Conference Coverage

Excessive drooling by patients with advanced Parkinson’s disease is an indicator of greater motor and nonmotor dysfunction, new research shows. “Sialorrhea is not just a cosmetic problem,” study investigator Francesca Morgante, MD, associate professor of neurology, St. George’s University, London, told this news organization.

“We need to understand the relationship between sialorrhea and these speech and swallowing disturbances and whether treatment for sialorrhea improves that,” Dr. Morgante added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

Underrecognized symptom

Sialorrhea is an underrecognized nonmotor symptom that can affect up to 70% of patients with Parkinson’s disease, said co-investigator Ioana Cociasu, PhD, postdoctoral research fellow, Neurosciences Research Center, St. George’s University. The impact on quality of life increases with disease severity, she said.

The current study included 101 consecutive patients attending an advanced Parkinson’s disease disorders clinic. Researchers collected demographic data that included information on gender, age, age at Parkinson’s disease onset, and disease duration. They also gathered data on motor symptoms by assessing total levodopa equivalent daily dose (LEDD) and LEDD dopamine agonists. They also assessed results on the Unified Parkinson’s Disease Rating Scale (UPDRS) part III and the Hoehn and Yahr scale for on- and off-medication states.

Nonmotor functioning was assessed using the Non-Motor Symptoms Scale (NMSS) and Scales for Outcomes in Parkinson’s disease–autonomic dysfunction (SCOPA-AUT) questionnaire. Among patients with Parkinson’s disease, autonomic dysfunction can precede motor impairment and can involve orthostatic and postprandial hypotension, among other symptoms, the investigators noted.

Health status and quality of life were assessed using the Parkinson’s disease questionnaire–39 items (PDQ-39). The Radboud Oral Motor Inventory for PD (ROMP) was used to measure orofacial symptoms. ROMP is a self-administered questionnaire that evaluates speech, swallowing disturbances, and drooling of saliva. The Montreal Cognitive Assessment test was also used.

Investigators compared participants with sialorrhea to those without sialorrhea, described as droolers and nondroolers. Droolers were defined as those scoring higher than 1 on the UPDRS-II item 6. This signified slight but definite presence of saliva in the mouth and/or the possibility of nighttime drooling.
 

Greater impairment

Among the participants, 65 (64.4%) were classified as droolers, and 36 (35.6%) as nondroolers.

Patients with both Parkinson’s disease and sialorrhea were significantly more impaired in terms of motor functioning than those without sialorrhea. In these patients, the UPDRS-III was more severe in both the off- (P = .03) and on-states (P = .002), and they had less improvement with the levodopa challenge test (P = .007).

Droolers were also more severely affected by nonmotor problems. They had more severe speech dysfunction (P < .0001) and swallowing dysfunction (P < .05), and they had higher scores on the NMSS (P = .0008) and SCOPA-AUT (P = .003) and poorer quality-of-life scores on the PDQ-39 (P = .049).

To evaluate respiratory tract infections, the researchers used electronic health records. About 15.4% of the study population had had a documented respiratory infection since they were diagnosed with Parkinson’s disease.

Upper and lower respiratory tract infections were more frequent among droolers than nondroolers (P = .05).

“Infections might arise from swallowing disturbances leading to aspiration and drooling,” Dr. Morgante noted.

The drooling did not appear to affect cognition or sleep in these patients.
 

Treatment options?

Following the study presentation, session co-chair Philippe G. Damier, MD, PhD, professor of neurology, University Hospital, Nantes, France, asked about the best treatment for sialorrhea for these patients.

In general, those with milder disease might try chewing gum to improve swallowing; patients with more severe cases may benefit from botulinum toxin injections, said Dr. Cociasu. The treatment choice, she added, “very much depends on the severity of the sialorrhea.”

Botulinum toxin therapy involves injections into the salivary gland to reduce saliva production. It is typically administered about every 4 months.

The second session co-chair, Elena Moro, MD, PhD, director of the Movement Disorders Unit at Grenoble Alpes University, France, pointed out that chewing gum may be a swallowing hazard for patients with PD and severe dementia.

Asked by Dr. Moro whether patients with higher scores on balance and posture were more likely to have sialorrhea, Dr. Cociasu said she and her colleagues are currently looking into this.

Dr. Morgante said that the current study did not examine the effect of treatment on speech disorders associated with sialorrhea. “We are running another study now to understand the effect of treatment of sialorrhea on these features,” she said.

Dr. Morgante and Dr. Cociasu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Excessive drooling by patients with advanced Parkinson’s disease is an indicator of greater motor and nonmotor dysfunction, new research shows. “Sialorrhea is not just a cosmetic problem,” study investigator Francesca Morgante, MD, associate professor of neurology, St. George’s University, London, told this news organization.

“We need to understand the relationship between sialorrhea and these speech and swallowing disturbances and whether treatment for sialorrhea improves that,” Dr. Morgante added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

Underrecognized symptom

Sialorrhea is an underrecognized nonmotor symptom that can affect up to 70% of patients with Parkinson’s disease, said co-investigator Ioana Cociasu, PhD, postdoctoral research fellow, Neurosciences Research Center, St. George’s University. The impact on quality of life increases with disease severity, she said.

The current study included 101 consecutive patients attending an advanced Parkinson’s disease disorders clinic. Researchers collected demographic data that included information on gender, age, age at Parkinson’s disease onset, and disease duration. They also gathered data on motor symptoms by assessing total levodopa equivalent daily dose (LEDD) and LEDD dopamine agonists. They also assessed results on the Unified Parkinson’s Disease Rating Scale (UPDRS) part III and the Hoehn and Yahr scale for on- and off-medication states.

Nonmotor functioning was assessed using the Non-Motor Symptoms Scale (NMSS) and Scales for Outcomes in Parkinson’s disease–autonomic dysfunction (SCOPA-AUT) questionnaire. Among patients with Parkinson’s disease, autonomic dysfunction can precede motor impairment and can involve orthostatic and postprandial hypotension, among other symptoms, the investigators noted.

Health status and quality of life were assessed using the Parkinson’s disease questionnaire–39 items (PDQ-39). The Radboud Oral Motor Inventory for PD (ROMP) was used to measure orofacial symptoms. ROMP is a self-administered questionnaire that evaluates speech, swallowing disturbances, and drooling of saliva. The Montreal Cognitive Assessment test was also used.

Investigators compared participants with sialorrhea to those without sialorrhea, described as droolers and nondroolers. Droolers were defined as those scoring higher than 1 on the UPDRS-II item 6. This signified slight but definite presence of saliva in the mouth and/or the possibility of nighttime drooling.
 

Greater impairment

Among the participants, 65 (64.4%) were classified as droolers, and 36 (35.6%) as nondroolers.

Patients with both Parkinson’s disease and sialorrhea were significantly more impaired in terms of motor functioning than those without sialorrhea. In these patients, the UPDRS-III was more severe in both the off- (P = .03) and on-states (P = .002), and they had less improvement with the levodopa challenge test (P = .007).

Droolers were also more severely affected by nonmotor problems. They had more severe speech dysfunction (P < .0001) and swallowing dysfunction (P < .05), and they had higher scores on the NMSS (P = .0008) and SCOPA-AUT (P = .003) and poorer quality-of-life scores on the PDQ-39 (P = .049).

To evaluate respiratory tract infections, the researchers used electronic health records. About 15.4% of the study population had had a documented respiratory infection since they were diagnosed with Parkinson’s disease.

Upper and lower respiratory tract infections were more frequent among droolers than nondroolers (P = .05).

“Infections might arise from swallowing disturbances leading to aspiration and drooling,” Dr. Morgante noted.

The drooling did not appear to affect cognition or sleep in these patients.
 

Treatment options?

Following the study presentation, session co-chair Philippe G. Damier, MD, PhD, professor of neurology, University Hospital, Nantes, France, asked about the best treatment for sialorrhea for these patients.

In general, those with milder disease might try chewing gum to improve swallowing; patients with more severe cases may benefit from botulinum toxin injections, said Dr. Cociasu. The treatment choice, she added, “very much depends on the severity of the sialorrhea.”

Botulinum toxin therapy involves injections into the salivary gland to reduce saliva production. It is typically administered about every 4 months.

The second session co-chair, Elena Moro, MD, PhD, director of the Movement Disorders Unit at Grenoble Alpes University, France, pointed out that chewing gum may be a swallowing hazard for patients with PD and severe dementia.

Asked by Dr. Moro whether patients with higher scores on balance and posture were more likely to have sialorrhea, Dr. Cociasu said she and her colleagues are currently looking into this.

Dr. Morgante said that the current study did not examine the effect of treatment on speech disorders associated with sialorrhea. “We are running another study now to understand the effect of treatment of sialorrhea on these features,” she said.

Dr. Morgante and Dr. Cociasu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Excessive drooling by patients with advanced Parkinson’s disease is an indicator of greater motor and nonmotor dysfunction, new research shows. “Sialorrhea is not just a cosmetic problem,” study investigator Francesca Morgante, MD, associate professor of neurology, St. George’s University, London, told this news organization.

“We need to understand the relationship between sialorrhea and these speech and swallowing disturbances and whether treatment for sialorrhea improves that,” Dr. Morgante added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

Underrecognized symptom

Sialorrhea is an underrecognized nonmotor symptom that can affect up to 70% of patients with Parkinson’s disease, said co-investigator Ioana Cociasu, PhD, postdoctoral research fellow, Neurosciences Research Center, St. George’s University. The impact on quality of life increases with disease severity, she said.

The current study included 101 consecutive patients attending an advanced Parkinson’s disease disorders clinic. Researchers collected demographic data that included information on gender, age, age at Parkinson’s disease onset, and disease duration. They also gathered data on motor symptoms by assessing total levodopa equivalent daily dose (LEDD) and LEDD dopamine agonists. They also assessed results on the Unified Parkinson’s Disease Rating Scale (UPDRS) part III and the Hoehn and Yahr scale for on- and off-medication states.

Nonmotor functioning was assessed using the Non-Motor Symptoms Scale (NMSS) and Scales for Outcomes in Parkinson’s disease–autonomic dysfunction (SCOPA-AUT) questionnaire. Among patients with Parkinson’s disease, autonomic dysfunction can precede motor impairment and can involve orthostatic and postprandial hypotension, among other symptoms, the investigators noted.

Health status and quality of life were assessed using the Parkinson’s disease questionnaire–39 items (PDQ-39). The Radboud Oral Motor Inventory for PD (ROMP) was used to measure orofacial symptoms. ROMP is a self-administered questionnaire that evaluates speech, swallowing disturbances, and drooling of saliva. The Montreal Cognitive Assessment test was also used.

Investigators compared participants with sialorrhea to those without sialorrhea, described as droolers and nondroolers. Droolers were defined as those scoring higher than 1 on the UPDRS-II item 6. This signified slight but definite presence of saliva in the mouth and/or the possibility of nighttime drooling.
 

Greater impairment

Among the participants, 65 (64.4%) were classified as droolers, and 36 (35.6%) as nondroolers.

Patients with both Parkinson’s disease and sialorrhea were significantly more impaired in terms of motor functioning than those without sialorrhea. In these patients, the UPDRS-III was more severe in both the off- (P = .03) and on-states (P = .002), and they had less improvement with the levodopa challenge test (P = .007).

Droolers were also more severely affected by nonmotor problems. They had more severe speech dysfunction (P < .0001) and swallowing dysfunction (P < .05), and they had higher scores on the NMSS (P = .0008) and SCOPA-AUT (P = .003) and poorer quality-of-life scores on the PDQ-39 (P = .049).

To evaluate respiratory tract infections, the researchers used electronic health records. About 15.4% of the study population had had a documented respiratory infection since they were diagnosed with Parkinson’s disease.

Upper and lower respiratory tract infections were more frequent among droolers than nondroolers (P = .05).

“Infections might arise from swallowing disturbances leading to aspiration and drooling,” Dr. Morgante noted.

The drooling did not appear to affect cognition or sleep in these patients.
 

Treatment options?

Following the study presentation, session co-chair Philippe G. Damier, MD, PhD, professor of neurology, University Hospital, Nantes, France, asked about the best treatment for sialorrhea for these patients.

In general, those with milder disease might try chewing gum to improve swallowing; patients with more severe cases may benefit from botulinum toxin injections, said Dr. Cociasu. The treatment choice, she added, “very much depends on the severity of the sialorrhea.”

Botulinum toxin therapy involves injections into the salivary gland to reduce saliva production. It is typically administered about every 4 months.

The second session co-chair, Elena Moro, MD, PhD, director of the Movement Disorders Unit at Grenoble Alpes University, France, pointed out that chewing gum may be a swallowing hazard for patients with PD and severe dementia.

Asked by Dr. Moro whether patients with higher scores on balance and posture were more likely to have sialorrhea, Dr. Cociasu said she and her colleagues are currently looking into this.

Dr. Morgante said that the current study did not examine the effect of treatment on speech disorders associated with sialorrhea. “We are running another study now to understand the effect of treatment of sialorrhea on these features,” she said.

Dr. Morgante and Dr. Cociasu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A software program based on artificial intelligence (AI) is effective for distinguishing young children with autism spectrum disorder (ASD) from those with other conditions, according to results of a pivotal trial presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

The AI-based software, which will be submitted to regulatory approval as a device, employs an algorithm that assembles inputs from a caregiver questionnaire, a video, and a clinician questionnaire, according to Sharief Taraman, MD, a pediatric neurologist at CHOC, a pediatric health care system in Orange County, Calif.

Although the device could be employed in a variety of settings, it is envisioned for use by primary care physicians. This will circumvent the need for specialist evaluation except in challenging cases. Currently, nearly all children with ASD are diagnosed in specialty care, according to data cited by Dr. Taraman.

“The lack of diagnostic tools for ASD in primary care settings contributes to an average delay of 3 years between first parental concern and diagnosis and to long wait lists for specialty evaluation,” he reported at the virtual meeting, presented by MedscapeLive.

When used with clinical judgment and criteria from the American Psychiatric Association’s 5th edition of the Diagnostic and Statistical Manual (DSM-5), the data from the trial suggest the diagnostic tool in the hands of primary care physicians “could efficiently and accurately assess ASD in children 18 to 72 months old,” said Dr. Taraman, also an associate clinical professor of pediatrics at the University of California, Irvine.*

The AI-assisted software was evaluated in 425 children at 14 sites in 6 states. The study population was reflective of U.S. demographics. Although only 36% of the children were female, this is consistent with ASD prevalence. Only 60% of the subjects were White. Nearly 30% were Black or Latinx and other populations, such as those of Asian heritage, were represented.

Children between the ages of 18 and 72 months were eligible if both a caregiver and a health care professional were concerned that the child had ASD. About the same time that a caregiver completed a 20-item questionnaire and the primary care physician completed a 15-item questionnaire on a mobile device, the caregiver uploaded two videos of 1-2 minutes in length.

This information, along with a 33-item questionnaire completed by an analyst of the submitted videos, was then processed by the software algorithm. It provided a patient status of positive or negative for ASD, or it concluded that the status was indeterminate.

“To reduce the risk of false classifications, the indeterminate status was included as a safety feature,” Dr. Taraman explained. However, Dr. Taraman considers an indeterminate designation potentially actionable. Rather than a negative result, this status suggests a complex neurodevelopmental disorder and indicates the need for further evaluation.

The reference standard diagnosis, completed in all participants in this study, was a specialist evaluation completed independently by two experts. The presence or absence of ASD was confirmed if the experts agreed. If they did not, a third specialist made the final determination.

On the basis of the software, there was a determinate result in 52% of the children. In comparison to the specialist determinations, all were correctly classified except for one child, in which the software was determined to have made a false-negative diagnosis. A diagnosis of ASD was reached in 29% of the study participants.

For those with a determinate designation, the sensitivity was 98.4% and the specificity was 78.9%. This translated into positive predictive and negative predictive values of 80.8% and 98.3%, respectively.

Of those identified as indeterminate by the AI-assisted algorithm, 91% were ultimately considered by specialist evaluation to have complex issues. In this group, ASD was part of the complex clinical picture in 20%. The others had non-ASD neurodevelopmental conditions, according to Dr. Taraman.

When the accuracy was evaluated across ages, ethnicity, and factors such as parent education or family income, the tool performed consistently, Dr. Taraman reported. This is important, he said, because the presence or absence of ASD is misdiagnosed in many underserved populations.

The focus on developing a methodology specific for use in primary care was based on evidence that the delay in the diagnosis of ASD is attributable to long wait times for specialty evaluations.

“There will never be enough specialists. There is a need for a way to streamline the diagnosis of ASD,” Dr. Taraman maintained. This is helpful not only to parents concerned about their children, he said, but also there are data to suggest that early intervention improves outcomes.

A specialist in ASD, Paul Carbone, MD, medical director of the child development program at the University of Utah, Salt Lake City, agreed. He said early diagnosis and intervention should be a goal.

“Reducing the age of ASD diagnosis is a priority because early entry into autism-specific interventions is a strong predictor of optimal developmental outcomes for children,” Dr. Carbone said.

Although he is not familiar with this experimental AI-assisted diagnostic program, he has published on the feasibility of ASD diagnosis at the primary care level. In his study, Dr. Carbone examined the Modified Checklist for Autism in Toddlers (M-CHAT) as one of several methodologies that might be considered.

Diagnosis of ASD “can be achieved through systematic processes within primary care that facilitate universal development surveillance and autism screening followed by prompt and timely diagnostic evaluations of at-risk children,” Dr. Carbone said.

MedscapeLive and this news organization are owned by the same parent company. Dr. Taraman reported a financial relationship with Cognoa, the company that is developing the ASD software for clinical use. Dr. Carbone reported that he has no conflicts of interest.

*Updated, 7/7/21

A software program based on artificial intelligence (AI) is effective for distinguishing young children with autism spectrum disorder (ASD) from those with other conditions, according to results of a pivotal trial presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

The AI-based software, which will be submitted to regulatory approval as a device, employs an algorithm that assembles inputs from a caregiver questionnaire, a video, and a clinician questionnaire, according to Sharief Taraman, MD, a pediatric neurologist at CHOC, a pediatric health care system in Orange County, Calif.

Although the device could be employed in a variety of settings, it is envisioned for use by primary care physicians. This will circumvent the need for specialist evaluation except in challenging cases. Currently, nearly all children with ASD are diagnosed in specialty care, according to data cited by Dr. Taraman.

“The lack of diagnostic tools for ASD in primary care settings contributes to an average delay of 3 years between first parental concern and diagnosis and to long wait lists for specialty evaluation,” he reported at the virtual meeting, presented by MedscapeLive.

When used with clinical judgment and criteria from the American Psychiatric Association’s 5th edition of the Diagnostic and Statistical Manual (DSM-5), the data from the trial suggest the diagnostic tool in the hands of primary care physicians “could efficiently and accurately assess ASD in children 18 to 72 months old,” said Dr. Taraman, also an associate clinical professor of pediatrics at the University of California, Irvine.*

The AI-assisted software was evaluated in 425 children at 14 sites in 6 states. The study population was reflective of U.S. demographics. Although only 36% of the children were female, this is consistent with ASD prevalence. Only 60% of the subjects were White. Nearly 30% were Black or Latinx and other populations, such as those of Asian heritage, were represented.

Children between the ages of 18 and 72 months were eligible if both a caregiver and a health care professional were concerned that the child had ASD. About the same time that a caregiver completed a 20-item questionnaire and the primary care physician completed a 15-item questionnaire on a mobile device, the caregiver uploaded two videos of 1-2 minutes in length.

This information, along with a 33-item questionnaire completed by an analyst of the submitted videos, was then processed by the software algorithm. It provided a patient status of positive or negative for ASD, or it concluded that the status was indeterminate.

“To reduce the risk of false classifications, the indeterminate status was included as a safety feature,” Dr. Taraman explained. However, Dr. Taraman considers an indeterminate designation potentially actionable. Rather than a negative result, this status suggests a complex neurodevelopmental disorder and indicates the need for further evaluation.

The reference standard diagnosis, completed in all participants in this study, was a specialist evaluation completed independently by two experts. The presence or absence of ASD was confirmed if the experts agreed. If they did not, a third specialist made the final determination.

On the basis of the software, there was a determinate result in 52% of the children. In comparison to the specialist determinations, all were correctly classified except for one child, in which the software was determined to have made a false-negative diagnosis. A diagnosis of ASD was reached in 29% of the study participants.

For those with a determinate designation, the sensitivity was 98.4% and the specificity was 78.9%. This translated into positive predictive and negative predictive values of 80.8% and 98.3%, respectively.

Of those identified as indeterminate by the AI-assisted algorithm, 91% were ultimately considered by specialist evaluation to have complex issues. In this group, ASD was part of the complex clinical picture in 20%. The others had non-ASD neurodevelopmental conditions, according to Dr. Taraman.

When the accuracy was evaluated across ages, ethnicity, and factors such as parent education or family income, the tool performed consistently, Dr. Taraman reported. This is important, he said, because the presence or absence of ASD is misdiagnosed in many underserved populations.

The focus on developing a methodology specific for use in primary care was based on evidence that the delay in the diagnosis of ASD is attributable to long wait times for specialty evaluations.

“There will never be enough specialists. There is a need for a way to streamline the diagnosis of ASD,” Dr. Taraman maintained. This is helpful not only to parents concerned about their children, he said, but also there are data to suggest that early intervention improves outcomes.

A specialist in ASD, Paul Carbone, MD, medical director of the child development program at the University of Utah, Salt Lake City, agreed. He said early diagnosis and intervention should be a goal.

“Reducing the age of ASD diagnosis is a priority because early entry into autism-specific interventions is a strong predictor of optimal developmental outcomes for children,” Dr. Carbone said.

Although he is not familiar with this experimental AI-assisted diagnostic program, he has published on the feasibility of ASD diagnosis at the primary care level. In his study, Dr. Carbone examined the Modified Checklist for Autism in Toddlers (M-CHAT) as one of several methodologies that might be considered.

Diagnosis of ASD “can be achieved through systematic processes within primary care that facilitate universal development surveillance and autism screening followed by prompt and timely diagnostic evaluations of at-risk children,” Dr. Carbone said.

MedscapeLive and this news organization are owned by the same parent company. Dr. Taraman reported a financial relationship with Cognoa, the company that is developing the ASD software for clinical use. Dr. Carbone reported that he has no conflicts of interest.

*Updated, 7/7/21

A software program based on artificial intelligence (AI) is effective for distinguishing young children with autism spectrum disorder (ASD) from those with other conditions, according to results of a pivotal trial presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

The AI-based software, which will be submitted to regulatory approval as a device, employs an algorithm that assembles inputs from a caregiver questionnaire, a video, and a clinician questionnaire, according to Sharief Taraman, MD, a pediatric neurologist at CHOC, a pediatric health care system in Orange County, Calif.

Although the device could be employed in a variety of settings, it is envisioned for use by primary care physicians. This will circumvent the need for specialist evaluation except in challenging cases. Currently, nearly all children with ASD are diagnosed in specialty care, according to data cited by Dr. Taraman.

“The lack of diagnostic tools for ASD in primary care settings contributes to an average delay of 3 years between first parental concern and diagnosis and to long wait lists for specialty evaluation,” he reported at the virtual meeting, presented by MedscapeLive.

When used with clinical judgment and criteria from the American Psychiatric Association’s 5th edition of the Diagnostic and Statistical Manual (DSM-5), the data from the trial suggest the diagnostic tool in the hands of primary care physicians “could efficiently and accurately assess ASD in children 18 to 72 months old,” said Dr. Taraman, also an associate clinical professor of pediatrics at the University of California, Irvine.*

The AI-assisted software was evaluated in 425 children at 14 sites in 6 states. The study population was reflective of U.S. demographics. Although only 36% of the children were female, this is consistent with ASD prevalence. Only 60% of the subjects were White. Nearly 30% were Black or Latinx and other populations, such as those of Asian heritage, were represented.

Children between the ages of 18 and 72 months were eligible if both a caregiver and a health care professional were concerned that the child had ASD. About the same time that a caregiver completed a 20-item questionnaire and the primary care physician completed a 15-item questionnaire on a mobile device, the caregiver uploaded two videos of 1-2 minutes in length.

This information, along with a 33-item questionnaire completed by an analyst of the submitted videos, was then processed by the software algorithm. It provided a patient status of positive or negative for ASD, or it concluded that the status was indeterminate.

“To reduce the risk of false classifications, the indeterminate status was included as a safety feature,” Dr. Taraman explained. However, Dr. Taraman considers an indeterminate designation potentially actionable. Rather than a negative result, this status suggests a complex neurodevelopmental disorder and indicates the need for further evaluation.

The reference standard diagnosis, completed in all participants in this study, was a specialist evaluation completed independently by two experts. The presence or absence of ASD was confirmed if the experts agreed. If they did not, a third specialist made the final determination.

On the basis of the software, there was a determinate result in 52% of the children. In comparison to the specialist determinations, all were correctly classified except for one child, in which the software was determined to have made a false-negative diagnosis. A diagnosis of ASD was reached in 29% of the study participants.

For those with a determinate designation, the sensitivity was 98.4% and the specificity was 78.9%. This translated into positive predictive and negative predictive values of 80.8% and 98.3%, respectively.

Of those identified as indeterminate by the AI-assisted algorithm, 91% were ultimately considered by specialist evaluation to have complex issues. In this group, ASD was part of the complex clinical picture in 20%. The others had non-ASD neurodevelopmental conditions, according to Dr. Taraman.

When the accuracy was evaluated across ages, ethnicity, and factors such as parent education or family income, the tool performed consistently, Dr. Taraman reported. This is important, he said, because the presence or absence of ASD is misdiagnosed in many underserved populations.

The focus on developing a methodology specific for use in primary care was based on evidence that the delay in the diagnosis of ASD is attributable to long wait times for specialty evaluations.

“There will never be enough specialists. There is a need for a way to streamline the diagnosis of ASD,” Dr. Taraman maintained. This is helpful not only to parents concerned about their children, he said, but also there are data to suggest that early intervention improves outcomes.

A specialist in ASD, Paul Carbone, MD, medical director of the child development program at the University of Utah, Salt Lake City, agreed. He said early diagnosis and intervention should be a goal.

“Reducing the age of ASD diagnosis is a priority because early entry into autism-specific interventions is a strong predictor of optimal developmental outcomes for children,” Dr. Carbone said.

Although he is not familiar with this experimental AI-assisted diagnostic program, he has published on the feasibility of ASD diagnosis at the primary care level. In his study, Dr. Carbone examined the Modified Checklist for Autism in Toddlers (M-CHAT) as one of several methodologies that might be considered.

Diagnosis of ASD “can be achieved through systematic processes within primary care that facilitate universal development surveillance and autism screening followed by prompt and timely diagnostic evaluations of at-risk children,” Dr. Carbone said.

MedscapeLive and this news organization are owned by the same parent company. Dr. Taraman reported a financial relationship with Cognoa, the company that is developing the ASD software for clinical use. Dr. Carbone reported that he has no conflicts of interest.

*Updated, 7/7/21

Using high-intensity focused electromagnetic (HIFEM) technology to strengthen pelvic floor muscles for the improvement of urinary incontinence (UI) and female sexual function was safe and effective at 9 months follow-up, results from a multicenter study showed.

“The pelvic floor consists of three pairs of muscles: the pubococcygeus, the iliococcygeus, and the puborectalis,” lead study author Joseph Berenholz, MD, and a diplomate of the American Board of Obstetics & Gynecology, said during the annual conference of the American Society for Laser Medicine and Surgery. “They control continence through support of pelvic organs. The urethra, the vagina, and the rectum pass through that diaphragm. It also contributes to sexual sensation and arousal. A deconditioning of the pelvic floor is usually the result of child-bearing years or aging, which usually results in urinary incontinence and impairment of sexual function. The noninvasive strengthening of the pelvic floor muscles helps to regain muscle tone and strength.”

In a prospective, open-label, single-arm study conducted at four sites, Dr. Berenholz, medical director of the Michigan Center for Women’s Health in Farmington Hills, and colleagues investigated the long-term effectiveness of HIFEM-induced pelvic floor muscle (PFM) strengthening for improvement of UI and sexual function. HIFEM selectively targets neuromuscular tissue and induces supramaximal PFM contractions that cannot be achieved voluntarily, he said, causing muscle strengthening due to muscle fiber hypertrophy, which helps patients to better isolate and command their muscles.

The study population consisted of 33 females with a mean age of 49 years who had UI and UI-related problems in sexual life. They received six 28-minute HIFEM treatments of the pelvic floor with the BTL Emsella, which is FDA cleared for both stress and urge incontinence. The frequency of visits was two treatments per week and the intensity of HIFEM was adjusted between 0% and 100% based on the patient’s tolerance threshold. Evaluations were conducted at baseline, after the last treatment, at 1, 3, 6, and 9 months. The primary outcomes were change in urine leakage based on the International Consultation on Incontinence Questionnaire–Short Form (ICIQ-UI-SF) and change in sexual function based on the Female Sexual Function Index (FSFI) and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Secondary endpoints were adverse events and the comfort of therapy based on a 7-point Likert scale.

Dr. Berenholz reported that from baseline the severity of UI based on the ICIQ-SF significantly decreased 60% by a mean of 8.1 points between baseline and 9 months (P < .001). At 1 month, the FSFI score improved 32% by a mean of 7.1 points (P < .001) and was sustained throughout the study. The most prominent changes were seen in the subdomains of desire, arousal, lubrication, and orgasm response.

The PISQ-12 score incrementally increased 25% to a mean improvement of 8.2 points at 9 months (P < .001). Subjects improved most in the emotive subdomain, reporting more frequent orgasms, increased desire, and sexual excitement. The minimal important difference was 6 points.

“This is a true paradigm shift in the treatment of incontinence and sexual dysfunction,” Dr. Berenholz said. “The therapy was safe, comfortable, no adverse events emerged, and 31 subjects (94%) described the therapy as comfortable. Interim data suggest that treatment effect was maintained for 9 months, and there were no significant declines in scores in the long term. The upcoming 12-month follow-up data will let us know if more maintenance therapy is needed.”

During a question-and-answer session, one of the abstract section chairs, Albert Wolkerstorfer, MD, PhD, wondered about the potential for combination treatments in this patient population. “I can imagine that something that is working on the muscle tone has a totally different mechanism than something that is working on the mucosa and the underlying tissue without really affecting the muscle,” said Dr. Wolkerstorfer, a dermatologist at the Netherlands Institute for Pigment Disorders, department of dermatology, University of Amsterdam. “Would a combination be the way to go?”

Dr. Berenholz said that he sometimes combines HIFEM with the ULTRA Femme 360, a radiofrequency thermal energy device. “We thought this addresses two issues,” he said. “One is fascial muscle, which is the underlying structural issue for incontinence. The other is thermal energy to aid in incontinence prevention by inducing production of elastin and collagen in the midurethra, but also to promote lubrication and heightened sensitivity in the patient who’s either menopausal or has undergone chemotherapy for breast cancer.”

Dr. Berenholz reported having no financial disclosures. Dr. Wolkerstorfer disclosed that he has received consulting fees from Lumenis and InCyte and equipment from Humeca and PerfAction Technologies. He has also received grant funding from Novartis and InCyte and he is a member of InCyte’s advisory board.

dbrunk@mdedge.com

Using high-intensity focused electromagnetic (HIFEM) technology to strengthen pelvic floor muscles for the improvement of urinary incontinence (UI) and female sexual function was safe and effective at 9 months follow-up, results from a multicenter study showed.

“The pelvic floor consists of three pairs of muscles: the pubococcygeus, the iliococcygeus, and the puborectalis,” lead study author Joseph Berenholz, MD, and a diplomate of the American Board of Obstetics & Gynecology, said during the annual conference of the American Society for Laser Medicine and Surgery. “They control continence through support of pelvic organs. The urethra, the vagina, and the rectum pass through that diaphragm. It also contributes to sexual sensation and arousal. A deconditioning of the pelvic floor is usually the result of child-bearing years or aging, which usually results in urinary incontinence and impairment of sexual function. The noninvasive strengthening of the pelvic floor muscles helps to regain muscle tone and strength.”

In a prospective, open-label, single-arm study conducted at four sites, Dr. Berenholz, medical director of the Michigan Center for Women’s Health in Farmington Hills, and colleagues investigated the long-term effectiveness of HIFEM-induced pelvic floor muscle (PFM) strengthening for improvement of UI and sexual function. HIFEM selectively targets neuromuscular tissue and induces supramaximal PFM contractions that cannot be achieved voluntarily, he said, causing muscle strengthening due to muscle fiber hypertrophy, which helps patients to better isolate and command their muscles.

The study population consisted of 33 females with a mean age of 49 years who had UI and UI-related problems in sexual life. They received six 28-minute HIFEM treatments of the pelvic floor with the BTL Emsella, which is FDA cleared for both stress and urge incontinence. The frequency of visits was two treatments per week and the intensity of HIFEM was adjusted between 0% and 100% based on the patient’s tolerance threshold. Evaluations were conducted at baseline, after the last treatment, at 1, 3, 6, and 9 months. The primary outcomes were change in urine leakage based on the International Consultation on Incontinence Questionnaire–Short Form (ICIQ-UI-SF) and change in sexual function based on the Female Sexual Function Index (FSFI) and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Secondary endpoints were adverse events and the comfort of therapy based on a 7-point Likert scale.

Dr. Berenholz reported that from baseline the severity of UI based on the ICIQ-SF significantly decreased 60% by a mean of 8.1 points between baseline and 9 months (P < .001). At 1 month, the FSFI score improved 32% by a mean of 7.1 points (P < .001) and was sustained throughout the study. The most prominent changes were seen in the subdomains of desire, arousal, lubrication, and orgasm response.

The PISQ-12 score incrementally increased 25% to a mean improvement of 8.2 points at 9 months (P < .001). Subjects improved most in the emotive subdomain, reporting more frequent orgasms, increased desire, and sexual excitement. The minimal important difference was 6 points.

“This is a true paradigm shift in the treatment of incontinence and sexual dysfunction,” Dr. Berenholz said. “The therapy was safe, comfortable, no adverse events emerged, and 31 subjects (94%) described the therapy as comfortable. Interim data suggest that treatment effect was maintained for 9 months, and there were no significant declines in scores in the long term. The upcoming 12-month follow-up data will let us know if more maintenance therapy is needed.”

During a question-and-answer session, one of the abstract section chairs, Albert Wolkerstorfer, MD, PhD, wondered about the potential for combination treatments in this patient population. “I can imagine that something that is working on the muscle tone has a totally different mechanism than something that is working on the mucosa and the underlying tissue without really affecting the muscle,” said Dr. Wolkerstorfer, a dermatologist at the Netherlands Institute for Pigment Disorders, department of dermatology, University of Amsterdam. “Would a combination be the way to go?”

Dr. Berenholz said that he sometimes combines HIFEM with the ULTRA Femme 360, a radiofrequency thermal energy device. “We thought this addresses two issues,” he said. “One is fascial muscle, which is the underlying structural issue for incontinence. The other is thermal energy to aid in incontinence prevention by inducing production of elastin and collagen in the midurethra, but also to promote lubrication and heightened sensitivity in the patient who’s either menopausal or has undergone chemotherapy for breast cancer.”

Dr. Berenholz reported having no financial disclosures. Dr. Wolkerstorfer disclosed that he has received consulting fees from Lumenis and InCyte and equipment from Humeca and PerfAction Technologies. He has also received grant funding from Novartis and InCyte and he is a member of InCyte’s advisory board.

dbrunk@mdedge.com

Using high-intensity focused electromagnetic (HIFEM) technology to strengthen pelvic floor muscles for the improvement of urinary incontinence (UI) and female sexual function was safe and effective at 9 months follow-up, results from a multicenter study showed.

“The pelvic floor consists of three pairs of muscles: the pubococcygeus, the iliococcygeus, and the puborectalis,” lead study author Joseph Berenholz, MD, and a diplomate of the American Board of Obstetics & Gynecology, said during the annual conference of the American Society for Laser Medicine and Surgery. “They control continence through support of pelvic organs. The urethra, the vagina, and the rectum pass through that diaphragm. It also contributes to sexual sensation and arousal. A deconditioning of the pelvic floor is usually the result of child-bearing years or aging, which usually results in urinary incontinence and impairment of sexual function. The noninvasive strengthening of the pelvic floor muscles helps to regain muscle tone and strength.”

In a prospective, open-label, single-arm study conducted at four sites, Dr. Berenholz, medical director of the Michigan Center for Women’s Health in Farmington Hills, and colleagues investigated the long-term effectiveness of HIFEM-induced pelvic floor muscle (PFM) strengthening for improvement of UI and sexual function. HIFEM selectively targets neuromuscular tissue and induces supramaximal PFM contractions that cannot be achieved voluntarily, he said, causing muscle strengthening due to muscle fiber hypertrophy, which helps patients to better isolate and command their muscles.

The study population consisted of 33 females with a mean age of 49 years who had UI and UI-related problems in sexual life. They received six 28-minute HIFEM treatments of the pelvic floor with the BTL Emsella, which is FDA cleared for both stress and urge incontinence. The frequency of visits was two treatments per week and the intensity of HIFEM was adjusted between 0% and 100% based on the patient’s tolerance threshold. Evaluations were conducted at baseline, after the last treatment, at 1, 3, 6, and 9 months. The primary outcomes were change in urine leakage based on the International Consultation on Incontinence Questionnaire–Short Form (ICIQ-UI-SF) and change in sexual function based on the Female Sexual Function Index (FSFI) and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Secondary endpoints were adverse events and the comfort of therapy based on a 7-point Likert scale.

Dr. Berenholz reported that from baseline the severity of UI based on the ICIQ-SF significantly decreased 60% by a mean of 8.1 points between baseline and 9 months (P < .001). At 1 month, the FSFI score improved 32% by a mean of 7.1 points (P < .001) and was sustained throughout the study. The most prominent changes were seen in the subdomains of desire, arousal, lubrication, and orgasm response.

The PISQ-12 score incrementally increased 25% to a mean improvement of 8.2 points at 9 months (P < .001). Subjects improved most in the emotive subdomain, reporting more frequent orgasms, increased desire, and sexual excitement. The minimal important difference was 6 points.

“This is a true paradigm shift in the treatment of incontinence and sexual dysfunction,” Dr. Berenholz said. “The therapy was safe, comfortable, no adverse events emerged, and 31 subjects (94%) described the therapy as comfortable. Interim data suggest that treatment effect was maintained for 9 months, and there were no significant declines in scores in the long term. The upcoming 12-month follow-up data will let us know if more maintenance therapy is needed.”

During a question-and-answer session, one of the abstract section chairs, Albert Wolkerstorfer, MD, PhD, wondered about the potential for combination treatments in this patient population. “I can imagine that something that is working on the muscle tone has a totally different mechanism than something that is working on the mucosa and the underlying tissue without really affecting the muscle,” said Dr. Wolkerstorfer, a dermatologist at the Netherlands Institute for Pigment Disorders, department of dermatology, University of Amsterdam. “Would a combination be the way to go?”

Dr. Berenholz said that he sometimes combines HIFEM with the ULTRA Femme 360, a radiofrequency thermal energy device. “We thought this addresses two issues,” he said. “One is fascial muscle, which is the underlying structural issue for incontinence. The other is thermal energy to aid in incontinence prevention by inducing production of elastin and collagen in the midurethra, but also to promote lubrication and heightened sensitivity in the patient who’s either menopausal or has undergone chemotherapy for breast cancer.”

Dr. Berenholz reported having no financial disclosures. Dr. Wolkerstorfer disclosed that he has received consulting fees from Lumenis and InCyte and equipment from Humeca and PerfAction Technologies. He has also received grant funding from Novartis and InCyte and he is a member of InCyte’s advisory board.

dbrunk@mdedge.com

If moderate to severe postpartum depression poses a risk to child development, that argues in favor of pharmacologic therapy, according to a detailed risk-benefit assessment presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

monkeybusinessimages/Thinkstock

“It is important to consider that there are potential risks of antidepressant drugs, but there are also potential risks from not providing effective treatment,” reported Neha Hudepohl, MD, at the virtual meeting, presented by MedscapeLive.

On a website maintained by the Centers for Disease Control and Prevention, the question of whether antidepressants pose a risk to breast-feeding children is answered with a “maybe.” Although many of these drugs can be detected in breast milk, according to the CDC, “most have little or no effect on milk supply or on infant well-being.”

This is enough uncertainty that antidepressants are not first-line intervention when postpartum depression is mild, said Dr. Hudepohl, director of women’s mental health at Prisma Health Upstate, Greenville, S.C. However, she noted that the American College of Obstetricians and Gynecologists is among the organizations that recommend drug treatment if symptoms are moderate to severe.

“Depression in the mother affects interactions in feeding practices, sleep routines and patterns, and safety practices,” said Dr. Hudepohl, citing published studies supporting each of these consequences.

For the child, there is some degree of uncertainty about risk from untreated maternal depression as well as from breast mild exposure to antidepressants. Conclusive statements are not offered by ACOG and others.

“Some but not all studies have shown an impact of either antenatal or postnatal depression on speech recognition in infancy of native versus nonnative languages, IQ, and cognitive development, and reduction in left frontal brain electrical activity associated with impaired positive emotions,” Dr. Hudepohl reported.

Sifting through published data, Dr. Hudepohl cited studies associating persistent postpartum depression with a more than fourfold risk of behavioral problems at the age of 3.5 years, lower grades in mathematics at age 16, and a higher prevalence of depression at age 18. Among children who had depressed mothers in infancy, there have also been studies showing a higher reactivity to stressors and higher baseline cortisol levels.

“The good news is that these effects in children appear to be largely reversible with maternal treatment,” Dr. Hudepohl said. In fact, she cited evidence of a correlation between improvement in maternal symptoms and a reduction in the complications in children, such as behavioral problems.

Postpartum depression, which can develop anytime in the first 12 months after childbirth, is not uncommon, occurring in approximately 15% of women, according to Dr. Hudepohl. Risk factors include personal or family history of depression, anxiety or depression during pregnancy, and a prior history of postpartum depression.

Postpartum depression increases the risk of maternal suicide by about 70-fold, Dr. Hudepohl reported. She noted that the peaks in suicide attempts in the 1st and 12th month after delivery. Adverse infant outcomes are not a predictor of increase risk of attempts, but fetal or infant death are.

According to one study, about 40% of mothers with postpartum depression have intrusive thoughts that involve harming their child. About 15% fear being alone with their infant. Behaviors such as decreased playfulness, less talking, or other interactions with the child, and inconsistent response to the child are all likely to contribute to impaired maternal-child bonding, Dr. Hudepohl reported.

For women who discontinued antidepressants for pregnancy but have now developed significant postpartum depression, Dr. Hudepohl recommended using “what has worked in the past.” She considered monotherapy preferable if possible, but severe symptoms warrant more aggressive intervention. Dr. Hudepohl pointed out that the risks of antidepressants taken by the breast-feeding mother to the infant remain unclear despite multiple studies attempting to establish and quantify risk.

“Antidepressants are the most researched medication in pregnancy,” she said.

Conversely, the risks of untreated symptoms to the mother are significant, and the potential risks to the infant and family – if variable – are not insignificant.

Overall, “nonpharmacologic treatment is preferred first line for mild symptoms,” Dr. Hudepohl, but she and others consider a risk-benefit ratio growing increasingly in favor of drug therapy when this approach is the best option for bringing moderate to severe symptoms under control.

Whether depression arises during pregnancy or in the postpartum period, “psychotherapy is generally considered first-line treatment,” agreed Nancy Byatt, DO, MS, MBA, professor of psychiatry and of obstetrics and gynecology at the University of Massachusetts, Worcester.

Dr. Byatt, who has published frequently on this topic, further agreed that risks to the mother and the child increase with uncontrolled depression in the postpartum period. With symptoms of greater intensity, the uncertain risks of medication are outweighed by substantial potential benefits.

“When a pregnant or postpartum individual has moderate to severe illness, treatment with medication is typically recommended, because the benefits are thought to outweigh the risks,” she said, echoing a consensus opinion among experts and organized medicine.

MedscapeLive and this news organization are owned by the same parent company. Dr. Hudepohl and Dr. Byatt reported no potential financial conflicts of interest.
 

If moderate to severe postpartum depression poses a risk to child development, that argues in favor of pharmacologic therapy, according to a detailed risk-benefit assessment presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

monkeybusinessimages/Thinkstock

“It is important to consider that there are potential risks of antidepressant drugs, but there are also potential risks from not providing effective treatment,” reported Neha Hudepohl, MD, at the virtual meeting, presented by MedscapeLive.

On a website maintained by the Centers for Disease Control and Prevention, the question of whether antidepressants pose a risk to breast-feeding children is answered with a “maybe.” Although many of these drugs can be detected in breast milk, according to the CDC, “most have little or no effect on milk supply or on infant well-being.”

This is enough uncertainty that antidepressants are not first-line intervention when postpartum depression is mild, said Dr. Hudepohl, director of women’s mental health at Prisma Health Upstate, Greenville, S.C. However, she noted that the American College of Obstetricians and Gynecologists is among the organizations that recommend drug treatment if symptoms are moderate to severe.

“Depression in the mother affects interactions in feeding practices, sleep routines and patterns, and safety practices,” said Dr. Hudepohl, citing published studies supporting each of these consequences.

For the child, there is some degree of uncertainty about risk from untreated maternal depression as well as from breast mild exposure to antidepressants. Conclusive statements are not offered by ACOG and others.

“Some but not all studies have shown an impact of either antenatal or postnatal depression on speech recognition in infancy of native versus nonnative languages, IQ, and cognitive development, and reduction in left frontal brain electrical activity associated with impaired positive emotions,” Dr. Hudepohl reported.

Sifting through published data, Dr. Hudepohl cited studies associating persistent postpartum depression with a more than fourfold risk of behavioral problems at the age of 3.5 years, lower grades in mathematics at age 16, and a higher prevalence of depression at age 18. Among children who had depressed mothers in infancy, there have also been studies showing a higher reactivity to stressors and higher baseline cortisol levels.

“The good news is that these effects in children appear to be largely reversible with maternal treatment,” Dr. Hudepohl said. In fact, she cited evidence of a correlation between improvement in maternal symptoms and a reduction in the complications in children, such as behavioral problems.

Postpartum depression, which can develop anytime in the first 12 months after childbirth, is not uncommon, occurring in approximately 15% of women, according to Dr. Hudepohl. Risk factors include personal or family history of depression, anxiety or depression during pregnancy, and a prior history of postpartum depression.

Postpartum depression increases the risk of maternal suicide by about 70-fold, Dr. Hudepohl reported. She noted that the peaks in suicide attempts in the 1st and 12th month after delivery. Adverse infant outcomes are not a predictor of increase risk of attempts, but fetal or infant death are.

According to one study, about 40% of mothers with postpartum depression have intrusive thoughts that involve harming their child. About 15% fear being alone with their infant. Behaviors such as decreased playfulness, less talking, or other interactions with the child, and inconsistent response to the child are all likely to contribute to impaired maternal-child bonding, Dr. Hudepohl reported.

For women who discontinued antidepressants for pregnancy but have now developed significant postpartum depression, Dr. Hudepohl recommended using “what has worked in the past.” She considered monotherapy preferable if possible, but severe symptoms warrant more aggressive intervention. Dr. Hudepohl pointed out that the risks of antidepressants taken by the breast-feeding mother to the infant remain unclear despite multiple studies attempting to establish and quantify risk.

“Antidepressants are the most researched medication in pregnancy,” she said.

Conversely, the risks of untreated symptoms to the mother are significant, and the potential risks to the infant and family – if variable – are not insignificant.

Overall, “nonpharmacologic treatment is preferred first line for mild symptoms,” Dr. Hudepohl, but she and others consider a risk-benefit ratio growing increasingly in favor of drug therapy when this approach is the best option for bringing moderate to severe symptoms under control.

Whether depression arises during pregnancy or in the postpartum period, “psychotherapy is generally considered first-line treatment,” agreed Nancy Byatt, DO, MS, MBA, professor of psychiatry and of obstetrics and gynecology at the University of Massachusetts, Worcester.

Dr. Byatt, who has published frequently on this topic, further agreed that risks to the mother and the child increase with uncontrolled depression in the postpartum period. With symptoms of greater intensity, the uncertain risks of medication are outweighed by substantial potential benefits.

“When a pregnant or postpartum individual has moderate to severe illness, treatment with medication is typically recommended, because the benefits are thought to outweigh the risks,” she said, echoing a consensus opinion among experts and organized medicine.

MedscapeLive and this news organization are owned by the same parent company. Dr. Hudepohl and Dr. Byatt reported no potential financial conflicts of interest.
 

If moderate to severe postpartum depression poses a risk to child development, that argues in favor of pharmacologic therapy, according to a detailed risk-benefit assessment presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

monkeybusinessimages/Thinkstock

“It is important to consider that there are potential risks of antidepressant drugs, but there are also potential risks from not providing effective treatment,” reported Neha Hudepohl, MD, at the virtual meeting, presented by MedscapeLive.

On a website maintained by the Centers for Disease Control and Prevention, the question of whether antidepressants pose a risk to breast-feeding children is answered with a “maybe.” Although many of these drugs can be detected in breast milk, according to the CDC, “most have little or no effect on milk supply or on infant well-being.”

This is enough uncertainty that antidepressants are not first-line intervention when postpartum depression is mild, said Dr. Hudepohl, director of women’s mental health at Prisma Health Upstate, Greenville, S.C. However, she noted that the American College of Obstetricians and Gynecologists is among the organizations that recommend drug treatment if symptoms are moderate to severe.

“Depression in the mother affects interactions in feeding practices, sleep routines and patterns, and safety practices,” said Dr. Hudepohl, citing published studies supporting each of these consequences.

For the child, there is some degree of uncertainty about risk from untreated maternal depression as well as from breast mild exposure to antidepressants. Conclusive statements are not offered by ACOG and others.

“Some but not all studies have shown an impact of either antenatal or postnatal depression on speech recognition in infancy of native versus nonnative languages, IQ, and cognitive development, and reduction in left frontal brain electrical activity associated with impaired positive emotions,” Dr. Hudepohl reported.

Sifting through published data, Dr. Hudepohl cited studies associating persistent postpartum depression with a more than fourfold risk of behavioral problems at the age of 3.5 years, lower grades in mathematics at age 16, and a higher prevalence of depression at age 18. Among children who had depressed mothers in infancy, there have also been studies showing a higher reactivity to stressors and higher baseline cortisol levels.

“The good news is that these effects in children appear to be largely reversible with maternal treatment,” Dr. Hudepohl said. In fact, she cited evidence of a correlation between improvement in maternal symptoms and a reduction in the complications in children, such as behavioral problems.

Postpartum depression, which can develop anytime in the first 12 months after childbirth, is not uncommon, occurring in approximately 15% of women, according to Dr. Hudepohl. Risk factors include personal or family history of depression, anxiety or depression during pregnancy, and a prior history of postpartum depression.

Postpartum depression increases the risk of maternal suicide by about 70-fold, Dr. Hudepohl reported. She noted that the peaks in suicide attempts in the 1st and 12th month after delivery. Adverse infant outcomes are not a predictor of increase risk of attempts, but fetal or infant death are.

According to one study, about 40% of mothers with postpartum depression have intrusive thoughts that involve harming their child. About 15% fear being alone with their infant. Behaviors such as decreased playfulness, less talking, or other interactions with the child, and inconsistent response to the child are all likely to contribute to impaired maternal-child bonding, Dr. Hudepohl reported.

For women who discontinued antidepressants for pregnancy but have now developed significant postpartum depression, Dr. Hudepohl recommended using “what has worked in the past.” She considered monotherapy preferable if possible, but severe symptoms warrant more aggressive intervention. Dr. Hudepohl pointed out that the risks of antidepressants taken by the breast-feeding mother to the infant remain unclear despite multiple studies attempting to establish and quantify risk.

“Antidepressants are the most researched medication in pregnancy,” she said.

Conversely, the risks of untreated symptoms to the mother are significant, and the potential risks to the infant and family – if variable – are not insignificant.

Overall, “nonpharmacologic treatment is preferred first line for mild symptoms,” Dr. Hudepohl, but she and others consider a risk-benefit ratio growing increasingly in favor of drug therapy when this approach is the best option for bringing moderate to severe symptoms under control.

Whether depression arises during pregnancy or in the postpartum period, “psychotherapy is generally considered first-line treatment,” agreed Nancy Byatt, DO, MS, MBA, professor of psychiatry and of obstetrics and gynecology at the University of Massachusetts, Worcester.

Dr. Byatt, who has published frequently on this topic, further agreed that risks to the mother and the child increase with uncontrolled depression in the postpartum period. With symptoms of greater intensity, the uncertain risks of medication are outweighed by substantial potential benefits.

“When a pregnant or postpartum individual has moderate to severe illness, treatment with medication is typically recommended, because the benefits are thought to outweigh the risks,” she said, echoing a consensus opinion among experts and organized medicine.

MedscapeLive and this news organization are owned by the same parent company. Dr. Hudepohl and Dr. Byatt reported no potential financial conflicts of interest.
 

A novel formulation containing meloxicam and rizatriptan provides effective pain relief for patients with migraine, new research suggests. Results from the phase 3 INTERCEPT trial show that the treatment, known as AXS-07 (Axsome Therapeutics), also provided greater relief from the patients’ most bothersome symptom (MBS) compared with placebo.

In addition, about 74% of patients who received AXS-07 experienced no progression of pain from 2 to 24 hours after dosing and were less than half as likely to use rescue medication through 24 hours than those who received placebo.

Similar to a previous formulation combining naproxen sodium and sumatriptan, AXS-07 combines a nonsteroidal anti-inflammatory drug with a triptan. The combination is synergistic, investigators note, because one drug addresses pain mechanisms that the other does not.

“Rizatriptan’s primary mechanism is peripheral, and NSAIDs have both peripheral and central benefit,” said study investigator Stewart J. Tepper, MD, professor of neurology, Geisel School of Medicine at Dartmouth, Hanover, N.H. “That is why the whole is greater than the sum of the parts,” Dr. Tepper added.

The findings were presented at the American Headache Society’s 2021 annual meeting.
 

Acute treatments needed

For many patients, current migraine treatments are inadequate. In addition, suboptimal acute treatment can increase risk for progression from episodic migraine to chronic migraine. It also increases the risk for medication-overuse headache.

The search for optimal acute treatments is therefore “really important for patients,” Dr. Tepper noted.

Because it contains rizatriptan, AXS-07 is believed to inhibit the release of calcitonin gene-related peptide, reverse the vasodilation that it causes, and decrease the transmission of pain signals. Meloxicam, on the other hand, is thought to reduce neuroinflammation and reverse central sensitization, which maintains chronic pain.

In the phase 3, double-blind INTERCEPT trial, the investigators examined AXS-07 for early treatment of migraine. Eligible patients were aged 18 to 65 years, had been diagnosed with migraine in accordance with ICHD-3 criteria, and averaged two to eight migraines per month.

The researchers randomly assigned a single dose of AXS-07 (n = 152) or placebo (n = 150). Participants were asked to administer treatment to themselves at the earliest sign of migraine pain.

The trial’s two primary endpoints were pain freedom and freedom from the MBS 2 hours after dosing. Secondary endpoints included sustained pain freedom and freedom from pain progression, functional disability, and use of rescue medication.

Demographic characteristics of the study population reflected those of the general population of people with migraine, according to the researchers. More than 85% of participants were women, and the study group’s mean age was 41 years. There were no demographic differences between the two treatment groups.
 

Reduced pain progression

Results showed that 2 hours after treatment, rate of pain freedom was 32.6% in the AXS-07 group and 16.3% in the placebo group (P = .002). At the same time point, rate of freedom from MBS was 43.9% and 26.7%, respectively (P = .003).

Approximately 64% of patients who received AXS-07 were pain free at 12 hours, and 69% were pain free at 24 hours. In contrast, 42% of the placebo group were pain free at 12 hours, and 47% were pain free at 24 hours (P < .001 for both comparisons).

The benefits AXS-07 provided were sustained; 22.7% of the active-treatment group achieved sustained pain freedom from 2 to 24 hours after treatment, compared with 12.6% of the placebo group (P = .03). Results were similar for sustained pain freedom from 2 to 48 hours after treatment (20.5% vs. 9.6%; P = .013).

In addition, 73.5% of patients who received AXS-07 had freedom from pain progression from 2 to 24 hours after treatment, versus 47.4% of those who received placebo (P < .001). The rate of rescue medication use through 24 hours was 15.3% and 42.2%, respectively (P < .001).

AXS-07 was also linked to significant reductions in functional disability. About 74% of patients who received it reported no disability at 24 hours, compared with 47% of patients who received placebo (P < .001). Scores on the Patient Global Impression of Change scale were very much improved or much improved 2 hours after dosing for 52.4% of the AXS-07 group, versus 27.7% of the placebo group (P < .001).

The overall rate of treatment-emergent adverse events (AEs) was 17.9% in the active group and 7.7% among the control group. The rate of somnolence was 4.3%, versus 2.1%; the rate of dizziness was 2.9%, versus 1.4%; and the rate of paresthesia was 2.1%, versus 0%. There were no serious AEs.

“Unexpectedly, and it’s hard to interpret this, but the nausea associated with the use of AXS-07 is less than with either of the active components or the placebo,” said Dr. Tepper. “It’s not dramatically different for dizziness.”
 

Improved adherence?

Meloxicam is generally used not as an acute medication but for prevention, Dr. Tepper noted. The drug is often administered to reduce inflammation in conditions such as chronic arthritis.

AXS-07 incorporates an altered pharmacokinetic delivery system to provide a quicker onset of effect for meloxicam.

“Most headache specialists would say that of all the oral triptans, rizatriptan is the fastest,” said Dr. Tepper.

The idea for the new agent was to hasten the onset of meloxicam’s effect so that both active components would work rapidly. “We know that there is a synergy between NSAIDs and triptans, in terms of complete headache response,” Dr. Tepper said.

Data indicate that when neurologists recommend that patients take an NSAID and triptan together at the beginning of an attack, patients rarely comply. “It’s a big adherence issue,” said Dr. Tepper. “They’re more likely to get a complete response if they take them together, especially if the tablet is designed to deliver the two products together in an optimal way.”
 

Uncertain therapeutic advantage

Commenting on the findings, Robert Shapiro, MD, PhD, professor of neurologic science at the University of Vermont, Burlington, noted that because of favorable data from past studies for the combination of 85 mg of sumatriptan with 500 mg of naproxen sodium, the coadministration of a triptan with an NSAID has been a standard of care for the past decade.

“It’s therefore unsurprising that a combination of rizatriptan 10 mg plus meloxicam 20 mg in a proprietary MoSEIC formulation might also prove to be more effective than either individual medication taken alone for acute migraine attacks,” said Dr. Shapiro, who was not involved with the research.

It is not possible to compare the efficacy and tolerability of AXS-07 with those of sumatriptan–naproxen sodium without head-to-head trials. However, the available data suggest that the latter formulation is superior, he added.

In 2008, researchers conducted two parallel-group, placebo-controlled trials of sumatriptan–naproxen sodium taken early in a migraine attack. These trials had protocols comparable to that of the current INTERCEPT trial for AXS-07, said Dr. Shapiro.

For the key primary endpoint of 2-hour pain freedom, the two sumatriptan–naproxen sodium trials found therapeutic gains of 35% and 36%, respectively, versus 16.3% for the AXS-07 trial. The placebo response rates (17% and 15% for sumatriptan–naproxen sodium, vs. 16.3% for the AXS-07 trial) were comparable.

Similarly, for the endpoint of 2- to 24-hour pain freedom, the sumatriptan–naproxen sodium trials found therapeutic gains of 33% and 26%, respectively, versus 15.1% for the AXS-07 trial. Again, response rates for placebo were comparable (12% and 14% for sumatriptan–naproxen sodium, vs. 12.6% for AXS-07).
The placebo-adjusted differences for reporting any treatment-emergent AE, otherwise known as “therapeutic penalty,” was 10.2% for AXS-07 in the INTERCEPT trial, versus 7% and 5%, respectively for participants in the two sumatriptan–naproxen sodium trials.

“In light of these data, it’s not immediately apparent what advantage AXS-07 might offer over sumatriptan–naproxen sodium,” said Dr. Shapiro.

“Furthermore, sumatriptan–naproxen sodium is currently available in generic form,” he added.

The study was funded by Axsome Therapeutics. Dr. Tepper is a consultant to Axsome Therapeutics. Dr. Shapiro has previously performed research consulting for Lilly and Lundbeck.

A version of this article first appeared on Medscape.com.

A novel formulation containing meloxicam and rizatriptan provides effective pain relief for patients with migraine, new research suggests. Results from the phase 3 INTERCEPT trial show that the treatment, known as AXS-07 (Axsome Therapeutics), also provided greater relief from the patients’ most bothersome symptom (MBS) compared with placebo.

In addition, about 74% of patients who received AXS-07 experienced no progression of pain from 2 to 24 hours after dosing and were less than half as likely to use rescue medication through 24 hours than those who received placebo.

Similar to a previous formulation combining naproxen sodium and sumatriptan, AXS-07 combines a nonsteroidal anti-inflammatory drug with a triptan. The combination is synergistic, investigators note, because one drug addresses pain mechanisms that the other does not.

“Rizatriptan’s primary mechanism is peripheral, and NSAIDs have both peripheral and central benefit,” said study investigator Stewart J. Tepper, MD, professor of neurology, Geisel School of Medicine at Dartmouth, Hanover, N.H. “That is why the whole is greater than the sum of the parts,” Dr. Tepper added.

The findings were presented at the American Headache Society’s 2021 annual meeting.
 

Acute treatments needed

For many patients, current migraine treatments are inadequate. In addition, suboptimal acute treatment can increase risk for progression from episodic migraine to chronic migraine. It also increases the risk for medication-overuse headache.

The search for optimal acute treatments is therefore “really important for patients,” Dr. Tepper noted.

Because it contains rizatriptan, AXS-07 is believed to inhibit the release of calcitonin gene-related peptide, reverse the vasodilation that it causes, and decrease the transmission of pain signals. Meloxicam, on the other hand, is thought to reduce neuroinflammation and reverse central sensitization, which maintains chronic pain.

In the phase 3, double-blind INTERCEPT trial, the investigators examined AXS-07 for early treatment of migraine. Eligible patients were aged 18 to 65 years, had been diagnosed with migraine in accordance with ICHD-3 criteria, and averaged two to eight migraines per month.

The researchers randomly assigned a single dose of AXS-07 (n = 152) or placebo (n = 150). Participants were asked to administer treatment to themselves at the earliest sign of migraine pain.

The trial’s two primary endpoints were pain freedom and freedom from the MBS 2 hours after dosing. Secondary endpoints included sustained pain freedom and freedom from pain progression, functional disability, and use of rescue medication.

Demographic characteristics of the study population reflected those of the general population of people with migraine, according to the researchers. More than 85% of participants were women, and the study group’s mean age was 41 years. There were no demographic differences between the two treatment groups.
 

Reduced pain progression

Results showed that 2 hours after treatment, rate of pain freedom was 32.6% in the AXS-07 group and 16.3% in the placebo group (P = .002). At the same time point, rate of freedom from MBS was 43.9% and 26.7%, respectively (P = .003).

Approximately 64% of patients who received AXS-07 were pain free at 12 hours, and 69% were pain free at 24 hours. In contrast, 42% of the placebo group were pain free at 12 hours, and 47% were pain free at 24 hours (P < .001 for both comparisons).

The benefits AXS-07 provided were sustained; 22.7% of the active-treatment group achieved sustained pain freedom from 2 to 24 hours after treatment, compared with 12.6% of the placebo group (P = .03). Results were similar for sustained pain freedom from 2 to 48 hours after treatment (20.5% vs. 9.6%; P = .013).

In addition, 73.5% of patients who received AXS-07 had freedom from pain progression from 2 to 24 hours after treatment, versus 47.4% of those who received placebo (P < .001). The rate of rescue medication use through 24 hours was 15.3% and 42.2%, respectively (P < .001).

AXS-07 was also linked to significant reductions in functional disability. About 74% of patients who received it reported no disability at 24 hours, compared with 47% of patients who received placebo (P < .001). Scores on the Patient Global Impression of Change scale were very much improved or much improved 2 hours after dosing for 52.4% of the AXS-07 group, versus 27.7% of the placebo group (P < .001).

The overall rate of treatment-emergent adverse events (AEs) was 17.9% in the active group and 7.7% among the control group. The rate of somnolence was 4.3%, versus 2.1%; the rate of dizziness was 2.9%, versus 1.4%; and the rate of paresthesia was 2.1%, versus 0%. There were no serious AEs.

“Unexpectedly, and it’s hard to interpret this, but the nausea associated with the use of AXS-07 is less than with either of the active components or the placebo,” said Dr. Tepper. “It’s not dramatically different for dizziness.”
 

Improved adherence?

Meloxicam is generally used not as an acute medication but for prevention, Dr. Tepper noted. The drug is often administered to reduce inflammation in conditions such as chronic arthritis.

AXS-07 incorporates an altered pharmacokinetic delivery system to provide a quicker onset of effect for meloxicam.

“Most headache specialists would say that of all the oral triptans, rizatriptan is the fastest,” said Dr. Tepper.

The idea for the new agent was to hasten the onset of meloxicam’s effect so that both active components would work rapidly. “We know that there is a synergy between NSAIDs and triptans, in terms of complete headache response,” Dr. Tepper said.

Data indicate that when neurologists recommend that patients take an NSAID and triptan together at the beginning of an attack, patients rarely comply. “It’s a big adherence issue,” said Dr. Tepper. “They’re more likely to get a complete response if they take them together, especially if the tablet is designed to deliver the two products together in an optimal way.”
 

Uncertain therapeutic advantage

Commenting on the findings, Robert Shapiro, MD, PhD, professor of neurologic science at the University of Vermont, Burlington, noted that because of favorable data from past studies for the combination of 85 mg of sumatriptan with 500 mg of naproxen sodium, the coadministration of a triptan with an NSAID has been a standard of care for the past decade.

“It’s therefore unsurprising that a combination of rizatriptan 10 mg plus meloxicam 20 mg in a proprietary MoSEIC formulation might also prove to be more effective than either individual medication taken alone for acute migraine attacks,” said Dr. Shapiro, who was not involved with the research.

It is not possible to compare the efficacy and tolerability of AXS-07 with those of sumatriptan–naproxen sodium without head-to-head trials. However, the available data suggest that the latter formulation is superior, he added.

In 2008, researchers conducted two parallel-group, placebo-controlled trials of sumatriptan–naproxen sodium taken early in a migraine attack. These trials had protocols comparable to that of the current INTERCEPT trial for AXS-07, said Dr. Shapiro.

For the key primary endpoint of 2-hour pain freedom, the two sumatriptan–naproxen sodium trials found therapeutic gains of 35% and 36%, respectively, versus 16.3% for the AXS-07 trial. The placebo response rates (17% and 15% for sumatriptan–naproxen sodium, vs. 16.3% for the AXS-07 trial) were comparable.

Similarly, for the endpoint of 2- to 24-hour pain freedom, the sumatriptan–naproxen sodium trials found therapeutic gains of 33% and 26%, respectively, versus 15.1% for the AXS-07 trial. Again, response rates for placebo were comparable (12% and 14% for sumatriptan–naproxen sodium, vs. 12.6% for AXS-07).
The placebo-adjusted differences for reporting any treatment-emergent AE, otherwise known as “therapeutic penalty,” was 10.2% for AXS-07 in the INTERCEPT trial, versus 7% and 5%, respectively for participants in the two sumatriptan–naproxen sodium trials.

“In light of these data, it’s not immediately apparent what advantage AXS-07 might offer over sumatriptan–naproxen sodium,” said Dr. Shapiro.

“Furthermore, sumatriptan–naproxen sodium is currently available in generic form,” he added.

The study was funded by Axsome Therapeutics. Dr. Tepper is a consultant to Axsome Therapeutics. Dr. Shapiro has previously performed research consulting for Lilly and Lundbeck.

A version of this article first appeared on Medscape.com.

A novel formulation containing meloxicam and rizatriptan provides effective pain relief for patients with migraine, new research suggests. Results from the phase 3 INTERCEPT trial show that the treatment, known as AXS-07 (Axsome Therapeutics), also provided greater relief from the patients’ most bothersome symptom (MBS) compared with placebo.

In addition, about 74% of patients who received AXS-07 experienced no progression of pain from 2 to 24 hours after dosing and were less than half as likely to use rescue medication through 24 hours than those who received placebo.

Similar to a previous formulation combining naproxen sodium and sumatriptan, AXS-07 combines a nonsteroidal anti-inflammatory drug with a triptan. The combination is synergistic, investigators note, because one drug addresses pain mechanisms that the other does not.

“Rizatriptan’s primary mechanism is peripheral, and NSAIDs have both peripheral and central benefit,” said study investigator Stewart J. Tepper, MD, professor of neurology, Geisel School of Medicine at Dartmouth, Hanover, N.H. “That is why the whole is greater than the sum of the parts,” Dr. Tepper added.

The findings were presented at the American Headache Society’s 2021 annual meeting.
 

Acute treatments needed

For many patients, current migraine treatments are inadequate. In addition, suboptimal acute treatment can increase risk for progression from episodic migraine to chronic migraine. It also increases the risk for medication-overuse headache.

The search for optimal acute treatments is therefore “really important for patients,” Dr. Tepper noted.

Because it contains rizatriptan, AXS-07 is believed to inhibit the release of calcitonin gene-related peptide, reverse the vasodilation that it causes, and decrease the transmission of pain signals. Meloxicam, on the other hand, is thought to reduce neuroinflammation and reverse central sensitization, which maintains chronic pain.

In the phase 3, double-blind INTERCEPT trial, the investigators examined AXS-07 for early treatment of migraine. Eligible patients were aged 18 to 65 years, had been diagnosed with migraine in accordance with ICHD-3 criteria, and averaged two to eight migraines per month.

The researchers randomly assigned a single dose of AXS-07 (n = 152) or placebo (n = 150). Participants were asked to administer treatment to themselves at the earliest sign of migraine pain.

The trial’s two primary endpoints were pain freedom and freedom from the MBS 2 hours after dosing. Secondary endpoints included sustained pain freedom and freedom from pain progression, functional disability, and use of rescue medication.

Demographic characteristics of the study population reflected those of the general population of people with migraine, according to the researchers. More than 85% of participants were women, and the study group’s mean age was 41 years. There were no demographic differences between the two treatment groups.
 

Reduced pain progression

Results showed that 2 hours after treatment, rate of pain freedom was 32.6% in the AXS-07 group and 16.3% in the placebo group (P = .002). At the same time point, rate of freedom from MBS was 43.9% and 26.7%, respectively (P = .003).

Approximately 64% of patients who received AXS-07 were pain free at 12 hours, and 69% were pain free at 24 hours. In contrast, 42% of the placebo group were pain free at 12 hours, and 47% were pain free at 24 hours (P < .001 for both comparisons).

The benefits AXS-07 provided were sustained; 22.7% of the active-treatment group achieved sustained pain freedom from 2 to 24 hours after treatment, compared with 12.6% of the placebo group (P = .03). Results were similar for sustained pain freedom from 2 to 48 hours after treatment (20.5% vs. 9.6%; P = .013).

In addition, 73.5% of patients who received AXS-07 had freedom from pain progression from 2 to 24 hours after treatment, versus 47.4% of those who received placebo (P < .001). The rate of rescue medication use through 24 hours was 15.3% and 42.2%, respectively (P < .001).

AXS-07 was also linked to significant reductions in functional disability. About 74% of patients who received it reported no disability at 24 hours, compared with 47% of patients who received placebo (P < .001). Scores on the Patient Global Impression of Change scale were very much improved or much improved 2 hours after dosing for 52.4% of the AXS-07 group, versus 27.7% of the placebo group (P < .001).

The overall rate of treatment-emergent adverse events (AEs) was 17.9% in the active group and 7.7% among the control group. The rate of somnolence was 4.3%, versus 2.1%; the rate of dizziness was 2.9%, versus 1.4%; and the rate of paresthesia was 2.1%, versus 0%. There were no serious AEs.

“Unexpectedly, and it’s hard to interpret this, but the nausea associated with the use of AXS-07 is less than with either of the active components or the placebo,” said Dr. Tepper. “It’s not dramatically different for dizziness.”
 

Improved adherence?

Meloxicam is generally used not as an acute medication but for prevention, Dr. Tepper noted. The drug is often administered to reduce inflammation in conditions such as chronic arthritis.

AXS-07 incorporates an altered pharmacokinetic delivery system to provide a quicker onset of effect for meloxicam.

“Most headache specialists would say that of all the oral triptans, rizatriptan is the fastest,” said Dr. Tepper.

The idea for the new agent was to hasten the onset of meloxicam’s effect so that both active components would work rapidly. “We know that there is a synergy between NSAIDs and triptans, in terms of complete headache response,” Dr. Tepper said.

Data indicate that when neurologists recommend that patients take an NSAID and triptan together at the beginning of an attack, patients rarely comply. “It’s a big adherence issue,” said Dr. Tepper. “They’re more likely to get a complete response if they take them together, especially if the tablet is designed to deliver the two products together in an optimal way.”
 

Uncertain therapeutic advantage

Commenting on the findings, Robert Shapiro, MD, PhD, professor of neurologic science at the University of Vermont, Burlington, noted that because of favorable data from past studies for the combination of 85 mg of sumatriptan with 500 mg of naproxen sodium, the coadministration of a triptan with an NSAID has been a standard of care for the past decade.

“It’s therefore unsurprising that a combination of rizatriptan 10 mg plus meloxicam 20 mg in a proprietary MoSEIC formulation might also prove to be more effective than either individual medication taken alone for acute migraine attacks,” said Dr. Shapiro, who was not involved with the research.

It is not possible to compare the efficacy and tolerability of AXS-07 with those of sumatriptan–naproxen sodium without head-to-head trials. However, the available data suggest that the latter formulation is superior, he added.

In 2008, researchers conducted two parallel-group, placebo-controlled trials of sumatriptan–naproxen sodium taken early in a migraine attack. These trials had protocols comparable to that of the current INTERCEPT trial for AXS-07, said Dr. Shapiro.

For the key primary endpoint of 2-hour pain freedom, the two sumatriptan–naproxen sodium trials found therapeutic gains of 35% and 36%, respectively, versus 16.3% for the AXS-07 trial. The placebo response rates (17% and 15% for sumatriptan–naproxen sodium, vs. 16.3% for the AXS-07 trial) were comparable.

Similarly, for the endpoint of 2- to 24-hour pain freedom, the sumatriptan–naproxen sodium trials found therapeutic gains of 33% and 26%, respectively, versus 15.1% for the AXS-07 trial. Again, response rates for placebo were comparable (12% and 14% for sumatriptan–naproxen sodium, vs. 12.6% for AXS-07).
The placebo-adjusted differences for reporting any treatment-emergent AE, otherwise known as “therapeutic penalty,” was 10.2% for AXS-07 in the INTERCEPT trial, versus 7% and 5%, respectively for participants in the two sumatriptan–naproxen sodium trials.

“In light of these data, it’s not immediately apparent what advantage AXS-07 might offer over sumatriptan–naproxen sodium,” said Dr. Shapiro.

“Furthermore, sumatriptan–naproxen sodium is currently available in generic form,” he added.

The study was funded by Axsome Therapeutics. Dr. Tepper is a consultant to Axsome Therapeutics. Dr. Shapiro has previously performed research consulting for Lilly and Lundbeck.

A version of this article first appeared on Medscape.com.

Hypomethylating agents are generally considered to be agents of choice for older adults with acute myeloid leukemia who cannot tolerate the rigors of more intensive therapies, but HMAs also can serve as a bridge to transplant for children and young adults with relapsed or refractory acute myeloid leukemia.

That’s according to Himalee S. Sabnis, MD, MSc and colleagues at Emory University and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.

In a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology, the investigators reported results of a retrospective study of HMA use in patients with relapsed or refractory pediatric AML treated in their center.
 

Curative intent and palliation

They identified 25 patients (15 boys) with a median age of 8.3 years (range 1.4 to 21 years) with relapsed/refractory AML who received HMAs for curative intent prior to hematopoietic stem cell transplant (HSCT), palliation, or in combination with donor leukocyte infusion (DLI).

Of the 21 patients with relapsed disease, 16 were in first relapse and 5 were in second relapse or greater. Four of the patients had primary refractory disease. The cytogenetic and molecular features were KMT2A rearrangements in six patients, monosomy 7/deletion 7 q in four patients, 8;21 translocation in three patients, and FLT3-ITD mutations in four patients.

The patients received a median of 5.3 HMA cycles each. Of the 133 total HMA cycles, 87 were with azacitidine, and 46 were with decitabine.

HMAs were used as monotherapy in 62% of cycles, and in combination with other therapies in 38%. Of the combinations, 16 were with donor leukocyte infusion, and 9 were gemtuzumab ozogamicin (Mylotarg).

Of the 13 patients for whom HMAs were used as part of treatment plan with curative intent, 5 proceeded to HSCT, and 8 did not. Of the 5 patients, 1 died from transplant-related causes, and 4 were alive post transplant. Of the 8 patients who did not undergo transplant, 1 had chimeric antigen receptor T- cell (CAR T) therapy, and 7 experienced disease progression.

The mean duration of palliative care was 144 days, with patients receiving from one to nine cycles with an HMA, and no treatment interruptions due to toxicity.

Of 5 patients who received donor leukocyte infusions, 3 reached minimal residual disease negativity; all 3 of these patients had late relapses but remained long-term survivors, the investigators reported.

They concluded that “hypomethylating agents can be used effectively as a bridge to transplantation in relapsed and refractory AML with gemtuzumab ozogamicin being the most common agent for combination therapy. Palliation with HMAs is associated with low toxicity and high tolerability in relapsed/refractory AML. Use of HMAs with DLI can induce sustained remissions in some patients.”

The authors propose prospective clinical trials using HMAs in the relapsed/refractory pediatric AML setting in combination with gemtuzumab ozogamicin, alternative targeted agents, and chemotherapy.

HMAs in treatment-related AML

Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, has experience administering HMAs primarily in the adolescent and young adult population with AML.

“Azacitidine and decitabine are good for treatment-related leukemias,” she said in an interview. “They can be used otherwise for people who have relapsed disease and are trying to navigate other options.”

Although they are not standard first-line agents in younger patients, HMAs can play a useful role in therapy for relapsed or refractory disease, she said.

The authors and Dr. Shahani reported having no conflicts of interest to disclose.

Hypomethylating agents are generally considered to be agents of choice for older adults with acute myeloid leukemia who cannot tolerate the rigors of more intensive therapies, but HMAs also can serve as a bridge to transplant for children and young adults with relapsed or refractory acute myeloid leukemia.

That’s according to Himalee S. Sabnis, MD, MSc and colleagues at Emory University and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.

In a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology, the investigators reported results of a retrospective study of HMA use in patients with relapsed or refractory pediatric AML treated in their center.
 

Curative intent and palliation

They identified 25 patients (15 boys) with a median age of 8.3 years (range 1.4 to 21 years) with relapsed/refractory AML who received HMAs for curative intent prior to hematopoietic stem cell transplant (HSCT), palliation, or in combination with donor leukocyte infusion (DLI).

Of the 21 patients with relapsed disease, 16 were in first relapse and 5 were in second relapse or greater. Four of the patients had primary refractory disease. The cytogenetic and molecular features were KMT2A rearrangements in six patients, monosomy 7/deletion 7 q in four patients, 8;21 translocation in three patients, and FLT3-ITD mutations in four patients.

The patients received a median of 5.3 HMA cycles each. Of the 133 total HMA cycles, 87 were with azacitidine, and 46 were with decitabine.

HMAs were used as monotherapy in 62% of cycles, and in combination with other therapies in 38%. Of the combinations, 16 were with donor leukocyte infusion, and 9 were gemtuzumab ozogamicin (Mylotarg).

Of the 13 patients for whom HMAs were used as part of treatment plan with curative intent, 5 proceeded to HSCT, and 8 did not. Of the 5 patients, 1 died from transplant-related causes, and 4 were alive post transplant. Of the 8 patients who did not undergo transplant, 1 had chimeric antigen receptor T- cell (CAR T) therapy, and 7 experienced disease progression.

The mean duration of palliative care was 144 days, with patients receiving from one to nine cycles with an HMA, and no treatment interruptions due to toxicity.

Of 5 patients who received donor leukocyte infusions, 3 reached minimal residual disease negativity; all 3 of these patients had late relapses but remained long-term survivors, the investigators reported.

They concluded that “hypomethylating agents can be used effectively as a bridge to transplantation in relapsed and refractory AML with gemtuzumab ozogamicin being the most common agent for combination therapy. Palliation with HMAs is associated with low toxicity and high tolerability in relapsed/refractory AML. Use of HMAs with DLI can induce sustained remissions in some patients.”

The authors propose prospective clinical trials using HMAs in the relapsed/refractory pediatric AML setting in combination with gemtuzumab ozogamicin, alternative targeted agents, and chemotherapy.

HMAs in treatment-related AML

Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, has experience administering HMAs primarily in the adolescent and young adult population with AML.

“Azacitidine and decitabine are good for treatment-related leukemias,” she said in an interview. “They can be used otherwise for people who have relapsed disease and are trying to navigate other options.”

Although they are not standard first-line agents in younger patients, HMAs can play a useful role in therapy for relapsed or refractory disease, she said.

The authors and Dr. Shahani reported having no conflicts of interest to disclose.

Hypomethylating agents are generally considered to be agents of choice for older adults with acute myeloid leukemia who cannot tolerate the rigors of more intensive therapies, but HMAs also can serve as a bridge to transplant for children and young adults with relapsed or refractory acute myeloid leukemia.

That’s according to Himalee S. Sabnis, MD, MSc and colleagues at Emory University and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.

In a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology, the investigators reported results of a retrospective study of HMA use in patients with relapsed or refractory pediatric AML treated in their center.
 

Curative intent and palliation

They identified 25 patients (15 boys) with a median age of 8.3 years (range 1.4 to 21 years) with relapsed/refractory AML who received HMAs for curative intent prior to hematopoietic stem cell transplant (HSCT), palliation, or in combination with donor leukocyte infusion (DLI).

Of the 21 patients with relapsed disease, 16 were in first relapse and 5 were in second relapse or greater. Four of the patients had primary refractory disease. The cytogenetic and molecular features were KMT2A rearrangements in six patients, monosomy 7/deletion 7 q in four patients, 8;21 translocation in three patients, and FLT3-ITD mutations in four patients.

The patients received a median of 5.3 HMA cycles each. Of the 133 total HMA cycles, 87 were with azacitidine, and 46 were with decitabine.

HMAs were used as monotherapy in 62% of cycles, and in combination with other therapies in 38%. Of the combinations, 16 were with donor leukocyte infusion, and 9 were gemtuzumab ozogamicin (Mylotarg).

Of the 13 patients for whom HMAs were used as part of treatment plan with curative intent, 5 proceeded to HSCT, and 8 did not. Of the 5 patients, 1 died from transplant-related causes, and 4 were alive post transplant. Of the 8 patients who did not undergo transplant, 1 had chimeric antigen receptor T- cell (CAR T) therapy, and 7 experienced disease progression.

The mean duration of palliative care was 144 days, with patients receiving from one to nine cycles with an HMA, and no treatment interruptions due to toxicity.

Of 5 patients who received donor leukocyte infusions, 3 reached minimal residual disease negativity; all 3 of these patients had late relapses but remained long-term survivors, the investigators reported.

They concluded that “hypomethylating agents can be used effectively as a bridge to transplantation in relapsed and refractory AML with gemtuzumab ozogamicin being the most common agent for combination therapy. Palliation with HMAs is associated with low toxicity and high tolerability in relapsed/refractory AML. Use of HMAs with DLI can induce sustained remissions in some patients.”

The authors propose prospective clinical trials using HMAs in the relapsed/refractory pediatric AML setting in combination with gemtuzumab ozogamicin, alternative targeted agents, and chemotherapy.

HMAs in treatment-related AML

Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, has experience administering HMAs primarily in the adolescent and young adult population with AML.

“Azacitidine and decitabine are good for treatment-related leukemias,” she said in an interview. “They can be used otherwise for people who have relapsed disease and are trying to navigate other options.”

Although they are not standard first-line agents in younger patients, HMAs can play a useful role in therapy for relapsed or refractory disease, she said.

The authors and Dr. Shahani reported having no conflicts of interest to disclose.

Pregnant women with migraine are at increased risk for more obstetric and postpartum complications and should be considered “high risk,” new research suggests. Although pregnancy is generally considered a “safe period” for women with migraine, “we actually found they have more diabetes, more hypertension, more blood clots, more complications during their delivery, and more postpartum complications,” said study investigator Nirit Lev, MD, PhD, head, department of neurology, Meir Medical Center, Kfar Saba Sackler Faculty of Medicine, Tel Aviv University.

The results highlight the need for clinicians “to take people with migraines seriously” and reinforce the idea that migraine is not “just a headache,” said Dr. Lev.

Pregnant women with migraine should be considered high risk and have specialized neurologic follow-up during pregnancy and the postpartum period, she added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

Prevalent, disabling

Migraine is one of the most prevalent and disabling neurologic disorders. Such disorders are major causes of death and disability.

In childhood, there’s no difference between the sexes in terms of migraine prevalence, but after puberty, migraine is about three times more common in women than men. Fluctuating levels of estrogen and progesterone likely explain these differences, said Dr. Lev.

The prevalence of migraine among females peaks during their reproductive years. Most female migraine patients report an improvement in headache symptoms during pregnancy, with some experiencing a “complete remission.” However, a minority report worsening of migraine when expecting a child, said Dr. Lev.

Some patients have their first aura during pregnancy. The most common migraine aura is visual, a problem with the visual field that can affect motor and sensory functioning, said Dr. Lev.

Managing migraine during pregnancy is “very complicated,” said Dr. Lev. She said the first-line treatment is paracetamol (acetaminophen) and stressed that taking opioids should be avoided.
 

Retrospective database study

For the study, the researchers retrospectively reviewed pregnancy and delivery records from a database of Clalit Medical Services, which has more than 4.5 million members and is the largest such database in Israel. They collected demographic data and information on mode of delivery, medical and obstetric complications, hospitalizations, emergency department visits, use of medications, laboratory reports, and medical consultations.

The study included 145,102 women who gave birth from 2014 to 2020.

Of these, 10,646 had migraine without aura, and 1,576 had migraine with aura. The migraine diagnoses, which were based on International Headache Society criteria and diagnostic codes, were made prior to pregnancy.

Dr. Lev noted that the number of patients with migraine is likely an underestimation because migraine is “not always diagnosed.”

Results showed that the risk for obstetric complications was higher among pregnant women with migraine, especially those with aura, in comparison with women without migraine. About 6.9% of patients with migraine without aura were admitted to high-risk hospital departments, compared with 6% of pregnant control patients who did not have migraine (P < .0001). For patients with migraine with aura, the risk for admissions was even higher (8.7%; P < .0001 vs. control patients and P < .03 vs. patients with migraine without aura) and was “very highly statistically significant,” said Dr. Lev.

Pregnant women with migraine were at significantly increased risk for gestational diabetes, hyperlipidemia, and being diagnosed with a psychiatric disorder (all P < .0001). These women were also more likely to experience preeclampsia and blood clots (P < .0001).
 

Unexpected finding

The finding that the risk for diabetes was higher was “unexpected,” inasmuch as older women with migraine are typically at increased risk for metabolic syndrome and higher body mass index, said Dr. Lev.

Migraine patients had significantly more consultations with family physicians, gynecologists, and neurologists (P < .0001). In addition, they were more likely to utilize emergency services; take more medications, mostly analgesics; and undergo more laboratory studies and brain imaging.

Those with aura had significantly more specialist consultations and took more medications compared with migraine patients without aura.

There was a statistically significant increase in the use of epidural anesthesia for migraine patients (40.5% of women without migraine; 45.7% of those with migraine accompanied by aura; and 47.5% of migraine patients without aura).

This was an “interesting” finding, said Dr. Lev. “We didn’t know what to expect; people with migraine are used to pain, so the question was, will they tolerate pain better or be more afraid of pain?”

Women with migraine also experienced more assisted deliveries with increased use of vacuums and forceps.

During the 3-month postpartum period, women with migraine sought more medical consultations and used more medications compared with control patients. They also underwent more lab examinations and more brain imaging during this period.

Dr. Lev noted that some of these evaluations may have been postponed because of the pregnancy.

Women with migraine also had a greater risk for postpartum depression, which Dr. Lev found “concerning.” She noted that depression is often underreported but is treatable. Women with migraine should be monitored for depression post partum, she said.

It’s unclear which factors contribute to the increased risk for pregnancy complications in women with migraine. Dr. Lev said she doesn’t believe it’s drug related.

“Although they’re taking more medications than people who don’t have migraine, we still are giving very low doses and only safe medicines, so I don’t think these increased risks are side effects,” she said.

She noted that women with migraine have more cardiovascular complications, including stroke and myocardial infarction, although these generally affect older patients.

Dr. Lev also noted that pain, especially chronic pain, can cause depression. “We know that people with migraine have more depression and anxiety, so maybe that also affects them during their pregnancy and after,” she said.

She suggested that pregnant women with migraine be considered high risk and be managed via specialized clinics.
 

Room for improvement

Commenting on the research, Lauren Doyle Strauss, DO, associate professor of neurology, Wake Forest University, Winston-Salem, N.C., who has written about the management of migraine during pregnancy, said studies such as this help raise awareness about pregnancy risks in migraine patients. Dr. Strauss did not attend the live presentation but is aware of the findings.

The increased use of epidurals during delivery among migraine patients in the study makes some sense, said Dr. Strauss. “It kind of shows a comfort level with medicines.”

She expressed concern that such research may be “skewed” because it includes patients with more severe migraine. If less severe cases were included in this research, “maybe there would still be higher risks, but not as high as what we have been finding in some of our studies,” she said.

Dr. Strauss said she feels the medical community should do a better job of identifying and diagnosing migraine. She said she would like to see migraine screening become a routine part of obstetric/gynecologic care. Doctors should counsel migraine patients who wish to become pregnant about potential risks, said Dr. Strauss. “We need to be up front in telling them when to seek care and when to report symptoms and not to wait for it to become super severe,” she said.

She also believes doctors should be “proactive” in helping patients develop a treatment plan before becoming pregnant, because the limited pain control options available for pregnant patients can take time to have an effect.

Also commenting on the study findings, Nina Riggins, MD, PhD, clinical associate professor of neurology at the University of California, San Francisco, said the study raises “important questions” and has “important aims.”

She believes the study reinforces the importance of collaboration between experts in primary care, obstetrics/gynecology, and neurology. However, she was surprised at some of the investigators’ assertions that there are no differences in migraine among prepubertal children and that the course of migraine for men is stable throughout their life span.

“There is literature that supports the view that the prevalence in boys is higher in prepuberty, and studies do show that migraine prevalence decreases in older adults – men and women,” she said.

There is still not enough evidence to determine that antiemetics and triptans are safe during pregnancy or that pregnant women with migraine should be taking acetylsalicylic acid, said Dr. Riggins.

The investigators, Dr. Strauss, and Dr. Riggins have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pregnant women with migraine are at increased risk for more obstetric and postpartum complications and should be considered “high risk,” new research suggests. Although pregnancy is generally considered a “safe period” for women with migraine, “we actually found they have more diabetes, more hypertension, more blood clots, more complications during their delivery, and more postpartum complications,” said study investigator Nirit Lev, MD, PhD, head, department of neurology, Meir Medical Center, Kfar Saba Sackler Faculty of Medicine, Tel Aviv University.

The results highlight the need for clinicians “to take people with migraines seriously” and reinforce the idea that migraine is not “just a headache,” said Dr. Lev.

Pregnant women with migraine should be considered high risk and have specialized neurologic follow-up during pregnancy and the postpartum period, she added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

Prevalent, disabling

Migraine is one of the most prevalent and disabling neurologic disorders. Such disorders are major causes of death and disability.

In childhood, there’s no difference between the sexes in terms of migraine prevalence, but after puberty, migraine is about three times more common in women than men. Fluctuating levels of estrogen and progesterone likely explain these differences, said Dr. Lev.

The prevalence of migraine among females peaks during their reproductive years. Most female migraine patients report an improvement in headache symptoms during pregnancy, with some experiencing a “complete remission.” However, a minority report worsening of migraine when expecting a child, said Dr. Lev.

Some patients have their first aura during pregnancy. The most common migraine aura is visual, a problem with the visual field that can affect motor and sensory functioning, said Dr. Lev.

Managing migraine during pregnancy is “very complicated,” said Dr. Lev. She said the first-line treatment is paracetamol (acetaminophen) and stressed that taking opioids should be avoided.
 

Retrospective database study

For the study, the researchers retrospectively reviewed pregnancy and delivery records from a database of Clalit Medical Services, which has more than 4.5 million members and is the largest such database in Israel. They collected demographic data and information on mode of delivery, medical and obstetric complications, hospitalizations, emergency department visits, use of medications, laboratory reports, and medical consultations.

The study included 145,102 women who gave birth from 2014 to 2020.

Of these, 10,646 had migraine without aura, and 1,576 had migraine with aura. The migraine diagnoses, which were based on International Headache Society criteria and diagnostic codes, were made prior to pregnancy.

Dr. Lev noted that the number of patients with migraine is likely an underestimation because migraine is “not always diagnosed.”

Results showed that the risk for obstetric complications was higher among pregnant women with migraine, especially those with aura, in comparison with women without migraine. About 6.9% of patients with migraine without aura were admitted to high-risk hospital departments, compared with 6% of pregnant control patients who did not have migraine (P < .0001). For patients with migraine with aura, the risk for admissions was even higher (8.7%; P < .0001 vs. control patients and P < .03 vs. patients with migraine without aura) and was “very highly statistically significant,” said Dr. Lev.

Pregnant women with migraine were at significantly increased risk for gestational diabetes, hyperlipidemia, and being diagnosed with a psychiatric disorder (all P < .0001). These women were also more likely to experience preeclampsia and blood clots (P < .0001).
 

Unexpected finding

The finding that the risk for diabetes was higher was “unexpected,” inasmuch as older women with migraine are typically at increased risk for metabolic syndrome and higher body mass index, said Dr. Lev.

Migraine patients had significantly more consultations with family physicians, gynecologists, and neurologists (P < .0001). In addition, they were more likely to utilize emergency services; take more medications, mostly analgesics; and undergo more laboratory studies and brain imaging.

Those with aura had significantly more specialist consultations and took more medications compared with migraine patients without aura.

There was a statistically significant increase in the use of epidural anesthesia for migraine patients (40.5% of women without migraine; 45.7% of those with migraine accompanied by aura; and 47.5% of migraine patients without aura).

This was an “interesting” finding, said Dr. Lev. “We didn’t know what to expect; people with migraine are used to pain, so the question was, will they tolerate pain better or be more afraid of pain?”

Women with migraine also experienced more assisted deliveries with increased use of vacuums and forceps.

During the 3-month postpartum period, women with migraine sought more medical consultations and used more medications compared with control patients. They also underwent more lab examinations and more brain imaging during this period.

Dr. Lev noted that some of these evaluations may have been postponed because of the pregnancy.

Women with migraine also had a greater risk for postpartum depression, which Dr. Lev found “concerning.” She noted that depression is often underreported but is treatable. Women with migraine should be monitored for depression post partum, she said.

It’s unclear which factors contribute to the increased risk for pregnancy complications in women with migraine. Dr. Lev said she doesn’t believe it’s drug related.

“Although they’re taking more medications than people who don’t have migraine, we still are giving very low doses and only safe medicines, so I don’t think these increased risks are side effects,” she said.

She noted that women with migraine have more cardiovascular complications, including stroke and myocardial infarction, although these generally affect older patients.

Dr. Lev also noted that pain, especially chronic pain, can cause depression. “We know that people with migraine have more depression and anxiety, so maybe that also affects them during their pregnancy and after,” she said.

She suggested that pregnant women with migraine be considered high risk and be managed via specialized clinics.
 

Room for improvement

Commenting on the research, Lauren Doyle Strauss, DO, associate professor of neurology, Wake Forest University, Winston-Salem, N.C., who has written about the management of migraine during pregnancy, said studies such as this help raise awareness about pregnancy risks in migraine patients. Dr. Strauss did not attend the live presentation but is aware of the findings.

The increased use of epidurals during delivery among migraine patients in the study makes some sense, said Dr. Strauss. “It kind of shows a comfort level with medicines.”

She expressed concern that such research may be “skewed” because it includes patients with more severe migraine. If less severe cases were included in this research, “maybe there would still be higher risks, but not as high as what we have been finding in some of our studies,” she said.

Dr. Strauss said she feels the medical community should do a better job of identifying and diagnosing migraine. She said she would like to see migraine screening become a routine part of obstetric/gynecologic care. Doctors should counsel migraine patients who wish to become pregnant about potential risks, said Dr. Strauss. “We need to be up front in telling them when to seek care and when to report symptoms and not to wait for it to become super severe,” she said.

She also believes doctors should be “proactive” in helping patients develop a treatment plan before becoming pregnant, because the limited pain control options available for pregnant patients can take time to have an effect.

Also commenting on the study findings, Nina Riggins, MD, PhD, clinical associate professor of neurology at the University of California, San Francisco, said the study raises “important questions” and has “important aims.”

She believes the study reinforces the importance of collaboration between experts in primary care, obstetrics/gynecology, and neurology. However, she was surprised at some of the investigators’ assertions that there are no differences in migraine among prepubertal children and that the course of migraine for men is stable throughout their life span.

“There is literature that supports the view that the prevalence in boys is higher in prepuberty, and studies do show that migraine prevalence decreases in older adults – men and women,” she said.

There is still not enough evidence to determine that antiemetics and triptans are safe during pregnancy or that pregnant women with migraine should be taking acetylsalicylic acid, said Dr. Riggins.

The investigators, Dr. Strauss, and Dr. Riggins have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pregnant women with migraine are at increased risk for more obstetric and postpartum complications and should be considered “high risk,” new research suggests. Although pregnancy is generally considered a “safe period” for women with migraine, “we actually found they have more diabetes, more hypertension, more blood clots, more complications during their delivery, and more postpartum complications,” said study investigator Nirit Lev, MD, PhD, head, department of neurology, Meir Medical Center, Kfar Saba Sackler Faculty of Medicine, Tel Aviv University.

The results highlight the need for clinicians “to take people with migraines seriously” and reinforce the idea that migraine is not “just a headache,” said Dr. Lev.

Pregnant women with migraine should be considered high risk and have specialized neurologic follow-up during pregnancy and the postpartum period, she added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

Prevalent, disabling

Migraine is one of the most prevalent and disabling neurologic disorders. Such disorders are major causes of death and disability.

In childhood, there’s no difference between the sexes in terms of migraine prevalence, but after puberty, migraine is about three times more common in women than men. Fluctuating levels of estrogen and progesterone likely explain these differences, said Dr. Lev.

The prevalence of migraine among females peaks during their reproductive years. Most female migraine patients report an improvement in headache symptoms during pregnancy, with some experiencing a “complete remission.” However, a minority report worsening of migraine when expecting a child, said Dr. Lev.

Some patients have their first aura during pregnancy. The most common migraine aura is visual, a problem with the visual field that can affect motor and sensory functioning, said Dr. Lev.

Managing migraine during pregnancy is “very complicated,” said Dr. Lev. She said the first-line treatment is paracetamol (acetaminophen) and stressed that taking opioids should be avoided.
 

Retrospective database study

For the study, the researchers retrospectively reviewed pregnancy and delivery records from a database of Clalit Medical Services, which has more than 4.5 million members and is the largest such database in Israel. They collected demographic data and information on mode of delivery, medical and obstetric complications, hospitalizations, emergency department visits, use of medications, laboratory reports, and medical consultations.

The study included 145,102 women who gave birth from 2014 to 2020.

Of these, 10,646 had migraine without aura, and 1,576 had migraine with aura. The migraine diagnoses, which were based on International Headache Society criteria and diagnostic codes, were made prior to pregnancy.

Dr. Lev noted that the number of patients with migraine is likely an underestimation because migraine is “not always diagnosed.”

Results showed that the risk for obstetric complications was higher among pregnant women with migraine, especially those with aura, in comparison with women without migraine. About 6.9% of patients with migraine without aura were admitted to high-risk hospital departments, compared with 6% of pregnant control patients who did not have migraine (P < .0001). For patients with migraine with aura, the risk for admissions was even higher (8.7%; P < .0001 vs. control patients and P < .03 vs. patients with migraine without aura) and was “very highly statistically significant,” said Dr. Lev.

Pregnant women with migraine were at significantly increased risk for gestational diabetes, hyperlipidemia, and being diagnosed with a psychiatric disorder (all P < .0001). These women were also more likely to experience preeclampsia and blood clots (P < .0001).
 

Unexpected finding

The finding that the risk for diabetes was higher was “unexpected,” inasmuch as older women with migraine are typically at increased risk for metabolic syndrome and higher body mass index, said Dr. Lev.

Migraine patients had significantly more consultations with family physicians, gynecologists, and neurologists (P < .0001). In addition, they were more likely to utilize emergency services; take more medications, mostly analgesics; and undergo more laboratory studies and brain imaging.

Those with aura had significantly more specialist consultations and took more medications compared with migraine patients without aura.

There was a statistically significant increase in the use of epidural anesthesia for migraine patients (40.5% of women without migraine; 45.7% of those with migraine accompanied by aura; and 47.5% of migraine patients without aura).

This was an “interesting” finding, said Dr. Lev. “We didn’t know what to expect; people with migraine are used to pain, so the question was, will they tolerate pain better or be more afraid of pain?”

Women with migraine also experienced more assisted deliveries with increased use of vacuums and forceps.

During the 3-month postpartum period, women with migraine sought more medical consultations and used more medications compared with control patients. They also underwent more lab examinations and more brain imaging during this period.

Dr. Lev noted that some of these evaluations may have been postponed because of the pregnancy.

Women with migraine also had a greater risk for postpartum depression, which Dr. Lev found “concerning.” She noted that depression is often underreported but is treatable. Women with migraine should be monitored for depression post partum, she said.

It’s unclear which factors contribute to the increased risk for pregnancy complications in women with migraine. Dr. Lev said she doesn’t believe it’s drug related.

“Although they’re taking more medications than people who don’t have migraine, we still are giving very low doses and only safe medicines, so I don’t think these increased risks are side effects,” she said.

She noted that women with migraine have more cardiovascular complications, including stroke and myocardial infarction, although these generally affect older patients.

Dr. Lev also noted that pain, especially chronic pain, can cause depression. “We know that people with migraine have more depression and anxiety, so maybe that also affects them during their pregnancy and after,” she said.

She suggested that pregnant women with migraine be considered high risk and be managed via specialized clinics.
 

Room for improvement

Commenting on the research, Lauren Doyle Strauss, DO, associate professor of neurology, Wake Forest University, Winston-Salem, N.C., who has written about the management of migraine during pregnancy, said studies such as this help raise awareness about pregnancy risks in migraine patients. Dr. Strauss did not attend the live presentation but is aware of the findings.

The increased use of epidurals during delivery among migraine patients in the study makes some sense, said Dr. Strauss. “It kind of shows a comfort level with medicines.”

She expressed concern that such research may be “skewed” because it includes patients with more severe migraine. If less severe cases were included in this research, “maybe there would still be higher risks, but not as high as what we have been finding in some of our studies,” she said.

Dr. Strauss said she feels the medical community should do a better job of identifying and diagnosing migraine. She said she would like to see migraine screening become a routine part of obstetric/gynecologic care. Doctors should counsel migraine patients who wish to become pregnant about potential risks, said Dr. Strauss. “We need to be up front in telling them when to seek care and when to report symptoms and not to wait for it to become super severe,” she said.

She also believes doctors should be “proactive” in helping patients develop a treatment plan before becoming pregnant, because the limited pain control options available for pregnant patients can take time to have an effect.

Also commenting on the study findings, Nina Riggins, MD, PhD, clinical associate professor of neurology at the University of California, San Francisco, said the study raises “important questions” and has “important aims.”

She believes the study reinforces the importance of collaboration between experts in primary care, obstetrics/gynecology, and neurology. However, she was surprised at some of the investigators’ assertions that there are no differences in migraine among prepubertal children and that the course of migraine for men is stable throughout their life span.

“There is literature that supports the view that the prevalence in boys is higher in prepuberty, and studies do show that migraine prevalence decreases in older adults – men and women,” she said.

There is still not enough evidence to determine that antiemetics and triptans are safe during pregnancy or that pregnant women with migraine should be taking acetylsalicylic acid, said Dr. Riggins.

The investigators, Dr. Strauss, and Dr. Riggins have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Long-awaited twincretin data, a study to inform prescribing in type 2 diabetes, COVID-19 and diabetes, and new guidance for treating type 1 diabetes in adults will be among the hot topics at the annual scientific sessions of the American Diabetes Association.

The meeting, to be held virtually for a second year, will take place June 25-29. As usual, the sessions will cover a wide range of basic, translational, and clinical material pertaining to type 1 and type 2 diabetes, complications, related subjects such as obesity and cardiovascular disease, and health care delivery.

New to this year’s agenda is COVID-19 and the many ways it has affected people with diabetes and health care delivery. And, more than in the past, the meeting will focus on ethnic and racial disparities in the delivery of care to people with diabetes.

And of course, there will be a tribute to another special aspect of 2021: the 100th anniversary of the discovery of insulin.

“I think there will undoubtedly be several things that will come out of this meeting that will change practice, and it will be important for clinicians to be aware of those, whether that’s groundbreaking trials or interpretation of data that will help us understand the interrelation between diabetes and COVID-19, which is still with us,” ADA chief scientific and medical officer Robert A. Gabbay, MD, PhD, said in an interview.

And ADA president of medicine and science Ruth S. Weinstock, MD, PhD, said in an interview: “I think there are many exciting sessions at this year’s meeting. ...I hope that it will help [clinicians] take better care of their patients with diabetes.

”

Will the twincretin tirzepatide live up to the hype?

Between December 2020 and May 2021, Eli Lilly issued a series of four press releases touting positive top-line results from a series of phase 3 studies on its novel agent tirzepatide, dubbed a twincretin for its dual actions as an agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide-1 receptors.  

Detailed results from those four trials, SURPASS-1, -2, -3, and -5, will be presented in a symposium on Tuesday, June 29. Results from SURPASS-4 will be presented at the annual meeting of the European Association for the Study of Diabetes in September 2021.

According to the company, the drug met its phase 3 primary efficacy endpoints for both hemoglobin A1c reduction and weight loss.

“At least the buzz on it has been good, but now we want to see the real data,” Dr. Gabbay said, noting that “the early data on weight loss in particular were quite good. So then the question would be: Do you go to a GLP-1 [agonist] or a dual agonist? There will be studies to tease that out.”

Regarding tirzepatide, Dr. Weinstock said: “Hopefully, more people with type 2 diabetes could achieve their glycemic goals, and those who would benefit from weight loss could have better weight loss. I haven’t seen the data, but if the addition of GIP can further improve glucose lowering as well as weight loss that would be great.”
 

How far will GRADE go in answering the second-drug question?

On Monday, June 28, results will be presented from the long-awaited Glycemia Reduction Approaches in Diabetes – A Comparative Effectiveness (GRADE) study.

Launched in 2013, the trial is funded by the National Institutes of Health and several pharmaceutical company partners. Over 5,000 patients diagnosed with type 2 diabetes within the prior 10 years and already taking metformin were randomized to one of four commonly used second-line glucose-lowering agents: glimepiride, sitagliptin, liraglutide, and basal insulin glargine. The aim was to determine which combination produced the best glycemic control with the fewest side effects.

Dr. Weinstock said: “Clinicians now have increasing numbers of medications to choose from when treating hyperglycemia in type 2 diabetes, and a common dilemma is which one to select. The results of GRADE should be informative for people taking care of type 2 diabetes in different populations.”

However, she also pointed out that GRADE does not include a group with a sodium-glucose transporter 2 inhibitor, as the trial was designed prior to the availability of the drug class. Now, SGLT2 inhibitors are widely used and recommended for cardiovascular and kidney benefit as well as glucose lowering.

“I believe the future is really precision medicine where we individualize treatment. So, for someone with heart failure you might choose an SGLT2 inhibitor, but there are plenty of other subpopulations. They are going to be looking at different subpopulations. I think we’re all very interested in seeing what the results are, but it’s not the end of the story. We will still have to individualize therapy and keep in mind their kidney, heart, heart failure status, and other factors,” she said.

Dr. Gabbay pointed out that GRADE is important because it’s one of the few comparative effectiveness trials conducted in diabetes. “I think it will be very rich [data] that will impact practice in a variety of ways. On the one hand, it doesn’t do everything we’d want it to do, but on the other hand, if you think of the number of comparative effectiveness trials in diabetes, there are not a lot ... I think it will be big.”
 

COVID-19 and diabetes: A lot to discuss  

In contrast to the ADA scientific sessions in 2020, which took place too soon after the start of the COVID-19 pandemic to include much material about it, this year’s meeting will address many different aspects of the novel coronavirus.

Sessions will cover minimizing risk in people with diabetes during the pandemic, the latest data on whether COVID-19 triggers diabetes, and if so, by what mechanism, mental health issues related to COVID-19, as well as the management of foot care, pregnancy, and the pediatric population during the pandemic.

On Sunday, June 27, a symposium will be devoted to results of the DARE-19 trial, which explored the effects of the SGLT2 inhibitor dapagliflozin in more than 1200 patients hospitalized with COVID-19. The overall results, presented in May 2021 at the scientific sessions of the American College of Cardiology, showed a nonsignificant trend for benefit in time to organ failure or death compared with placebo. At ADA, separate efficacy and safety results for patients with and without diabetes will be presented.

According to Dr. Weinstock, “We know that in nonhospitalized patients with type 2 diabetes the SGLT2 inhibitors can help preserve kidney function and reduce heart failure. But we also know there can be diabetic ketoacidosis and genital infections and other side effects, so it’s been unclear up till now in type 2 diabetes whether they are safe and effective in people hospitalized in respiratory failure with COVID-19. And, given that people with type 2 diabetes and COVID-19 are more likely to require mechanical ventilation and are at greater risk of mortality, we’re anxious to see what these results are.”

Dr. Gabbay commented that, when the DARE study was initiated in April 2020, there were concerns about whether it was safe. And even now, “we’re still not sure about whether SGLT2 inhibitors should be stopped in hospitalized patients. The recommendations say to stop. I think this will be interesting.”

Also to be addressed in several meeting sessions are related issues the pandemic has brought forth, such as the use of telehealth for routine diabetes management, inpatient use of continuous glucose monitoring, and, of course, health care disparities.

“A lot of important issues related to COVID-19 of great interest will be discussed in a variety of sessions,” Dr. Weinstock said.
 

Type 1 diabetes in adults: It’s not just a pediatric disease  

On Monday, June 28, a draft of the first-ever ADA/EASD consensus report on the management of type 1 diabetes in adults will be presented, with the final version slated for the annual meeting of the EASD in September 2021.

A previous ADA position statement had addressed management of type 1 diabetes across all age groups, but this will be the first to focus on adults. This is important, given that type 1 diabetes was formerly called juvenile diabetes and is still often perceived as a childhood disease. Adults who develop it are commonly misdiagnosed as having type 2 diabetes, Dr. Gabbay noted.

“A big-time issue is recognition of type 1 in adults. We often see patients come in who were misdiagnosed, on metformin, and not given insulin. Often they go for a while and get sicker and sicker.” Or, he said, sometimes they’re prescribed insulin but not the intensive regimens that are required for adequate glycemic control in type 1 diabetes. “They can be suboptimally treated and it can take years to get the right therapy. ... It’s unfortunate that they have to experience that.”

Dr. Weinstock, one of the authors of the statement, said it will cover a range of issues, including care schedules, therapies, psychosocial issues, and social determinants of health. “We tried to be comprehensive in this in terms of glycemic management. It doesn’t include a discussion of complications or their management. It really focuses on diagnosis and glycemic management.”
 

Dealing with disparities: ADA has taken several steps

A priority of the ADA is addressing disparities in the delivery of health care to people with diabetes, both Dr. Weinstock and Dr. Gabbay stressed. Quite a few sessions at the meeting will touch on various aspects, including sessions on Friday afternoon on “Health Care as a Social Justice Issue in the Diagnosis and Management of Diabetes,” and separate sessions on “Challenges and Successes With Health Inequities and Health Disparities in Diabetes” in adult and pediatric populations.

“For us at ADA, addressing health disparities is extremely important and we have a number of new programs this year to address this very important issue,” Dr. Weinstock said.

In August 2020, the ADA issued a Health Equity Bill of Rights, which includes access to insulin and other medications, affordable health care, and freedom from stigma and discrimination. The Association has also requested applications from researchers studying disparities in diabetes care.
 

Celebrating 100 years of lifesaving medication

Of course, the ADA will be celebrating the 100th anniversary of the discovery of insulin. A session on Saturday afternoon, entitled, “Insulin at Its 100th Birthday,” will cover the history of the landmark discovery, as well as insulin biosynthesis and mechanisms of action, and “the future of insulin as a therapy.”

Dr. Weinstock noted: “The discovery of insulin was an incredible achievement that, of course, saved the lives of many millions of children and adults. Before insulin became available, children and adults only survived for days or at most a few years after diagnosis. We will commemorate this anniversary.”
 

The virtual platform: Like last year, only better

Dr. Gabbay said in an interview that the virtual setup will be similar to last year’s in that talks will be prerecorded to ensure there are no technical glitches, but for many, presenters will be available afterward for live question and answers.

This year, though, the chat functionality will be enhanced to allow for discussion during the presentation, separate from the scientific question and answers. And, he noted, the virtual exhibit hall will be “bigger and better.”

Despite these improvements, Dr. Gabbay said, the plan is to go back to an in-person meeting in 2022 in New Orleans.

Dr. Weinstock’s institution receives research grants from Medtronic, Insulet, Lilly, Novo Nordisk, and Boehringer Ingelheim. Dr. Gabbay reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Long-awaited twincretin data, a study to inform prescribing in type 2 diabetes, COVID-19 and diabetes, and new guidance for treating type 1 diabetes in adults will be among the hot topics at the annual scientific sessions of the American Diabetes Association.

The meeting, to be held virtually for a second year, will take place June 25-29. As usual, the sessions will cover a wide range of basic, translational, and clinical material pertaining to type 1 and type 2 diabetes, complications, related subjects such as obesity and cardiovascular disease, and health care delivery.

New to this year’s agenda is COVID-19 and the many ways it has affected people with diabetes and health care delivery. And, more than in the past, the meeting will focus on ethnic and racial disparities in the delivery of care to people with diabetes.

And of course, there will be a tribute to another special aspect of 2021: the 100th anniversary of the discovery of insulin.

“I think there will undoubtedly be several things that will come out of this meeting that will change practice, and it will be important for clinicians to be aware of those, whether that’s groundbreaking trials or interpretation of data that will help us understand the interrelation between diabetes and COVID-19, which is still with us,” ADA chief scientific and medical officer Robert A. Gabbay, MD, PhD, said in an interview.

And ADA president of medicine and science Ruth S. Weinstock, MD, PhD, said in an interview: “I think there are many exciting sessions at this year’s meeting. ...I hope that it will help [clinicians] take better care of their patients with diabetes.

”

Will the twincretin tirzepatide live up to the hype?

Between December 2020 and May 2021, Eli Lilly issued a series of four press releases touting positive top-line results from a series of phase 3 studies on its novel agent tirzepatide, dubbed a twincretin for its dual actions as an agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide-1 receptors.  

Detailed results from those four trials, SURPASS-1, -2, -3, and -5, will be presented in a symposium on Tuesday, June 29. Results from SURPASS-4 will be presented at the annual meeting of the European Association for the Study of Diabetes in September 2021.

According to the company, the drug met its phase 3 primary efficacy endpoints for both hemoglobin A1c reduction and weight loss.

“At least the buzz on it has been good, but now we want to see the real data,” Dr. Gabbay said, noting that “the early data on weight loss in particular were quite good. So then the question would be: Do you go to a GLP-1 [agonist] or a dual agonist? There will be studies to tease that out.”

Regarding tirzepatide, Dr. Weinstock said: “Hopefully, more people with type 2 diabetes could achieve their glycemic goals, and those who would benefit from weight loss could have better weight loss. I haven’t seen the data, but if the addition of GIP can further improve glucose lowering as well as weight loss that would be great.”
 

How far will GRADE go in answering the second-drug question?

On Monday, June 28, results will be presented from the long-awaited Glycemia Reduction Approaches in Diabetes – A Comparative Effectiveness (GRADE) study.

Launched in 2013, the trial is funded by the National Institutes of Health and several pharmaceutical company partners. Over 5,000 patients diagnosed with type 2 diabetes within the prior 10 years and already taking metformin were randomized to one of four commonly used second-line glucose-lowering agents: glimepiride, sitagliptin, liraglutide, and basal insulin glargine. The aim was to determine which combination produced the best glycemic control with the fewest side effects.

Dr. Weinstock said: “Clinicians now have increasing numbers of medications to choose from when treating hyperglycemia in type 2 diabetes, and a common dilemma is which one to select. The results of GRADE should be informative for people taking care of type 2 diabetes in different populations.”

However, she also pointed out that GRADE does not include a group with a sodium-glucose transporter 2 inhibitor, as the trial was designed prior to the availability of the drug class. Now, SGLT2 inhibitors are widely used and recommended for cardiovascular and kidney benefit as well as glucose lowering.

“I believe the future is really precision medicine where we individualize treatment. So, for someone with heart failure you might choose an SGLT2 inhibitor, but there are plenty of other subpopulations. They are going to be looking at different subpopulations. I think we’re all very interested in seeing what the results are, but it’s not the end of the story. We will still have to individualize therapy and keep in mind their kidney, heart, heart failure status, and other factors,” she said.

Dr. Gabbay pointed out that GRADE is important because it’s one of the few comparative effectiveness trials conducted in diabetes. “I think it will be very rich [data] that will impact practice in a variety of ways. On the one hand, it doesn’t do everything we’d want it to do, but on the other hand, if you think of the number of comparative effectiveness trials in diabetes, there are not a lot ... I think it will be big.”
 

COVID-19 and diabetes: A lot to discuss  

In contrast to the ADA scientific sessions in 2020, which took place too soon after the start of the COVID-19 pandemic to include much material about it, this year’s meeting will address many different aspects of the novel coronavirus.

Sessions will cover minimizing risk in people with diabetes during the pandemic, the latest data on whether COVID-19 triggers diabetes, and if so, by what mechanism, mental health issues related to COVID-19, as well as the management of foot care, pregnancy, and the pediatric population during the pandemic.

On Sunday, June 27, a symposium will be devoted to results of the DARE-19 trial, which explored the effects of the SGLT2 inhibitor dapagliflozin in more than 1200 patients hospitalized with COVID-19. The overall results, presented in May 2021 at the scientific sessions of the American College of Cardiology, showed a nonsignificant trend for benefit in time to organ failure or death compared with placebo. At ADA, separate efficacy and safety results for patients with and without diabetes will be presented.

According to Dr. Weinstock, “We know that in nonhospitalized patients with type 2 diabetes the SGLT2 inhibitors can help preserve kidney function and reduce heart failure. But we also know there can be diabetic ketoacidosis and genital infections and other side effects, so it’s been unclear up till now in type 2 diabetes whether they are safe and effective in people hospitalized in respiratory failure with COVID-19. And, given that people with type 2 diabetes and COVID-19 are more likely to require mechanical ventilation and are at greater risk of mortality, we’re anxious to see what these results are.”

Dr. Gabbay commented that, when the DARE study was initiated in April 2020, there were concerns about whether it was safe. And even now, “we’re still not sure about whether SGLT2 inhibitors should be stopped in hospitalized patients. The recommendations say to stop. I think this will be interesting.”

Also to be addressed in several meeting sessions are related issues the pandemic has brought forth, such as the use of telehealth for routine diabetes management, inpatient use of continuous glucose monitoring, and, of course, health care disparities.

“A lot of important issues related to COVID-19 of great interest will be discussed in a variety of sessions,” Dr. Weinstock said.
 

Type 1 diabetes in adults: It’s not just a pediatric disease  

On Monday, June 28, a draft of the first-ever ADA/EASD consensus report on the management of type 1 diabetes in adults will be presented, with the final version slated for the annual meeting of the EASD in September 2021.

A previous ADA position statement had addressed management of type 1 diabetes across all age groups, but this will be the first to focus on adults. This is important, given that type 1 diabetes was formerly called juvenile diabetes and is still often perceived as a childhood disease. Adults who develop it are commonly misdiagnosed as having type 2 diabetes, Dr. Gabbay noted.

“A big-time issue is recognition of type 1 in adults. We often see patients come in who were misdiagnosed, on metformin, and not given insulin. Often they go for a while and get sicker and sicker.” Or, he said, sometimes they’re prescribed insulin but not the intensive regimens that are required for adequate glycemic control in type 1 diabetes. “They can be suboptimally treated and it can take years to get the right therapy. ... It’s unfortunate that they have to experience that.”

Dr. Weinstock, one of the authors of the statement, said it will cover a range of issues, including care schedules, therapies, psychosocial issues, and social determinants of health. “We tried to be comprehensive in this in terms of glycemic management. It doesn’t include a discussion of complications or their management. It really focuses on diagnosis and glycemic management.”
 

Dealing with disparities: ADA has taken several steps

A priority of the ADA is addressing disparities in the delivery of health care to people with diabetes, both Dr. Weinstock and Dr. Gabbay stressed. Quite a few sessions at the meeting will touch on various aspects, including sessions on Friday afternoon on “Health Care as a Social Justice Issue in the Diagnosis and Management of Diabetes,” and separate sessions on “Challenges and Successes With Health Inequities and Health Disparities in Diabetes” in adult and pediatric populations.

“For us at ADA, addressing health disparities is extremely important and we have a number of new programs this year to address this very important issue,” Dr. Weinstock said.

In August 2020, the ADA issued a Health Equity Bill of Rights, which includes access to insulin and other medications, affordable health care, and freedom from stigma and discrimination. The Association has also requested applications from researchers studying disparities in diabetes care.
 

Celebrating 100 years of lifesaving medication

Of course, the ADA will be celebrating the 100th anniversary of the discovery of insulin. A session on Saturday afternoon, entitled, “Insulin at Its 100th Birthday,” will cover the history of the landmark discovery, as well as insulin biosynthesis and mechanisms of action, and “the future of insulin as a therapy.”

Dr. Weinstock noted: “The discovery of insulin was an incredible achievement that, of course, saved the lives of many millions of children and adults. Before insulin became available, children and adults only survived for days or at most a few years after diagnosis. We will commemorate this anniversary.”
 

The virtual platform: Like last year, only better

Dr. Gabbay said in an interview that the virtual setup will be similar to last year’s in that talks will be prerecorded to ensure there are no technical glitches, but for many, presenters will be available afterward for live question and answers.

This year, though, the chat functionality will be enhanced to allow for discussion during the presentation, separate from the scientific question and answers. And, he noted, the virtual exhibit hall will be “bigger and better.”

Despite these improvements, Dr. Gabbay said, the plan is to go back to an in-person meeting in 2022 in New Orleans.

Dr. Weinstock’s institution receives research grants from Medtronic, Insulet, Lilly, Novo Nordisk, and Boehringer Ingelheim. Dr. Gabbay reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Long-awaited twincretin data, a study to inform prescribing in type 2 diabetes, COVID-19 and diabetes, and new guidance for treating type 1 diabetes in adults will be among the hot topics at the annual scientific sessions of the American Diabetes Association.

The meeting, to be held virtually for a second year, will take place June 25-29. As usual, the sessions will cover a wide range of basic, translational, and clinical material pertaining to type 1 and type 2 diabetes, complications, related subjects such as obesity and cardiovascular disease, and health care delivery.

New to this year’s agenda is COVID-19 and the many ways it has affected people with diabetes and health care delivery. And, more than in the past, the meeting will focus on ethnic and racial disparities in the delivery of care to people with diabetes.

And of course, there will be a tribute to another special aspect of 2021: the 100th anniversary of the discovery of insulin.

“I think there will undoubtedly be several things that will come out of this meeting that will change practice, and it will be important for clinicians to be aware of those, whether that’s groundbreaking trials or interpretation of data that will help us understand the interrelation between diabetes and COVID-19, which is still with us,” ADA chief scientific and medical officer Robert A. Gabbay, MD, PhD, said in an interview.

And ADA president of medicine and science Ruth S. Weinstock, MD, PhD, said in an interview: “I think there are many exciting sessions at this year’s meeting. ...I hope that it will help [clinicians] take better care of their patients with diabetes.

”

Will the twincretin tirzepatide live up to the hype?

Between December 2020 and May 2021, Eli Lilly issued a series of four press releases touting positive top-line results from a series of phase 3 studies on its novel agent tirzepatide, dubbed a twincretin for its dual actions as an agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide-1 receptors.  

Detailed results from those four trials, SURPASS-1, -2, -3, and -5, will be presented in a symposium on Tuesday, June 29. Results from SURPASS-4 will be presented at the annual meeting of the European Association for the Study of Diabetes in September 2021.

According to the company, the drug met its phase 3 primary efficacy endpoints for both hemoglobin A1c reduction and weight loss.

“At least the buzz on it has been good, but now we want to see the real data,” Dr. Gabbay said, noting that “the early data on weight loss in particular were quite good. So then the question would be: Do you go to a GLP-1 [agonist] or a dual agonist? There will be studies to tease that out.”

Regarding tirzepatide, Dr. Weinstock said: “Hopefully, more people with type 2 diabetes could achieve their glycemic goals, and those who would benefit from weight loss could have better weight loss. I haven’t seen the data, but if the addition of GIP can further improve glucose lowering as well as weight loss that would be great.”
 

How far will GRADE go in answering the second-drug question?

On Monday, June 28, results will be presented from the long-awaited Glycemia Reduction Approaches in Diabetes – A Comparative Effectiveness (GRADE) study.

Launched in 2013, the trial is funded by the National Institutes of Health and several pharmaceutical company partners. Over 5,000 patients diagnosed with type 2 diabetes within the prior 10 years and already taking metformin were randomized to one of four commonly used second-line glucose-lowering agents: glimepiride, sitagliptin, liraglutide, and basal insulin glargine. The aim was to determine which combination produced the best glycemic control with the fewest side effects.

Dr. Weinstock said: “Clinicians now have increasing numbers of medications to choose from when treating hyperglycemia in type 2 diabetes, and a common dilemma is which one to select. The results of GRADE should be informative for people taking care of type 2 diabetes in different populations.”

However, she also pointed out that GRADE does not include a group with a sodium-glucose transporter 2 inhibitor, as the trial was designed prior to the availability of the drug class. Now, SGLT2 inhibitors are widely used and recommended for cardiovascular and kidney benefit as well as glucose lowering.

“I believe the future is really precision medicine where we individualize treatment. So, for someone with heart failure you might choose an SGLT2 inhibitor, but there are plenty of other subpopulations. They are going to be looking at different subpopulations. I think we’re all very interested in seeing what the results are, but it’s not the end of the story. We will still have to individualize therapy and keep in mind their kidney, heart, heart failure status, and other factors,” she said.

Dr. Gabbay pointed out that GRADE is important because it’s one of the few comparative effectiveness trials conducted in diabetes. “I think it will be very rich [data] that will impact practice in a variety of ways. On the one hand, it doesn’t do everything we’d want it to do, but on the other hand, if you think of the number of comparative effectiveness trials in diabetes, there are not a lot ... I think it will be big.”
 

COVID-19 and diabetes: A lot to discuss  

In contrast to the ADA scientific sessions in 2020, which took place too soon after the start of the COVID-19 pandemic to include much material about it, this year’s meeting will address many different aspects of the novel coronavirus.

Sessions will cover minimizing risk in people with diabetes during the pandemic, the latest data on whether COVID-19 triggers diabetes, and if so, by what mechanism, mental health issues related to COVID-19, as well as the management of foot care, pregnancy, and the pediatric population during the pandemic.

On Sunday, June 27, a symposium will be devoted to results of the DARE-19 trial, which explored the effects of the SGLT2 inhibitor dapagliflozin in more than 1200 patients hospitalized with COVID-19. The overall results, presented in May 2021 at the scientific sessions of the American College of Cardiology, showed a nonsignificant trend for benefit in time to organ failure or death compared with placebo. At ADA, separate efficacy and safety results for patients with and without diabetes will be presented.

According to Dr. Weinstock, “We know that in nonhospitalized patients with type 2 diabetes the SGLT2 inhibitors can help preserve kidney function and reduce heart failure. But we also know there can be diabetic ketoacidosis and genital infections and other side effects, so it’s been unclear up till now in type 2 diabetes whether they are safe and effective in people hospitalized in respiratory failure with COVID-19. And, given that people with type 2 diabetes and COVID-19 are more likely to require mechanical ventilation and are at greater risk of mortality, we’re anxious to see what these results are.”

Dr. Gabbay commented that, when the DARE study was initiated in April 2020, there were concerns about whether it was safe. And even now, “we’re still not sure about whether SGLT2 inhibitors should be stopped in hospitalized patients. The recommendations say to stop. I think this will be interesting.”

Also to be addressed in several meeting sessions are related issues the pandemic has brought forth, such as the use of telehealth for routine diabetes management, inpatient use of continuous glucose monitoring, and, of course, health care disparities.

“A lot of important issues related to COVID-19 of great interest will be discussed in a variety of sessions,” Dr. Weinstock said.
 

Type 1 diabetes in adults: It’s not just a pediatric disease  

On Monday, June 28, a draft of the first-ever ADA/EASD consensus report on the management of type 1 diabetes in adults will be presented, with the final version slated for the annual meeting of the EASD in September 2021.

A previous ADA position statement had addressed management of type 1 diabetes across all age groups, but this will be the first to focus on adults. This is important, given that type 1 diabetes was formerly called juvenile diabetes and is still often perceived as a childhood disease. Adults who develop it are commonly misdiagnosed as having type 2 diabetes, Dr. Gabbay noted.

“A big-time issue is recognition of type 1 in adults. We often see patients come in who were misdiagnosed, on metformin, and not given insulin. Often they go for a while and get sicker and sicker.” Or, he said, sometimes they’re prescribed insulin but not the intensive regimens that are required for adequate glycemic control in type 1 diabetes. “They can be suboptimally treated and it can take years to get the right therapy. ... It’s unfortunate that they have to experience that.”

Dr. Weinstock, one of the authors of the statement, said it will cover a range of issues, including care schedules, therapies, psychosocial issues, and social determinants of health. “We tried to be comprehensive in this in terms of glycemic management. It doesn’t include a discussion of complications or their management. It really focuses on diagnosis and glycemic management.”
 

Dealing with disparities: ADA has taken several steps

A priority of the ADA is addressing disparities in the delivery of health care to people with diabetes, both Dr. Weinstock and Dr. Gabbay stressed. Quite a few sessions at the meeting will touch on various aspects, including sessions on Friday afternoon on “Health Care as a Social Justice Issue in the Diagnosis and Management of Diabetes,” and separate sessions on “Challenges and Successes With Health Inequities and Health Disparities in Diabetes” in adult and pediatric populations.

“For us at ADA, addressing health disparities is extremely important and we have a number of new programs this year to address this very important issue,” Dr. Weinstock said.

In August 2020, the ADA issued a Health Equity Bill of Rights, which includes access to insulin and other medications, affordable health care, and freedom from stigma and discrimination. The Association has also requested applications from researchers studying disparities in diabetes care.
 

Celebrating 100 years of lifesaving medication

Of course, the ADA will be celebrating the 100th anniversary of the discovery of insulin. A session on Saturday afternoon, entitled, “Insulin at Its 100th Birthday,” will cover the history of the landmark discovery, as well as insulin biosynthesis and mechanisms of action, and “the future of insulin as a therapy.”

Dr. Weinstock noted: “The discovery of insulin was an incredible achievement that, of course, saved the lives of many millions of children and adults. Before insulin became available, children and adults only survived for days or at most a few years after diagnosis. We will commemorate this anniversary.”
 

The virtual platform: Like last year, only better

Dr. Gabbay said in an interview that the virtual setup will be similar to last year’s in that talks will be prerecorded to ensure there are no technical glitches, but for many, presenters will be available afterward for live question and answers.

This year, though, the chat functionality will be enhanced to allow for discussion during the presentation, separate from the scientific question and answers. And, he noted, the virtual exhibit hall will be “bigger and better.”

Despite these improvements, Dr. Gabbay said, the plan is to go back to an in-person meeting in 2022 in New Orleans.

Dr. Weinstock’s institution receives research grants from Medtronic, Insulet, Lilly, Novo Nordisk, and Boehringer Ingelheim. Dr. Gabbay reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A novel therapeutic approach using aptamers – short single strands of DNA or RNA designed to selectively bind to a target – shows promise for treating von Willebrand Disease (VWD), and other congenital bleed disorders such as hemophilia A, investigators say.

In a proof-of-concept study using healthy volunteers, the experimental anti–von Willebrand factor (VWF) molecule BT200 appeared to decrease clearance of VWF and resulted in a twofold increase in endogenous levels of VWF and factor VIII at low doses.

BT200 is currently being explored in a phase 2 trial in patients with hemophilia A and VWD type 2B, Katarina Kovacevic, MPharm, from the Medical University of Vienna, reported at the European Hematology Association annual congress.

“We expect to see a half-life increase of 2 to 4 times of factor VIII products, which will allow us to have a longer time between treatments,” she said in an oral abstract presentation (Abstract S302).
 

Lab-made nucleotide strings

Aptamers are sometimes call “chemical antibodies” because of their high affinity and high specificity for extracellular targets, Dr. Kovacevic said. Unlike conventional humanized or human-derived antibodies, however, they are nonimmunogenic and are less costly to manufacture.

In a previous study from her center, a different anti-VWF aptamer labeled ARC1779 increased plasma levels of VWF, factor VIII, and platelet counts in patients with VWD type 2B.

However, the drug was inconvenient to use, requiring 72-hour infusions, she noted.

In a study published in Feb. 4, 2021 in Scientific Reports, Dr. Kovacevic and colleagues reported that BT200 blocks VWF and platelet function in patients with ischemic strokes, even in the presence of high levels of VWF in patients with left carotid artery atherosclerotic strokes.

The ability of the molecule to block VWF platelet binding may explain how the anti-VWF agent actually results in higher circulating levels of VWF, which also carries factor VIII, said Veronica H. Flood, MD, a VWD specialist at Children’s Hospital of Wisconsin and associate professor at the Medical College of Wisconsin in Milwaukee.

“It might inhibit clearance of the von Willebrand factor, so it’s almost like this was an incidental side effect,” she said in an interview. “Incidentally, this happens to also give you higher levels of the von Willebrand factor and the factor VIII, and with a longer half-life than anything we currently have, so it’s a super-creative strategy,” she said.

Dr. Flood was not involved in the study.
 

Long half-life

BT200 is a third-generation peglyated anti-VWF aptamer that has been shown in preclinical studies to have a long half-life in nonhuman primates. It inhibits the A1 domain of VWF to prevent it from binding to platelet glycoprotein 1b (GP1b).

In the randomized, double-blind, placebo-controlled trial reported at the EHA congress, 88 healthy volunteers received single doses of BT200 ranging from 0.l8 mg to 48 mg by subcutaneous injection or intravenous infusion, 8 received multiple doses, 8 were evaluated for possible interactions with desmopressin, and 8 were evaluated for bioavailability of the aptamer.

The investigators observed a dose-related increase in BT200 concentrations, with a mean plasma terminal elimination half life of between 118 and 284 hours (about 5-12 days). There was also a dose-dependent increase in bioavailability of the agents, reaching 90% at the highest dose level.

The ability of BT200 to inhibit the A1 domains of VWF also was dose dependent, with the largest effect seen with doses of 12 mg and higher. The molecule decreased VWF activity and ristocetin-induced platelet aggregation, and prolonged collagen adenosine diphosphate closure time.

At the highest doses, BT200 caused complete inhibition of VWF (P < .001), and volunteers developed clinical signs of mild mucosal bleeding.

But the aptamer also increased in a dose-dependent fashion VWF antigen levels and factor VIII clotting activity more than fourfold (P <.001).

“This resulted in increased thrombogenicity as measured by thrombin generation and enhanced clotting. In the absence of an increase in VWF propeptide levels, this effect is considered due to decreased clearance of VWF,” the investigators wrote in the study abstract.

They noted that they saw a clinically meaningful twofold increase in both VWF and factor VIII at doses lower than 6 mg.
 

‘Super-exciting strategy’

“This trial identified a novel mechanism of action for BT200: It decreases the clearance of VWF/FVIII, which can be exploited for congenital bleeding disorders. This built a solid foundation for an ongoing basket trial in patients with von Willebrand disease or hemophilia A, which already confirms the expected effect sizes,” Dr. Kovacevic and colleagues wrote.

“I will be interested to see what the clinical side effects are, because there may be some off-target effects, but in reality it is a super-exciting strategy, and there is really a dire need for longer half-life products for these patients,” Dr. Flood said.

The study was sponsored by Band Therapeutics, a division of Guardian Therapeutics. Dr. Kovacevic and Dr. Flood reported having no conflicts of interest to disclose.

A novel therapeutic approach using aptamers – short single strands of DNA or RNA designed to selectively bind to a target – shows promise for treating von Willebrand Disease (VWD), and other congenital bleed disorders such as hemophilia A, investigators say.

In a proof-of-concept study using healthy volunteers, the experimental anti–von Willebrand factor (VWF) molecule BT200 appeared to decrease clearance of VWF and resulted in a twofold increase in endogenous levels of VWF and factor VIII at low doses.

BT200 is currently being explored in a phase 2 trial in patients with hemophilia A and VWD type 2B, Katarina Kovacevic, MPharm, from the Medical University of Vienna, reported at the European Hematology Association annual congress.

“We expect to see a half-life increase of 2 to 4 times of factor VIII products, which will allow us to have a longer time between treatments,” she said in an oral abstract presentation (Abstract S302).
 

Lab-made nucleotide strings

Aptamers are sometimes call “chemical antibodies” because of their high affinity and high specificity for extracellular targets, Dr. Kovacevic said. Unlike conventional humanized or human-derived antibodies, however, they are nonimmunogenic and are less costly to manufacture.

In a previous study from her center, a different anti-VWF aptamer labeled ARC1779 increased plasma levels of VWF, factor VIII, and platelet counts in patients with VWD type 2B.

However, the drug was inconvenient to use, requiring 72-hour infusions, she noted.

In a study published in Feb. 4, 2021 in Scientific Reports, Dr. Kovacevic and colleagues reported that BT200 blocks VWF and platelet function in patients with ischemic strokes, even in the presence of high levels of VWF in patients with left carotid artery atherosclerotic strokes.

The ability of the molecule to block VWF platelet binding may explain how the anti-VWF agent actually results in higher circulating levels of VWF, which also carries factor VIII, said Veronica H. Flood, MD, a VWD specialist at Children’s Hospital of Wisconsin and associate professor at the Medical College of Wisconsin in Milwaukee.

“It might inhibit clearance of the von Willebrand factor, so it’s almost like this was an incidental side effect,” she said in an interview. “Incidentally, this happens to also give you higher levels of the von Willebrand factor and the factor VIII, and with a longer half-life than anything we currently have, so it’s a super-creative strategy,” she said.

Dr. Flood was not involved in the study.
 

Long half-life

BT200 is a third-generation peglyated anti-VWF aptamer that has been shown in preclinical studies to have a long half-life in nonhuman primates. It inhibits the A1 domain of VWF to prevent it from binding to platelet glycoprotein 1b (GP1b).

In the randomized, double-blind, placebo-controlled trial reported at the EHA congress, 88 healthy volunteers received single doses of BT200 ranging from 0.l8 mg to 48 mg by subcutaneous injection or intravenous infusion, 8 received multiple doses, 8 were evaluated for possible interactions with desmopressin, and 8 were evaluated for bioavailability of the aptamer.

The investigators observed a dose-related increase in BT200 concentrations, with a mean plasma terminal elimination half life of between 118 and 284 hours (about 5-12 days). There was also a dose-dependent increase in bioavailability of the agents, reaching 90% at the highest dose level.

The ability of BT200 to inhibit the A1 domains of VWF also was dose dependent, with the largest effect seen with doses of 12 mg and higher. The molecule decreased VWF activity and ristocetin-induced platelet aggregation, and prolonged collagen adenosine diphosphate closure time.

At the highest doses, BT200 caused complete inhibition of VWF (P < .001), and volunteers developed clinical signs of mild mucosal bleeding.

But the aptamer also increased in a dose-dependent fashion VWF antigen levels and factor VIII clotting activity more than fourfold (P <.001).

“This resulted in increased thrombogenicity as measured by thrombin generation and enhanced clotting. In the absence of an increase in VWF propeptide levels, this effect is considered due to decreased clearance of VWF,” the investigators wrote in the study abstract.

They noted that they saw a clinically meaningful twofold increase in both VWF and factor VIII at doses lower than 6 mg.
 

‘Super-exciting strategy’

“This trial identified a novel mechanism of action for BT200: It decreases the clearance of VWF/FVIII, which can be exploited for congenital bleeding disorders. This built a solid foundation for an ongoing basket trial in patients with von Willebrand disease or hemophilia A, which already confirms the expected effect sizes,” Dr. Kovacevic and colleagues wrote.

“I will be interested to see what the clinical side effects are, because there may be some off-target effects, but in reality it is a super-exciting strategy, and there is really a dire need for longer half-life products for these patients,” Dr. Flood said.

The study was sponsored by Band Therapeutics, a division of Guardian Therapeutics. Dr. Kovacevic and Dr. Flood reported having no conflicts of interest to disclose.

A novel therapeutic approach using aptamers – short single strands of DNA or RNA designed to selectively bind to a target – shows promise for treating von Willebrand Disease (VWD), and other congenital bleed disorders such as hemophilia A, investigators say.

In a proof-of-concept study using healthy volunteers, the experimental anti–von Willebrand factor (VWF) molecule BT200 appeared to decrease clearance of VWF and resulted in a twofold increase in endogenous levels of VWF and factor VIII at low doses.

BT200 is currently being explored in a phase 2 trial in patients with hemophilia A and VWD type 2B, Katarina Kovacevic, MPharm, from the Medical University of Vienna, reported at the European Hematology Association annual congress.

“We expect to see a half-life increase of 2 to 4 times of factor VIII products, which will allow us to have a longer time between treatments,” she said in an oral abstract presentation (Abstract S302).
 

Lab-made nucleotide strings

Aptamers are sometimes call “chemical antibodies” because of their high affinity and high specificity for extracellular targets, Dr. Kovacevic said. Unlike conventional humanized or human-derived antibodies, however, they are nonimmunogenic and are less costly to manufacture.

In a previous study from her center, a different anti-VWF aptamer labeled ARC1779 increased plasma levels of VWF, factor VIII, and platelet counts in patients with VWD type 2B.

However, the drug was inconvenient to use, requiring 72-hour infusions, she noted.

In a study published in Feb. 4, 2021 in Scientific Reports, Dr. Kovacevic and colleagues reported that BT200 blocks VWF and platelet function in patients with ischemic strokes, even in the presence of high levels of VWF in patients with left carotid artery atherosclerotic strokes.

The ability of the molecule to block VWF platelet binding may explain how the anti-VWF agent actually results in higher circulating levels of VWF, which also carries factor VIII, said Veronica H. Flood, MD, a VWD specialist at Children’s Hospital of Wisconsin and associate professor at the Medical College of Wisconsin in Milwaukee.

“It might inhibit clearance of the von Willebrand factor, so it’s almost like this was an incidental side effect,” she said in an interview. “Incidentally, this happens to also give you higher levels of the von Willebrand factor and the factor VIII, and with a longer half-life than anything we currently have, so it’s a super-creative strategy,” she said.

Dr. Flood was not involved in the study.
 

Long half-life

BT200 is a third-generation peglyated anti-VWF aptamer that has been shown in preclinical studies to have a long half-life in nonhuman primates. It inhibits the A1 domain of VWF to prevent it from binding to platelet glycoprotein 1b (GP1b).

In the randomized, double-blind, placebo-controlled trial reported at the EHA congress, 88 healthy volunteers received single doses of BT200 ranging from 0.l8 mg to 48 mg by subcutaneous injection or intravenous infusion, 8 received multiple doses, 8 were evaluated for possible interactions with desmopressin, and 8 were evaluated for bioavailability of the aptamer.

The investigators observed a dose-related increase in BT200 concentrations, with a mean plasma terminal elimination half life of between 118 and 284 hours (about 5-12 days). There was also a dose-dependent increase in bioavailability of the agents, reaching 90% at the highest dose level.

The ability of BT200 to inhibit the A1 domains of VWF also was dose dependent, with the largest effect seen with doses of 12 mg and higher. The molecule decreased VWF activity and ristocetin-induced platelet aggregation, and prolonged collagen adenosine diphosphate closure time.

At the highest doses, BT200 caused complete inhibition of VWF (P < .001), and volunteers developed clinical signs of mild mucosal bleeding.

But the aptamer also increased in a dose-dependent fashion VWF antigen levels and factor VIII clotting activity more than fourfold (P <.001).

“This resulted in increased thrombogenicity as measured by thrombin generation and enhanced clotting. In the absence of an increase in VWF propeptide levels, this effect is considered due to decreased clearance of VWF,” the investigators wrote in the study abstract.

They noted that they saw a clinically meaningful twofold increase in both VWF and factor VIII at doses lower than 6 mg.
 

‘Super-exciting strategy’

“This trial identified a novel mechanism of action for BT200: It decreases the clearance of VWF/FVIII, which can be exploited for congenital bleeding disorders. This built a solid foundation for an ongoing basket trial in patients with von Willebrand disease or hemophilia A, which already confirms the expected effect sizes,” Dr. Kovacevic and colleagues wrote.

“I will be interested to see what the clinical side effects are, because there may be some off-target effects, but in reality it is a super-exciting strategy, and there is really a dire need for longer half-life products for these patients,” Dr. Flood said.

The study was sponsored by Band Therapeutics, a division of Guardian Therapeutics. Dr. Kovacevic and Dr. Flood reported having no conflicts of interest to disclose.

It is safe for patients with migraine to receive any of the COVID-19 vaccines without concern about the vaccination interfering with their migraine medications or the medications reducing an immune response to the vaccine, according to a presentation at the American Headache Society’s 2021 annual meeting.

Amy Gelfand, MD, director of pediatric headache at University of California, San Francisco, reviewed common concerns migraine patients or their clinicians might have related any of the three vaccines, starting with a review of how the vaccines work – by targeting the spike protein of the SARS-CoV-2 virus.

“The vaccines induce response to that protein, but only that protein, so there’s no reason to think they’re going to cause the body to produce neutralizing antibodies against any of our migraine therapeutics,” Dr. Gelfand said. She added that the phase 3 clinical trials included participants from a wide range of ages and comorbidities, so there were likely many people in the trials who have migraine, though no subgroup analyses have been performed for this group or are likely to be performed.

Common questions

The two treatments people have the most questions about concerning the COVID-19 vaccine are onabotulinumtoxinA and CGRP pathway monoclonal antibodies (mAbs), likely because both of these are injections, as is the vaccine, Dr. Gelfand said. First, she reminded attendees that onabotulinumtoxinA is not a dermal filler, since some reports following administration of the Moderna vaccine suggested that some people with dermal fillers had swelling in those areas after vaccination.

In addition, “there’s no reason to think the onabotulinumtoxinA would influence our body’s immune response to any vaccine, so there’s no need to retime the onabotulinumtoxinA injections around COVID-19 vaccine administration,” Dr. Gelfand said.

Regarding mAbs, she acknowledged that some white blood cells have CGRP receptors, which may have a pro- or anti-inflammatory role, but clinical trials of mAbs did not show any evidence of being immunosuppressive or myelosuppressive.

“The monoclonal antibodies themselves have undergone engineering so that they are just going after their one target,” Dr. Gelfand said. “They’re not going to be expected to bind to anything else outside of their targets, so I don’t think there’s anything there to make us retime the monoclonal antibody administration relative to the COVID-19 vaccine.”

She did note that patients who choose to get mAbs injections in their arm instead of their thigh or abdomen may want to receive it in the opposite arm than they one they have gotten or will get the vaccine in since the vaccine can cause discomfort.

The other common question patients may have is whether taking any NSAIDs or acetaminophen before getting the COVID-19 vaccine will reduce their immune response to the vaccination. This concern arises because of past evidence showing that some infants tended to have lower immunologic responses when they received acetaminophen after their primary vaccines’ series, but the clinical significance of those reduced responses is not clear since they still had strong responses. Further, this effect was not seen with booster shots, suggesting it’s an age-dependent effect.

During the clinical trials of the AstraZeneca vaccine, several sites gave prophylactic paracetamol without any apparent detrimental effect on antibody response, Dr. Gelfand said. Further, the mRNA and adenovirus-vectored vaccines appear to induce antibodies far above what many believe is needed for protection.

“Even if there were a slight decrease, it’s not clear that that would have any kind of clinical significance for that person in terms of their level of protection against COVID-19,” she said. “Bottom line, it’s fine for patients to use either of these after administration of the COVID-19 vaccine.” The Centers for Disease Control and Prevention doesn’t recommend it prophylactically beforehand, but it’s fine to take it for a fever, aches or headache after getting the vaccine.

Migraine or vaccine reaction?

Dr. Gelfand then addressed whether it should affect physicians’ headache differential if seeing a patient who recently received an adenovirus-vectored vaccine, such as the Johnson & Johnson or AstraZeneca vaccines. The question relates to the discovery of a very rare potential adverse event from these vaccines: cerebral venous sinus thrombosis (CVST) with thrombocytopenia and thromboses in other major vessels, together called thrombosis thrombocytopenia syndrome (TTS). No TTS cases have been reported following mRNA vaccines.

TTS’s mechanism appears similar to autoimmune heparin-induced thrombocytopenia, where the body produces platelet-activating antibodies. TTS currently has three diagnostic criteria: new-onset thrombocytopenia (<150,000/microliter) without evidence of platelet clumping, venous or arterial thrombosis, and absence of prior exposure to heparin.

So far, TTS has been limited only to the vaccines that use an adenovirus vector. One male clinical trial participant experienced CVST with thrombocytopenia in Johnson & Johnson phase 3 trials, and 12 cases out of approximately 8 million Johnson & Johnson doses were reported to the Vaccine Adverse Event Reporting System between March 2 and April 21, 2021. Three TTS more cases followed these, resulting in 15 TTS events per 8 million doses.

In terms of clinical features, all 15 cases were females under age 60, mostly white, and all 11 who were tested were positive for the heparin-platelet factor 4 antibody test. TTS occurred 6-15 days after vaccination for these cases, and all but one had a headache. Their platelet count was 9,000-127,000. None were pregnant or postpartum.

“For us, as headache clinicians, the epidemiology of TTS overlaps with the epidemiology of migraine – they’re happening to the same group of patients,” Dr. Gelfand said. Most of the cases occurred in women aged 30-39 years, while the estimated incidence in women aged 50 or older is 0.9 cases per million doses.

The CDC has proceeded with the Johnson & Johnson vaccine because a risk-benefit analysis revealed that use of the vaccine will result in fewer hospitalization and deaths from COVID-19, compared with adverse events from the vaccine, Dr. Gelfand explained. However, the CDC notes that “women younger than 50 years old should be made aware of a rare risk of blood clots with low platelets following vaccination and the availability of other COVID-19 vaccines where this risk has not been observed.”

For clinicians, the existence of TTS raises a question when patients with a history of migraine call after having received the Johnson & Johnson vaccine, Dr. Gelfand said: “How do we know if this is a spontaneous attack, if it’s a headache provoked by receiving the vaccine, or they have one of these rare cases of [TTS]?”

Three things help with this differential, she said: timing, epidemiology, and headache phenotype. Headache after a vaccine is very common, but it usually happens within the first couple of hours or days after the vaccine. By day 4 after vaccination, few people had headaches in the clinical trials. Since TTS requires production of antibodies, a headache within a few hours of vaccination should not raise concerns about TTS. It should be considered, however, for patients who experience a headache within a week or 2 after vaccination.

Then consider the epidemiology: If it’s a woman between ages 18 and49 calling, the risk is higher than if it’s a male over age 50. Then consider whether there are any unusual headache features, positionality, encephalopathy, or clinical features that could suggest clots in other parts of the body, such as abdominal pain, shortness of breath, or pain in the legs.

“At the end of the day, if it’s a person who’s in this epidemiological window and they’re calling a week or 2 out from the Johnson & Johnson vaccine, we may just need to work it up and see,” Dr. Gelfand said. Work-up involves a CBC, a platelet count to see if they’re thrombocytopenic, and perhaps imaging, preferentially using MRI/MRV over CT since it’s a younger population. Treatment for CVST with thrombocytopenia is a nonheparin anticoagulant, and platelet transfusion should not occur before consulting with hematology.

Continue to vaccinate

“The big take home is that we should continue to vaccinate patients with migraine and that your current therapies do not interfere with the vaccine working and that the vaccine does not interact with our therapies,” Brian D. Loftus, MD, BSChE, immediate past president of the Southern Headache Society and a neurologist at Bellaire (Pa.) Neurology, said of the presentation. He also felt it was helpful to know that NSAIDs likely have no impact on the vaccines’ effectiveness as well.

“The most important new information for me was that the median onset of the CSVT was 8 days post vaccine,” Dr. Loftus said. “Typically, postvaccine headache is seen much sooner, within 1-2 days, so this is a useful clinical feature to separate out who needs to closer follow-up and possible neuroimaging.”

Given the epidemiology of those most likely to have TTS, Dr. Loftus said he would advise his female patients younger than 60 to simply get the Pfizer or Moderna vaccine since they appear safer for this demographic.

Dr. Gelfand is editor of the journal Headache but has no industry disclosures. Her spouse has received clinical trial grant support from Genentech and honoraria for editorial work from Dynamed Plus. Dr. Loftus has received grants or fees from Teva, Amgen, Abbvie, and Biohaven.

It is safe for patients with migraine to receive any of the COVID-19 vaccines without concern about the vaccination interfering with their migraine medications or the medications reducing an immune response to the vaccine, according to a presentation at the American Headache Society’s 2021 annual meeting.

Amy Gelfand, MD, director of pediatric headache at University of California, San Francisco, reviewed common concerns migraine patients or their clinicians might have related any of the three vaccines, starting with a review of how the vaccines work – by targeting the spike protein of the SARS-CoV-2 virus.

“The vaccines induce response to that protein, but only that protein, so there’s no reason to think they’re going to cause the body to produce neutralizing antibodies against any of our migraine therapeutics,” Dr. Gelfand said. She added that the phase 3 clinical trials included participants from a wide range of ages and comorbidities, so there were likely many people in the trials who have migraine, though no subgroup analyses have been performed for this group or are likely to be performed.

Common questions

The two treatments people have the most questions about concerning the COVID-19 vaccine are onabotulinumtoxinA and CGRP pathway monoclonal antibodies (mAbs), likely because both of these are injections, as is the vaccine, Dr. Gelfand said. First, she reminded attendees that onabotulinumtoxinA is not a dermal filler, since some reports following administration of the Moderna vaccine suggested that some people with dermal fillers had swelling in those areas after vaccination.

In addition, “there’s no reason to think the onabotulinumtoxinA would influence our body’s immune response to any vaccine, so there’s no need to retime the onabotulinumtoxinA injections around COVID-19 vaccine administration,” Dr. Gelfand said.

Regarding mAbs, she acknowledged that some white blood cells have CGRP receptors, which may have a pro- or anti-inflammatory role, but clinical trials of mAbs did not show any evidence of being immunosuppressive or myelosuppressive.

“The monoclonal antibodies themselves have undergone engineering so that they are just going after their one target,” Dr. Gelfand said. “They’re not going to be expected to bind to anything else outside of their targets, so I don’t think there’s anything there to make us retime the monoclonal antibody administration relative to the COVID-19 vaccine.”

She did note that patients who choose to get mAbs injections in their arm instead of their thigh or abdomen may want to receive it in the opposite arm than they one they have gotten or will get the vaccine in since the vaccine can cause discomfort.

The other common question patients may have is whether taking any NSAIDs or acetaminophen before getting the COVID-19 vaccine will reduce their immune response to the vaccination. This concern arises because of past evidence showing that some infants tended to have lower immunologic responses when they received acetaminophen after their primary vaccines’ series, but the clinical significance of those reduced responses is not clear since they still had strong responses. Further, this effect was not seen with booster shots, suggesting it’s an age-dependent effect.

During the clinical trials of the AstraZeneca vaccine, several sites gave prophylactic paracetamol without any apparent detrimental effect on antibody response, Dr. Gelfand said. Further, the mRNA and adenovirus-vectored vaccines appear to induce antibodies far above what many believe is needed for protection.

“Even if there were a slight decrease, it’s not clear that that would have any kind of clinical significance for that person in terms of their level of protection against COVID-19,” she said. “Bottom line, it’s fine for patients to use either of these after administration of the COVID-19 vaccine.” The Centers for Disease Control and Prevention doesn’t recommend it prophylactically beforehand, but it’s fine to take it for a fever, aches or headache after getting the vaccine.

Migraine or vaccine reaction?

Dr. Gelfand then addressed whether it should affect physicians’ headache differential if seeing a patient who recently received an adenovirus-vectored vaccine, such as the Johnson & Johnson or AstraZeneca vaccines. The question relates to the discovery of a very rare potential adverse event from these vaccines: cerebral venous sinus thrombosis (CVST) with thrombocytopenia and thromboses in other major vessels, together called thrombosis thrombocytopenia syndrome (TTS). No TTS cases have been reported following mRNA vaccines.

TTS’s mechanism appears similar to autoimmune heparin-induced thrombocytopenia, where the body produces platelet-activating antibodies. TTS currently has three diagnostic criteria: new-onset thrombocytopenia (<150,000/microliter) without evidence of platelet clumping, venous or arterial thrombosis, and absence of prior exposure to heparin.

So far, TTS has been limited only to the vaccines that use an adenovirus vector. One male clinical trial participant experienced CVST with thrombocytopenia in Johnson & Johnson phase 3 trials, and 12 cases out of approximately 8 million Johnson & Johnson doses were reported to the Vaccine Adverse Event Reporting System between March 2 and April 21, 2021. Three TTS more cases followed these, resulting in 15 TTS events per 8 million doses.

In terms of clinical features, all 15 cases were females under age 60, mostly white, and all 11 who were tested were positive for the heparin-platelet factor 4 antibody test. TTS occurred 6-15 days after vaccination for these cases, and all but one had a headache. Their platelet count was 9,000-127,000. None were pregnant or postpartum.

“For us, as headache clinicians, the epidemiology of TTS overlaps with the epidemiology of migraine – they’re happening to the same group of patients,” Dr. Gelfand said. Most of the cases occurred in women aged 30-39 years, while the estimated incidence in women aged 50 or older is 0.9 cases per million doses.

The CDC has proceeded with the Johnson & Johnson vaccine because a risk-benefit analysis revealed that use of the vaccine will result in fewer hospitalization and deaths from COVID-19, compared with adverse events from the vaccine, Dr. Gelfand explained. However, the CDC notes that “women younger than 50 years old should be made aware of a rare risk of blood clots with low platelets following vaccination and the availability of other COVID-19 vaccines where this risk has not been observed.”

For clinicians, the existence of TTS raises a question when patients with a history of migraine call after having received the Johnson & Johnson vaccine, Dr. Gelfand said: “How do we know if this is a spontaneous attack, if it’s a headache provoked by receiving the vaccine, or they have one of these rare cases of [TTS]?”

Three things help with this differential, she said: timing, epidemiology, and headache phenotype. Headache after a vaccine is very common, but it usually happens within the first couple of hours or days after the vaccine. By day 4 after vaccination, few people had headaches in the clinical trials. Since TTS requires production of antibodies, a headache within a few hours of vaccination should not raise concerns about TTS. It should be considered, however, for patients who experience a headache within a week or 2 after vaccination.

Then consider the epidemiology: If it’s a woman between ages 18 and49 calling, the risk is higher than if it’s a male over age 50. Then consider whether there are any unusual headache features, positionality, encephalopathy, or clinical features that could suggest clots in other parts of the body, such as abdominal pain, shortness of breath, or pain in the legs.

“At the end of the day, if it’s a person who’s in this epidemiological window and they’re calling a week or 2 out from the Johnson & Johnson vaccine, we may just need to work it up and see,” Dr. Gelfand said. Work-up involves a CBC, a platelet count to see if they’re thrombocytopenic, and perhaps imaging, preferentially using MRI/MRV over CT since it’s a younger population. Treatment for CVST with thrombocytopenia is a nonheparin anticoagulant, and platelet transfusion should not occur before consulting with hematology.

Continue to vaccinate

“The big take home is that we should continue to vaccinate patients with migraine and that your current therapies do not interfere with the vaccine working and that the vaccine does not interact with our therapies,” Brian D. Loftus, MD, BSChE, immediate past president of the Southern Headache Society and a neurologist at Bellaire (Pa.) Neurology, said of the presentation. He also felt it was helpful to know that NSAIDs likely have no impact on the vaccines’ effectiveness as well.

“The most important new information for me was that the median onset of the CSVT was 8 days post vaccine,” Dr. Loftus said. “Typically, postvaccine headache is seen much sooner, within 1-2 days, so this is a useful clinical feature to separate out who needs to closer follow-up and possible neuroimaging.”

Given the epidemiology of those most likely to have TTS, Dr. Loftus said he would advise his female patients younger than 60 to simply get the Pfizer or Moderna vaccine since they appear safer for this demographic.

Dr. Gelfand is editor of the journal Headache but has no industry disclosures. Her spouse has received clinical trial grant support from Genentech and honoraria for editorial work from Dynamed Plus. Dr. Loftus has received grants or fees from Teva, Amgen, Abbvie, and Biohaven.

It is safe for patients with migraine to receive any of the COVID-19 vaccines without concern about the vaccination interfering with their migraine medications or the medications reducing an immune response to the vaccine, according to a presentation at the American Headache Society’s 2021 annual meeting.

Amy Gelfand, MD, director of pediatric headache at University of California, San Francisco, reviewed common concerns migraine patients or their clinicians might have related any of the three vaccines, starting with a review of how the vaccines work – by targeting the spike protein of the SARS-CoV-2 virus.

“The vaccines induce response to that protein, but only that protein, so there’s no reason to think they’re going to cause the body to produce neutralizing antibodies against any of our migraine therapeutics,” Dr. Gelfand said. She added that the phase 3 clinical trials included participants from a wide range of ages and comorbidities, so there were likely many people in the trials who have migraine, though no subgroup analyses have been performed for this group or are likely to be performed.

Common questions

The two treatments people have the most questions about concerning the COVID-19 vaccine are onabotulinumtoxinA and CGRP pathway monoclonal antibodies (mAbs), likely because both of these are injections, as is the vaccine, Dr. Gelfand said. First, she reminded attendees that onabotulinumtoxinA is not a dermal filler, since some reports following administration of the Moderna vaccine suggested that some people with dermal fillers had swelling in those areas after vaccination.

In addition, “there’s no reason to think the onabotulinumtoxinA would influence our body’s immune response to any vaccine, so there’s no need to retime the onabotulinumtoxinA injections around COVID-19 vaccine administration,” Dr. Gelfand said.

Regarding mAbs, she acknowledged that some white blood cells have CGRP receptors, which may have a pro- or anti-inflammatory role, but clinical trials of mAbs did not show any evidence of being immunosuppressive or myelosuppressive.

“The monoclonal antibodies themselves have undergone engineering so that they are just going after their one target,” Dr. Gelfand said. “They’re not going to be expected to bind to anything else outside of their targets, so I don’t think there’s anything there to make us retime the monoclonal antibody administration relative to the COVID-19 vaccine.”

She did note that patients who choose to get mAbs injections in their arm instead of their thigh or abdomen may want to receive it in the opposite arm than they one they have gotten or will get the vaccine in since the vaccine can cause discomfort.

The other common question patients may have is whether taking any NSAIDs or acetaminophen before getting the COVID-19 vaccine will reduce their immune response to the vaccination. This concern arises because of past evidence showing that some infants tended to have lower immunologic responses when they received acetaminophen after their primary vaccines’ series, but the clinical significance of those reduced responses is not clear since they still had strong responses. Further, this effect was not seen with booster shots, suggesting it’s an age-dependent effect.

During the clinical trials of the AstraZeneca vaccine, several sites gave prophylactic paracetamol without any apparent detrimental effect on antibody response, Dr. Gelfand said. Further, the mRNA and adenovirus-vectored vaccines appear to induce antibodies far above what many believe is needed for protection.

“Even if there were a slight decrease, it’s not clear that that would have any kind of clinical significance for that person in terms of their level of protection against COVID-19,” she said. “Bottom line, it’s fine for patients to use either of these after administration of the COVID-19 vaccine.” The Centers for Disease Control and Prevention doesn’t recommend it prophylactically beforehand, but it’s fine to take it for a fever, aches or headache after getting the vaccine.

Migraine or vaccine reaction?

Dr. Gelfand then addressed whether it should affect physicians’ headache differential if seeing a patient who recently received an adenovirus-vectored vaccine, such as the Johnson & Johnson or AstraZeneca vaccines. The question relates to the discovery of a very rare potential adverse event from these vaccines: cerebral venous sinus thrombosis (CVST) with thrombocytopenia and thromboses in other major vessels, together called thrombosis thrombocytopenia syndrome (TTS). No TTS cases have been reported following mRNA vaccines.

TTS’s mechanism appears similar to autoimmune heparin-induced thrombocytopenia, where the body produces platelet-activating antibodies. TTS currently has three diagnostic criteria: new-onset thrombocytopenia (<150,000/microliter) without evidence of platelet clumping, venous or arterial thrombosis, and absence of prior exposure to heparin.

So far, TTS has been limited only to the vaccines that use an adenovirus vector. One male clinical trial participant experienced CVST with thrombocytopenia in Johnson & Johnson phase 3 trials, and 12 cases out of approximately 8 million Johnson & Johnson doses were reported to the Vaccine Adverse Event Reporting System between March 2 and April 21, 2021. Three TTS more cases followed these, resulting in 15 TTS events per 8 million doses.

In terms of clinical features, all 15 cases were females under age 60, mostly white, and all 11 who were tested were positive for the heparin-platelet factor 4 antibody test. TTS occurred 6-15 days after vaccination for these cases, and all but one had a headache. Their platelet count was 9,000-127,000. None were pregnant or postpartum.

“For us, as headache clinicians, the epidemiology of TTS overlaps with the epidemiology of migraine – they’re happening to the same group of patients,” Dr. Gelfand said. Most of the cases occurred in women aged 30-39 years, while the estimated incidence in women aged 50 or older is 0.9 cases per million doses.

The CDC has proceeded with the Johnson & Johnson vaccine because a risk-benefit analysis revealed that use of the vaccine will result in fewer hospitalization and deaths from COVID-19, compared with adverse events from the vaccine, Dr. Gelfand explained. However, the CDC notes that “women younger than 50 years old should be made aware of a rare risk of blood clots with low platelets following vaccination and the availability of other COVID-19 vaccines where this risk has not been observed.”

For clinicians, the existence of TTS raises a question when patients with a history of migraine call after having received the Johnson & Johnson vaccine, Dr. Gelfand said: “How do we know if this is a spontaneous attack, if it’s a headache provoked by receiving the vaccine, or they have one of these rare cases of [TTS]?”

Three things help with this differential, she said: timing, epidemiology, and headache phenotype. Headache after a vaccine is very common, but it usually happens within the first couple of hours or days after the vaccine. By day 4 after vaccination, few people had headaches in the clinical trials. Since TTS requires production of antibodies, a headache within a few hours of vaccination should not raise concerns about TTS. It should be considered, however, for patients who experience a headache within a week or 2 after vaccination.

Then consider the epidemiology: If it’s a woman between ages 18 and49 calling, the risk is higher than if it’s a male over age 50. Then consider whether there are any unusual headache features, positionality, encephalopathy, or clinical features that could suggest clots in other parts of the body, such as abdominal pain, shortness of breath, or pain in the legs.

“At the end of the day, if it’s a person who’s in this epidemiological window and they’re calling a week or 2 out from the Johnson & Johnson vaccine, we may just need to work it up and see,” Dr. Gelfand said. Work-up involves a CBC, a platelet count to see if they’re thrombocytopenic, and perhaps imaging, preferentially using MRI/MRV over CT since it’s a younger population. Treatment for CVST with thrombocytopenia is a nonheparin anticoagulant, and platelet transfusion should not occur before consulting with hematology.

Continue to vaccinate

“The big take home is that we should continue to vaccinate patients with migraine and that your current therapies do not interfere with the vaccine working and that the vaccine does not interact with our therapies,” Brian D. Loftus, MD, BSChE, immediate past president of the Southern Headache Society and a neurologist at Bellaire (Pa.) Neurology, said of the presentation. He also felt it was helpful to know that NSAIDs likely have no impact on the vaccines’ effectiveness as well.

“The most important new information for me was that the median onset of the CSVT was 8 days post vaccine,” Dr. Loftus said. “Typically, postvaccine headache is seen much sooner, within 1-2 days, so this is a useful clinical feature to separate out who needs to closer follow-up and possible neuroimaging.”

Given the epidemiology of those most likely to have TTS, Dr. Loftus said he would advise his female patients younger than 60 to simply get the Pfizer or Moderna vaccine since they appear safer for this demographic.

Dr. Gelfand is editor of the journal Headache but has no industry disclosures. Her spouse has received clinical trial grant support from Genentech and honoraria for editorial work from Dynamed Plus. Dr. Loftus has received grants or fees from Teva, Amgen, Abbvie, and Biohaven.