purpose.
In the triage pathway, a negative blood biomarker test would flag individuals unlikely to have detectable brain amyloid pathology. This outcome would prompt clinicians to focus on evaluating non–Alzheimer’s disease-related causes of cognitive impairment, which may streamline the diagnosis of other causes of cognitive impairment, the authors said.
A positive triage blood test would suggest a higher likelihood of amyloid pathology and prompt referral to secondary care for further assessment and consideration for a second, more accurate test, such as amyloid PET or CSF for amyloid confirmation.
In the confirmatory pathway, a positive blood biomarker test result would identify amyloid pathology without the need for a second test, providing a faster route to diagnosis, the authors noted.
Mielke emphasized that these recommendations represent a “first step” and will need to be updated as experiences with the Alzheimer’s disease blood biomarkers in clinical care increase and additional barriers and facilitators are identified.
“These updates will likely include community-informed approaches that incorporate feedback from patients as well as healthcare providers, alongside results from validation in diverse real-world settings,” said workgroup co-chair Chi Udeh-Momoh, PhD, MSc, with Wake Forest University School of Medicine and the Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.
The Alzheimer’s Association published “appropriate use” recommendations for blood biomarkers in 2022.
“Currently, the Alzheimer’s Association is building an updated library of clinical guidance that distills the scientific evidence using de novo systematic reviews and translates them into clear and actionable recommendations for clinical practice,” said Rebecca M. Edelmayer, PhD, vice president of scientific engagement, Alzheimer’s Association.
“The first major effort with our new process will be the upcoming Evidence-based Clinical Practice Guideline on the Use of Blood-based Biomarkers (BBMs) in Specialty Care Settings. This guideline’s recommendations will be published in early 2025,” Edelmayer said.
Availability and Accuracy
Research has shown that amyloid beta and tau protein blood biomarkers — especially a high plasma phosphorylated (p)–tau217 levels — are highly accurate in identifying Alzheimer’s disease in patients with cognitive symptoms attending primary and secondary care clinics.
Several tests targeting plasma p-tau217 are now available for use. They include the PrecivityAD2 blood test from C2N Diagnostics and the Simoa p-Tau 217 Planar Kit and LucentAD p-Tau 217 — both from Quanterix.
In a recent head-to-head comparison of seven leading blood tests for AD pathology, measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with Alzheimer’s disease outcomes.
A recent Swedish study showed that the PrecivityAD2 test had an accuracy of 91% for correctly classifying clinical, biomarker-verified Alzheimer’s disease.
“We’ve been using these blood biomarkers in research for a long time and we’re now taking the jump to start using them in clinic to risk stratify patients,” said Fanny Elahi, MD, PhD, director of fluid biomarker research for the Barbara and Maurice Deane Center for Wellness and Cognitive Health at Icahn Mount Sinai in New York City.
New York’s Mount Sinai Health System is among the first in the northeast to offer blood tests across primary and specialty care settings for early diagnosis of AD and related dementias.
Edelmayer cautioned, “There is no single, stand-alone test to diagnose Alzheimer’s disease today. Blood testing is one piece of the diagnostic process.”
“Currently, physicians use well-established diagnostic tools combined with medical history and other information, including neurological exams, cognitive and functional assessments as well as brain imaging and spinal fluid analysis and blood to make an accurate diagnosis and to understand which patients are eligible for approved treatments,” she said.
There are also emerging biomarkers in the research pipeline, Edelmayer said.
“For example, some researchers think retinal imaging has the potential to detect biological signs of Alzheimer’s disease within certain areas of the eye,” she explained.
“Other emerging biomarkers include examining components in saliva and the skin for signals that may indicate early biological changes in the brain. These biomarkers are still very exploratory, and more research is needed before these tests or biomarkers can be used more routinely to study risk or aid in diagnosis,” Edelmayer said.
Ideal Candidates for Alzheimer’s Disease Blood Testing?
Experts agree that blood tests represent a convenient and scalable option to address the anticipated surge in demand for biomarker testing with the availability of disease-modifying treatments. For now, however, they are not for all older adults worried about their memory.
“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid,” the authors of a recent JAMA editorial noted.
At Mount Sinai, “we’re not starting with stone-cold asymptomatic individuals. But ultimately, this is what the blood tests are intended for — screening,” Elahi noted.
She also noted that Mount Sinai has a “very diverse population” — some with young onset cognitive symptoms, so the entry criteria for testing are “very wide.”
“Anyone above age 40 with symptoms can qualify to get a blood test. We do ask at this stage that either the individual report symptoms or someone in their life or their clinician be worried about their cognition or their brain function,” Elahi said.
Ethical Considerations, Counseling
Elahi emphasized the importance of counseling patients who come to the clinic seeking an Alzheimer’s disease blood test. This should include how the diagnostic process will unfold and what the next steps are with a given result.
Elahi said patients need to be informed that Alzheimer’s disease blood biomarkers are still “relatively new,” and a test can help a patient “know the likelihood of having the disease, but it won’t be 100% definitive.”
To ensure the ethical principle of “do no harm,” counseling should ensure that patients are fully prepared for the implications of the test results and ensure that the decision to test aligns with the patient’s readiness and well-being, Elahi said.
Edelmayer said the forthcoming clinical practice guidelines will provide “evidence-based recommendations for physicians to help guide them through the decision-making process around who should be tested and when. In the meantime, the Alzheimer’s Association urges providers to refer to the 2022 appropriate use recommendations for blood tests in clinical practice and trial settings.”
Mielke has served on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio. Edelmayer and Elahi had no relevant disclosures.
A version of this article appeared on Medscape.com.
With the approval of anti-amyloid monoclonal antibodies to treat early-stage Alzheimer’s disease, the need for accurate and early diagnosis is crucial.
Recently, an expert workgroup convened by the Global CEO Initiative on Alzheimer’s Disease published recommendations for the clinical implementation of Alzheimer’s disease blood-based biomarkers.
“Our hope was to provide some recommendations that clinicians could use to develop the best pathways for their clinical practice,” said workgroup co-chair Michelle M. Mielke, PhD, with Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Triage and Confirmatory Pathways
The group recommends two implementation pathways for Alzheimer’s disease blood biomarkers — one for current use for triaging and another for future use to confirm amyloid pathology once blood biomarker tests have reached sufficient performance for this purpose.
In the triage pathway, a negative blood biomarker test would flag individuals unlikely to have detectable brain amyloid pathology. This outcome would prompt clinicians to focus on evaluating non–Alzheimer’s disease-related causes of cognitive impairment, which may streamline the diagnosis of other causes of cognitive impairment, the authors said.
A positive triage blood test would suggest a higher likelihood of amyloid pathology and prompt referral to secondary care for further assessment and consideration for a second, more accurate test, such as amyloid PET or CSF for amyloid confirmation.
In the confirmatory pathway, a positive blood biomarker test result would identify amyloid pathology without the need for a second test, providing a faster route to diagnosis, the authors noted.
Mielke emphasized that these recommendations represent a “first step” and will need to be updated as experiences with the Alzheimer’s disease blood biomarkers in clinical care increase and additional barriers and facilitators are identified.
“These updates will likely include community-informed approaches that incorporate feedback from patients as well as healthcare providers, alongside results from validation in diverse real-world settings,” said workgroup co-chair Chi Udeh-Momoh, PhD, MSc, with Wake Forest University School of Medicine and the Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.
The Alzheimer’s Association published “appropriate use” recommendations for blood biomarkers in 2022.
“Currently, the Alzheimer’s Association is building an updated library of clinical guidance that distills the scientific evidence using de novo systematic reviews and translates them into clear and actionable recommendations for clinical practice,” said Rebecca M. Edelmayer, PhD, vice president of scientific engagement, Alzheimer’s Association.
“The first major effort with our new process will be the upcoming Evidence-based Clinical Practice Guideline on the Use of Blood-based Biomarkers (BBMs) in Specialty Care Settings. This guideline’s recommendations will be published in early 2025,” Edelmayer said.
Availability and Accuracy
Research has shown that amyloid beta and tau protein blood biomarkers — especially a high plasma phosphorylated (p)–tau217 levels — are highly accurate in identifying Alzheimer’s disease in patients with cognitive symptoms attending primary and secondary care clinics.
Several tests targeting plasma p-tau217 are now available for use. They include the PrecivityAD2 blood test from C2N Diagnostics and the Simoa p-Tau 217 Planar Kit and LucentAD p-Tau 217 — both from Quanterix.
In a recent head-to-head comparison of seven leading blood tests for AD pathology, measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with Alzheimer’s disease outcomes.
A recent Swedish study showed that the PrecivityAD2 test had an accuracy of 91% for correctly classifying clinical, biomarker-verified Alzheimer’s disease.
“We’ve been using these blood biomarkers in research for a long time and we’re now taking the jump to start using them in clinic to risk stratify patients,” said Fanny Elahi, MD, PhD, director of fluid biomarker research for the Barbara and Maurice Deane Center for Wellness and Cognitive Health at Icahn Mount Sinai in New York City.
New York’s Mount Sinai Health System is among the first in the northeast to offer blood tests across primary and specialty care settings for early diagnosis of AD and related dementias.
Edelmayer cautioned, “There is no single, stand-alone test to diagnose Alzheimer’s disease today. Blood testing is one piece of the diagnostic process.”
“Currently, physicians use well-established diagnostic tools combined with medical history and other information, including neurological exams, cognitive and functional assessments as well as brain imaging and spinal fluid analysis and blood to make an accurate diagnosis and to understand which patients are eligible for approved treatments,” she said.
There are also emerging biomarkers in the research pipeline, Edelmayer said.
“For example, some researchers think retinal imaging has the potential to detect biological signs of Alzheimer’s disease within certain areas of the eye,” she explained.
“Other emerging biomarkers include examining components in saliva and the skin for signals that may indicate early biological changes in the brain. These biomarkers are still very exploratory, and more research is needed before these tests or biomarkers can be used more routinely to study risk or aid in diagnosis,” Edelmayer said.
Ideal Candidates for Alzheimer’s Disease Blood Testing?
Experts agree that blood tests represent a convenient and scalable option to address the anticipated surge in demand for biomarker testing with the availability of disease-modifying treatments. For now, however, they are not for all older adults worried about their memory.
“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid,” the authors of a recent JAMA editorial noted.
At Mount Sinai, “we’re not starting with stone-cold asymptomatic individuals. But ultimately, this is what the blood tests are intended for — screening,” Elahi noted.
She also noted that Mount Sinai has a “very diverse population” — some with young onset cognitive symptoms, so the entry criteria for testing are “very wide.”
“Anyone above age 40 with symptoms can qualify to get a blood test. We do ask at this stage that either the individual report symptoms or someone in their life or their clinician be worried about their cognition or their brain function,” Elahi said.
Ethical Considerations, Counseling
Elahi emphasized the importance of counseling patients who come to the clinic seeking an Alzheimer’s disease blood test. This should include how the diagnostic process will unfold and what the next steps are with a given result.
Elahi said patients need to be informed that Alzheimer’s disease blood biomarkers are still “relatively new,” and a test can help a patient “know the likelihood of having the disease, but it won’t be 100% definitive.”
To ensure the ethical principle of “do no harm,” counseling should ensure that patients are fully prepared for the implications of the test results and ensure that the decision to test aligns with the patient’s readiness and well-being, Elahi said.
Edelmayer said the forthcoming clinical practice guidelines will provide “evidence-based recommendations for physicians to help guide them through the decision-making process around who should be tested and when. In the meantime, the Alzheimer’s Association urges providers to refer to the 2022 appropriate use recommendations for blood tests in clinical practice and trial settings.”
Mielke has served on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio. Edelmayer and Elahi had no relevant disclosures.
A version of this article appeared on Medscape.com.
ASA Releases New Primary Stroke Prevention Guideline
The first update in a decade, the 2024 Guideline for the Primary Prevention of Stroke, replaces the 2014 version and is intended to be a resource for clinicians to help them implement a variety of prevention strategies in patients with no previous history of stroke. It aligns with the American Heart Association’s Life’s Essential 8.
“This guideline is an important and timely update from 2014 for multiple reasons. First, there have been groundbreaking clinical trials that have been published with new medications to not only treat the target disease [including] diabetes/obesity and high cholesterol], but also lower the risk of stroke and heart disease,” said chair of the guideline writing group, Cheryl D. Bushnell, MD, MHS, FAHA, and vice chair of the research, Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
It was published online on October 21 in Stroke.
Up to 80% of Strokes Preventable
Estimates show that every year in the United States, more than 500,000 individuals have a first stroke. However, the guideline authors noted that up to 80% of strokes may be preventable. As a result, they called for better primary stroke prevention that includes improved screening and lifestyle changes.
This includes adoption of the Mediterranean diet, which has been shown to significantly reduce stroke risk, especially when supplemented with consumption of nuts and olive oil.
The guideline recommendations also emphasize the need for physical activity, which is “essential” for cardiovascular health and stroke reduction. The authors underscored this point and provided a new recommendation to screen for sedentary behavior and advise patients to avoid inactivity and engage in regular moderate to vigorous physical activity.
Another new recommendation is based on “robust” data that glucagon-like peptide 1 receptor agonists (GLP-1s) significantly improve the management of type 2 diabetes, weight loss, and lower the risk for cardiovascular disease. As a result, guideline authors called for the use of GLP-1s in patients with diabetes and high cardiovascular risk or established cardiovascular disease.
“The glucagon-like peptide receptor agonists have been shown to not only drastically reduce blood sugars in patients with diabetes, but they also lead to significant weight loss in these patients, which has many downstream benefits. Together, this reduces the risk of stroke and other complications of diabetes,” said Bushnell.
She also noted that another drug class introduced since the 2014 guidelines were published, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have proven to be highly effective in lowering low-density lipoprotein cholesterol. These medications have also been shown to reduce the risk for stroke.
At Least Two Meds Needed to Reduce BP
Effective blood pressure (BP) management is crucial for stroke prevention. Randomized controlled trials show that a single antihypertensive medication helps only about 30% of participants reach their BP target.
Most patients only achieve the desired BP target with two to three medications. In line with these data, the committee recommends using at least two antihypertensives for primary stroke prevention in most patients who require BP-lowering medications for hypertension.
In patients with antiphospholipid syndrome or systemic lupus erythematosus and no history of stroke or unprovoked venous thromboembolism, the authors recommended antiplatelet therapy to prevent stroke. They added that patients with antiphospholipid syndrome who have had a prior unprovoked venous thrombosis will likely benefit from vitamin K antagonist therapy (target international normalized ratio, 2-3) over direct oral anticoagulants.
Emphasis on Women’s Health
Preventing pregnancy-related stroke is achieved primarily by managing hypertension, the guideline authors noted. They recommended treating verified systolic BP over 160 mm Hg or diastolic BP over 110 mm Hg during pregnancy and up to 6 weeks postpartum to lower the risk for fatal maternal intracerebral hemorrhage.
They noted that adverse pregnancy outcomes are also common and linked to chronic hypertension, which increases stroke risk later in life. Therefore, they recommended screening for these outcomes to assess and manage vascular risk factors. The guideline includes a screening tool to help with this in clinical practice.
Endometriosis, premature ovarian failure (before age 40 years), and early-onset menopause (before age 45 years) are all associated with increased stroke risk. As a result, the guideline authors said screening for all three of these conditions is a “reasonable step in the evaluation and management of vascular risk factors in these individuals to reduce stroke risk.”
Finally, the guideline authors addressed primary stroke prevention in transgender individuals, noting that transgender women undergoing estrogen therapy for gender affirmation are at increased risk. They emphasized that evaluating and modifying risk factors could be beneficial for reducing stroke risk in this patient population.
Challenges Lie Ahead
Now that the guideline has been published, the challenge lies in determining how best to implement “its screening recommendations in primary care and other practices when these clinicians are already pushed to see as many patients as possible,” Bushnell said.
Development of screening tools that can be easily incorporated into the clinic visit or the electronic health record, as well as additional personnel to provide counseling, are probably needed to disseminate them, she added.
Bushnell also emphasized that the guideline includes a strong focus on social determinants of health and related social needs.
“We worked hard to use inclusive language and to consider populations historically excluded from research. In acknowledging that social determinants of health including access to healthcare, access to education, economic stability, neighborhood and geographic location, and social and community context have a tremendous influence on stroke risk, we describe how these factors are closely tied to the prevalence and management of many medical risks like obesity, hypertension, and diabetes.
“Our recommendations offer practical steps for screening and addressing essential health-related social needs, including access to nutritious food, stable housing, and reliable transportation, within clinical practice. By considering these factors more comprehensively, we believe we can make meaningful strides toward reducing the disparities in stroke risk,” said Bushnell.
A version of this article appeared on Medscape.com.
The first update in a decade, the 2024 Guideline for the Primary Prevention of Stroke, replaces the 2014 version and is intended to be a resource for clinicians to help them implement a variety of prevention strategies in patients with no previous history of stroke. It aligns with the American Heart Association’s Life’s Essential 8.
“This guideline is an important and timely update from 2014 for multiple reasons. First, there have been groundbreaking clinical trials that have been published with new medications to not only treat the target disease [including] diabetes/obesity and high cholesterol], but also lower the risk of stroke and heart disease,” said chair of the guideline writing group, Cheryl D. Bushnell, MD, MHS, FAHA, and vice chair of the research, Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
It was published online on October 21 in Stroke.
Up to 80% of Strokes Preventable
Estimates show that every year in the United States, more than 500,000 individuals have a first stroke. However, the guideline authors noted that up to 80% of strokes may be preventable. As a result, they called for better primary stroke prevention that includes improved screening and lifestyle changes.
This includes adoption of the Mediterranean diet, which has been shown to significantly reduce stroke risk, especially when supplemented with consumption of nuts and olive oil.
The guideline recommendations also emphasize the need for physical activity, which is “essential” for cardiovascular health and stroke reduction. The authors underscored this point and provided a new recommendation to screen for sedentary behavior and advise patients to avoid inactivity and engage in regular moderate to vigorous physical activity.
Another new recommendation is based on “robust” data that glucagon-like peptide 1 receptor agonists (GLP-1s) significantly improve the management of type 2 diabetes, weight loss, and lower the risk for cardiovascular disease. As a result, guideline authors called for the use of GLP-1s in patients with diabetes and high cardiovascular risk or established cardiovascular disease.
“The glucagon-like peptide receptor agonists have been shown to not only drastically reduce blood sugars in patients with diabetes, but they also lead to significant weight loss in these patients, which has many downstream benefits. Together, this reduces the risk of stroke and other complications of diabetes,” said Bushnell.
She also noted that another drug class introduced since the 2014 guidelines were published, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have proven to be highly effective in lowering low-density lipoprotein cholesterol. These medications have also been shown to reduce the risk for stroke.
At Least Two Meds Needed to Reduce BP
Effective blood pressure (BP) management is crucial for stroke prevention. Randomized controlled trials show that a single antihypertensive medication helps only about 30% of participants reach their BP target.
Most patients only achieve the desired BP target with two to three medications. In line with these data, the committee recommends using at least two antihypertensives for primary stroke prevention in most patients who require BP-lowering medications for hypertension.
In patients with antiphospholipid syndrome or systemic lupus erythematosus and no history of stroke or unprovoked venous thromboembolism, the authors recommended antiplatelet therapy to prevent stroke. They added that patients with antiphospholipid syndrome who have had a prior unprovoked venous thrombosis will likely benefit from vitamin K antagonist therapy (target international normalized ratio, 2-3) over direct oral anticoagulants.
Emphasis on Women’s Health
Preventing pregnancy-related stroke is achieved primarily by managing hypertension, the guideline authors noted. They recommended treating verified systolic BP over 160 mm Hg or diastolic BP over 110 mm Hg during pregnancy and up to 6 weeks postpartum to lower the risk for fatal maternal intracerebral hemorrhage.
They noted that adverse pregnancy outcomes are also common and linked to chronic hypertension, which increases stroke risk later in life. Therefore, they recommended screening for these outcomes to assess and manage vascular risk factors. The guideline includes a screening tool to help with this in clinical practice.
Endometriosis, premature ovarian failure (before age 40 years), and early-onset menopause (before age 45 years) are all associated with increased stroke risk. As a result, the guideline authors said screening for all three of these conditions is a “reasonable step in the evaluation and management of vascular risk factors in these individuals to reduce stroke risk.”
Finally, the guideline authors addressed primary stroke prevention in transgender individuals, noting that transgender women undergoing estrogen therapy for gender affirmation are at increased risk. They emphasized that evaluating and modifying risk factors could be beneficial for reducing stroke risk in this patient population.
Challenges Lie Ahead
Now that the guideline has been published, the challenge lies in determining how best to implement “its screening recommendations in primary care and other practices when these clinicians are already pushed to see as many patients as possible,” Bushnell said.
Development of screening tools that can be easily incorporated into the clinic visit or the electronic health record, as well as additional personnel to provide counseling, are probably needed to disseminate them, she added.
Bushnell also emphasized that the guideline includes a strong focus on social determinants of health and related social needs.
“We worked hard to use inclusive language and to consider populations historically excluded from research. In acknowledging that social determinants of health including access to healthcare, access to education, economic stability, neighborhood and geographic location, and social and community context have a tremendous influence on stroke risk, we describe how these factors are closely tied to the prevalence and management of many medical risks like obesity, hypertension, and diabetes.
“Our recommendations offer practical steps for screening and addressing essential health-related social needs, including access to nutritious food, stable housing, and reliable transportation, within clinical practice. By considering these factors more comprehensively, we believe we can make meaningful strides toward reducing the disparities in stroke risk,” said Bushnell.
A version of this article appeared on Medscape.com.
The first update in a decade, the 2024 Guideline for the Primary Prevention of Stroke, replaces the 2014 version and is intended to be a resource for clinicians to help them implement a variety of prevention strategies in patients with no previous history of stroke. It aligns with the American Heart Association’s Life’s Essential 8.
“This guideline is an important and timely update from 2014 for multiple reasons. First, there have been groundbreaking clinical trials that have been published with new medications to not only treat the target disease [including] diabetes/obesity and high cholesterol], but also lower the risk of stroke and heart disease,” said chair of the guideline writing group, Cheryl D. Bushnell, MD, MHS, FAHA, and vice chair of the research, Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
It was published online on October 21 in Stroke.
Up to 80% of Strokes Preventable
Estimates show that every year in the United States, more than 500,000 individuals have a first stroke. However, the guideline authors noted that up to 80% of strokes may be preventable. As a result, they called for better primary stroke prevention that includes improved screening and lifestyle changes.
This includes adoption of the Mediterranean diet, which has been shown to significantly reduce stroke risk, especially when supplemented with consumption of nuts and olive oil.
The guideline recommendations also emphasize the need for physical activity, which is “essential” for cardiovascular health and stroke reduction. The authors underscored this point and provided a new recommendation to screen for sedentary behavior and advise patients to avoid inactivity and engage in regular moderate to vigorous physical activity.
Another new recommendation is based on “robust” data that glucagon-like peptide 1 receptor agonists (GLP-1s) significantly improve the management of type 2 diabetes, weight loss, and lower the risk for cardiovascular disease. As a result, guideline authors called for the use of GLP-1s in patients with diabetes and high cardiovascular risk or established cardiovascular disease.
“The glucagon-like peptide receptor agonists have been shown to not only drastically reduce blood sugars in patients with diabetes, but they also lead to significant weight loss in these patients, which has many downstream benefits. Together, this reduces the risk of stroke and other complications of diabetes,” said Bushnell.
She also noted that another drug class introduced since the 2014 guidelines were published, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have proven to be highly effective in lowering low-density lipoprotein cholesterol. These medications have also been shown to reduce the risk for stroke.
At Least Two Meds Needed to Reduce BP
Effective blood pressure (BP) management is crucial for stroke prevention. Randomized controlled trials show that a single antihypertensive medication helps only about 30% of participants reach their BP target.
Most patients only achieve the desired BP target with two to three medications. In line with these data, the committee recommends using at least two antihypertensives for primary stroke prevention in most patients who require BP-lowering medications for hypertension.
In patients with antiphospholipid syndrome or systemic lupus erythematosus and no history of stroke or unprovoked venous thromboembolism, the authors recommended antiplatelet therapy to prevent stroke. They added that patients with antiphospholipid syndrome who have had a prior unprovoked venous thrombosis will likely benefit from vitamin K antagonist therapy (target international normalized ratio, 2-3) over direct oral anticoagulants.
Emphasis on Women’s Health
Preventing pregnancy-related stroke is achieved primarily by managing hypertension, the guideline authors noted. They recommended treating verified systolic BP over 160 mm Hg or diastolic BP over 110 mm Hg during pregnancy and up to 6 weeks postpartum to lower the risk for fatal maternal intracerebral hemorrhage.
They noted that adverse pregnancy outcomes are also common and linked to chronic hypertension, which increases stroke risk later in life. Therefore, they recommended screening for these outcomes to assess and manage vascular risk factors. The guideline includes a screening tool to help with this in clinical practice.
Endometriosis, premature ovarian failure (before age 40 years), and early-onset menopause (before age 45 years) are all associated with increased stroke risk. As a result, the guideline authors said screening for all three of these conditions is a “reasonable step in the evaluation and management of vascular risk factors in these individuals to reduce stroke risk.”
Finally, the guideline authors addressed primary stroke prevention in transgender individuals, noting that transgender women undergoing estrogen therapy for gender affirmation are at increased risk. They emphasized that evaluating and modifying risk factors could be beneficial for reducing stroke risk in this patient population.
Challenges Lie Ahead
Now that the guideline has been published, the challenge lies in determining how best to implement “its screening recommendations in primary care and other practices when these clinicians are already pushed to see as many patients as possible,” Bushnell said.
Development of screening tools that can be easily incorporated into the clinic visit or the electronic health record, as well as additional personnel to provide counseling, are probably needed to disseminate them, she added.
Bushnell also emphasized that the guideline includes a strong focus on social determinants of health and related social needs.
“We worked hard to use inclusive language and to consider populations historically excluded from research. In acknowledging that social determinants of health including access to healthcare, access to education, economic stability, neighborhood and geographic location, and social and community context have a tremendous influence on stroke risk, we describe how these factors are closely tied to the prevalence and management of many medical risks like obesity, hypertension, and diabetes.
“Our recommendations offer practical steps for screening and addressing essential health-related social needs, including access to nutritious food, stable housing, and reliable transportation, within clinical practice. By considering these factors more comprehensively, we believe we can make meaningful strides toward reducing the disparities in stroke risk,” said Bushnell.
A version of this article appeared on Medscape.com.
AHA Scientific Statement Links Three Common Cardiovascular Diseases to Cognitive Decline, Dementia
The statement includes an extensive research review and offers compelling evidence of the inextricable link between heart health and brain health, which investigators said underscores the benefit of early intervention.
The cumulative evidence “confirms that the trajectories of cardiac health and brain health are inextricably intertwined through modifiable and nonmodifiable factors,” the authors wrote.
Investigators say the findings reinforce the message that addressing cardiovascular health early in life may deter the onset or progression of cognitive impairment later on.
And the earlier this is done, the better, said lead author Fernando D. Testai, MD, PhD, a professor of neurology and the vascular neurology section head, Department of Neurology and Rehabilitation, University of Illinois, Chicago.
The statement was published online in Stroke.
Bridging the Research Gap
It’s well known that there’s a bidirectional relationship between heart and brain function. For example, heart failure can lead to decreased blood flow that can damage the brain, and stroke in some areas of the brain can affect the heart.
However, that’s only part of the puzzle and doesn’t address all the gaps in the understanding of how cardiovascular disease contributes to cognition, said Testai.
“What we’re trying to do here is to go one step further and describe other connections between the heart and the brain,” he said.
Investigators carried out an extensive PubMed search for heart failure, atrial fibrillation, and coronary heart disease. Researchers detailed the frequency of each condition, mechanisms by which they might cause cognitive impairment, and prospects for prevention and treatment to maintain brain health.
A recurring theme in the paper is the role of inflammation. Evidence shows there are “remarkable similarities in the inflammatory response that takes place,” with both cardiac disease and cognitive decline, said Testai.
Another potential shared mechanism relates to biomarkers, particularly amyloid, which is strongly linked to Alzheimer’s disease.
“But some studies show amyloid can also be present in the heart, especially in patients who have decreased ejection fraction,” said Testai.
Robust Heart-Brain Connection
The statement’s authors collected a substantial amount of evidence showing vascular risk factors such as hypertension and diabetes “can change how the brain processes and clears up amyloid,” Testai added.
The paper also provides a compilation of evidence of shared genetic predispositions when it comes to heart and brain disorders.
“We noticed that some genetic signatures that have historically been associated with heart disease seem to also correlate with structural changes in the brain. That means that at the end of the day, some patients may be born with a genetic predisposition to developing both conditions,” said Testai.
This indicates that the link between the two organs “begins as early as conception” and underscores the importance of adopting healthy lifestyle habits as early as possible, he added.
“That means you can avoid bad habits that eventually lead to hypertension, diabetes, and cholesterol, that eventually will lead to cardiac disease, which eventually will lead to stroke, which eventually will lead to cognitive decline,” Testai noted.
However, cardiovascular health is more complicated than having good genes and adhering to a healthy lifestyle. It’s not clear, for example, why some people who should be predisposed to developing heart disease do not develop it, something Testai refers to as enhanced “resilience.”
For example, Hispanic or Latino patients, who have relatively poor cardiovascular risk factor profiles, seem to be less susceptible to developing cardiac disease.
More Research Needed
While genetics may partly explain the paradox, Testai believes other protective factors are at play, including strong social support networks.
Testai referred to the AHA’s “Life’s Essential 8” — the eight components of cardiovascular health. These include a healthy diet, participation in physical activity, nicotine avoidance, healthy sleep, healthy weight, and healthy levels of blood lipids, blood glucose, and blood pressure.
More evidence is needed to show that effective management of cardiac disease positively affects cognition. Currently, cognitive measures are rarely included in studies examining various heart disease treatments, said Testai.
“There should probably be an effort to include brain health outcomes in some of the cardiac literature to make sure we can also measure whether the intervention in the heart leads to an advantage for the brain,” he said.
More research is also needed to determine whether immunomodulation has a beneficial effect on the cognitive trajectory, the statement’s authors noted.
They point out that the interpretation and generalizability of the studies described in the statement are confounded by disparate methodologies, including small sample sizes, cross-sectional designs, and underrepresentation of Black and Hispanic individuals.
‘An Important Step’
Reached for a comment, Natalia S. Rost, MD, Chief of the Stroke Division at Massachusetts General Hospital and professor of neurology at Harvard Medical School, both in Boston, said this paper “is an important step” in terms of pulling together pertinent information on the topic of heart-brain health.
She praised the authors for gathering evidence on risk factors related to atrial fibrillation, heart failure, and coronary heart disease, which is “the part of the puzzle that is controllable.”
This helps reinforce the message that controlling vascular risk factors helps with brain health, said Rost.
But brain health is “much more complex than just vascular health,” she said. It includes other elements such as freedom from epilepsy, migraine, traumatic brain injury, and adult learning disabilities.
No relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
The statement includes an extensive research review and offers compelling evidence of the inextricable link between heart health and brain health, which investigators said underscores the benefit of early intervention.
The cumulative evidence “confirms that the trajectories of cardiac health and brain health are inextricably intertwined through modifiable and nonmodifiable factors,” the authors wrote.
Investigators say the findings reinforce the message that addressing cardiovascular health early in life may deter the onset or progression of cognitive impairment later on.
And the earlier this is done, the better, said lead author Fernando D. Testai, MD, PhD, a professor of neurology and the vascular neurology section head, Department of Neurology and Rehabilitation, University of Illinois, Chicago.
The statement was published online in Stroke.
Bridging the Research Gap
It’s well known that there’s a bidirectional relationship between heart and brain function. For example, heart failure can lead to decreased blood flow that can damage the brain, and stroke in some areas of the brain can affect the heart.
However, that’s only part of the puzzle and doesn’t address all the gaps in the understanding of how cardiovascular disease contributes to cognition, said Testai.
“What we’re trying to do here is to go one step further and describe other connections between the heart and the brain,” he said.
Investigators carried out an extensive PubMed search for heart failure, atrial fibrillation, and coronary heart disease. Researchers detailed the frequency of each condition, mechanisms by which they might cause cognitive impairment, and prospects for prevention and treatment to maintain brain health.
A recurring theme in the paper is the role of inflammation. Evidence shows there are “remarkable similarities in the inflammatory response that takes place,” with both cardiac disease and cognitive decline, said Testai.
Another potential shared mechanism relates to biomarkers, particularly amyloid, which is strongly linked to Alzheimer’s disease.
“But some studies show amyloid can also be present in the heart, especially in patients who have decreased ejection fraction,” said Testai.
Robust Heart-Brain Connection
The statement’s authors collected a substantial amount of evidence showing vascular risk factors such as hypertension and diabetes “can change how the brain processes and clears up amyloid,” Testai added.
The paper also provides a compilation of evidence of shared genetic predispositions when it comes to heart and brain disorders.
“We noticed that some genetic signatures that have historically been associated with heart disease seem to also correlate with structural changes in the brain. That means that at the end of the day, some patients may be born with a genetic predisposition to developing both conditions,” said Testai.
This indicates that the link between the two organs “begins as early as conception” and underscores the importance of adopting healthy lifestyle habits as early as possible, he added.
“That means you can avoid bad habits that eventually lead to hypertension, diabetes, and cholesterol, that eventually will lead to cardiac disease, which eventually will lead to stroke, which eventually will lead to cognitive decline,” Testai noted.
However, cardiovascular health is more complicated than having good genes and adhering to a healthy lifestyle. It’s not clear, for example, why some people who should be predisposed to developing heart disease do not develop it, something Testai refers to as enhanced “resilience.”
For example, Hispanic or Latino patients, who have relatively poor cardiovascular risk factor profiles, seem to be less susceptible to developing cardiac disease.
More Research Needed
While genetics may partly explain the paradox, Testai believes other protective factors are at play, including strong social support networks.
Testai referred to the AHA’s “Life’s Essential 8” — the eight components of cardiovascular health. These include a healthy diet, participation in physical activity, nicotine avoidance, healthy sleep, healthy weight, and healthy levels of blood lipids, blood glucose, and blood pressure.
More evidence is needed to show that effective management of cardiac disease positively affects cognition. Currently, cognitive measures are rarely included in studies examining various heart disease treatments, said Testai.
“There should probably be an effort to include brain health outcomes in some of the cardiac literature to make sure we can also measure whether the intervention in the heart leads to an advantage for the brain,” he said.
More research is also needed to determine whether immunomodulation has a beneficial effect on the cognitive trajectory, the statement’s authors noted.
They point out that the interpretation and generalizability of the studies described in the statement are confounded by disparate methodologies, including small sample sizes, cross-sectional designs, and underrepresentation of Black and Hispanic individuals.
‘An Important Step’
Reached for a comment, Natalia S. Rost, MD, Chief of the Stroke Division at Massachusetts General Hospital and professor of neurology at Harvard Medical School, both in Boston, said this paper “is an important step” in terms of pulling together pertinent information on the topic of heart-brain health.
She praised the authors for gathering evidence on risk factors related to atrial fibrillation, heart failure, and coronary heart disease, which is “the part of the puzzle that is controllable.”
This helps reinforce the message that controlling vascular risk factors helps with brain health, said Rost.
But brain health is “much more complex than just vascular health,” she said. It includes other elements such as freedom from epilepsy, migraine, traumatic brain injury, and adult learning disabilities.
No relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
The statement includes an extensive research review and offers compelling evidence of the inextricable link between heart health and brain health, which investigators said underscores the benefit of early intervention.
The cumulative evidence “confirms that the trajectories of cardiac health and brain health are inextricably intertwined through modifiable and nonmodifiable factors,” the authors wrote.
Investigators say the findings reinforce the message that addressing cardiovascular health early in life may deter the onset or progression of cognitive impairment later on.
And the earlier this is done, the better, said lead author Fernando D. Testai, MD, PhD, a professor of neurology and the vascular neurology section head, Department of Neurology and Rehabilitation, University of Illinois, Chicago.
The statement was published online in Stroke.
Bridging the Research Gap
It’s well known that there’s a bidirectional relationship between heart and brain function. For example, heart failure can lead to decreased blood flow that can damage the brain, and stroke in some areas of the brain can affect the heart.
However, that’s only part of the puzzle and doesn’t address all the gaps in the understanding of how cardiovascular disease contributes to cognition, said Testai.
“What we’re trying to do here is to go one step further and describe other connections between the heart and the brain,” he said.
Investigators carried out an extensive PubMed search for heart failure, atrial fibrillation, and coronary heart disease. Researchers detailed the frequency of each condition, mechanisms by which they might cause cognitive impairment, and prospects for prevention and treatment to maintain brain health.
A recurring theme in the paper is the role of inflammation. Evidence shows there are “remarkable similarities in the inflammatory response that takes place,” with both cardiac disease and cognitive decline, said Testai.
Another potential shared mechanism relates to biomarkers, particularly amyloid, which is strongly linked to Alzheimer’s disease.
“But some studies show amyloid can also be present in the heart, especially in patients who have decreased ejection fraction,” said Testai.
Robust Heart-Brain Connection
The statement’s authors collected a substantial amount of evidence showing vascular risk factors such as hypertension and diabetes “can change how the brain processes and clears up amyloid,” Testai added.
The paper also provides a compilation of evidence of shared genetic predispositions when it comes to heart and brain disorders.
“We noticed that some genetic signatures that have historically been associated with heart disease seem to also correlate with structural changes in the brain. That means that at the end of the day, some patients may be born with a genetic predisposition to developing both conditions,” said Testai.
This indicates that the link between the two organs “begins as early as conception” and underscores the importance of adopting healthy lifestyle habits as early as possible, he added.
“That means you can avoid bad habits that eventually lead to hypertension, diabetes, and cholesterol, that eventually will lead to cardiac disease, which eventually will lead to stroke, which eventually will lead to cognitive decline,” Testai noted.
However, cardiovascular health is more complicated than having good genes and adhering to a healthy lifestyle. It’s not clear, for example, why some people who should be predisposed to developing heart disease do not develop it, something Testai refers to as enhanced “resilience.”
For example, Hispanic or Latino patients, who have relatively poor cardiovascular risk factor profiles, seem to be less susceptible to developing cardiac disease.
More Research Needed
While genetics may partly explain the paradox, Testai believes other protective factors are at play, including strong social support networks.
Testai referred to the AHA’s “Life’s Essential 8” — the eight components of cardiovascular health. These include a healthy diet, participation in physical activity, nicotine avoidance, healthy sleep, healthy weight, and healthy levels of blood lipids, blood glucose, and blood pressure.
More evidence is needed to show that effective management of cardiac disease positively affects cognition. Currently, cognitive measures are rarely included in studies examining various heart disease treatments, said Testai.
“There should probably be an effort to include brain health outcomes in some of the cardiac literature to make sure we can also measure whether the intervention in the heart leads to an advantage for the brain,” he said.
More research is also needed to determine whether immunomodulation has a beneficial effect on the cognitive trajectory, the statement’s authors noted.
They point out that the interpretation and generalizability of the studies described in the statement are confounded by disparate methodologies, including small sample sizes, cross-sectional designs, and underrepresentation of Black and Hispanic individuals.
‘An Important Step’
Reached for a comment, Natalia S. Rost, MD, Chief of the Stroke Division at Massachusetts General Hospital and professor of neurology at Harvard Medical School, both in Boston, said this paper “is an important step” in terms of pulling together pertinent information on the topic of heart-brain health.
She praised the authors for gathering evidence on risk factors related to atrial fibrillation, heart failure, and coronary heart disease, which is “the part of the puzzle that is controllable.”
This helps reinforce the message that controlling vascular risk factors helps with brain health, said Rost.
But brain health is “much more complex than just vascular health,” she said. It includes other elements such as freedom from epilepsy, migraine, traumatic brain injury, and adult learning disabilities.
No relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
FROM STROKE
Crisugabalin Alleviates Postherpetic Neuralgia Symptoms in Phase 3 Study
TOPLINE:
METHODOLOGY:
- Researchers conducted a phase 3 multicenter, double-blind study involving 366 patients in China (median age, 63 years; 52.7% men) with PHN with an average daily pain score (ADPS) of 4 or greater on the numeric pain rating scale who were randomly assigned to receive either crisugabalin 40 mg/d (n = 121), 80 mg/d (n = 121), or placebo (n = 124) for 12 weeks.
- Patients who did not experience any serious toxic effects in these 12 weeks entered a 14-week open-label extension phase and received crisugabalin 40 mg twice daily.
- The primary efficacy endpoint was the change in ADPS from baseline at week 12.
- Secondary efficacy endpoints included the proportion of patients achieving at least 30% and 50% reduction in ADPS at week 12; changes in the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analog Scale, and Average Daily Sleep Interference Scale scores at week 12; and change in the SF-MPQ Present Pain Intensity scores at weeks 12 and 26.
TAKEAWAY:
- At week 12, among those on crisugabalin 40 mg/d and 80 mg/d, there were significant reductions in ADPS compared with placebo (least squares mean [LSM] change from baseline, −2.2 and −2.6 vs −1.1, respectively; P < .001).
- A greater proportion of patients on crisugabalin 40 mg/d (61.2%) and 80 mg/d (54.5%) achieved 30% or greater reduction in ADPS (P < .001) than patients who received placebo (35.5%). Similarly, a 50% or greater reduction in ADPS was achieved by 37.2% of patients on crisugabalin 40 mg/d (P = .002) and 38% on 80 mg/d (P < .001), compared with 20.2% for placebo.
- Crisugabalin 40 mg/d and crisugabalin 80 mg/d were associated with greater reductions in the pain intensity at week 12 than placebo (LSM, −1.0 and −1.2 vs −0.5, respectively; P < .001). Similar patterns were noted for other pain-related measures at weeks 12 and 26.
- Serious treatment-emergent adverse events occurred in four patients in each group; only 2.4% of those on 40 mg/d and 1.6% on 80 mg/d discontinued treatment because of side effects.
IN PRACTICE:
“Crisugabalin 40 mg/d or crisugabalin 80 mg/d was well-tolerated and significantly improved ADPS compared to placebo,” the authors wrote, adding that “crisugabalin can be flexibly selected depending on individual patient response and tolerability at 40 mg/d or 80 mg/d.”
SOURCE:
The study was led by Daying Zhang, PhD, of the Department of Pain Medicine at The First Affiliated Hospital of Nanchang University, Nanchang, China. It was published online in JAMA Dermatology.
LIMITATIONS:
The findings may not be generalizable to the global population as the study population was limited to Chinese patients. The study only provided short-term efficacy and safety data on crisugabalin, lacked an active comparator, and did not reflect the standard of care observed in the United States or Europe, where oral tricyclic antidepressants, pregabalin, and the lidocaine patch are recommended as first-line therapies.
DISCLOSURES:
The study was sponsored and funded by Haisco Pharmaceutical. Dr. Zhang and another author reported receiving support from Haisco. Two authors are company employees.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a phase 3 multicenter, double-blind study involving 366 patients in China (median age, 63 years; 52.7% men) with PHN with an average daily pain score (ADPS) of 4 or greater on the numeric pain rating scale who were randomly assigned to receive either crisugabalin 40 mg/d (n = 121), 80 mg/d (n = 121), or placebo (n = 124) for 12 weeks.
- Patients who did not experience any serious toxic effects in these 12 weeks entered a 14-week open-label extension phase and received crisugabalin 40 mg twice daily.
- The primary efficacy endpoint was the change in ADPS from baseline at week 12.
- Secondary efficacy endpoints included the proportion of patients achieving at least 30% and 50% reduction in ADPS at week 12; changes in the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analog Scale, and Average Daily Sleep Interference Scale scores at week 12; and change in the SF-MPQ Present Pain Intensity scores at weeks 12 and 26.
TAKEAWAY:
- At week 12, among those on crisugabalin 40 mg/d and 80 mg/d, there were significant reductions in ADPS compared with placebo (least squares mean [LSM] change from baseline, −2.2 and −2.6 vs −1.1, respectively; P < .001).
- A greater proportion of patients on crisugabalin 40 mg/d (61.2%) and 80 mg/d (54.5%) achieved 30% or greater reduction in ADPS (P < .001) than patients who received placebo (35.5%). Similarly, a 50% or greater reduction in ADPS was achieved by 37.2% of patients on crisugabalin 40 mg/d (P = .002) and 38% on 80 mg/d (P < .001), compared with 20.2% for placebo.
- Crisugabalin 40 mg/d and crisugabalin 80 mg/d were associated with greater reductions in the pain intensity at week 12 than placebo (LSM, −1.0 and −1.2 vs −0.5, respectively; P < .001). Similar patterns were noted for other pain-related measures at weeks 12 and 26.
- Serious treatment-emergent adverse events occurred in four patients in each group; only 2.4% of those on 40 mg/d and 1.6% on 80 mg/d discontinued treatment because of side effects.
IN PRACTICE:
“Crisugabalin 40 mg/d or crisugabalin 80 mg/d was well-tolerated and significantly improved ADPS compared to placebo,” the authors wrote, adding that “crisugabalin can be flexibly selected depending on individual patient response and tolerability at 40 mg/d or 80 mg/d.”
SOURCE:
The study was led by Daying Zhang, PhD, of the Department of Pain Medicine at The First Affiliated Hospital of Nanchang University, Nanchang, China. It was published online in JAMA Dermatology.
LIMITATIONS:
The findings may not be generalizable to the global population as the study population was limited to Chinese patients. The study only provided short-term efficacy and safety data on crisugabalin, lacked an active comparator, and did not reflect the standard of care observed in the United States or Europe, where oral tricyclic antidepressants, pregabalin, and the lidocaine patch are recommended as first-line therapies.
DISCLOSURES:
The study was sponsored and funded by Haisco Pharmaceutical. Dr. Zhang and another author reported receiving support from Haisco. Two authors are company employees.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a phase 3 multicenter, double-blind study involving 366 patients in China (median age, 63 years; 52.7% men) with PHN with an average daily pain score (ADPS) of 4 or greater on the numeric pain rating scale who were randomly assigned to receive either crisugabalin 40 mg/d (n = 121), 80 mg/d (n = 121), or placebo (n = 124) for 12 weeks.
- Patients who did not experience any serious toxic effects in these 12 weeks entered a 14-week open-label extension phase and received crisugabalin 40 mg twice daily.
- The primary efficacy endpoint was the change in ADPS from baseline at week 12.
- Secondary efficacy endpoints included the proportion of patients achieving at least 30% and 50% reduction in ADPS at week 12; changes in the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analog Scale, and Average Daily Sleep Interference Scale scores at week 12; and change in the SF-MPQ Present Pain Intensity scores at weeks 12 and 26.
TAKEAWAY:
- At week 12, among those on crisugabalin 40 mg/d and 80 mg/d, there were significant reductions in ADPS compared with placebo (least squares mean [LSM] change from baseline, −2.2 and −2.6 vs −1.1, respectively; P < .001).
- A greater proportion of patients on crisugabalin 40 mg/d (61.2%) and 80 mg/d (54.5%) achieved 30% or greater reduction in ADPS (P < .001) than patients who received placebo (35.5%). Similarly, a 50% or greater reduction in ADPS was achieved by 37.2% of patients on crisugabalin 40 mg/d (P = .002) and 38% on 80 mg/d (P < .001), compared with 20.2% for placebo.
- Crisugabalin 40 mg/d and crisugabalin 80 mg/d were associated with greater reductions in the pain intensity at week 12 than placebo (LSM, −1.0 and −1.2 vs −0.5, respectively; P < .001). Similar patterns were noted for other pain-related measures at weeks 12 and 26.
- Serious treatment-emergent adverse events occurred in four patients in each group; only 2.4% of those on 40 mg/d and 1.6% on 80 mg/d discontinued treatment because of side effects.
IN PRACTICE:
“Crisugabalin 40 mg/d or crisugabalin 80 mg/d was well-tolerated and significantly improved ADPS compared to placebo,” the authors wrote, adding that “crisugabalin can be flexibly selected depending on individual patient response and tolerability at 40 mg/d or 80 mg/d.”
SOURCE:
The study was led by Daying Zhang, PhD, of the Department of Pain Medicine at The First Affiliated Hospital of Nanchang University, Nanchang, China. It was published online in JAMA Dermatology.
LIMITATIONS:
The findings may not be generalizable to the global population as the study population was limited to Chinese patients. The study only provided short-term efficacy and safety data on crisugabalin, lacked an active comparator, and did not reflect the standard of care observed in the United States or Europe, where oral tricyclic antidepressants, pregabalin, and the lidocaine patch are recommended as first-line therapies.
DISCLOSURES:
The study was sponsored and funded by Haisco Pharmaceutical. Dr. Zhang and another author reported receiving support from Haisco. Two authors are company employees.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Erenumab Reduces Nonopioid Medication Overuse Headache in Chronic Migraine
In a recent study of 6 monthly injections of 140 mg erenumab (Aimovig, Amgen), most patients with chronic migraine and nonopioid medication overuse headache (MOH) achieved remission. Published online in JAMA Neurology, the study is the first prospective, double-blind, randomized, placebo-controlled attempt to investigate patients with chronic migraine and MOH related to nonopioid medications, according to lead author Stewart J. Tepper, MD, and his coauthors.
Prior Studies Did Not Focus on MOH
Several prior phase 2 and 3 trials of calcitonin gene-related peptide (CGRP) ligand or receptor inhibitors that have been FDA-approved for migraine prevention have been performed. These drugs include erenumab, fremanezumab (Ajovy, Teva), galcanezumab (Emgality, Lilly), and eptinezumab (Vyepti, Lundbeck), for patients with and without medication overuse, said Alan M. Rapoport, MD, who was not involved with the new study. Dr. Rapoport is a clinical professor of neurology at the David Geffen School of Medicine of the University of California, in Los Angeles; past president of the International Headache Society; and founder and director emeritus of The New England Center for Headache in Stamford, Connecticut.
“But we could not call them patients with MOH because they weren’t studied prospectively, so that they had medication overuse according to International Classification of Headache Disorders (ICHD-3) criteria,” said Dr. Rapoport.
Phase 4, Randomized, Placebo-Controlled Trial
In the present clinical trial, investigators enrolled 584 patients with nonopioid MOH and history of failing at least one preventive treatment. After a 4-week baseline phase, researchers randomized patients 1:1:1 to 6 months’ treatment with erenumab 70 mg, erenumab 140 mg, or placebo.
Investigators defined remission as either of the following through months 4-6:
- < 10 mean monthly acute headache medication days per month (AHMD)
- < 14 mean monthly headache days (MHD)
In the primary analysis, 69.1% of patients in the 140 mg cohort achieved remission (P < .001) versus placebo. Remission rates in the 70 mg and the placebo cohorts were 60.3% (P < .13) and 52.6%, respectively. AHMD for the 140-mg, 70-mg, and placebo groups fell by 9.4, 7.8, and 6.6 days per month, respectively. Migraine Physical Function Impact Diary (non-EU sites) and Headache Impact Test-6 (EU sites) scores also showed greater improvement for patients treated with erenumab.
No new safety signals emerged, although erenumab-treated participants experienced 2-2.5 times as much COVID-19 disease.
Regarding the primary endpoint, said Dr. Rapoport, the 70-mg dose might also have yielded statistically significant improvement over placebo with a larger sample size. “I have seen that the higher dose of erenumab can be superior for efficacy than the lower in some of the double-blind trials,” he said. The 52.6% placebo response rate was rather high, he added, but not necessarily higher than in other migraine prevention trials.
“Placebo is a type of treatment,” Dr. Rapoport said. “It’s not as strong as the actual medication, which is specific for prevention, but it does work on the brain to some extent.”
He was more concerned, however, that authors did not counsel study patients about reducing or discontinuing their overused medications in a unified manner. Rather, it was left to individual investigators’ discretion, in different countries, as to whether to educate patients about the harms of medication overuse. “The fascinating aspect of this paper was that no patient was asked to detoxify from the overused medication,” said Dr. Rapoport, “and yet so many patients no longer had MOH at 6 months.”
Detox Versus No Detox
In a pioneering study of migraine medication overuse headache (then called rebound headache) published by Lee Kudrow, MD, in Advances in Neurology in 1982, patients who discontinued the overused medication fared much better than those who did not. Adding amitriptyline for migraine prevention further improved results, mostly in those who discontinued their overused medication.
Anticipating possible concerns, the authors wrote that their approach “may also be seen as a strength, as it represents a scenario closer to real life and avoids undue interference with the physician-patient relationship.” Indeed, said Dr. Rapoport, study results are perhaps more impressive because they were achieved through treatment with erenumab alone, without detoxification.
Managing Chronic Migraine and MOH
Until erenumab’s 2018 approval, migraine prevention options were limited to tricyclic antidepressants, beta blockers, and antiseizure medicines – though these medicines never seemed to work very well without detoxification, said Dr. Rapoport. Neurologists still use these categories for migraine prevention, he added, “because insurance companies insist that before we give the more expensive, newer medications like those that block CGRP, patients must fail 2 of those 3 categories of older medications which are not approved for chronic migraine.” Only onabotulinumtoxinA (Botox) is FDA-approved for chronic migraine. “There has been no head-to-head comparison of it and any of the monoclonal antibodies against CGRP,” he said.
In a March 2024 publication in Headache, the American Headache Society stated that requiring patients to fail older drugs is inappropriate, and that CGRP inhibitors, though costly, should be first-line for headache prevention. The key advantage of any drug that blocks CGRP in treating MOH is that unlike older drugs, CGRP inhibitors appear to work well even without detoxification, said Dr. Rapoport.
Additional study limitations included the possibility that the 24-week treatment period might not have allowed complete evaluation of long-term efficacy, the authors wrote. “These are usually pretty sick patients,” said Dr. Rapoport, who acknowledged the difficulty of keeping placebo patients off preventive medication altogether for 6 months. The study was extended to 12 months, and the results of an opiate overusers cohort also will be published.
Authors noted that according to a study published in Headache in 2022, most Americans with chronic migraine commonly go without preventive medications. Moreover, such medications do not always work. Accordingly, Dr. Rapoport said, the study duration was reasonable provided patients understood that they had a 33% chance of receiving no effective preventive medication over 6 months.
Extending the study’s month-long baseline period to 3 months before starting erenumab might have been helpful, he added, as that is the timeframe required to confirm MOH diagnosis according to ICHD-3. “However,” said Dr. Rapoport, “3 months with only usual medications, and then 1/3 of patients going 6-12 months with only placebo, would be tough for some patients.”
Dr. Rapoport reports no relevant financial conflicts.
In a recent study of 6 monthly injections of 140 mg erenumab (Aimovig, Amgen), most patients with chronic migraine and nonopioid medication overuse headache (MOH) achieved remission. Published online in JAMA Neurology, the study is the first prospective, double-blind, randomized, placebo-controlled attempt to investigate patients with chronic migraine and MOH related to nonopioid medications, according to lead author Stewart J. Tepper, MD, and his coauthors.
Prior Studies Did Not Focus on MOH
Several prior phase 2 and 3 trials of calcitonin gene-related peptide (CGRP) ligand or receptor inhibitors that have been FDA-approved for migraine prevention have been performed. These drugs include erenumab, fremanezumab (Ajovy, Teva), galcanezumab (Emgality, Lilly), and eptinezumab (Vyepti, Lundbeck), for patients with and without medication overuse, said Alan M. Rapoport, MD, who was not involved with the new study. Dr. Rapoport is a clinical professor of neurology at the David Geffen School of Medicine of the University of California, in Los Angeles; past president of the International Headache Society; and founder and director emeritus of The New England Center for Headache in Stamford, Connecticut.
“But we could not call them patients with MOH because they weren’t studied prospectively, so that they had medication overuse according to International Classification of Headache Disorders (ICHD-3) criteria,” said Dr. Rapoport.
Phase 4, Randomized, Placebo-Controlled Trial
In the present clinical trial, investigators enrolled 584 patients with nonopioid MOH and history of failing at least one preventive treatment. After a 4-week baseline phase, researchers randomized patients 1:1:1 to 6 months’ treatment with erenumab 70 mg, erenumab 140 mg, or placebo.
Investigators defined remission as either of the following through months 4-6:
- < 10 mean monthly acute headache medication days per month (AHMD)
- < 14 mean monthly headache days (MHD)
In the primary analysis, 69.1% of patients in the 140 mg cohort achieved remission (P < .001) versus placebo. Remission rates in the 70 mg and the placebo cohorts were 60.3% (P < .13) and 52.6%, respectively. AHMD for the 140-mg, 70-mg, and placebo groups fell by 9.4, 7.8, and 6.6 days per month, respectively. Migraine Physical Function Impact Diary (non-EU sites) and Headache Impact Test-6 (EU sites) scores also showed greater improvement for patients treated with erenumab.
No new safety signals emerged, although erenumab-treated participants experienced 2-2.5 times as much COVID-19 disease.
Regarding the primary endpoint, said Dr. Rapoport, the 70-mg dose might also have yielded statistically significant improvement over placebo with a larger sample size. “I have seen that the higher dose of erenumab can be superior for efficacy than the lower in some of the double-blind trials,” he said. The 52.6% placebo response rate was rather high, he added, but not necessarily higher than in other migraine prevention trials.
“Placebo is a type of treatment,” Dr. Rapoport said. “It’s not as strong as the actual medication, which is specific for prevention, but it does work on the brain to some extent.”
He was more concerned, however, that authors did not counsel study patients about reducing or discontinuing their overused medications in a unified manner. Rather, it was left to individual investigators’ discretion, in different countries, as to whether to educate patients about the harms of medication overuse. “The fascinating aspect of this paper was that no patient was asked to detoxify from the overused medication,” said Dr. Rapoport, “and yet so many patients no longer had MOH at 6 months.”
Detox Versus No Detox
In a pioneering study of migraine medication overuse headache (then called rebound headache) published by Lee Kudrow, MD, in Advances in Neurology in 1982, patients who discontinued the overused medication fared much better than those who did not. Adding amitriptyline for migraine prevention further improved results, mostly in those who discontinued their overused medication.
Anticipating possible concerns, the authors wrote that their approach “may also be seen as a strength, as it represents a scenario closer to real life and avoids undue interference with the physician-patient relationship.” Indeed, said Dr. Rapoport, study results are perhaps more impressive because they were achieved through treatment with erenumab alone, without detoxification.
Managing Chronic Migraine and MOH
Until erenumab’s 2018 approval, migraine prevention options were limited to tricyclic antidepressants, beta blockers, and antiseizure medicines – though these medicines never seemed to work very well without detoxification, said Dr. Rapoport. Neurologists still use these categories for migraine prevention, he added, “because insurance companies insist that before we give the more expensive, newer medications like those that block CGRP, patients must fail 2 of those 3 categories of older medications which are not approved for chronic migraine.” Only onabotulinumtoxinA (Botox) is FDA-approved for chronic migraine. “There has been no head-to-head comparison of it and any of the monoclonal antibodies against CGRP,” he said.
In a March 2024 publication in Headache, the American Headache Society stated that requiring patients to fail older drugs is inappropriate, and that CGRP inhibitors, though costly, should be first-line for headache prevention. The key advantage of any drug that blocks CGRP in treating MOH is that unlike older drugs, CGRP inhibitors appear to work well even without detoxification, said Dr. Rapoport.
Additional study limitations included the possibility that the 24-week treatment period might not have allowed complete evaluation of long-term efficacy, the authors wrote. “These are usually pretty sick patients,” said Dr. Rapoport, who acknowledged the difficulty of keeping placebo patients off preventive medication altogether for 6 months. The study was extended to 12 months, and the results of an opiate overusers cohort also will be published.
Authors noted that according to a study published in Headache in 2022, most Americans with chronic migraine commonly go without preventive medications. Moreover, such medications do not always work. Accordingly, Dr. Rapoport said, the study duration was reasonable provided patients understood that they had a 33% chance of receiving no effective preventive medication over 6 months.
Extending the study’s month-long baseline period to 3 months before starting erenumab might have been helpful, he added, as that is the timeframe required to confirm MOH diagnosis according to ICHD-3. “However,” said Dr. Rapoport, “3 months with only usual medications, and then 1/3 of patients going 6-12 months with only placebo, would be tough for some patients.”
Dr. Rapoport reports no relevant financial conflicts.
In a recent study of 6 monthly injections of 140 mg erenumab (Aimovig, Amgen), most patients with chronic migraine and nonopioid medication overuse headache (MOH) achieved remission. Published online in JAMA Neurology, the study is the first prospective, double-blind, randomized, placebo-controlled attempt to investigate patients with chronic migraine and MOH related to nonopioid medications, according to lead author Stewart J. Tepper, MD, and his coauthors.
Prior Studies Did Not Focus on MOH
Several prior phase 2 and 3 trials of calcitonin gene-related peptide (CGRP) ligand or receptor inhibitors that have been FDA-approved for migraine prevention have been performed. These drugs include erenumab, fremanezumab (Ajovy, Teva), galcanezumab (Emgality, Lilly), and eptinezumab (Vyepti, Lundbeck), for patients with and without medication overuse, said Alan M. Rapoport, MD, who was not involved with the new study. Dr. Rapoport is a clinical professor of neurology at the David Geffen School of Medicine of the University of California, in Los Angeles; past president of the International Headache Society; and founder and director emeritus of The New England Center for Headache in Stamford, Connecticut.
“But we could not call them patients with MOH because they weren’t studied prospectively, so that they had medication overuse according to International Classification of Headache Disorders (ICHD-3) criteria,” said Dr. Rapoport.
Phase 4, Randomized, Placebo-Controlled Trial
In the present clinical trial, investigators enrolled 584 patients with nonopioid MOH and history of failing at least one preventive treatment. After a 4-week baseline phase, researchers randomized patients 1:1:1 to 6 months’ treatment with erenumab 70 mg, erenumab 140 mg, or placebo.
Investigators defined remission as either of the following through months 4-6:
- < 10 mean monthly acute headache medication days per month (AHMD)
- < 14 mean monthly headache days (MHD)
In the primary analysis, 69.1% of patients in the 140 mg cohort achieved remission (P < .001) versus placebo. Remission rates in the 70 mg and the placebo cohorts were 60.3% (P < .13) and 52.6%, respectively. AHMD for the 140-mg, 70-mg, and placebo groups fell by 9.4, 7.8, and 6.6 days per month, respectively. Migraine Physical Function Impact Diary (non-EU sites) and Headache Impact Test-6 (EU sites) scores also showed greater improvement for patients treated with erenumab.
No new safety signals emerged, although erenumab-treated participants experienced 2-2.5 times as much COVID-19 disease.
Regarding the primary endpoint, said Dr. Rapoport, the 70-mg dose might also have yielded statistically significant improvement over placebo with a larger sample size. “I have seen that the higher dose of erenumab can be superior for efficacy than the lower in some of the double-blind trials,” he said. The 52.6% placebo response rate was rather high, he added, but not necessarily higher than in other migraine prevention trials.
“Placebo is a type of treatment,” Dr. Rapoport said. “It’s not as strong as the actual medication, which is specific for prevention, but it does work on the brain to some extent.”
He was more concerned, however, that authors did not counsel study patients about reducing or discontinuing their overused medications in a unified manner. Rather, it was left to individual investigators’ discretion, in different countries, as to whether to educate patients about the harms of medication overuse. “The fascinating aspect of this paper was that no patient was asked to detoxify from the overused medication,” said Dr. Rapoport, “and yet so many patients no longer had MOH at 6 months.”
Detox Versus No Detox
In a pioneering study of migraine medication overuse headache (then called rebound headache) published by Lee Kudrow, MD, in Advances in Neurology in 1982, patients who discontinued the overused medication fared much better than those who did not. Adding amitriptyline for migraine prevention further improved results, mostly in those who discontinued their overused medication.
Anticipating possible concerns, the authors wrote that their approach “may also be seen as a strength, as it represents a scenario closer to real life and avoids undue interference with the physician-patient relationship.” Indeed, said Dr. Rapoport, study results are perhaps more impressive because they were achieved through treatment with erenumab alone, without detoxification.
Managing Chronic Migraine and MOH
Until erenumab’s 2018 approval, migraine prevention options were limited to tricyclic antidepressants, beta blockers, and antiseizure medicines – though these medicines never seemed to work very well without detoxification, said Dr. Rapoport. Neurologists still use these categories for migraine prevention, he added, “because insurance companies insist that before we give the more expensive, newer medications like those that block CGRP, patients must fail 2 of those 3 categories of older medications which are not approved for chronic migraine.” Only onabotulinumtoxinA (Botox) is FDA-approved for chronic migraine. “There has been no head-to-head comparison of it and any of the monoclonal antibodies against CGRP,” he said.
In a March 2024 publication in Headache, the American Headache Society stated that requiring patients to fail older drugs is inappropriate, and that CGRP inhibitors, though costly, should be first-line for headache prevention. The key advantage of any drug that blocks CGRP in treating MOH is that unlike older drugs, CGRP inhibitors appear to work well even without detoxification, said Dr. Rapoport.
Additional study limitations included the possibility that the 24-week treatment period might not have allowed complete evaluation of long-term efficacy, the authors wrote. “These are usually pretty sick patients,” said Dr. Rapoport, who acknowledged the difficulty of keeping placebo patients off preventive medication altogether for 6 months. The study was extended to 12 months, and the results of an opiate overusers cohort also will be published.
Authors noted that according to a study published in Headache in 2022, most Americans with chronic migraine commonly go without preventive medications. Moreover, such medications do not always work. Accordingly, Dr. Rapoport said, the study duration was reasonable provided patients understood that they had a 33% chance of receiving no effective preventive medication over 6 months.
Extending the study’s month-long baseline period to 3 months before starting erenumab might have been helpful, he added, as that is the timeframe required to confirm MOH diagnosis according to ICHD-3. “However,” said Dr. Rapoport, “3 months with only usual medications, and then 1/3 of patients going 6-12 months with only placebo, would be tough for some patients.”
Dr. Rapoport reports no relevant financial conflicts.
FROM JAMA NEUROLOGY
Does Medicare Advantage Offer Higher-Value Chemotherapy?
TOPLINE:
METHODOLOGY:
- Private Medicare Advantage plans enroll more than half of the Medicare population, but it is unknown if or how the cost restrictions they impose affect chemotherapy, which accounts for a large portion of cancer care costs.
- Researchers conducted a cohort study using national Medicare data from January 2015 to December 2019 to look at Medicare Advantage enrollment and treatment patterns for patients with cancer receiving chemotherapy.
- The study included 96,501 Medicare Advantage enrollees and 206,274 traditional Medicare beneficiaries who initiated chemotherapy between January 2016 and December 2019 (mean age, ~73 years; ~56% women; Hispanic individuals, 15% and 8%; Black individuals, 15% and 8%; and White individuals, 75% and 86%, respectively).
- Resource use and care quality were measured during a 6-month period following chemotherapy initiation, and survival days were measured 18 months after beginning chemotherapy.
- Resource use measures included hospital inpatient services, outpatient care, prescription drugs, hospice services, and chemotherapy services. Quality measures included chemotherapy-related emergency visits and hospital admissions, as well as avoidable emergency visits and preventable hospitalizations.
TAKEAWAY:
- Medicare Advantage plans had lower resource use than traditional Medicare per enrollee with cancer undergoing chemotherapy ($8718 lower; 95% CI, $8343-$9094).
- The lower resource use was largely caused by fewer chemotherapy visits and less expensive chemotherapy per visit in Medicare Advantage plans ($5032 lower; 95% CI, $4772-$5293).
- Medicare Advantage enrollees had 2.5 percentage points fewer chemotherapy-related emergency department visits and 0.7 percentage points fewer chemotherapy-related hospitalizations than traditional Medicare beneficiaries.
- There was no clinically meaningful difference in survival between Medicare Advantage and traditional Medicare beneficiaries during the 18 months following chemotherapy initiation.
IN PRACTICE:
“Our new finding is that MA [Medicare Advantage] plans had lower resource use than TM [traditional Medicare] among enrollees with cancer undergoing chemotherapy — a serious condition managed by specialists and requiring expensive treatments. This suggests that MA’s cost advantages over TM are not limited to conditions for which low-cost primary care management can avoid costly services,” the authors wrote.
SOURCE:
The study was led by Yamini Kalidindi, PhD, McDermott+ Consulting, Washington, DC. It was published online on September 20, 2024, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2024.34707), with a commentary.
LIMITATIONS:
The study’s findings may be affected by unobserved patient characteristics despite the use of inverse-probability weighting. The exclusion of Medicare Advantage enrollees in contracts with incomplete encounter data limits the generalizability of the results. The study does not apply to beneficiaries without Part D drug coverage. Quality measures were limited to those available from claims and encounter data, lacking information on patients’ cancer stage. The 18-month measure of survival might not adequately capture survival differences associated with early-stage cancers. The study did not measure whether patient care followed recommended guidelines.
DISCLOSURES:
Various authors reported grants from the National Institute on Aging, the National Institutes of Health, The Commonwealth Fund, Arnold Ventures, the National Cancer Institute, the Department of Defense, and the National Institute of Health Care Management. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Private Medicare Advantage plans enroll more than half of the Medicare population, but it is unknown if or how the cost restrictions they impose affect chemotherapy, which accounts for a large portion of cancer care costs.
- Researchers conducted a cohort study using national Medicare data from January 2015 to December 2019 to look at Medicare Advantage enrollment and treatment patterns for patients with cancer receiving chemotherapy.
- The study included 96,501 Medicare Advantage enrollees and 206,274 traditional Medicare beneficiaries who initiated chemotherapy between January 2016 and December 2019 (mean age, ~73 years; ~56% women; Hispanic individuals, 15% and 8%; Black individuals, 15% and 8%; and White individuals, 75% and 86%, respectively).
- Resource use and care quality were measured during a 6-month period following chemotherapy initiation, and survival days were measured 18 months after beginning chemotherapy.
- Resource use measures included hospital inpatient services, outpatient care, prescription drugs, hospice services, and chemotherapy services. Quality measures included chemotherapy-related emergency visits and hospital admissions, as well as avoidable emergency visits and preventable hospitalizations.
TAKEAWAY:
- Medicare Advantage plans had lower resource use than traditional Medicare per enrollee with cancer undergoing chemotherapy ($8718 lower; 95% CI, $8343-$9094).
- The lower resource use was largely caused by fewer chemotherapy visits and less expensive chemotherapy per visit in Medicare Advantage plans ($5032 lower; 95% CI, $4772-$5293).
- Medicare Advantage enrollees had 2.5 percentage points fewer chemotherapy-related emergency department visits and 0.7 percentage points fewer chemotherapy-related hospitalizations than traditional Medicare beneficiaries.
- There was no clinically meaningful difference in survival between Medicare Advantage and traditional Medicare beneficiaries during the 18 months following chemotherapy initiation.
IN PRACTICE:
“Our new finding is that MA [Medicare Advantage] plans had lower resource use than TM [traditional Medicare] among enrollees with cancer undergoing chemotherapy — a serious condition managed by specialists and requiring expensive treatments. This suggests that MA’s cost advantages over TM are not limited to conditions for which low-cost primary care management can avoid costly services,” the authors wrote.
SOURCE:
The study was led by Yamini Kalidindi, PhD, McDermott+ Consulting, Washington, DC. It was published online on September 20, 2024, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2024.34707), with a commentary.
LIMITATIONS:
The study’s findings may be affected by unobserved patient characteristics despite the use of inverse-probability weighting. The exclusion of Medicare Advantage enrollees in contracts with incomplete encounter data limits the generalizability of the results. The study does not apply to beneficiaries without Part D drug coverage. Quality measures were limited to those available from claims and encounter data, lacking information on patients’ cancer stage. The 18-month measure of survival might not adequately capture survival differences associated with early-stage cancers. The study did not measure whether patient care followed recommended guidelines.
DISCLOSURES:
Various authors reported grants from the National Institute on Aging, the National Institutes of Health, The Commonwealth Fund, Arnold Ventures, the National Cancer Institute, the Department of Defense, and the National Institute of Health Care Management. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Private Medicare Advantage plans enroll more than half of the Medicare population, but it is unknown if or how the cost restrictions they impose affect chemotherapy, which accounts for a large portion of cancer care costs.
- Researchers conducted a cohort study using national Medicare data from January 2015 to December 2019 to look at Medicare Advantage enrollment and treatment patterns for patients with cancer receiving chemotherapy.
- The study included 96,501 Medicare Advantage enrollees and 206,274 traditional Medicare beneficiaries who initiated chemotherapy between January 2016 and December 2019 (mean age, ~73 years; ~56% women; Hispanic individuals, 15% and 8%; Black individuals, 15% and 8%; and White individuals, 75% and 86%, respectively).
- Resource use and care quality were measured during a 6-month period following chemotherapy initiation, and survival days were measured 18 months after beginning chemotherapy.
- Resource use measures included hospital inpatient services, outpatient care, prescription drugs, hospice services, and chemotherapy services. Quality measures included chemotherapy-related emergency visits and hospital admissions, as well as avoidable emergency visits and preventable hospitalizations.
TAKEAWAY:
- Medicare Advantage plans had lower resource use than traditional Medicare per enrollee with cancer undergoing chemotherapy ($8718 lower; 95% CI, $8343-$9094).
- The lower resource use was largely caused by fewer chemotherapy visits and less expensive chemotherapy per visit in Medicare Advantage plans ($5032 lower; 95% CI, $4772-$5293).
- Medicare Advantage enrollees had 2.5 percentage points fewer chemotherapy-related emergency department visits and 0.7 percentage points fewer chemotherapy-related hospitalizations than traditional Medicare beneficiaries.
- There was no clinically meaningful difference in survival between Medicare Advantage and traditional Medicare beneficiaries during the 18 months following chemotherapy initiation.
IN PRACTICE:
“Our new finding is that MA [Medicare Advantage] plans had lower resource use than TM [traditional Medicare] among enrollees with cancer undergoing chemotherapy — a serious condition managed by specialists and requiring expensive treatments. This suggests that MA’s cost advantages over TM are not limited to conditions for which low-cost primary care management can avoid costly services,” the authors wrote.
SOURCE:
The study was led by Yamini Kalidindi, PhD, McDermott+ Consulting, Washington, DC. It was published online on September 20, 2024, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2024.34707), with a commentary.
LIMITATIONS:
The study’s findings may be affected by unobserved patient characteristics despite the use of inverse-probability weighting. The exclusion of Medicare Advantage enrollees in contracts with incomplete encounter data limits the generalizability of the results. The study does not apply to beneficiaries without Part D drug coverage. Quality measures were limited to those available from claims and encounter data, lacking information on patients’ cancer stage. The 18-month measure of survival might not adequately capture survival differences associated with early-stage cancers. The study did not measure whether patient care followed recommended guidelines.
DISCLOSURES:
Various authors reported grants from the National Institute on Aging, the National Institutes of Health, The Commonwealth Fund, Arnold Ventures, the National Cancer Institute, the Department of Defense, and the National Institute of Health Care Management. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
AACR Cancer Progress Report: Big Strides and Big Gaps
The AACR’s 216-page report — an annual endeavor now in its 14th year — focused on the “tremendous” strides made in cancer care, prevention, and early detection and highlighted areas where more research and attention are warranted.
One key area is funding. For the first time since 2016, federal funding for the National Institutes of Health (NIH) and National Cancer Institute (NCI) decreased in the past year. The cuts followed nearly a decade of funding increases that saw the NIH budget expand by nearly $15 billion, and that allowed for a “rapid pace and broad scope” of advances in cancer, AACR’s chief executive officer Margaret Foti, MD, PhD, said during a press briefing.
These recent cuts “threaten to curtail the medical progress seen in recent years and stymie future advancements,” said Dr. Foti, who called on Congress to commit to funding cancer research at significant and consistent levels to “maintain the momentum of progress against cancer.”
Inside the Report: Big Progress
Overall, advances in prevention, early detection, and treatment have helped catch more cancers earlier and save lives.
According to the AACR report, the age-adjusted overall cancer death rate in the United States fell by 33% between 1991 and 2021, meaning about 4.1 million cancer deaths were averted. The overall cancer death rate for children and adolescents has declined by 24% in the past 2 decades. The 5-year relative survival rate for children diagnosed with cancer in the US has improved from 58% for those diagnosed in the mid-1970s to 85% for those diagnosed between 2013 and 2019.
The past fiscal year has seen many new approvals for cancer drugs, diagnostics, and screening tests. From July 1, 2023, to June 30, 2024, the Food and Drug Administration (FDA) approved 15 new anticancer therapeutics, as well as 15 new indications for previously approved agents, one new imaging agent, several artificial intelligence (AI) tools to improve early cancer detection and diagnosis, and two minimally invasive tests for assessing inherited cancer risk or early cancer detection, according to the report.
“Cancer diagnostics are becoming more sophisticated,” AACR president Patricia M. LoRusso, DO, PhD, said during the briefing. “New technologies, such as spatial transcriptomics, are helping us study tumors at a cellular level, and helping to unveil things that we did not initially even begin to understand or think of. AI-based approaches are beginning to transform cancer detection, diagnosis, clinical decision-making, and treatment response monitoring.”
The report also highlights the significant progress in many childhood and adolescent/young adult cancers, Dr. LoRusso noted. These include FDA approvals for two new molecularly targeted therapeutics: tovorafenib for children with certain types of brain tumor and repotrectinib for children with a wide array of cancer types that have a specific genetic alteration known as NTRK gene fusion. It also includes an expanded approval for eflornithine to reduce the risk for relapse in children with high-risk neuroblastoma.
“Decades — decades — of basic research discoveries, have led to these clinical breakthroughs,” she stressed. “These gains against cancer are because of the rapid progress in our ability to decode the cancer genome, which has opened new and innovative avenues for drug development.”
The Gaps
Even with progress in cancer prevention, early detection, and treatment, cancer remains a significant issue.
“In 2024, it is estimated that more than 2 million new cases of cancer will be diagnosed in the United States. More than 611,000 people will die from the disease,” according to the report.
The 2024 report shows that incidence rates for some cancers are increasing in the United States, including vaccine-preventable cancers such as human papillomavirus (HPV)–associated oral cancers and, in young adults, cervical cancers. A recent analysis also found that overall cervical cancer incidence among women aged 30-34 years increased by 2.5% a year between 2012 and 2019.
Furthermore, despite clear evidence demonstrating that the HPV vaccine reduces cervical cancer incidence, uptake has remained poor, with only 38.6% of US children and adolescents aged 9-17 years receiving at least one dose of the vaccine in 2022.
Early-onset cancers are also increasing. Rates of breast, colorectal, and other cancers are on the rise in adults younger than 50 years, the report noted.
The report also pointed to data that 40% of all cancer cases in the United States can be attributed to preventable factors, such as smoking, excess body weight, and alcohol. However, our understanding of these risk factors has improved. Excessive levels of alcohol consumption have, for instance, been shown to increase the risk for six different types of cancer: certain types of head and neck cancer, esophageal squamous cell carcinoma, and breast, colorectal, liver, and stomach cancers.
Financial toxicity remains prevalent as well.
The report explains that financial hardship following a cancer diagnosis is widespread, and the effects can last for years. In fact, more than 40% of patients can spend their entire life savings within the first 2 years of cancer treatment. Among adult survivors of childhood cancers, 20.7% had trouble paying their medical bills, 29.9% said they had been sent to debt collection for unpaid bills, 14.1% had forgone medical care, and 26.8% could not afford nutritious meals.
For young cancer survivors, the lifetime costs associated with a diagnosis of cancer are substantial, reaching an average of $259,324 per person.
On a global level, it is estimated that from 2020 to 2050, the cumulative economic burden of cancer will be $25.2 trillion.
The Path Forward
Despite these challenges, Dr. LoRusso said, “it is unquestionable that we are in a time of unparalleled opportunities in cancer research.
“I am excited about what the future holds for cancer research, and especially for patient care,” she said.
However, funding commitments are needed to avoid impeding this momentum and losing a “talented and creative young workforce” that has brought new ideas and new technologies to the table.
Continued robust funding will help “to markedly improve cancer care, increase cancer survivorship, spur economic growth, and maintain the United States’ position as the global leader in science and medical research,” she added.
The AACR report specifically calls on Congress to:
- Appropriate at least $51.3 billion in fiscal year 2025 for the base budget of the NIH and at least $7.934 billion for the NCI.
- Provide $3.6 billion in dedicated funding for Cancer Moonshot activities through fiscal year 2026 in addition to other funding, consistent with the President’s fiscal year 2025 budget.
- Appropriate at least $472.4 million in fiscal year 2025 for the CDC’s Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
- Allocate $55 million in funding for the Oncology Center of Excellence at FDA in fiscal year 2025 to provide regulators with the staff and tools necessary to conduct expedited review of cancer-related medical products.
By working together with Congress and other stakeholders, “we will be able to accelerate the pace of progress and make major strides toward the lifesaving goal of preventing and curing all cancers at the earliest possible time,” Dr. Foti said. “I believe if we do that ... one day we will win this war on cancer.”
A version of this article first appeared on Medscape.com.
The AACR’s 216-page report — an annual endeavor now in its 14th year — focused on the “tremendous” strides made in cancer care, prevention, and early detection and highlighted areas where more research and attention are warranted.
One key area is funding. For the first time since 2016, federal funding for the National Institutes of Health (NIH) and National Cancer Institute (NCI) decreased in the past year. The cuts followed nearly a decade of funding increases that saw the NIH budget expand by nearly $15 billion, and that allowed for a “rapid pace and broad scope” of advances in cancer, AACR’s chief executive officer Margaret Foti, MD, PhD, said during a press briefing.
These recent cuts “threaten to curtail the medical progress seen in recent years and stymie future advancements,” said Dr. Foti, who called on Congress to commit to funding cancer research at significant and consistent levels to “maintain the momentum of progress against cancer.”
Inside the Report: Big Progress
Overall, advances in prevention, early detection, and treatment have helped catch more cancers earlier and save lives.
According to the AACR report, the age-adjusted overall cancer death rate in the United States fell by 33% between 1991 and 2021, meaning about 4.1 million cancer deaths were averted. The overall cancer death rate for children and adolescents has declined by 24% in the past 2 decades. The 5-year relative survival rate for children diagnosed with cancer in the US has improved from 58% for those diagnosed in the mid-1970s to 85% for those diagnosed between 2013 and 2019.
The past fiscal year has seen many new approvals for cancer drugs, diagnostics, and screening tests. From July 1, 2023, to June 30, 2024, the Food and Drug Administration (FDA) approved 15 new anticancer therapeutics, as well as 15 new indications for previously approved agents, one new imaging agent, several artificial intelligence (AI) tools to improve early cancer detection and diagnosis, and two minimally invasive tests for assessing inherited cancer risk or early cancer detection, according to the report.
“Cancer diagnostics are becoming more sophisticated,” AACR president Patricia M. LoRusso, DO, PhD, said during the briefing. “New technologies, such as spatial transcriptomics, are helping us study tumors at a cellular level, and helping to unveil things that we did not initially even begin to understand or think of. AI-based approaches are beginning to transform cancer detection, diagnosis, clinical decision-making, and treatment response monitoring.”
The report also highlights the significant progress in many childhood and adolescent/young adult cancers, Dr. LoRusso noted. These include FDA approvals for two new molecularly targeted therapeutics: tovorafenib for children with certain types of brain tumor and repotrectinib for children with a wide array of cancer types that have a specific genetic alteration known as NTRK gene fusion. It also includes an expanded approval for eflornithine to reduce the risk for relapse in children with high-risk neuroblastoma.
“Decades — decades — of basic research discoveries, have led to these clinical breakthroughs,” she stressed. “These gains against cancer are because of the rapid progress in our ability to decode the cancer genome, which has opened new and innovative avenues for drug development.”
The Gaps
Even with progress in cancer prevention, early detection, and treatment, cancer remains a significant issue.
“In 2024, it is estimated that more than 2 million new cases of cancer will be diagnosed in the United States. More than 611,000 people will die from the disease,” according to the report.
The 2024 report shows that incidence rates for some cancers are increasing in the United States, including vaccine-preventable cancers such as human papillomavirus (HPV)–associated oral cancers and, in young adults, cervical cancers. A recent analysis also found that overall cervical cancer incidence among women aged 30-34 years increased by 2.5% a year between 2012 and 2019.
Furthermore, despite clear evidence demonstrating that the HPV vaccine reduces cervical cancer incidence, uptake has remained poor, with only 38.6% of US children and adolescents aged 9-17 years receiving at least one dose of the vaccine in 2022.
Early-onset cancers are also increasing. Rates of breast, colorectal, and other cancers are on the rise in adults younger than 50 years, the report noted.
The report also pointed to data that 40% of all cancer cases in the United States can be attributed to preventable factors, such as smoking, excess body weight, and alcohol. However, our understanding of these risk factors has improved. Excessive levels of alcohol consumption have, for instance, been shown to increase the risk for six different types of cancer: certain types of head and neck cancer, esophageal squamous cell carcinoma, and breast, colorectal, liver, and stomach cancers.
Financial toxicity remains prevalent as well.
The report explains that financial hardship following a cancer diagnosis is widespread, and the effects can last for years. In fact, more than 40% of patients can spend their entire life savings within the first 2 years of cancer treatment. Among adult survivors of childhood cancers, 20.7% had trouble paying their medical bills, 29.9% said they had been sent to debt collection for unpaid bills, 14.1% had forgone medical care, and 26.8% could not afford nutritious meals.
For young cancer survivors, the lifetime costs associated with a diagnosis of cancer are substantial, reaching an average of $259,324 per person.
On a global level, it is estimated that from 2020 to 2050, the cumulative economic burden of cancer will be $25.2 trillion.
The Path Forward
Despite these challenges, Dr. LoRusso said, “it is unquestionable that we are in a time of unparalleled opportunities in cancer research.
“I am excited about what the future holds for cancer research, and especially for patient care,” she said.
However, funding commitments are needed to avoid impeding this momentum and losing a “talented and creative young workforce” that has brought new ideas and new technologies to the table.
Continued robust funding will help “to markedly improve cancer care, increase cancer survivorship, spur economic growth, and maintain the United States’ position as the global leader in science and medical research,” she added.
The AACR report specifically calls on Congress to:
- Appropriate at least $51.3 billion in fiscal year 2025 for the base budget of the NIH and at least $7.934 billion for the NCI.
- Provide $3.6 billion in dedicated funding for Cancer Moonshot activities through fiscal year 2026 in addition to other funding, consistent with the President’s fiscal year 2025 budget.
- Appropriate at least $472.4 million in fiscal year 2025 for the CDC’s Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
- Allocate $55 million in funding for the Oncology Center of Excellence at FDA in fiscal year 2025 to provide regulators with the staff and tools necessary to conduct expedited review of cancer-related medical products.
By working together with Congress and other stakeholders, “we will be able to accelerate the pace of progress and make major strides toward the lifesaving goal of preventing and curing all cancers at the earliest possible time,” Dr. Foti said. “I believe if we do that ... one day we will win this war on cancer.”
A version of this article first appeared on Medscape.com.
The AACR’s 216-page report — an annual endeavor now in its 14th year — focused on the “tremendous” strides made in cancer care, prevention, and early detection and highlighted areas where more research and attention are warranted.
One key area is funding. For the first time since 2016, federal funding for the National Institutes of Health (NIH) and National Cancer Institute (NCI) decreased in the past year. The cuts followed nearly a decade of funding increases that saw the NIH budget expand by nearly $15 billion, and that allowed for a “rapid pace and broad scope” of advances in cancer, AACR’s chief executive officer Margaret Foti, MD, PhD, said during a press briefing.
These recent cuts “threaten to curtail the medical progress seen in recent years and stymie future advancements,” said Dr. Foti, who called on Congress to commit to funding cancer research at significant and consistent levels to “maintain the momentum of progress against cancer.”
Inside the Report: Big Progress
Overall, advances in prevention, early detection, and treatment have helped catch more cancers earlier and save lives.
According to the AACR report, the age-adjusted overall cancer death rate in the United States fell by 33% between 1991 and 2021, meaning about 4.1 million cancer deaths were averted. The overall cancer death rate for children and adolescents has declined by 24% in the past 2 decades. The 5-year relative survival rate for children diagnosed with cancer in the US has improved from 58% for those diagnosed in the mid-1970s to 85% for those diagnosed between 2013 and 2019.
The past fiscal year has seen many new approvals for cancer drugs, diagnostics, and screening tests. From July 1, 2023, to June 30, 2024, the Food and Drug Administration (FDA) approved 15 new anticancer therapeutics, as well as 15 new indications for previously approved agents, one new imaging agent, several artificial intelligence (AI) tools to improve early cancer detection and diagnosis, and two minimally invasive tests for assessing inherited cancer risk or early cancer detection, according to the report.
“Cancer diagnostics are becoming more sophisticated,” AACR president Patricia M. LoRusso, DO, PhD, said during the briefing. “New technologies, such as spatial transcriptomics, are helping us study tumors at a cellular level, and helping to unveil things that we did not initially even begin to understand or think of. AI-based approaches are beginning to transform cancer detection, diagnosis, clinical decision-making, and treatment response monitoring.”
The report also highlights the significant progress in many childhood and adolescent/young adult cancers, Dr. LoRusso noted. These include FDA approvals for two new molecularly targeted therapeutics: tovorafenib for children with certain types of brain tumor and repotrectinib for children with a wide array of cancer types that have a specific genetic alteration known as NTRK gene fusion. It also includes an expanded approval for eflornithine to reduce the risk for relapse in children with high-risk neuroblastoma.
“Decades — decades — of basic research discoveries, have led to these clinical breakthroughs,” she stressed. “These gains against cancer are because of the rapid progress in our ability to decode the cancer genome, which has opened new and innovative avenues for drug development.”
The Gaps
Even with progress in cancer prevention, early detection, and treatment, cancer remains a significant issue.
“In 2024, it is estimated that more than 2 million new cases of cancer will be diagnosed in the United States. More than 611,000 people will die from the disease,” according to the report.
The 2024 report shows that incidence rates for some cancers are increasing in the United States, including vaccine-preventable cancers such as human papillomavirus (HPV)–associated oral cancers and, in young adults, cervical cancers. A recent analysis also found that overall cervical cancer incidence among women aged 30-34 years increased by 2.5% a year between 2012 and 2019.
Furthermore, despite clear evidence demonstrating that the HPV vaccine reduces cervical cancer incidence, uptake has remained poor, with only 38.6% of US children and adolescents aged 9-17 years receiving at least one dose of the vaccine in 2022.
Early-onset cancers are also increasing. Rates of breast, colorectal, and other cancers are on the rise in adults younger than 50 years, the report noted.
The report also pointed to data that 40% of all cancer cases in the United States can be attributed to preventable factors, such as smoking, excess body weight, and alcohol. However, our understanding of these risk factors has improved. Excessive levels of alcohol consumption have, for instance, been shown to increase the risk for six different types of cancer: certain types of head and neck cancer, esophageal squamous cell carcinoma, and breast, colorectal, liver, and stomach cancers.
Financial toxicity remains prevalent as well.
The report explains that financial hardship following a cancer diagnosis is widespread, and the effects can last for years. In fact, more than 40% of patients can spend their entire life savings within the first 2 years of cancer treatment. Among adult survivors of childhood cancers, 20.7% had trouble paying their medical bills, 29.9% said they had been sent to debt collection for unpaid bills, 14.1% had forgone medical care, and 26.8% could not afford nutritious meals.
For young cancer survivors, the lifetime costs associated with a diagnosis of cancer are substantial, reaching an average of $259,324 per person.
On a global level, it is estimated that from 2020 to 2050, the cumulative economic burden of cancer will be $25.2 trillion.
The Path Forward
Despite these challenges, Dr. LoRusso said, “it is unquestionable that we are in a time of unparalleled opportunities in cancer research.
“I am excited about what the future holds for cancer research, and especially for patient care,” she said.
However, funding commitments are needed to avoid impeding this momentum and losing a “talented and creative young workforce” that has brought new ideas and new technologies to the table.
Continued robust funding will help “to markedly improve cancer care, increase cancer survivorship, spur economic growth, and maintain the United States’ position as the global leader in science and medical research,” she added.
The AACR report specifically calls on Congress to:
- Appropriate at least $51.3 billion in fiscal year 2025 for the base budget of the NIH and at least $7.934 billion for the NCI.
- Provide $3.6 billion in dedicated funding for Cancer Moonshot activities through fiscal year 2026 in addition to other funding, consistent with the President’s fiscal year 2025 budget.
- Appropriate at least $472.4 million in fiscal year 2025 for the CDC’s Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
- Allocate $55 million in funding for the Oncology Center of Excellence at FDA in fiscal year 2025 to provide regulators with the staff and tools necessary to conduct expedited review of cancer-related medical products.
By working together with Congress and other stakeholders, “we will be able to accelerate the pace of progress and make major strides toward the lifesaving goal of preventing and curing all cancers at the earliest possible time,” Dr. Foti said. “I believe if we do that ... one day we will win this war on cancer.”
A version of this article first appeared on Medscape.com.
Triptans Trump Newer, More Expensive Meds for Acute Migraine
new research suggested.
Results of a large systematic review and meta-analysis showed that eletriptan, rizatriptan, sumatriptan, and zolmitriptan were more effective than lasmiditan, rimegepant, and ubrogepant, which investigators found were as effective as nonsteroidal anti-inflammatory drugs (NSAIDs).
International guidelines generally endorse NSAIDs as the first-line treatment for migraine and recommend triptans for moderate to severe episodes or when the response to NSAIDs is insufficient.
However, based on the study’s findings, these four triptans should be considered the treatment of choice for migraine, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry at the University of Oxford in England and director of the Oxford Health Clinical Research Facility, told a press briefing.
The investigators added that these particular triptans should be “included in the WHO [World Health Organization] List of Essential Medicines to promote global accessibility and uniform standards of care.”
The study was published online in The BMJ.
Filling the Knowledge Gap
To date, almost all migraine studies have compared migraine drugs with placebo, so there’s a knowledge gap, said Dr. Cipriani. As a result, “there’s no clear consensus among experts and guidelines about which specific drug classes should be prescribed initially, and this is a clinical problem.”
The researchers pointed out that, in recent years, lasmiditan and gepants have been introduced as further treatment options, especially for patients in whom triptans are contraindicated because of their potential vasoconstrictive effects and higher risk for ischemic events.
The analysis included 137 double-blind, randomized, controlled trials that were primarily sponsored by the pharmaceutical industry. It included 89,445 adult outpatients with migraine (mean age, 40.3 years; 85.6% women).
Only drugs licensed for migraine or headache that are recommended in at least one country were included. Researchers divided these 17 drugs into five categories: Antipyretics (paracetamol), ditans (lasmiditan), gepants (rimegepant and ubrogepant), NSAIDs (acetylsalicylic acid, celecoxib, diclofenac potassium, ibuprofen, naproxen sodium, and phenazone), and triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan).
The study’s primary outcomes were freedom from pain at 2 hours and at 2-24 hours, without the use of rescue drugs.
Investigators used sumatriptan as the reference intervention because it is the most commonly prescribed migraine drug and is included in the WHO Model Lists of Essential Medicines.
The study showed all active interventions were better than placebo for pain freedom at 2 hours; with the exception of paracetamol and naratriptan, all were better for sustained pain freedom from 2 to 24 hours.
When the active interventions were compared with each other, eletriptan outperformed other drugs for achieving pain freedom at 2 hours. It was followed by rizatriptan, sumatriptan, and zolmitriptan (odds ratio [OR], 1.35-3.01). For sustained pain freedom up to 24 hours, the most efficacious interventions were eletriptan (OR, 1.41-2.73) and ibuprofen (OR, 3.16-4.82).
As for secondary efficacy outcomes, in head-to-head comparisons, eletriptan was superior to nearly all other active interventions for pain relief at 2 hours and for the use of rescue drugs.
As for adverse events, dizziness was more commonly associated with lasmiditan, eletriptan, sumatriptan, and zolmitriptan, while fatigue and sedation occurred more frequently with eletriptan and lasmiditan. Nausea was more often associated with lasmiditan, sumatriptan, zolmitriptan, and ubrogepant. Eletriptan was the only intervention most frequently associated with chest pain or discomfort.
Need to Update Guidelines?
Considering the new results, Dr. Cipriani and study coauthor Messoud Ashina, MD, PhD, professor of neurology, University of Copenhagen in Denmark, said clinical guidelines for acute migraine management should be updated.
While triptans are contraindicated in patients with vascular disease, the researchers noted that “cerebrovascular events may present primarily as migraine-like headaches, and misdiagnosis of transient ischemic attack and minor stroke as migraine is not rare.”
Recently, lasmiditan, rimegepant, and ubrogepant — which are not associated with vasoconstrictive effects — have been promoted as alternatives in patients for whom triptans are contraindicated or not tolerated. But the high costs of these drugs put them out of reach for some patients, the investigators noted.
Triptans are widely underutilized, Dr. Ashina noted during the press briefing. Current use ranges from 17% to 22% in the United States and from 3% to 22.5% in Europe.
The investigators said that triptans have been shown to be superior and should be promoted globally, adding that the limited access and substantial underutilization of these medications are “missed opportunities to offer more effective treatments.”
The new results underscore the importance of head-to-head trials, which is the gold standard, said Dr. Cipriani.
The investigators noted that the study’s main limitation was the quality of the data, which was deemed to be low, or very low, for most comparisons. Other potential limitations included lack of individual patient data; exclusion of combination drugs; inclusion of only oral treatments; and not considering type of oral formulation, consistency in response across migraine episodes, or cost-effectiveness.
The study also did not cover important clinical issues that might inform treatment decision-making, including drug overuse headache or potential withdrawal symptoms. And the authors were unable to quantify some outcomes, such as global functioning.
‘Best Profile’?
Reached for comment, Neurologist Nina Riggins, MD, PhD, Headache Center of Excellence, Palo Alto VA Medical Center in California, praised the authors for a “great job” of bringing attention to the topic.
However, she noted that the investigators’ characterization of the four triptans as having the “best profile” for acute migraine gave her pause.
“Calling triptans the medication with the ‘best profile’ might be not applicable in many cases,” she said. For example, those who need acute medication more than two to three times a week in addition to those with cardiovascular contraindications to triptans may fall outside of that category.
Dr. Riggins said that “it makes sense” that longer-acting triptans like frovatriptan and naratriptan may not rank highly for efficacy within the first 2 hours. However, these agents likely offer a superior therapeutic profile in specific contexts, such as menstrual-related migraine.
In addition, while triptans are known to cause medication overuse headache, this may not be the case with gepants, she noted.
In a release from the Science Media Center, a nonprofit organization promoting voices and views of the scientific community, Eloísa Rubio-Beltrán, PhD, research associate with The Migraine Trust at the Wolfson Sensory, Pain and Regeneration Centre, King’s College London in England, said the findings should affect migraine treatment guidelines.
“As the study highlights, due to their high efficacy and low cost, triptans should be the first-line treatment option for the acute treatment of migraine. These results should inform treatment guidelines and support the inclusion of the best performing triptans into the List of Essential Medicines, to optimize treatment, allowing patients to access more efficacious options,” said Dr. Rubio-Beltrán.
It is also important to note that gepants and ditans were developed to offer alternatives for patients who show no improvement from triptans, she added.
She pointed out that these medications were not developed as a substitute for triptans, but rather to expand the number of treatment options for migraine.
“Nonetheless,” she added, “this study highlights the need for further research on the pathophysiology of migraine, which will allow the discovery of novel targets, and thus, novel treatments options that will benefit all patient populations.”
The study was funded by the NIHR Oxford Health Biomedical Research Centre and the Lundbeck Foundation. Dr. Cipriani reported receiving research, educational, and consultancy fees from Italian Network for Pediatric Clinical Trials, Fondazione Cariplo, Lundbeck, and Angelini Pharma. Dr. Ashina is a consultant, speaker, or scientific adviser for AbbVie, Amgen, AstraZeneca, Eli Lilly, GSK, Lundbeck, Novartis, Pfizer, and Teva; is the past president of the International Headache Society; and an associate editor of The Journal of Headache and Pain and Brain. Dr. Riggins has consulted for Gerson Lehrman Group; participated in compensated work with AcademicCME and Association of Migraine Disorders; was a principal investigator on research with electroCore, Theranica, and Eli Lilly; serves on advisory boards for Theranica, Teva, Lundbeck, Amneal Pharmaceuticals, NeurologyLive, and Miles for Migraine; and is a project advisor for Clinical Awareness Initiative with Clinical Neurological Society of America. Dr. Rubio-Beltrán reported serving as a junior editorial board member of The Journal of Headache and Pain and a junior representative of the International Headache Society; receiving research support from The Migraine Trust, Eli Lilly, CoLucid Pharmaceuticals, Amgen, Novartis, and Kallyope; and receiving travel support from CoLucid Pharmaceuticals, Allergan, and Novartis.
A version of this article first appeared on Medscape.com.
new research suggested.
Results of a large systematic review and meta-analysis showed that eletriptan, rizatriptan, sumatriptan, and zolmitriptan were more effective than lasmiditan, rimegepant, and ubrogepant, which investigators found were as effective as nonsteroidal anti-inflammatory drugs (NSAIDs).
International guidelines generally endorse NSAIDs as the first-line treatment for migraine and recommend triptans for moderate to severe episodes or when the response to NSAIDs is insufficient.
However, based on the study’s findings, these four triptans should be considered the treatment of choice for migraine, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry at the University of Oxford in England and director of the Oxford Health Clinical Research Facility, told a press briefing.
The investigators added that these particular triptans should be “included in the WHO [World Health Organization] List of Essential Medicines to promote global accessibility and uniform standards of care.”
The study was published online in The BMJ.
Filling the Knowledge Gap
To date, almost all migraine studies have compared migraine drugs with placebo, so there’s a knowledge gap, said Dr. Cipriani. As a result, “there’s no clear consensus among experts and guidelines about which specific drug classes should be prescribed initially, and this is a clinical problem.”
The researchers pointed out that, in recent years, lasmiditan and gepants have been introduced as further treatment options, especially for patients in whom triptans are contraindicated because of their potential vasoconstrictive effects and higher risk for ischemic events.
The analysis included 137 double-blind, randomized, controlled trials that were primarily sponsored by the pharmaceutical industry. It included 89,445 adult outpatients with migraine (mean age, 40.3 years; 85.6% women).
Only drugs licensed for migraine or headache that are recommended in at least one country were included. Researchers divided these 17 drugs into five categories: Antipyretics (paracetamol), ditans (lasmiditan), gepants (rimegepant and ubrogepant), NSAIDs (acetylsalicylic acid, celecoxib, diclofenac potassium, ibuprofen, naproxen sodium, and phenazone), and triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan).
The study’s primary outcomes were freedom from pain at 2 hours and at 2-24 hours, without the use of rescue drugs.
Investigators used sumatriptan as the reference intervention because it is the most commonly prescribed migraine drug and is included in the WHO Model Lists of Essential Medicines.
The study showed all active interventions were better than placebo for pain freedom at 2 hours; with the exception of paracetamol and naratriptan, all were better for sustained pain freedom from 2 to 24 hours.
When the active interventions were compared with each other, eletriptan outperformed other drugs for achieving pain freedom at 2 hours. It was followed by rizatriptan, sumatriptan, and zolmitriptan (odds ratio [OR], 1.35-3.01). For sustained pain freedom up to 24 hours, the most efficacious interventions were eletriptan (OR, 1.41-2.73) and ibuprofen (OR, 3.16-4.82).
As for secondary efficacy outcomes, in head-to-head comparisons, eletriptan was superior to nearly all other active interventions for pain relief at 2 hours and for the use of rescue drugs.
As for adverse events, dizziness was more commonly associated with lasmiditan, eletriptan, sumatriptan, and zolmitriptan, while fatigue and sedation occurred more frequently with eletriptan and lasmiditan. Nausea was more often associated with lasmiditan, sumatriptan, zolmitriptan, and ubrogepant. Eletriptan was the only intervention most frequently associated with chest pain or discomfort.
Need to Update Guidelines?
Considering the new results, Dr. Cipriani and study coauthor Messoud Ashina, MD, PhD, professor of neurology, University of Copenhagen in Denmark, said clinical guidelines for acute migraine management should be updated.
While triptans are contraindicated in patients with vascular disease, the researchers noted that “cerebrovascular events may present primarily as migraine-like headaches, and misdiagnosis of transient ischemic attack and minor stroke as migraine is not rare.”
Recently, lasmiditan, rimegepant, and ubrogepant — which are not associated with vasoconstrictive effects — have been promoted as alternatives in patients for whom triptans are contraindicated or not tolerated. But the high costs of these drugs put them out of reach for some patients, the investigators noted.
Triptans are widely underutilized, Dr. Ashina noted during the press briefing. Current use ranges from 17% to 22% in the United States and from 3% to 22.5% in Europe.
The investigators said that triptans have been shown to be superior and should be promoted globally, adding that the limited access and substantial underutilization of these medications are “missed opportunities to offer more effective treatments.”
The new results underscore the importance of head-to-head trials, which is the gold standard, said Dr. Cipriani.
The investigators noted that the study’s main limitation was the quality of the data, which was deemed to be low, or very low, for most comparisons. Other potential limitations included lack of individual patient data; exclusion of combination drugs; inclusion of only oral treatments; and not considering type of oral formulation, consistency in response across migraine episodes, or cost-effectiveness.
The study also did not cover important clinical issues that might inform treatment decision-making, including drug overuse headache or potential withdrawal symptoms. And the authors were unable to quantify some outcomes, such as global functioning.
‘Best Profile’?
Reached for comment, Neurologist Nina Riggins, MD, PhD, Headache Center of Excellence, Palo Alto VA Medical Center in California, praised the authors for a “great job” of bringing attention to the topic.
However, she noted that the investigators’ characterization of the four triptans as having the “best profile” for acute migraine gave her pause.
“Calling triptans the medication with the ‘best profile’ might be not applicable in many cases,” she said. For example, those who need acute medication more than two to three times a week in addition to those with cardiovascular contraindications to triptans may fall outside of that category.
Dr. Riggins said that “it makes sense” that longer-acting triptans like frovatriptan and naratriptan may not rank highly for efficacy within the first 2 hours. However, these agents likely offer a superior therapeutic profile in specific contexts, such as menstrual-related migraine.
In addition, while triptans are known to cause medication overuse headache, this may not be the case with gepants, she noted.
In a release from the Science Media Center, a nonprofit organization promoting voices and views of the scientific community, Eloísa Rubio-Beltrán, PhD, research associate with The Migraine Trust at the Wolfson Sensory, Pain and Regeneration Centre, King’s College London in England, said the findings should affect migraine treatment guidelines.
“As the study highlights, due to their high efficacy and low cost, triptans should be the first-line treatment option for the acute treatment of migraine. These results should inform treatment guidelines and support the inclusion of the best performing triptans into the List of Essential Medicines, to optimize treatment, allowing patients to access more efficacious options,” said Dr. Rubio-Beltrán.
It is also important to note that gepants and ditans were developed to offer alternatives for patients who show no improvement from triptans, she added.
She pointed out that these medications were not developed as a substitute for triptans, but rather to expand the number of treatment options for migraine.
“Nonetheless,” she added, “this study highlights the need for further research on the pathophysiology of migraine, which will allow the discovery of novel targets, and thus, novel treatments options that will benefit all patient populations.”
The study was funded by the NIHR Oxford Health Biomedical Research Centre and the Lundbeck Foundation. Dr. Cipriani reported receiving research, educational, and consultancy fees from Italian Network for Pediatric Clinical Trials, Fondazione Cariplo, Lundbeck, and Angelini Pharma. Dr. Ashina is a consultant, speaker, or scientific adviser for AbbVie, Amgen, AstraZeneca, Eli Lilly, GSK, Lundbeck, Novartis, Pfizer, and Teva; is the past president of the International Headache Society; and an associate editor of The Journal of Headache and Pain and Brain. Dr. Riggins has consulted for Gerson Lehrman Group; participated in compensated work with AcademicCME and Association of Migraine Disorders; was a principal investigator on research with electroCore, Theranica, and Eli Lilly; serves on advisory boards for Theranica, Teva, Lundbeck, Amneal Pharmaceuticals, NeurologyLive, and Miles for Migraine; and is a project advisor for Clinical Awareness Initiative with Clinical Neurological Society of America. Dr. Rubio-Beltrán reported serving as a junior editorial board member of The Journal of Headache and Pain and a junior representative of the International Headache Society; receiving research support from The Migraine Trust, Eli Lilly, CoLucid Pharmaceuticals, Amgen, Novartis, and Kallyope; and receiving travel support from CoLucid Pharmaceuticals, Allergan, and Novartis.
A version of this article first appeared on Medscape.com.
new research suggested.
Results of a large systematic review and meta-analysis showed that eletriptan, rizatriptan, sumatriptan, and zolmitriptan were more effective than lasmiditan, rimegepant, and ubrogepant, which investigators found were as effective as nonsteroidal anti-inflammatory drugs (NSAIDs).
International guidelines generally endorse NSAIDs as the first-line treatment for migraine and recommend triptans for moderate to severe episodes or when the response to NSAIDs is insufficient.
However, based on the study’s findings, these four triptans should be considered the treatment of choice for migraine, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry at the University of Oxford in England and director of the Oxford Health Clinical Research Facility, told a press briefing.
The investigators added that these particular triptans should be “included in the WHO [World Health Organization] List of Essential Medicines to promote global accessibility and uniform standards of care.”
The study was published online in The BMJ.
Filling the Knowledge Gap
To date, almost all migraine studies have compared migraine drugs with placebo, so there’s a knowledge gap, said Dr. Cipriani. As a result, “there’s no clear consensus among experts and guidelines about which specific drug classes should be prescribed initially, and this is a clinical problem.”
The researchers pointed out that, in recent years, lasmiditan and gepants have been introduced as further treatment options, especially for patients in whom triptans are contraindicated because of their potential vasoconstrictive effects and higher risk for ischemic events.
The analysis included 137 double-blind, randomized, controlled trials that were primarily sponsored by the pharmaceutical industry. It included 89,445 adult outpatients with migraine (mean age, 40.3 years; 85.6% women).
Only drugs licensed for migraine or headache that are recommended in at least one country were included. Researchers divided these 17 drugs into five categories: Antipyretics (paracetamol), ditans (lasmiditan), gepants (rimegepant and ubrogepant), NSAIDs (acetylsalicylic acid, celecoxib, diclofenac potassium, ibuprofen, naproxen sodium, and phenazone), and triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan).
The study’s primary outcomes were freedom from pain at 2 hours and at 2-24 hours, without the use of rescue drugs.
Investigators used sumatriptan as the reference intervention because it is the most commonly prescribed migraine drug and is included in the WHO Model Lists of Essential Medicines.
The study showed all active interventions were better than placebo for pain freedom at 2 hours; with the exception of paracetamol and naratriptan, all were better for sustained pain freedom from 2 to 24 hours.
When the active interventions were compared with each other, eletriptan outperformed other drugs for achieving pain freedom at 2 hours. It was followed by rizatriptan, sumatriptan, and zolmitriptan (odds ratio [OR], 1.35-3.01). For sustained pain freedom up to 24 hours, the most efficacious interventions were eletriptan (OR, 1.41-2.73) and ibuprofen (OR, 3.16-4.82).
As for secondary efficacy outcomes, in head-to-head comparisons, eletriptan was superior to nearly all other active interventions for pain relief at 2 hours and for the use of rescue drugs.
As for adverse events, dizziness was more commonly associated with lasmiditan, eletriptan, sumatriptan, and zolmitriptan, while fatigue and sedation occurred more frequently with eletriptan and lasmiditan. Nausea was more often associated with lasmiditan, sumatriptan, zolmitriptan, and ubrogepant. Eletriptan was the only intervention most frequently associated with chest pain or discomfort.
Need to Update Guidelines?
Considering the new results, Dr. Cipriani and study coauthor Messoud Ashina, MD, PhD, professor of neurology, University of Copenhagen in Denmark, said clinical guidelines for acute migraine management should be updated.
While triptans are contraindicated in patients with vascular disease, the researchers noted that “cerebrovascular events may present primarily as migraine-like headaches, and misdiagnosis of transient ischemic attack and minor stroke as migraine is not rare.”
Recently, lasmiditan, rimegepant, and ubrogepant — which are not associated with vasoconstrictive effects — have been promoted as alternatives in patients for whom triptans are contraindicated or not tolerated. But the high costs of these drugs put them out of reach for some patients, the investigators noted.
Triptans are widely underutilized, Dr. Ashina noted during the press briefing. Current use ranges from 17% to 22% in the United States and from 3% to 22.5% in Europe.
The investigators said that triptans have been shown to be superior and should be promoted globally, adding that the limited access and substantial underutilization of these medications are “missed opportunities to offer more effective treatments.”
The new results underscore the importance of head-to-head trials, which is the gold standard, said Dr. Cipriani.
The investigators noted that the study’s main limitation was the quality of the data, which was deemed to be low, or very low, for most comparisons. Other potential limitations included lack of individual patient data; exclusion of combination drugs; inclusion of only oral treatments; and not considering type of oral formulation, consistency in response across migraine episodes, or cost-effectiveness.
The study also did not cover important clinical issues that might inform treatment decision-making, including drug overuse headache or potential withdrawal symptoms. And the authors were unable to quantify some outcomes, such as global functioning.
‘Best Profile’?
Reached for comment, Neurologist Nina Riggins, MD, PhD, Headache Center of Excellence, Palo Alto VA Medical Center in California, praised the authors for a “great job” of bringing attention to the topic.
However, she noted that the investigators’ characterization of the four triptans as having the “best profile” for acute migraine gave her pause.
“Calling triptans the medication with the ‘best profile’ might be not applicable in many cases,” she said. For example, those who need acute medication more than two to three times a week in addition to those with cardiovascular contraindications to triptans may fall outside of that category.
Dr. Riggins said that “it makes sense” that longer-acting triptans like frovatriptan and naratriptan may not rank highly for efficacy within the first 2 hours. However, these agents likely offer a superior therapeutic profile in specific contexts, such as menstrual-related migraine.
In addition, while triptans are known to cause medication overuse headache, this may not be the case with gepants, she noted.
In a release from the Science Media Center, a nonprofit organization promoting voices and views of the scientific community, Eloísa Rubio-Beltrán, PhD, research associate with The Migraine Trust at the Wolfson Sensory, Pain and Regeneration Centre, King’s College London in England, said the findings should affect migraine treatment guidelines.
“As the study highlights, due to their high efficacy and low cost, triptans should be the first-line treatment option for the acute treatment of migraine. These results should inform treatment guidelines and support the inclusion of the best performing triptans into the List of Essential Medicines, to optimize treatment, allowing patients to access more efficacious options,” said Dr. Rubio-Beltrán.
It is also important to note that gepants and ditans were developed to offer alternatives for patients who show no improvement from triptans, she added.
She pointed out that these medications were not developed as a substitute for triptans, but rather to expand the number of treatment options for migraine.
“Nonetheless,” she added, “this study highlights the need for further research on the pathophysiology of migraine, which will allow the discovery of novel targets, and thus, novel treatments options that will benefit all patient populations.”
The study was funded by the NIHR Oxford Health Biomedical Research Centre and the Lundbeck Foundation. Dr. Cipriani reported receiving research, educational, and consultancy fees from Italian Network for Pediatric Clinical Trials, Fondazione Cariplo, Lundbeck, and Angelini Pharma. Dr. Ashina is a consultant, speaker, or scientific adviser for AbbVie, Amgen, AstraZeneca, Eli Lilly, GSK, Lundbeck, Novartis, Pfizer, and Teva; is the past president of the International Headache Society; and an associate editor of The Journal of Headache and Pain and Brain. Dr. Riggins has consulted for Gerson Lehrman Group; participated in compensated work with AcademicCME and Association of Migraine Disorders; was a principal investigator on research with electroCore, Theranica, and Eli Lilly; serves on advisory boards for Theranica, Teva, Lundbeck, Amneal Pharmaceuticals, NeurologyLive, and Miles for Migraine; and is a project advisor for Clinical Awareness Initiative with Clinical Neurological Society of America. Dr. Rubio-Beltrán reported serving as a junior editorial board member of The Journal of Headache and Pain and a junior representative of the International Headache Society; receiving research support from The Migraine Trust, Eli Lilly, CoLucid Pharmaceuticals, Amgen, Novartis, and Kallyope; and receiving travel support from CoLucid Pharmaceuticals, Allergan, and Novartis.
A version of this article first appeared on Medscape.com.
FROM THE BMJ
Can Antihistamines Trigger Seizures in Young Kids?
TOPLINE:
new research shows. The risk appears to be most pronounced in children aged 6-24 months.
METHODOLOGY:
- Researchers in Korea used a self-controlled case-crossover design to assess the risk for seizures associated with prescriptions of first-generation antihistamines.
- They analyzed data from 11,729 children who had a seizure event (an emergency department visit with a diagnosis of epilepsy, status epilepticus, or convulsion) and had previously received a prescription for a first-generation antihistamine, including chlorpheniramine maleate, mequitazine, oxatomide, piprinhydrinate, or hydroxyzine hydrochloride.
- Prescriptions during the 15 days before a seizure were considered to have been received during a hazard period, whereas earlier prescriptions were considered to have been received during a control period.
- The researchers excluded patients with febrile seizures.
TAKEAWAY:
- In an adjusted analysis, a prescription for an antihistamine during the hazard period was associated with a 22% higher risk for seizures in children (adjusted odds ratio, 1.22; 95% CI, 1.13-1.31).
- The seizure risk was significant in children aged 6-24 months, with an adjusted odds ratio of 1.49 (95% CI, 1.31-1.70).
- For older children, the risk was not statistically significant.
IN PRACTICE:
“The study underscores a substantial increase in seizure risk associated with antihistamine prescription among children aged 6-24 months,” the authors of the study wrote. “We are not aware of any other studies that have pointed out the increased risk of seizures with first-generation antihistamines in this particular age group. ... The benefits and risks of antihistamine use should always be carefully considered, especially when prescribing H1 antihistamines to vulnerable infants.”
The findings raise a host of questions for clinicians, including how a “relatively small risk” should translate into practice, and whether the risk may be attenuated with newer antihistamines, wrote Frank Max Charles Besag, MB, ChB, with East London NHS Foundation Trust in England, in an editorial accompanying the study. “It would be reasonable to inform families that at least one study has suggested a relatively small increase in the risk of seizures with first-generation antihistamines, adding that there are still too few data to draw any firm conclusions and also providing families with the information on what to do if the child were to have a seizure.”
SOURCE:
Seonkyeong Rhie, MD, and Man Yong Han, MD, both with the Department of Pediatrics at CHA University School of Medicine, in Seongnam, South Korea, were the corresponding authors on the study. The research was published online in JAMA Network Open.
LIMITATIONS:
The researchers did not have details about seizure symptoms, did not include children seen in outpatient clinics, and were unable to verify the actual intake of the prescribed antihistamines. Although second-generation antihistamines may be less likely to cross the blood-brain barrier, one newer medication, desloratadine, has been associated with seizures.
DISCLOSURES:
The study was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, the Ministry of Health and Welfare, Republic of Korea.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
new research shows. The risk appears to be most pronounced in children aged 6-24 months.
METHODOLOGY:
- Researchers in Korea used a self-controlled case-crossover design to assess the risk for seizures associated with prescriptions of first-generation antihistamines.
- They analyzed data from 11,729 children who had a seizure event (an emergency department visit with a diagnosis of epilepsy, status epilepticus, or convulsion) and had previously received a prescription for a first-generation antihistamine, including chlorpheniramine maleate, mequitazine, oxatomide, piprinhydrinate, or hydroxyzine hydrochloride.
- Prescriptions during the 15 days before a seizure were considered to have been received during a hazard period, whereas earlier prescriptions were considered to have been received during a control period.
- The researchers excluded patients with febrile seizures.
TAKEAWAY:
- In an adjusted analysis, a prescription for an antihistamine during the hazard period was associated with a 22% higher risk for seizures in children (adjusted odds ratio, 1.22; 95% CI, 1.13-1.31).
- The seizure risk was significant in children aged 6-24 months, with an adjusted odds ratio of 1.49 (95% CI, 1.31-1.70).
- For older children, the risk was not statistically significant.
IN PRACTICE:
“The study underscores a substantial increase in seizure risk associated with antihistamine prescription among children aged 6-24 months,” the authors of the study wrote. “We are not aware of any other studies that have pointed out the increased risk of seizures with first-generation antihistamines in this particular age group. ... The benefits and risks of antihistamine use should always be carefully considered, especially when prescribing H1 antihistamines to vulnerable infants.”
The findings raise a host of questions for clinicians, including how a “relatively small risk” should translate into practice, and whether the risk may be attenuated with newer antihistamines, wrote Frank Max Charles Besag, MB, ChB, with East London NHS Foundation Trust in England, in an editorial accompanying the study. “It would be reasonable to inform families that at least one study has suggested a relatively small increase in the risk of seizures with first-generation antihistamines, adding that there are still too few data to draw any firm conclusions and also providing families with the information on what to do if the child were to have a seizure.”
SOURCE:
Seonkyeong Rhie, MD, and Man Yong Han, MD, both with the Department of Pediatrics at CHA University School of Medicine, in Seongnam, South Korea, were the corresponding authors on the study. The research was published online in JAMA Network Open.
LIMITATIONS:
The researchers did not have details about seizure symptoms, did not include children seen in outpatient clinics, and were unable to verify the actual intake of the prescribed antihistamines. Although second-generation antihistamines may be less likely to cross the blood-brain barrier, one newer medication, desloratadine, has been associated with seizures.
DISCLOSURES:
The study was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, the Ministry of Health and Welfare, Republic of Korea.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
new research shows. The risk appears to be most pronounced in children aged 6-24 months.
METHODOLOGY:
- Researchers in Korea used a self-controlled case-crossover design to assess the risk for seizures associated with prescriptions of first-generation antihistamines.
- They analyzed data from 11,729 children who had a seizure event (an emergency department visit with a diagnosis of epilepsy, status epilepticus, or convulsion) and had previously received a prescription for a first-generation antihistamine, including chlorpheniramine maleate, mequitazine, oxatomide, piprinhydrinate, or hydroxyzine hydrochloride.
- Prescriptions during the 15 days before a seizure were considered to have been received during a hazard period, whereas earlier prescriptions were considered to have been received during a control period.
- The researchers excluded patients with febrile seizures.
TAKEAWAY:
- In an adjusted analysis, a prescription for an antihistamine during the hazard period was associated with a 22% higher risk for seizures in children (adjusted odds ratio, 1.22; 95% CI, 1.13-1.31).
- The seizure risk was significant in children aged 6-24 months, with an adjusted odds ratio of 1.49 (95% CI, 1.31-1.70).
- For older children, the risk was not statistically significant.
IN PRACTICE:
“The study underscores a substantial increase in seizure risk associated with antihistamine prescription among children aged 6-24 months,” the authors of the study wrote. “We are not aware of any other studies that have pointed out the increased risk of seizures with first-generation antihistamines in this particular age group. ... The benefits and risks of antihistamine use should always be carefully considered, especially when prescribing H1 antihistamines to vulnerable infants.”
The findings raise a host of questions for clinicians, including how a “relatively small risk” should translate into practice, and whether the risk may be attenuated with newer antihistamines, wrote Frank Max Charles Besag, MB, ChB, with East London NHS Foundation Trust in England, in an editorial accompanying the study. “It would be reasonable to inform families that at least one study has suggested a relatively small increase in the risk of seizures with first-generation antihistamines, adding that there are still too few data to draw any firm conclusions and also providing families with the information on what to do if the child were to have a seizure.”
SOURCE:
Seonkyeong Rhie, MD, and Man Yong Han, MD, both with the Department of Pediatrics at CHA University School of Medicine, in Seongnam, South Korea, were the corresponding authors on the study. The research was published online in JAMA Network Open.
LIMITATIONS:
The researchers did not have details about seizure symptoms, did not include children seen in outpatient clinics, and were unable to verify the actual intake of the prescribed antihistamines. Although second-generation antihistamines may be less likely to cross the blood-brain barrier, one newer medication, desloratadine, has been associated with seizures.
DISCLOSURES:
The study was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, the Ministry of Health and Welfare, Republic of Korea.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.