Neurology

The U.S. Food and Drug Administration has approved vamorolone oral suspension (Agamree, Santhera) for the treatment of Duchenne muscular dystrophy (DMD) in patients as young as age 2 years, the company has announced Vamorolone is a structurally unique steroidal anti-inflammatory drug that potently inhibits proinflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor.

Olivier Le Moal/Getty Images

“Corticosteroids have been a first line treatment for DMD for many years, but their utility has always been limited by the side effect profile, which includes weight gain, short stature, and decreased bone density, among others,” Sharon Hesterlee, PhD, chief research officer for the Muscular Dystrophy Association, said in a statement.

The approval of vamorolone “provides people living with Duchenne, and their families, a powerful tool to treat the disease, while limiting some negative side effects associated with corticosteroids,” Dr. Hesterlee added.

The approval was based on data from the phase 2b VISION-DMD study, supplemented with safety information collected from three open-label studies.

Vamorolone was administered at doses ranging from 2-6 mg/kg/d for a period of up to 48 months.

Vamorolone demonstrated efficacy similar to that of traditional corticosteroids, with data suggesting a reduction in adverse events – notably related to bone health, growth trajectory, and behavior.

Vamorolone had received orphan drug status for DMD, as well as fast track and rare pediatric disease designations. It will be made available in the United States by Catalyst Pharmaceuticals.

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

The U.S. Food and Drug Administration has approved vamorolone oral suspension (Agamree, Santhera) for the treatment of Duchenne muscular dystrophy (DMD) in patients as young as age 2 years, the company has announced Vamorolone is a structurally unique steroidal anti-inflammatory drug that potently inhibits proinflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor.

Olivier Le Moal/Getty Images

“Corticosteroids have been a first line treatment for DMD for many years, but their utility has always been limited by the side effect profile, which includes weight gain, short stature, and decreased bone density, among others,” Sharon Hesterlee, PhD, chief research officer for the Muscular Dystrophy Association, said in a statement.

The approval of vamorolone “provides people living with Duchenne, and their families, a powerful tool to treat the disease, while limiting some negative side effects associated with corticosteroids,” Dr. Hesterlee added.

The approval was based on data from the phase 2b VISION-DMD study, supplemented with safety information collected from three open-label studies.

Vamorolone was administered at doses ranging from 2-6 mg/kg/d for a period of up to 48 months.

Vamorolone demonstrated efficacy similar to that of traditional corticosteroids, with data suggesting a reduction in adverse events – notably related to bone health, growth trajectory, and behavior.

Vamorolone had received orphan drug status for DMD, as well as fast track and rare pediatric disease designations. It will be made available in the United States by Catalyst Pharmaceuticals.

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

The U.S. Food and Drug Administration has approved vamorolone oral suspension (Agamree, Santhera) for the treatment of Duchenne muscular dystrophy (DMD) in patients as young as age 2 years, the company has announced Vamorolone is a structurally unique steroidal anti-inflammatory drug that potently inhibits proinflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor.

Olivier Le Moal/Getty Images

“Corticosteroids have been a first line treatment for DMD for many years, but their utility has always been limited by the side effect profile, which includes weight gain, short stature, and decreased bone density, among others,” Sharon Hesterlee, PhD, chief research officer for the Muscular Dystrophy Association, said in a statement.

The approval of vamorolone “provides people living with Duchenne, and their families, a powerful tool to treat the disease, while limiting some negative side effects associated with corticosteroids,” Dr. Hesterlee added.

The approval was based on data from the phase 2b VISION-DMD study, supplemented with safety information collected from three open-label studies.

Vamorolone was administered at doses ranging from 2-6 mg/kg/d for a period of up to 48 months.

Vamorolone demonstrated efficacy similar to that of traditional corticosteroids, with data suggesting a reduction in adverse events – notably related to bone health, growth trajectory, and behavior.

Vamorolone had received orphan drug status for DMD, as well as fast track and rare pediatric disease designations. It will be made available in the United States by Catalyst Pharmaceuticals.

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

WASHINGTON – Get the back story before rushing to diagnose a seizure disorder in a child, Michael Strunc, MD, said in a presentation at the annual meeting of the American Academy of Pediatrics.

Clinicians should ask parents or caregivers about the child’s behavior before the suspected seizure, whether there were any triggers, and if so, what might they have been, according to Dr. Strunc, a child neurologist and sleep medicine specialist at Children’s Hospital of the King’s Daughters, Norfolk, Va.

“Most seizures don’t have triggers,” he said. Rather, patients often become stiff, experience a motor event that builds in intensity then slows and stops, and finally, the patient is sleepy and tired. Clinicians should also find out whether the event had a beginning, middle, and end.

Approximately 0.6% of children younger than 17 years in the United States have active epilepsy, according to the Centers for Disease Control and Prevention.

Dr. Strunc offered a few more tips for diagnosing a child:

• Ask whether the patient’s eyes were open during the event. If the eyes were closed or squished closed, “it is almost never a seizure,” he said.
• Find out whether the patient was awake or asleep, and how, if at all, caregivers attempted to stop the event.
• Ask if the child’s experiences were repeating and predictable, and inquire about a family history of seizures or other events.
• Inquire about any developmental changes and other changes in the child, such as irritability, regression, or ataxia.

The differential diagnosis for a seizure includes nonepileptic events that occur with and without changes in consciousness or sleep. These events range from breath-holding and hyperventilation to night terrors, narcolepsy, migraine, and attention-deficit/hyperactivity disorder, he said.
 

Is it epilepsy?

Dr. Strunc shared several cases of neurologic “events” ranging from simple to severe.

In one case, a 10-month-old infant girl with a potential tonic/staring seizure presented with a history of events that involved getting stuck in a stiff position, usually while sitting in a car seat or highchair, with adducting of legs, redness of face, and “zoned-out” expression. The infant was healthy, smart, and precocious, with no illness, fever, or trauma, but the mother was very concerned, Dr. Strunc said.

The diagnosis: Self-gratification, which is benign and usually outgrown, although it can become extreme, he said.

By contrast, “absence,” also known as idiopathic generalized epilepsy, presents as brief events of 4-10 seconds that may occur up to hundreds of times a day. This type of epilepsy is associated with the sudden onset of impaired consciousness and unresponsiveness. These events end abruptly, and the child may be unaware. Absence is more common in girls. It usually occurs after age 4 and usually remits by about age 12, Dr. Strunc said.

However, the onset of absence in patients younger than age 3 is associated with increased odds of neurodevelopmental abnormalities “and probably represents another epilepsy syndrome,” he said.

Absence symptoms may mirror those of children who are simply daydreamers, Dr. Strunc noted. One way to confirm absence is by provoking hyperventilation, which will bring on an episode of absence if present, he said. EEGs provide evidence as well.

Acute ataxia in children has a wide differential that sends kids and families to the pediatrician or emergency department, Dr. Strunc said. Acute cerebellar ataxia is characterized by abrupt and symmetric symptoms, with no mental status changes, no fever, no meningitis, and no headache. A wide, unstable gait is a distinguishing feature, Dr. Strunc said.

However, other causes of acute ataxia should be ruled out, including toxic ingestion, tick paralysis, central nervous system infections, vascular conditions, and genetic conditions.
 

Don’t miss those ticks

Especially during periods when kids are outdoors, clinicians should consider a tick bite as a source of ataxia and neurologic symptoms in children, Dr. Strunc emphasized. Tick paralysis notably resembles many symptoms of Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).

Dr. Strunc described a case involving a 5-year-old girl who developed sudden problems with gait. The problems worsened quickly and prompted an emergency department visit.

The girl had an unremarkable history, she had not experienced mental status changes, her strength was normal, and she had just returned from a Girl Scouts trip. The patient was presumed to have Guillain-Barré. IVIG was initiated when an emergency nurse found a tick on her scalp. The tick was removed, and the patient left the hospital within 24 hours.

Children with tick paralysis are usually symptomatic after 5-7 days with the tick attached, Dr. Strunc said. They recover within a day after tick removal.

Overall, actual seizures are less common than other neurologic events in children, according to Dr. Strunc. Details on history, lack or presence of neurologic feature, and normal child development can help guide evaluation.

Take advantage of videos, he emphasized, as many parents and caregivers record a child’s neurologic events.

“Ataxia is scary, but exam and associated findings will help you with etiology,” he said.

Dr. Strunc has received research support from Jazz and Harmony and has served on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Avadel, unrelated to his presentation.

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

WASHINGTON – Get the back story before rushing to diagnose a seizure disorder in a child, Michael Strunc, MD, said in a presentation at the annual meeting of the American Academy of Pediatrics.

Clinicians should ask parents or caregivers about the child’s behavior before the suspected seizure, whether there were any triggers, and if so, what might they have been, according to Dr. Strunc, a child neurologist and sleep medicine specialist at Children’s Hospital of the King’s Daughters, Norfolk, Va.

“Most seizures don’t have triggers,” he said. Rather, patients often become stiff, experience a motor event that builds in intensity then slows and stops, and finally, the patient is sleepy and tired. Clinicians should also find out whether the event had a beginning, middle, and end.

Approximately 0.6% of children younger than 17 years in the United States have active epilepsy, according to the Centers for Disease Control and Prevention.

Dr. Strunc offered a few more tips for diagnosing a child:

• Ask whether the patient’s eyes were open during the event. If the eyes were closed or squished closed, “it is almost never a seizure,” he said.
• Find out whether the patient was awake or asleep, and how, if at all, caregivers attempted to stop the event.
• Ask if the child’s experiences were repeating and predictable, and inquire about a family history of seizures or other events.
• Inquire about any developmental changes and other changes in the child, such as irritability, regression, or ataxia.

The differential diagnosis for a seizure includes nonepileptic events that occur with and without changes in consciousness or sleep. These events range from breath-holding and hyperventilation to night terrors, narcolepsy, migraine, and attention-deficit/hyperactivity disorder, he said.
 

Is it epilepsy?

Dr. Strunc shared several cases of neurologic “events” ranging from simple to severe.

In one case, a 10-month-old infant girl with a potential tonic/staring seizure presented with a history of events that involved getting stuck in a stiff position, usually while sitting in a car seat or highchair, with adducting of legs, redness of face, and “zoned-out” expression. The infant was healthy, smart, and precocious, with no illness, fever, or trauma, but the mother was very concerned, Dr. Strunc said.

The diagnosis: Self-gratification, which is benign and usually outgrown, although it can become extreme, he said.

By contrast, “absence,” also known as idiopathic generalized epilepsy, presents as brief events of 4-10 seconds that may occur up to hundreds of times a day. This type of epilepsy is associated with the sudden onset of impaired consciousness and unresponsiveness. These events end abruptly, and the child may be unaware. Absence is more common in girls. It usually occurs after age 4 and usually remits by about age 12, Dr. Strunc said.

However, the onset of absence in patients younger than age 3 is associated with increased odds of neurodevelopmental abnormalities “and probably represents another epilepsy syndrome,” he said.

Absence symptoms may mirror those of children who are simply daydreamers, Dr. Strunc noted. One way to confirm absence is by provoking hyperventilation, which will bring on an episode of absence if present, he said. EEGs provide evidence as well.

Acute ataxia in children has a wide differential that sends kids and families to the pediatrician or emergency department, Dr. Strunc said. Acute cerebellar ataxia is characterized by abrupt and symmetric symptoms, with no mental status changes, no fever, no meningitis, and no headache. A wide, unstable gait is a distinguishing feature, Dr. Strunc said.

However, other causes of acute ataxia should be ruled out, including toxic ingestion, tick paralysis, central nervous system infections, vascular conditions, and genetic conditions.
 

Don’t miss those ticks

Especially during periods when kids are outdoors, clinicians should consider a tick bite as a source of ataxia and neurologic symptoms in children, Dr. Strunc emphasized. Tick paralysis notably resembles many symptoms of Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).

Dr. Strunc described a case involving a 5-year-old girl who developed sudden problems with gait. The problems worsened quickly and prompted an emergency department visit.

The girl had an unremarkable history, she had not experienced mental status changes, her strength was normal, and she had just returned from a Girl Scouts trip. The patient was presumed to have Guillain-Barré. IVIG was initiated when an emergency nurse found a tick on her scalp. The tick was removed, and the patient left the hospital within 24 hours.

Children with tick paralysis are usually symptomatic after 5-7 days with the tick attached, Dr. Strunc said. They recover within a day after tick removal.

Overall, actual seizures are less common than other neurologic events in children, according to Dr. Strunc. Details on history, lack or presence of neurologic feature, and normal child development can help guide evaluation.

Take advantage of videos, he emphasized, as many parents and caregivers record a child’s neurologic events.

“Ataxia is scary, but exam and associated findings will help you with etiology,” he said.

Dr. Strunc has received research support from Jazz and Harmony and has served on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Avadel, unrelated to his presentation.

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

WASHINGTON – Get the back story before rushing to diagnose a seizure disorder in a child, Michael Strunc, MD, said in a presentation at the annual meeting of the American Academy of Pediatrics.

Clinicians should ask parents or caregivers about the child’s behavior before the suspected seizure, whether there were any triggers, and if so, what might they have been, according to Dr. Strunc, a child neurologist and sleep medicine specialist at Children’s Hospital of the King’s Daughters, Norfolk, Va.

“Most seizures don’t have triggers,” he said. Rather, patients often become stiff, experience a motor event that builds in intensity then slows and stops, and finally, the patient is sleepy and tired. Clinicians should also find out whether the event had a beginning, middle, and end.

Approximately 0.6% of children younger than 17 years in the United States have active epilepsy, according to the Centers for Disease Control and Prevention.

Dr. Strunc offered a few more tips for diagnosing a child:

• Ask whether the patient’s eyes were open during the event. If the eyes were closed or squished closed, “it is almost never a seizure,” he said.
• Find out whether the patient was awake or asleep, and how, if at all, caregivers attempted to stop the event.
• Ask if the child’s experiences were repeating and predictable, and inquire about a family history of seizures or other events.
• Inquire about any developmental changes and other changes in the child, such as irritability, regression, or ataxia.

The differential diagnosis for a seizure includes nonepileptic events that occur with and without changes in consciousness or sleep. These events range from breath-holding and hyperventilation to night terrors, narcolepsy, migraine, and attention-deficit/hyperactivity disorder, he said.
 

Is it epilepsy?

Dr. Strunc shared several cases of neurologic “events” ranging from simple to severe.

In one case, a 10-month-old infant girl with a potential tonic/staring seizure presented with a history of events that involved getting stuck in a stiff position, usually while sitting in a car seat or highchair, with adducting of legs, redness of face, and “zoned-out” expression. The infant was healthy, smart, and precocious, with no illness, fever, or trauma, but the mother was very concerned, Dr. Strunc said.

The diagnosis: Self-gratification, which is benign and usually outgrown, although it can become extreme, he said.

By contrast, “absence,” also known as idiopathic generalized epilepsy, presents as brief events of 4-10 seconds that may occur up to hundreds of times a day. This type of epilepsy is associated with the sudden onset of impaired consciousness and unresponsiveness. These events end abruptly, and the child may be unaware. Absence is more common in girls. It usually occurs after age 4 and usually remits by about age 12, Dr. Strunc said.

However, the onset of absence in patients younger than age 3 is associated with increased odds of neurodevelopmental abnormalities “and probably represents another epilepsy syndrome,” he said.

Absence symptoms may mirror those of children who are simply daydreamers, Dr. Strunc noted. One way to confirm absence is by provoking hyperventilation, which will bring on an episode of absence if present, he said. EEGs provide evidence as well.

Acute ataxia in children has a wide differential that sends kids and families to the pediatrician or emergency department, Dr. Strunc said. Acute cerebellar ataxia is characterized by abrupt and symmetric symptoms, with no mental status changes, no fever, no meningitis, and no headache. A wide, unstable gait is a distinguishing feature, Dr. Strunc said.

However, other causes of acute ataxia should be ruled out, including toxic ingestion, tick paralysis, central nervous system infections, vascular conditions, and genetic conditions.
 

Don’t miss those ticks

Especially during periods when kids are outdoors, clinicians should consider a tick bite as a source of ataxia and neurologic symptoms in children, Dr. Strunc emphasized. Tick paralysis notably resembles many symptoms of Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).

Dr. Strunc described a case involving a 5-year-old girl who developed sudden problems with gait. The problems worsened quickly and prompted an emergency department visit.

The girl had an unremarkable history, she had not experienced mental status changes, her strength was normal, and she had just returned from a Girl Scouts trip. The patient was presumed to have Guillain-Barré. IVIG was initiated when an emergency nurse found a tick on her scalp. The tick was removed, and the patient left the hospital within 24 hours.

Children with tick paralysis are usually symptomatic after 5-7 days with the tick attached, Dr. Strunc said. They recover within a day after tick removal.

Overall, actual seizures are less common than other neurologic events in children, according to Dr. Strunc. Details on history, lack or presence of neurologic feature, and normal child development can help guide evaluation.

Take advantage of videos, he emphasized, as many parents and caregivers record a child’s neurologic events.

“Ataxia is scary, but exam and associated findings will help you with etiology,” he said.

Dr. Strunc has received research support from Jazz and Harmony and has served on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Avadel, unrelated to his presentation.

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

A device that stimulates the median nerve and a D1 receptor antagonist are among the promising new treatment approaches for patients with Tourette syndrome (TS), according to an overview of new therapies presented at the XXVI World Congress of Neurology.

One recent study by University of Nottingham researchers showed a wrist-worn stimulating device significantly reduces the frequency and severity of tics – repetitive movements or vocalizations that can occur several times a day.

“Wearable nerve stimulation holds great promise because it will be good across the age spectrum; adults can wear it to work, and children can go to school with it to help them concentrate on their schoolwork, and then they take it off at night,” Eileen Joyce, PhD, MB BChir, professor of neuropsychiatry at the Institute of Neurology, University College London, told this news organization.

Dr. Joyce, who was not part of the study, discussed this and other new advances in tic therapy at the meeting.

About 24% of children will suffer from tics at some point. The prevalence of Tourette syndrome among males is about four times that of females, Dr. Joyce told delegates. She added the typical age of onset is about 7 years with peak severity at about 12 years.

Predictors of tics persisting into adulthood include comorbid attention deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder, and autism spectrum disorder, said Dr. Joyce, who also discussed the “highly heritable” nature of the syndrome and the numerous related genes identified to date.
 

Current and emerging treatments

Current treatments include psychological therapy, Botox for focal tics, and medications such as antipsychotics. Emerging therapies included deep brain stimulation and the new median nerve stimulation approach.

A study published  earlier this year included 135 patients with moderate to severe tic disorder who were randomly assigned to receive the investigational neuromodulation treatment, a sham treatment, or a wait-list treatment group.

The intervention involves rhythmic pulse trains of median nerve stimulation delivered via a device worn at the wrist. The device was programmed to deliver rhythmic (10 Hz) trains of low-intensity (1-19 mA) electrical stimulation to the median nerve at home once daily, 5 days a week for 4 weeks.

At 4 weeks, tic severity, as measured by the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTSS), was reduced by 7.1 points (35% reduction) in the active stimulation group compared to 2.13 points in the sham and 2.11 points in wait-list control groups.

The reduction for active stimulation was substantially larger, clinically meaningful (effect size, 0.5), and statistically significant (P = .02) compared to both the sham stimulation and wait-list control groups, which did not differ from one another.

Tic frequency (tics per minute or TPM) was reduced more in the active than sham stimulation groups (−15.6 TPM vs. −7.7 TPM; P < .03) and the reduction in tic frequency was clinically meaningful (>25% reduction; effect-size, 0.3).

When the active stimulator was turned off, the tics worsened, noted Dr. Joyce.

“The study showed that if you stimulate the median nerve at the wrist, you can train brain oscillations that are linked to the suppression of movement,” Dr. Joyce said. “So based on physiological knowledge, they have developed a median nerve stimulator to entrain cortical rhythms.”
 

Simple and exciting

The new device is “really exciting”, she added. “It’s not invasive and is quite simple to use and could help a lot of people with Tourette syndrome.”

Asked to comment, Alan Carson, MD, consultant neuropsychiatrist and honorary professor of neuropsychiatry, University of Edinburgh, who co-chaired the neuropsychiatry session featuring this presentation, called the device “promising.”

“Deep brain stimulation appears to be very effective but it’s a major procedure, so a simple wearable device seems highly desirable,” Dr. Carson said.

Dr. Joyce also discussed a study on the efficacy of cannabis (nabiximols; Sativex) as an intervention for tic management in males, those with severe tics, and those with comorbid ADHD.

And a new oral medication, ecopipam, a highly selective D1 receptor antagonist, is also raising hopes, said Dr. Joyce, with results from a randomized controlled trial  showing the drug significantly improved tics and had few adverse effects.

Dr. Joyce and Dr. Carson report no relevant financial relationships.

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

A device that stimulates the median nerve and a D1 receptor antagonist are among the promising new treatment approaches for patients with Tourette syndrome (TS), according to an overview of new therapies presented at the XXVI World Congress of Neurology.

One recent study by University of Nottingham researchers showed a wrist-worn stimulating device significantly reduces the frequency and severity of tics – repetitive movements or vocalizations that can occur several times a day.

“Wearable nerve stimulation holds great promise because it will be good across the age spectrum; adults can wear it to work, and children can go to school with it to help them concentrate on their schoolwork, and then they take it off at night,” Eileen Joyce, PhD, MB BChir, professor of neuropsychiatry at the Institute of Neurology, University College London, told this news organization.

Dr. Joyce, who was not part of the study, discussed this and other new advances in tic therapy at the meeting.

About 24% of children will suffer from tics at some point. The prevalence of Tourette syndrome among males is about four times that of females, Dr. Joyce told delegates. She added the typical age of onset is about 7 years with peak severity at about 12 years.

Predictors of tics persisting into adulthood include comorbid attention deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder, and autism spectrum disorder, said Dr. Joyce, who also discussed the “highly heritable” nature of the syndrome and the numerous related genes identified to date.
 

Current and emerging treatments

Current treatments include psychological therapy, Botox for focal tics, and medications such as antipsychotics. Emerging therapies included deep brain stimulation and the new median nerve stimulation approach.

A study published  earlier this year included 135 patients with moderate to severe tic disorder who were randomly assigned to receive the investigational neuromodulation treatment, a sham treatment, or a wait-list treatment group.

The intervention involves rhythmic pulse trains of median nerve stimulation delivered via a device worn at the wrist. The device was programmed to deliver rhythmic (10 Hz) trains of low-intensity (1-19 mA) electrical stimulation to the median nerve at home once daily, 5 days a week for 4 weeks.

At 4 weeks, tic severity, as measured by the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTSS), was reduced by 7.1 points (35% reduction) in the active stimulation group compared to 2.13 points in the sham and 2.11 points in wait-list control groups.

The reduction for active stimulation was substantially larger, clinically meaningful (effect size, 0.5), and statistically significant (P = .02) compared to both the sham stimulation and wait-list control groups, which did not differ from one another.

Tic frequency (tics per minute or TPM) was reduced more in the active than sham stimulation groups (−15.6 TPM vs. −7.7 TPM; P < .03) and the reduction in tic frequency was clinically meaningful (>25% reduction; effect-size, 0.3).

When the active stimulator was turned off, the tics worsened, noted Dr. Joyce.

“The study showed that if you stimulate the median nerve at the wrist, you can train brain oscillations that are linked to the suppression of movement,” Dr. Joyce said. “So based on physiological knowledge, they have developed a median nerve stimulator to entrain cortical rhythms.”
 

Simple and exciting

The new device is “really exciting”, she added. “It’s not invasive and is quite simple to use and could help a lot of people with Tourette syndrome.”

Asked to comment, Alan Carson, MD, consultant neuropsychiatrist and honorary professor of neuropsychiatry, University of Edinburgh, who co-chaired the neuropsychiatry session featuring this presentation, called the device “promising.”

“Deep brain stimulation appears to be very effective but it’s a major procedure, so a simple wearable device seems highly desirable,” Dr. Carson said.

Dr. Joyce also discussed a study on the efficacy of cannabis (nabiximols; Sativex) as an intervention for tic management in males, those with severe tics, and those with comorbid ADHD.

And a new oral medication, ecopipam, a highly selective D1 receptor antagonist, is also raising hopes, said Dr. Joyce, with results from a randomized controlled trial  showing the drug significantly improved tics and had few adverse effects.

Dr. Joyce and Dr. Carson report no relevant financial relationships.

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

A device that stimulates the median nerve and a D1 receptor antagonist are among the promising new treatment approaches for patients with Tourette syndrome (TS), according to an overview of new therapies presented at the XXVI World Congress of Neurology.

One recent study by University of Nottingham researchers showed a wrist-worn stimulating device significantly reduces the frequency and severity of tics – repetitive movements or vocalizations that can occur several times a day.

“Wearable nerve stimulation holds great promise because it will be good across the age spectrum; adults can wear it to work, and children can go to school with it to help them concentrate on their schoolwork, and then they take it off at night,” Eileen Joyce, PhD, MB BChir, professor of neuropsychiatry at the Institute of Neurology, University College London, told this news organization.

Dr. Joyce, who was not part of the study, discussed this and other new advances in tic therapy at the meeting.

About 24% of children will suffer from tics at some point. The prevalence of Tourette syndrome among males is about four times that of females, Dr. Joyce told delegates. She added the typical age of onset is about 7 years with peak severity at about 12 years.

Predictors of tics persisting into adulthood include comorbid attention deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder, and autism spectrum disorder, said Dr. Joyce, who also discussed the “highly heritable” nature of the syndrome and the numerous related genes identified to date.
 

Current and emerging treatments

Current treatments include psychological therapy, Botox for focal tics, and medications such as antipsychotics. Emerging therapies included deep brain stimulation and the new median nerve stimulation approach.

A study published  earlier this year included 135 patients with moderate to severe tic disorder who were randomly assigned to receive the investigational neuromodulation treatment, a sham treatment, or a wait-list treatment group.

The intervention involves rhythmic pulse trains of median nerve stimulation delivered via a device worn at the wrist. The device was programmed to deliver rhythmic (10 Hz) trains of low-intensity (1-19 mA) electrical stimulation to the median nerve at home once daily, 5 days a week for 4 weeks.

At 4 weeks, tic severity, as measured by the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTSS), was reduced by 7.1 points (35% reduction) in the active stimulation group compared to 2.13 points in the sham and 2.11 points in wait-list control groups.

The reduction for active stimulation was substantially larger, clinically meaningful (effect size, 0.5), and statistically significant (P = .02) compared to both the sham stimulation and wait-list control groups, which did not differ from one another.

Tic frequency (tics per minute or TPM) was reduced more in the active than sham stimulation groups (−15.6 TPM vs. −7.7 TPM; P < .03) and the reduction in tic frequency was clinically meaningful (>25% reduction; effect-size, 0.3).

When the active stimulator was turned off, the tics worsened, noted Dr. Joyce.

“The study showed that if you stimulate the median nerve at the wrist, you can train brain oscillations that are linked to the suppression of movement,” Dr. Joyce said. “So based on physiological knowledge, they have developed a median nerve stimulator to entrain cortical rhythms.”
 

Simple and exciting

The new device is “really exciting”, she added. “It’s not invasive and is quite simple to use and could help a lot of people with Tourette syndrome.”

Asked to comment, Alan Carson, MD, consultant neuropsychiatrist and honorary professor of neuropsychiatry, University of Edinburgh, who co-chaired the neuropsychiatry session featuring this presentation, called the device “promising.”

“Deep brain stimulation appears to be very effective but it’s a major procedure, so a simple wearable device seems highly desirable,” Dr. Carson said.

Dr. Joyce also discussed a study on the efficacy of cannabis (nabiximols; Sativex) as an intervention for tic management in males, those with severe tics, and those with comorbid ADHD.

And a new oral medication, ecopipam, a highly selective D1 receptor antagonist, is also raising hopes, said Dr. Joyce, with results from a randomized controlled trial  showing the drug significantly improved tics and had few adverse effects.

Dr. Joyce and Dr. Carson report no relevant financial relationships.

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

TOPLINE:

The risk for Guillain-Barré syndrome (GBS) is six times higher in people with COVID-19 in the 6 weeks following infection, according to a new study that also showed receipt of the Pfizer-BioNTech mRNA vaccine reduced GSB risk by 59%.

METHODOLOGY:

• The nested-case control study analyzed data from the largest healthcare provider in Israel for 3.2 million patients aged 16 years and older, with no history of GBS.
• GBS cases (n = 76) were identified based on hospital discharge data from January 2021 to June 2022.
• For every GBS case, investigators chose 10 controls at random, matched for age, gender, and follow-up duration (n = 760).
• Investigators examined the association between GBS and SARS-CoV-2 infection, established through documentation of prior positive SARS-CoV-2 test (PCR or antigen), and any COVID-19 vaccine administration.

TAKEAWAY:

• Among those diagnosed with GBS, 8 were exposed to SARS-CoV-2 infection only, 7 were exposed to COVID-19 vaccination only, and 1 patient was exposed to both SARS-CoV-2 infection and COVID-19 vaccination in the prior 6 weeks, leaving 60 GBS patients without exposure to either infection or vaccination.
• All COVID-19 vaccine doses administered in GBS cases within 6 weeks of the index date, and all but two doses administered in controls in the same timeframe, were Pfizer-BioNTech vaccines.
• Compared with people without GBS, those with the condition were more than six times as likely to have had SARS-CoV-2 infection within 6 weeks of GBS diagnosis (adjusted odds ratio, 6.30; 95% confidence interval, 2.55-15.56).
• People who received the COVID-19 vaccine were 59% less likely to develop GBS than those who did not get the vaccine (aOR, 0.41; 95% CI, 0.17-0.96).

IN PRACTICE:

“While Guillain-Barré is extremely rare, people should be aware that having a COVID infection can increase their risk of developing the disorder, and receiving an mRNA vaccine can decrease their risk,” study author Anat Arbel, MD, of Lady Davis Carmel Medical Center and the Technion-Israel Institute of Technology, Haifa, Israel, said in a press release.

SOURCE:

In addition to Dr. Arbel, the other lead author is Haya Bishara, MD, of Lady Davis Carmel Medical Center. The research was published online  in the journal Neurology.

LIMITATIONS:

There is a possibility of misclassification of SARS-CoV-2 infection, which could lead to an overestimation of the magnitude of association between infection and GBS. The diagnosis of GBS relied solely on ICD-9 coding, which has been shown in prior studies to contain errors.

DISCLOSURES:

The study was unfunded. Dr. Bishara and Dr. Arbel report no relevant financial relationships. One co-author, Eitan Auriel, MD, has received lecturer fees from Novo Nordisk, Pfizer, Boehringer Ingelheim, and Medison.

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

TOPLINE:

The risk for Guillain-Barré syndrome (GBS) is six times higher in people with COVID-19 in the 6 weeks following infection, according to a new study that also showed receipt of the Pfizer-BioNTech mRNA vaccine reduced GSB risk by 59%.

METHODOLOGY:

• The nested-case control study analyzed data from the largest healthcare provider in Israel for 3.2 million patients aged 16 years and older, with no history of GBS.
• GBS cases (n = 76) were identified based on hospital discharge data from January 2021 to June 2022.
• For every GBS case, investigators chose 10 controls at random, matched for age, gender, and follow-up duration (n = 760).
• Investigators examined the association between GBS and SARS-CoV-2 infection, established through documentation of prior positive SARS-CoV-2 test (PCR or antigen), and any COVID-19 vaccine administration.

TAKEAWAY:

• Among those diagnosed with GBS, 8 were exposed to SARS-CoV-2 infection only, 7 were exposed to COVID-19 vaccination only, and 1 patient was exposed to both SARS-CoV-2 infection and COVID-19 vaccination in the prior 6 weeks, leaving 60 GBS patients without exposure to either infection or vaccination.
• All COVID-19 vaccine doses administered in GBS cases within 6 weeks of the index date, and all but two doses administered in controls in the same timeframe, were Pfizer-BioNTech vaccines.
• Compared with people without GBS, those with the condition were more than six times as likely to have had SARS-CoV-2 infection within 6 weeks of GBS diagnosis (adjusted odds ratio, 6.30; 95% confidence interval, 2.55-15.56).
• People who received the COVID-19 vaccine were 59% less likely to develop GBS than those who did not get the vaccine (aOR, 0.41; 95% CI, 0.17-0.96).

IN PRACTICE:

“While Guillain-Barré is extremely rare, people should be aware that having a COVID infection can increase their risk of developing the disorder, and receiving an mRNA vaccine can decrease their risk,” study author Anat Arbel, MD, of Lady Davis Carmel Medical Center and the Technion-Israel Institute of Technology, Haifa, Israel, said in a press release.

SOURCE:

In addition to Dr. Arbel, the other lead author is Haya Bishara, MD, of Lady Davis Carmel Medical Center. The research was published online  in the journal Neurology.

LIMITATIONS:

There is a possibility of misclassification of SARS-CoV-2 infection, which could lead to an overestimation of the magnitude of association between infection and GBS. The diagnosis of GBS relied solely on ICD-9 coding, which has been shown in prior studies to contain errors.

DISCLOSURES:

The study was unfunded. Dr. Bishara and Dr. Arbel report no relevant financial relationships. One co-author, Eitan Auriel, MD, has received lecturer fees from Novo Nordisk, Pfizer, Boehringer Ingelheim, and Medison.

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

TOPLINE:

The risk for Guillain-Barré syndrome (GBS) is six times higher in people with COVID-19 in the 6 weeks following infection, according to a new study that also showed receipt of the Pfizer-BioNTech mRNA vaccine reduced GSB risk by 59%.

METHODOLOGY:

• The nested-case control study analyzed data from the largest healthcare provider in Israel for 3.2 million patients aged 16 years and older, with no history of GBS.
• GBS cases (n = 76) were identified based on hospital discharge data from January 2021 to June 2022.
• For every GBS case, investigators chose 10 controls at random, matched for age, gender, and follow-up duration (n = 760).
• Investigators examined the association between GBS and SARS-CoV-2 infection, established through documentation of prior positive SARS-CoV-2 test (PCR or antigen), and any COVID-19 vaccine administration.

TAKEAWAY:

• Among those diagnosed with GBS, 8 were exposed to SARS-CoV-2 infection only, 7 were exposed to COVID-19 vaccination only, and 1 patient was exposed to both SARS-CoV-2 infection and COVID-19 vaccination in the prior 6 weeks, leaving 60 GBS patients without exposure to either infection or vaccination.
• All COVID-19 vaccine doses administered in GBS cases within 6 weeks of the index date, and all but two doses administered in controls in the same timeframe, were Pfizer-BioNTech vaccines.
• Compared with people without GBS, those with the condition were more than six times as likely to have had SARS-CoV-2 infection within 6 weeks of GBS diagnosis (adjusted odds ratio, 6.30; 95% confidence interval, 2.55-15.56).
• People who received the COVID-19 vaccine were 59% less likely to develop GBS than those who did not get the vaccine (aOR, 0.41; 95% CI, 0.17-0.96).

IN PRACTICE:

“While Guillain-Barré is extremely rare, people should be aware that having a COVID infection can increase their risk of developing the disorder, and receiving an mRNA vaccine can decrease their risk,” study author Anat Arbel, MD, of Lady Davis Carmel Medical Center and the Technion-Israel Institute of Technology, Haifa, Israel, said in a press release.

SOURCE:

In addition to Dr. Arbel, the other lead author is Haya Bishara, MD, of Lady Davis Carmel Medical Center. The research was published online  in the journal Neurology.

LIMITATIONS:

There is a possibility of misclassification of SARS-CoV-2 infection, which could lead to an overestimation of the magnitude of association between infection and GBS. The diagnosis of GBS relied solely on ICD-9 coding, which has been shown in prior studies to contain errors.

DISCLOSURES:

The study was unfunded. Dr. Bishara and Dr. Arbel report no relevant financial relationships. One co-author, Eitan Auriel, MD, has received lecturer fees from Novo Nordisk, Pfizer, Boehringer Ingelheim, and Medison.

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

MILAN – Subcutaneous administration of anti-CD20 monoclonal antibody therapy offers ongoing clinical efficacy in the management of patients with relapsing and primary progressive multiple sclerosis (MS), suggest results from two clinical trials.

For OCARINA II, more than 325 patients with MS were randomly assigned to either subcutaneous or intravenous treatment with the anti-CD20 monoclonal antibody ocrelizumab (Ocrevus).

After 24 weeks, the presence of lesions on imaging and the occurrence of clinical remissions were almost completely suppressed by both treatments albeit with a higher rate of mild to moderate injection reactions with subcutaneous administration.

The study “makes me feel pretty comfortable that regardless of where you’re delivering the therapy, IV or subcutaneously, it’s getting in there and doing the job that we want it to do,” said lead author Scott D. Newsome, DO, director, Stiff Person Syndrome Center, Johns Hopkins University, Baltimore.

The second study, OLIKOS, involved just over 100 patients with relapsing MS who had previously been treated with an anti-CD20 monoclonal antibody and were switched to subcutaneous therapy with another: ofatumumab (Arzerra).

Le H. Hua, MD, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, and colleagues report that the novel treatment maintained clinical efficacy in all patients, with no safety concerns and no changes in serum immunoglobulin levels.

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Anti-CD20–naive

OCARINA II involved patients aged 18-65 years with relapsing or primary progressive MS who had never received ocrelizumab or any other anti-CD20 therapy and had an Expanded Disability Status Scale (EDSS) score of 0.0-6.5.

They were randomly assigned to subcutaneous or IV ocrelizumab as a first dose. At week 24, all patients were scheduled to receive subcutaneous ocrelizumab every 24 weeks up to week 96.

In all, 326 patients were randomly assigned to the two treatment arms. They had a mean age of approximately 40 years, and 59.3%-65.3% were women. The mean time since symptom onset was 6.8-7.7 years, and the mean EDSS score at baseline was 2.5-3.0. The majority (89.8%-89.0%) had relapsing MS.

The results showed that subcutaneous and IV administration led to similar exposure to ocrelizumab, and both resulted in rapid reduction in CD19+ B-cell counts.

By week 24, the mean number of lesions on MRI reduced to zero, resulting in “near-complete suppression” of disease activity, the team says, which was reflected in 99% of patients have no clinical evidence of relapse.

The overall adverse event rate was higher with subcutaneous vs. IV administration of ocrelizumab, at 73.7% vs. 45.8%, driven by both local and systemic injection reactions, which were mild to moderate in nature.

However, a similar proportion of patients in the subcutaneous and IV arms experienced serious adverse events, at 2.5% and 3.4%, respectively.

Crucially, the patients were “overwhelmingly positive” about the subcutaneous administration, Dr. Newsome said, and at his institution, “all the patients want to continue, if and when this gets approved.”

He said that, overall, he would like to have both routes available “because, coming down to patient preference, some prefer to have IV over subcutaneous in general, and that could be for a variety of reasons, so I would love to have as many different routes of administration as possible to offer.”
 

Efficacy maintained

The OLIKOS trial included patients aged 18-60 years with relapsing MS who had received at least two consecutive courses of anti-CD20 therapy with either ocrelizumab or rituximab and who had an EDSS score ≤ 5.5 and were neurologically stable.

After an initial loading regimen of subcutaneous ofatumumab on days 1, 7, and 14, the patients continued open-label subcutaneous ofatumumab once a month for 12 months, with assessments carried out at baseline and at 1, 6, and 12 months.

Of 142 patients assessed, 102 received treatment and were evaluated. Their mean age was 43.5 years, and 67.6% were women. The mean baseline EDSS score was 2.9, and the mean disease duration since diagnosis was 9.4 years.

The vast majority of patients (99.0%) had previously received ocrelizumab for an average duration of 26.7 months.

At this interim analysis, 100% of the 77 patients with follow-up MRI met the primary endpoint at month 6 of no change or a reduction in the number of lesions.

The team says there were “no new safety signals,” with 75.5% of patients experiencing a treatment-emergent adverse event, but only 1.0% having a serious adverse event. Injection site reactions occurred in 7.8%; 15.7% had a systemic injection reaction.

They also report that there were no changes in IgG and IgM concentrations between baseline and follow-up, which remained within normal reference ranges.
 

Reassuring results

“It’s exciting to see reassuring results from clinical studies of two high-efficacy therapies for multiple sclerosis, especially given their route of administration,” commented Julie Fiol, LMSW, BSN, RN, MSCN, associate vice president of Clinical Innovation and Strategy for the U.S. National MS Society.

“Subcutaneous injections allow people with multiple sclerosis more flexibility when selecting a therapy that matches their lifestyle and preferences,” she said in an interview.

“Adherence to therapy is critical in multiple sclerosis, and additional options for route of administration and site of care enhance the likelihood that someone with multiple sclerosis will find a medication that effectively manages their disease and fits into their lifestyle,” Dr. Fiol explained.

“Subcutaneous injections also have the potential to be more affordable as they could be administered at home or over a shorter duration than an infused medication,” she noted.

In terms of these two particular studies, she added, “it’s reassuring to see that the safety and efficacy of subcutaneous ocrelizumab was similar to intravenous. It was also reassuring to see those who switched from ocrelizumab and rituximab to ofatumumab remained clinically stable.”

OCARINA II was supported by F. Hoffmann-La Roche. OLIKOS was supported by Novartis. Dr. Newsome declares relationships with Biogen, Genentech, Bristol-Myers Squibb, EMD Serono, Greenwich Biosciences, Horizon Therapeutics, Novartis, Roche, and TG Therapeutics and institutional relationships with Biogen, Lundbeck, Roche, Genentech, National MS Society, The Stiff Person Syndrome Research Foundation, Department of Defense, and the Patient-Centered Outcomes Research Institute. Dr. Hua declares relationships with Alexion, Biogen, Bristol-Meyers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Horizon Therapeutics, and Novartis. Other authors also declare relationships.

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

MILAN – Subcutaneous administration of anti-CD20 monoclonal antibody therapy offers ongoing clinical efficacy in the management of patients with relapsing and primary progressive multiple sclerosis (MS), suggest results from two clinical trials.

For OCARINA II, more than 325 patients with MS were randomly assigned to either subcutaneous or intravenous treatment with the anti-CD20 monoclonal antibody ocrelizumab (Ocrevus).

After 24 weeks, the presence of lesions on imaging and the occurrence of clinical remissions were almost completely suppressed by both treatments albeit with a higher rate of mild to moderate injection reactions with subcutaneous administration.

The study “makes me feel pretty comfortable that regardless of where you’re delivering the therapy, IV or subcutaneously, it’s getting in there and doing the job that we want it to do,” said lead author Scott D. Newsome, DO, director, Stiff Person Syndrome Center, Johns Hopkins University, Baltimore.

The second study, OLIKOS, involved just over 100 patients with relapsing MS who had previously been treated with an anti-CD20 monoclonal antibody and were switched to subcutaneous therapy with another: ofatumumab (Arzerra).

Le H. Hua, MD, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, and colleagues report that the novel treatment maintained clinical efficacy in all patients, with no safety concerns and no changes in serum immunoglobulin levels.

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Anti-CD20–naive

OCARINA II involved patients aged 18-65 years with relapsing or primary progressive MS who had never received ocrelizumab or any other anti-CD20 therapy and had an Expanded Disability Status Scale (EDSS) score of 0.0-6.5.

They were randomly assigned to subcutaneous or IV ocrelizumab as a first dose. At week 24, all patients were scheduled to receive subcutaneous ocrelizumab every 24 weeks up to week 96.

In all, 326 patients were randomly assigned to the two treatment arms. They had a mean age of approximately 40 years, and 59.3%-65.3% were women. The mean time since symptom onset was 6.8-7.7 years, and the mean EDSS score at baseline was 2.5-3.0. The majority (89.8%-89.0%) had relapsing MS.

The results showed that subcutaneous and IV administration led to similar exposure to ocrelizumab, and both resulted in rapid reduction in CD19+ B-cell counts.

By week 24, the mean number of lesions on MRI reduced to zero, resulting in “near-complete suppression” of disease activity, the team says, which was reflected in 99% of patients have no clinical evidence of relapse.

The overall adverse event rate was higher with subcutaneous vs. IV administration of ocrelizumab, at 73.7% vs. 45.8%, driven by both local and systemic injection reactions, which were mild to moderate in nature.

However, a similar proportion of patients in the subcutaneous and IV arms experienced serious adverse events, at 2.5% and 3.4%, respectively.

Crucially, the patients were “overwhelmingly positive” about the subcutaneous administration, Dr. Newsome said, and at his institution, “all the patients want to continue, if and when this gets approved.”

He said that, overall, he would like to have both routes available “because, coming down to patient preference, some prefer to have IV over subcutaneous in general, and that could be for a variety of reasons, so I would love to have as many different routes of administration as possible to offer.”
 

Efficacy maintained

The OLIKOS trial included patients aged 18-60 years with relapsing MS who had received at least two consecutive courses of anti-CD20 therapy with either ocrelizumab or rituximab and who had an EDSS score ≤ 5.5 and were neurologically stable.

After an initial loading regimen of subcutaneous ofatumumab on days 1, 7, and 14, the patients continued open-label subcutaneous ofatumumab once a month for 12 months, with assessments carried out at baseline and at 1, 6, and 12 months.

Of 142 patients assessed, 102 received treatment and were evaluated. Their mean age was 43.5 years, and 67.6% were women. The mean baseline EDSS score was 2.9, and the mean disease duration since diagnosis was 9.4 years.

The vast majority of patients (99.0%) had previously received ocrelizumab for an average duration of 26.7 months.

At this interim analysis, 100% of the 77 patients with follow-up MRI met the primary endpoint at month 6 of no change or a reduction in the number of lesions.

The team says there were “no new safety signals,” with 75.5% of patients experiencing a treatment-emergent adverse event, but only 1.0% having a serious adverse event. Injection site reactions occurred in 7.8%; 15.7% had a systemic injection reaction.

They also report that there were no changes in IgG and IgM concentrations between baseline and follow-up, which remained within normal reference ranges.
 

Reassuring results

“It’s exciting to see reassuring results from clinical studies of two high-efficacy therapies for multiple sclerosis, especially given their route of administration,” commented Julie Fiol, LMSW, BSN, RN, MSCN, associate vice president of Clinical Innovation and Strategy for the U.S. National MS Society.

“Subcutaneous injections allow people with multiple sclerosis more flexibility when selecting a therapy that matches their lifestyle and preferences,” she said in an interview.

“Adherence to therapy is critical in multiple sclerosis, and additional options for route of administration and site of care enhance the likelihood that someone with multiple sclerosis will find a medication that effectively manages their disease and fits into their lifestyle,” Dr. Fiol explained.

“Subcutaneous injections also have the potential to be more affordable as they could be administered at home or over a shorter duration than an infused medication,” she noted.

In terms of these two particular studies, she added, “it’s reassuring to see that the safety and efficacy of subcutaneous ocrelizumab was similar to intravenous. It was also reassuring to see those who switched from ocrelizumab and rituximab to ofatumumab remained clinically stable.”

OCARINA II was supported by F. Hoffmann-La Roche. OLIKOS was supported by Novartis. Dr. Newsome declares relationships with Biogen, Genentech, Bristol-Myers Squibb, EMD Serono, Greenwich Biosciences, Horizon Therapeutics, Novartis, Roche, and TG Therapeutics and institutional relationships with Biogen, Lundbeck, Roche, Genentech, National MS Society, The Stiff Person Syndrome Research Foundation, Department of Defense, and the Patient-Centered Outcomes Research Institute. Dr. Hua declares relationships with Alexion, Biogen, Bristol-Meyers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Horizon Therapeutics, and Novartis. Other authors also declare relationships.

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

MILAN – Subcutaneous administration of anti-CD20 monoclonal antibody therapy offers ongoing clinical efficacy in the management of patients with relapsing and primary progressive multiple sclerosis (MS), suggest results from two clinical trials.

For OCARINA II, more than 325 patients with MS were randomly assigned to either subcutaneous or intravenous treatment with the anti-CD20 monoclonal antibody ocrelizumab (Ocrevus).

After 24 weeks, the presence of lesions on imaging and the occurrence of clinical remissions were almost completely suppressed by both treatments albeit with a higher rate of mild to moderate injection reactions with subcutaneous administration.

The study “makes me feel pretty comfortable that regardless of where you’re delivering the therapy, IV or subcutaneously, it’s getting in there and doing the job that we want it to do,” said lead author Scott D. Newsome, DO, director, Stiff Person Syndrome Center, Johns Hopkins University, Baltimore.

The second study, OLIKOS, involved just over 100 patients with relapsing MS who had previously been treated with an anti-CD20 monoclonal antibody and were switched to subcutaneous therapy with another: ofatumumab (Arzerra).

Le H. Hua, MD, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, and colleagues report that the novel treatment maintained clinical efficacy in all patients, with no safety concerns and no changes in serum immunoglobulin levels.

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Anti-CD20–naive

OCARINA II involved patients aged 18-65 years with relapsing or primary progressive MS who had never received ocrelizumab or any other anti-CD20 therapy and had an Expanded Disability Status Scale (EDSS) score of 0.0-6.5.

They were randomly assigned to subcutaneous or IV ocrelizumab as a first dose. At week 24, all patients were scheduled to receive subcutaneous ocrelizumab every 24 weeks up to week 96.

In all, 326 patients were randomly assigned to the two treatment arms. They had a mean age of approximately 40 years, and 59.3%-65.3% were women. The mean time since symptom onset was 6.8-7.7 years, and the mean EDSS score at baseline was 2.5-3.0. The majority (89.8%-89.0%) had relapsing MS.

The results showed that subcutaneous and IV administration led to similar exposure to ocrelizumab, and both resulted in rapid reduction in CD19+ B-cell counts.

By week 24, the mean number of lesions on MRI reduced to zero, resulting in “near-complete suppression” of disease activity, the team says, which was reflected in 99% of patients have no clinical evidence of relapse.

The overall adverse event rate was higher with subcutaneous vs. IV administration of ocrelizumab, at 73.7% vs. 45.8%, driven by both local and systemic injection reactions, which were mild to moderate in nature.

However, a similar proportion of patients in the subcutaneous and IV arms experienced serious adverse events, at 2.5% and 3.4%, respectively.

Crucially, the patients were “overwhelmingly positive” about the subcutaneous administration, Dr. Newsome said, and at his institution, “all the patients want to continue, if and when this gets approved.”

He said that, overall, he would like to have both routes available “because, coming down to patient preference, some prefer to have IV over subcutaneous in general, and that could be for a variety of reasons, so I would love to have as many different routes of administration as possible to offer.”
 

Efficacy maintained

The OLIKOS trial included patients aged 18-60 years with relapsing MS who had received at least two consecutive courses of anti-CD20 therapy with either ocrelizumab or rituximab and who had an EDSS score ≤ 5.5 and were neurologically stable.

After an initial loading regimen of subcutaneous ofatumumab on days 1, 7, and 14, the patients continued open-label subcutaneous ofatumumab once a month for 12 months, with assessments carried out at baseline and at 1, 6, and 12 months.

Of 142 patients assessed, 102 received treatment and were evaluated. Their mean age was 43.5 years, and 67.6% were women. The mean baseline EDSS score was 2.9, and the mean disease duration since diagnosis was 9.4 years.

The vast majority of patients (99.0%) had previously received ocrelizumab for an average duration of 26.7 months.

At this interim analysis, 100% of the 77 patients with follow-up MRI met the primary endpoint at month 6 of no change or a reduction in the number of lesions.

The team says there were “no new safety signals,” with 75.5% of patients experiencing a treatment-emergent adverse event, but only 1.0% having a serious adverse event. Injection site reactions occurred in 7.8%; 15.7% had a systemic injection reaction.

They also report that there were no changes in IgG and IgM concentrations between baseline and follow-up, which remained within normal reference ranges.
 

Reassuring results

“It’s exciting to see reassuring results from clinical studies of two high-efficacy therapies for multiple sclerosis, especially given their route of administration,” commented Julie Fiol, LMSW, BSN, RN, MSCN, associate vice president of Clinical Innovation and Strategy for the U.S. National MS Society.

“Subcutaneous injections allow people with multiple sclerosis more flexibility when selecting a therapy that matches their lifestyle and preferences,” she said in an interview.

“Adherence to therapy is critical in multiple sclerosis, and additional options for route of administration and site of care enhance the likelihood that someone with multiple sclerosis will find a medication that effectively manages their disease and fits into their lifestyle,” Dr. Fiol explained.

“Subcutaneous injections also have the potential to be more affordable as they could be administered at home or over a shorter duration than an infused medication,” she noted.

In terms of these two particular studies, she added, “it’s reassuring to see that the safety and efficacy of subcutaneous ocrelizumab was similar to intravenous. It was also reassuring to see those who switched from ocrelizumab and rituximab to ofatumumab remained clinically stable.”

OCARINA II was supported by F. Hoffmann-La Roche. OLIKOS was supported by Novartis. Dr. Newsome declares relationships with Biogen, Genentech, Bristol-Myers Squibb, EMD Serono, Greenwich Biosciences, Horizon Therapeutics, Novartis, Roche, and TG Therapeutics and institutional relationships with Biogen, Lundbeck, Roche, Genentech, National MS Society, The Stiff Person Syndrome Research Foundation, Department of Defense, and the Patient-Centered Outcomes Research Institute. Dr. Hua declares relationships with Alexion, Biogen, Bristol-Meyers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Horizon Therapeutics, and Novartis. Other authors also declare relationships.

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

T3D-959, an oral dual delta/gamma peroxisome proliferator-activated nuclear receptor (PPAR) agonist, has shown promise in a phase 2 randomized, placebo-controlled study of adults with mild to moderate Alzheimer’s disease (AD).

Topline results provide “clinical evidence of a modification of multiple AD pathologies associated with amyloid plaque burden,” said John Didsbury, PhD, chief executive officer of T3D Therapeutics Inc., the company developing the drug.

While the primary cognitive endpoints were not met in the overall study population, the data suggest that a “high plasma pTau-217/non–pTau-217 ratio, a marker of AD pathology, likely defines an AD population responsive to T3D-959 therapy,” Dr. Didsbury said.

He said it’s important to note that no PET imaging (amyloid/tau) or biomarkers were used as entry criteria and, in hindsight, some participants likely did not have AD, which likely played a role in the negative primary outcome.

The findings from the PIONEER study were presented at the annual Clinical Trials on Alzheimer’s Disease conference.
 

‘Surprised and shocked’

The PPAR family of proteins helps regulate blood sugar and triglyceride levels. The rationale for evaluating PPAR agonists in AD is based on the hypothesis that sporadic AD is fundamentally an age-related metabolic disease.

T3D-959 is the first PPAR delta-activating compound to be developed for the treatment of AD. Uniquely, this drug also activates PPAR gamma, which may provide potential additive or synergistic effects in regulating dysfunctional brain glucose energy and lipid metabolism in AD.

The PIONEER tested three doses of T3D-959 (15 mg, 30 mg, and 45 mg) vs. placebo in 250 adults with mild to moderate AD (Mini-Mental State Examination [MMSE] 14-26, Clinical Dementia Rating (CDR)-Global 0.5-2.0, and Sum of Boxes [CDR-SB] ≥ 3.0). T3D-959 or placebo was taken once daily for 24 weeks.

In the overall population, the primary endpoints – Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-Cog11) and Clinical Global Impression of Change (CGIC) – were not met.

“Plain and simple, when we saw this data, we were surprised and shocked,” said Dr. Didsbury, and wondered, “How can placebo be doing so well on a 6-month AD trial?”

“We suspect the presence of non-AD subjects in the trial based on the lower-than-typical number of ApoE4 positive subjects, increased cognitive performance and learning effects observed, and only 45% of trial subjects having a low pTau-217 ratio, a biomarker indicating that they would have no AD pathology plasma,” he explained.

Plasma baseline pTau-217 ratio correlates with AD risk and severity and is a marker of AD pathology; in the subgroup with high pTau-217 ratio, the ADAS-Cog11 endpoint was met in the 30-mg T3D-959 group vs. the placebo group (–0.74 vs. 1.27; P = .112), “consistent with clinical benefit,” Dr. Didsbury noted.

The secondary endpoint of change in plasma amyloid-beta (Ab)42/40 ratio was also met in the 30-mg T3D-959 group – increasing at week 24 with T3D-959 vs. decreasing with placebo (P = .0206), with even greater improvement in the high pTau-217 ratio group. In this group, improvement of Ab42/40 ratio was nearly twofold greater than the overall group.

T3D-959 had a similar magnitude of effect on Ab42/40 as lecanemab (Leqembi) at 6 months, the researchers point out in their late-breaking abstract.

Biomarkers of all three AD diagnostic criteria (amyloid/tau/neurodegeneration) were improved, as well as markers of inflammation, insulin resistance, and dysfunctional lipid metabolism – results that demonstrate “peripheral targeted engagement,” Dr. Didsbury said.

“Along with the strong safety profile of T3D-959, the evidence supports a larger study evaluating T3D-959 30 mg/day in patients with mild to moderate AD and a baseline plasma p-Tau-217/non–pTau-217 ratio of ≥ 0.015,” the researchers conclude in their abstract.
 

Lessons learned

Commenting on the research for this article, Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, noted that “the idea behind this treatment is that impaired glucose metabolism in the brain leads to toxic misfolded proteins, including amyloid and tau in people with Alzheimer’s disease.”

“The treatment focuses on improving regulation of glucose and lipid metabolism in the brain. This is one of more than 140 approaches that are being tested today to target the biological drivers and contributors to Alzheimer’s disease,” Dr. Edelmayer said.

Because biomarkers were not used to enroll participants, “there was a high population of people in the trial who did not have Alzheimer’s. This very likely contributed to the negative result,” she noted.

However, the results also suggest that those taking the drug who had a high pTau217 ratio – and are likely to have brain amyloid plaques – had less cognitive decline, she noted.

Lessons learned from this negative trial include “the proper dose to balance efficacy and safety, and how to screen participants for their next study,” Dr. Edelmayer said.

Funding for the study was provided by the National Institute on Aging/National Institutes of Health and the Alzheimer’s Association. Dr. Didsbury and Dr. Edelmayer report no relevant financial relationships.

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

T3D-959, an oral dual delta/gamma peroxisome proliferator-activated nuclear receptor (PPAR) agonist, has shown promise in a phase 2 randomized, placebo-controlled study of adults with mild to moderate Alzheimer’s disease (AD).

Topline results provide “clinical evidence of a modification of multiple AD pathologies associated with amyloid plaque burden,” said John Didsbury, PhD, chief executive officer of T3D Therapeutics Inc., the company developing the drug.

While the primary cognitive endpoints were not met in the overall study population, the data suggest that a “high plasma pTau-217/non–pTau-217 ratio, a marker of AD pathology, likely defines an AD population responsive to T3D-959 therapy,” Dr. Didsbury said.

He said it’s important to note that no PET imaging (amyloid/tau) or biomarkers were used as entry criteria and, in hindsight, some participants likely did not have AD, which likely played a role in the negative primary outcome.

The findings from the PIONEER study were presented at the annual Clinical Trials on Alzheimer’s Disease conference.
 

‘Surprised and shocked’

The PPAR family of proteins helps regulate blood sugar and triglyceride levels. The rationale for evaluating PPAR agonists in AD is based on the hypothesis that sporadic AD is fundamentally an age-related metabolic disease.

T3D-959 is the first PPAR delta-activating compound to be developed for the treatment of AD. Uniquely, this drug also activates PPAR gamma, which may provide potential additive or synergistic effects in regulating dysfunctional brain glucose energy and lipid metabolism in AD.

The PIONEER tested three doses of T3D-959 (15 mg, 30 mg, and 45 mg) vs. placebo in 250 adults with mild to moderate AD (Mini-Mental State Examination [MMSE] 14-26, Clinical Dementia Rating (CDR)-Global 0.5-2.0, and Sum of Boxes [CDR-SB] ≥ 3.0). T3D-959 or placebo was taken once daily for 24 weeks.

In the overall population, the primary endpoints – Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-Cog11) and Clinical Global Impression of Change (CGIC) – were not met.

“Plain and simple, when we saw this data, we were surprised and shocked,” said Dr. Didsbury, and wondered, “How can placebo be doing so well on a 6-month AD trial?”

“We suspect the presence of non-AD subjects in the trial based on the lower-than-typical number of ApoE4 positive subjects, increased cognitive performance and learning effects observed, and only 45% of trial subjects having a low pTau-217 ratio, a biomarker indicating that they would have no AD pathology plasma,” he explained.

Plasma baseline pTau-217 ratio correlates with AD risk and severity and is a marker of AD pathology; in the subgroup with high pTau-217 ratio, the ADAS-Cog11 endpoint was met in the 30-mg T3D-959 group vs. the placebo group (–0.74 vs. 1.27; P = .112), “consistent with clinical benefit,” Dr. Didsbury noted.

The secondary endpoint of change in plasma amyloid-beta (Ab)42/40 ratio was also met in the 30-mg T3D-959 group – increasing at week 24 with T3D-959 vs. decreasing with placebo (P = .0206), with even greater improvement in the high pTau-217 ratio group. In this group, improvement of Ab42/40 ratio was nearly twofold greater than the overall group.

T3D-959 had a similar magnitude of effect on Ab42/40 as lecanemab (Leqembi) at 6 months, the researchers point out in their late-breaking abstract.

Biomarkers of all three AD diagnostic criteria (amyloid/tau/neurodegeneration) were improved, as well as markers of inflammation, insulin resistance, and dysfunctional lipid metabolism – results that demonstrate “peripheral targeted engagement,” Dr. Didsbury said.

“Along with the strong safety profile of T3D-959, the evidence supports a larger study evaluating T3D-959 30 mg/day in patients with mild to moderate AD and a baseline plasma p-Tau-217/non–pTau-217 ratio of ≥ 0.015,” the researchers conclude in their abstract.
 

Lessons learned

Commenting on the research for this article, Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, noted that “the idea behind this treatment is that impaired glucose metabolism in the brain leads to toxic misfolded proteins, including amyloid and tau in people with Alzheimer’s disease.”

“The treatment focuses on improving regulation of glucose and lipid metabolism in the brain. This is one of more than 140 approaches that are being tested today to target the biological drivers and contributors to Alzheimer’s disease,” Dr. Edelmayer said.

Because biomarkers were not used to enroll participants, “there was a high population of people in the trial who did not have Alzheimer’s. This very likely contributed to the negative result,” she noted.

However, the results also suggest that those taking the drug who had a high pTau217 ratio – and are likely to have brain amyloid plaques – had less cognitive decline, she noted.

Lessons learned from this negative trial include “the proper dose to balance efficacy and safety, and how to screen participants for their next study,” Dr. Edelmayer said.

Funding for the study was provided by the National Institute on Aging/National Institutes of Health and the Alzheimer’s Association. Dr. Didsbury and Dr. Edelmayer report no relevant financial relationships.

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

T3D-959, an oral dual delta/gamma peroxisome proliferator-activated nuclear receptor (PPAR) agonist, has shown promise in a phase 2 randomized, placebo-controlled study of adults with mild to moderate Alzheimer’s disease (AD).

Topline results provide “clinical evidence of a modification of multiple AD pathologies associated with amyloid plaque burden,” said John Didsbury, PhD, chief executive officer of T3D Therapeutics Inc., the company developing the drug.

While the primary cognitive endpoints were not met in the overall study population, the data suggest that a “high plasma pTau-217/non–pTau-217 ratio, a marker of AD pathology, likely defines an AD population responsive to T3D-959 therapy,” Dr. Didsbury said.

He said it’s important to note that no PET imaging (amyloid/tau) or biomarkers were used as entry criteria and, in hindsight, some participants likely did not have AD, which likely played a role in the negative primary outcome.

The findings from the PIONEER study were presented at the annual Clinical Trials on Alzheimer’s Disease conference.
 

‘Surprised and shocked’

The PPAR family of proteins helps regulate blood sugar and triglyceride levels. The rationale for evaluating PPAR agonists in AD is based on the hypothesis that sporadic AD is fundamentally an age-related metabolic disease.

T3D-959 is the first PPAR delta-activating compound to be developed for the treatment of AD. Uniquely, this drug also activates PPAR gamma, which may provide potential additive or synergistic effects in regulating dysfunctional brain glucose energy and lipid metabolism in AD.

The PIONEER tested three doses of T3D-959 (15 mg, 30 mg, and 45 mg) vs. placebo in 250 adults with mild to moderate AD (Mini-Mental State Examination [MMSE] 14-26, Clinical Dementia Rating (CDR)-Global 0.5-2.0, and Sum of Boxes [CDR-SB] ≥ 3.0). T3D-959 or placebo was taken once daily for 24 weeks.

In the overall population, the primary endpoints – Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-Cog11) and Clinical Global Impression of Change (CGIC) – were not met.

“Plain and simple, when we saw this data, we were surprised and shocked,” said Dr. Didsbury, and wondered, “How can placebo be doing so well on a 6-month AD trial?”

“We suspect the presence of non-AD subjects in the trial based on the lower-than-typical number of ApoE4 positive subjects, increased cognitive performance and learning effects observed, and only 45% of trial subjects having a low pTau-217 ratio, a biomarker indicating that they would have no AD pathology plasma,” he explained.

Plasma baseline pTau-217 ratio correlates with AD risk and severity and is a marker of AD pathology; in the subgroup with high pTau-217 ratio, the ADAS-Cog11 endpoint was met in the 30-mg T3D-959 group vs. the placebo group (–0.74 vs. 1.27; P = .112), “consistent with clinical benefit,” Dr. Didsbury noted.

The secondary endpoint of change in plasma amyloid-beta (Ab)42/40 ratio was also met in the 30-mg T3D-959 group – increasing at week 24 with T3D-959 vs. decreasing with placebo (P = .0206), with even greater improvement in the high pTau-217 ratio group. In this group, improvement of Ab42/40 ratio was nearly twofold greater than the overall group.

T3D-959 had a similar magnitude of effect on Ab42/40 as lecanemab (Leqembi) at 6 months, the researchers point out in their late-breaking abstract.

Biomarkers of all three AD diagnostic criteria (amyloid/tau/neurodegeneration) were improved, as well as markers of inflammation, insulin resistance, and dysfunctional lipid metabolism – results that demonstrate “peripheral targeted engagement,” Dr. Didsbury said.

“Along with the strong safety profile of T3D-959, the evidence supports a larger study evaluating T3D-959 30 mg/day in patients with mild to moderate AD and a baseline plasma p-Tau-217/non–pTau-217 ratio of ≥ 0.015,” the researchers conclude in their abstract.
 

Lessons learned

Commenting on the research for this article, Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, noted that “the idea behind this treatment is that impaired glucose metabolism in the brain leads to toxic misfolded proteins, including amyloid and tau in people with Alzheimer’s disease.”

“The treatment focuses on improving regulation of glucose and lipid metabolism in the brain. This is one of more than 140 approaches that are being tested today to target the biological drivers and contributors to Alzheimer’s disease,” Dr. Edelmayer said.

Because biomarkers were not used to enroll participants, “there was a high population of people in the trial who did not have Alzheimer’s. This very likely contributed to the negative result,” she noted.

However, the results also suggest that those taking the drug who had a high pTau217 ratio – and are likely to have brain amyloid plaques – had less cognitive decline, she noted.

Lessons learned from this negative trial include “the proper dose to balance efficacy and safety, and how to screen participants for their next study,” Dr. Edelmayer said.

Funding for the study was provided by the National Institute on Aging/National Institutes of Health and the Alzheimer’s Association. Dr. Didsbury and Dr. Edelmayer report no relevant financial relationships.

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

A very long time ago, when I ran clinical labs, one of the most ordered tests was the “sed rate” (aka ESR, the erythrocyte sedimentation rate). Easy, quick, and low cost, with high sensitivity but very low specificity. If the sed rate was normal, the patient probably did not have an infectious or inflammatory disease. If it was elevated, they probably did, but no telling what. Later, the C-reactive protein (CRP) test came into common use. Same general inferences: If the CRP was low, the patient was unlikely to have an inflammatory process; if high, they were sick, but we didn’t know what with.

Could the heart rate variability (HRV) score come to be thought of similarly? Much as the sed rate and CRP are sensitivity indicators of infectious or inflammatory diseases, might the HRV score be a sensitivity indicator for nervous system (central and autonomic) and cardiovascular (especially heart rhythm) malfunctions?

A substantial and relatively old body of heart rhythm literature ties HRV alterations to posttraumatic stress disorder, physician occupational stress, sleep disorders, depression, autonomic nervous system derangements, various cardiac arrhythmias, fatigue, overexertion, medications, and age itself.

More than 100 million Americans are now believed to use smartwatches or personal fitness monitors. Some 30%-40% of these devices measure HRV. So what? Credible research about this huge mass of accumulating data from “wearables” is lacking.
 

What is HRV?

HRV is the variation in time between each heartbeat, in milliseconds. HRV is influenced by the autonomic nervous system, perhaps reflecting sympathetic-parasympathetic balance. Some devices measure HRV 24/7. My Fitbit Inspire 2 reports only nighttime measures during 3 hours of sustained sleep. Most trackers report averages; some calculate the root mean squares; others calculate standard deviations. All fitness trackers warn not to use the data for medical purposes.

Normal values (reference ranges) for HRV begin at an average of 100 msec in the first decade of life and decline by approximately 10 msec per decade lived. At age 30-40, the average is 70 msec; age 60-70, it’s 40 msec; and at age 90-100, it’s 10 msec.

As a long-time lab guy, I used to teach proper use of lab tests. Fitness trackers are “lab tests” of a sort. We taught never to do a lab test unless you know what you are going to do with the result, no matter what it is. We also taught “never do anything just because you can.” Curiosity, we know, is a frequent driver of lab test ordering.

That underlying philosophy gives me a hard time when it comes to wearables. I have been enamored of watching my step count, active zone minutes, resting heart rate, active heart rate, various sleep scores, and breathing rate (and, of course, a manually entered early morning daily body weight) for several years. I even check my “readiness score” (a calculation using resting heart rate, recent sleep, recent active zone minutes, and perhaps HRV) each morning and adjust my behaviors accordingly.
 

Why monitor HRV?

But what should we do with HRV scores? Ignore them? Try to understand them, perhaps as a screening tool? Or monitor HRV for consistency or change? “Monitoring” is a proper and common use of lab tests.

Some say we should improve the HRV score by managing stress, getting regular exercise, eating a healthy diet, getting enough sleep, and not smoking or consuming excess alcohol. Duh! I do all of that anyway.

The claims that HRV is a “simple but powerful tool that can be used to track overall health and well-being” might turn out to be true. Proper study and sharing of data will enable that determination.

To advance understanding, I offer an n-of-1, a real-world personal anecdote about HRV.

I did not request the HRV function on my Fitbit Inspire 2. It simply appeared, and I ignored it for some time.

A year or two ago, I started noticing my HRV score every morning. Initially, I did not like to see my “low” score, until I learned that the reference range was dramatically affected by age and I was in my late 80s at the time. The vast majority of my HRV readings were in the range of 17 msec to 27 msec.

Last week, I was administered the new Moderna COVID-19 Spikevax vaccine and the old folks’ influenza vaccine simultaneously. In my case, side effects from each vaccine have been modest in the past, but I never previously had both administered at the same time. My immune response was, shall we say, robust. Chills, muscle aches, headache, fatigue, deltoid swelling, fitful sleep, and increased resting heart rate.

My nightly average HRV had been running between 17 msec and 35 msec for many months. WHOA! After the shots, my overnight HRV score plummeted from 24 msec to 10 msec, my lowest ever. Instant worry. The next day, it rebounded to 28 msec, and it has been in the high teens or low 20s since then.

Off to PubMed. A recent study of HRV on the second and 10th days after administering the Pfizer mRNA vaccine to 75 healthy volunteers found that the HRV on day 2 was dramatically lower than prevaccination levels and by day 10, it had returned to prevaccination levels. Some comfort there.

Another review article has reported a rapid fall and rapid rebound of HRV after COVID-19 vaccination. A 2010 report demonstrated a significant but not dramatic short-term lowering of HRV after influenza A vaccination and correlated it with CRP changes.

Some believe that the decline in HRV after vaccination reflects an increased immune response and sympathetic nervous activity.

I don’t plan to receive my flu and COVID vaccines on the same day again.

So, I went back to review what happened to my HRV when I had COVID in 2023. My HRV was 14 msec and 12 msec on the first 2 days of symptoms, and then returned to the 20 msec range.

I received the RSV vaccine this year without adverse effects, and my HRV scores were 29 msec, 33 msec, and 32 msec on the first 3 days after vaccination. Finally, after receiving a pneumococcal vaccine in 2023, I had no adverse effects, and my HRV scores on the 5 days after vaccination were indeterminate: 19 msec, 14 msec, 18 msec, 13 msec, and 17 msec.

Of course, correlation is not causation. Cause and effect remain undetermined. But I find these observations interesting for a potentially useful screening test.

George D. Lundberg, MD, is the Editor in Chief of Cancer Commons.

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

A very long time ago, when I ran clinical labs, one of the most ordered tests was the “sed rate” (aka ESR, the erythrocyte sedimentation rate). Easy, quick, and low cost, with high sensitivity but very low specificity. If the sed rate was normal, the patient probably did not have an infectious or inflammatory disease. If it was elevated, they probably did, but no telling what. Later, the C-reactive protein (CRP) test came into common use. Same general inferences: If the CRP was low, the patient was unlikely to have an inflammatory process; if high, they were sick, but we didn’t know what with.

Could the heart rate variability (HRV) score come to be thought of similarly? Much as the sed rate and CRP are sensitivity indicators of infectious or inflammatory diseases, might the HRV score be a sensitivity indicator for nervous system (central and autonomic) and cardiovascular (especially heart rhythm) malfunctions?

A substantial and relatively old body of heart rhythm literature ties HRV alterations to posttraumatic stress disorder, physician occupational stress, sleep disorders, depression, autonomic nervous system derangements, various cardiac arrhythmias, fatigue, overexertion, medications, and age itself.

More than 100 million Americans are now believed to use smartwatches or personal fitness monitors. Some 30%-40% of these devices measure HRV. So what? Credible research about this huge mass of accumulating data from “wearables” is lacking.
 

What is HRV?

HRV is the variation in time between each heartbeat, in milliseconds. HRV is influenced by the autonomic nervous system, perhaps reflecting sympathetic-parasympathetic balance. Some devices measure HRV 24/7. My Fitbit Inspire 2 reports only nighttime measures during 3 hours of sustained sleep. Most trackers report averages; some calculate the root mean squares; others calculate standard deviations. All fitness trackers warn not to use the data for medical purposes.

Normal values (reference ranges) for HRV begin at an average of 100 msec in the first decade of life and decline by approximately 10 msec per decade lived. At age 30-40, the average is 70 msec; age 60-70, it’s 40 msec; and at age 90-100, it’s 10 msec.

As a long-time lab guy, I used to teach proper use of lab tests. Fitness trackers are “lab tests” of a sort. We taught never to do a lab test unless you know what you are going to do with the result, no matter what it is. We also taught “never do anything just because you can.” Curiosity, we know, is a frequent driver of lab test ordering.

That underlying philosophy gives me a hard time when it comes to wearables. I have been enamored of watching my step count, active zone minutes, resting heart rate, active heart rate, various sleep scores, and breathing rate (and, of course, a manually entered early morning daily body weight) for several years. I even check my “readiness score” (a calculation using resting heart rate, recent sleep, recent active zone minutes, and perhaps HRV) each morning and adjust my behaviors accordingly.
 

Why monitor HRV?

But what should we do with HRV scores? Ignore them? Try to understand them, perhaps as a screening tool? Or monitor HRV for consistency or change? “Monitoring” is a proper and common use of lab tests.

Some say we should improve the HRV score by managing stress, getting regular exercise, eating a healthy diet, getting enough sleep, and not smoking or consuming excess alcohol. Duh! I do all of that anyway.

The claims that HRV is a “simple but powerful tool that can be used to track overall health and well-being” might turn out to be true. Proper study and sharing of data will enable that determination.

To advance understanding, I offer an n-of-1, a real-world personal anecdote about HRV.

I did not request the HRV function on my Fitbit Inspire 2. It simply appeared, and I ignored it for some time.

A year or two ago, I started noticing my HRV score every morning. Initially, I did not like to see my “low” score, until I learned that the reference range was dramatically affected by age and I was in my late 80s at the time. The vast majority of my HRV readings were in the range of 17 msec to 27 msec.

Last week, I was administered the new Moderna COVID-19 Spikevax vaccine and the old folks’ influenza vaccine simultaneously. In my case, side effects from each vaccine have been modest in the past, but I never previously had both administered at the same time. My immune response was, shall we say, robust. Chills, muscle aches, headache, fatigue, deltoid swelling, fitful sleep, and increased resting heart rate.

My nightly average HRV had been running between 17 msec and 35 msec for many months. WHOA! After the shots, my overnight HRV score plummeted from 24 msec to 10 msec, my lowest ever. Instant worry. The next day, it rebounded to 28 msec, and it has been in the high teens or low 20s since then.

Off to PubMed. A recent study of HRV on the second and 10th days after administering the Pfizer mRNA vaccine to 75 healthy volunteers found that the HRV on day 2 was dramatically lower than prevaccination levels and by day 10, it had returned to prevaccination levels. Some comfort there.

Another review article has reported a rapid fall and rapid rebound of HRV after COVID-19 vaccination. A 2010 report demonstrated a significant but not dramatic short-term lowering of HRV after influenza A vaccination and correlated it with CRP changes.

Some believe that the decline in HRV after vaccination reflects an increased immune response and sympathetic nervous activity.

I don’t plan to receive my flu and COVID vaccines on the same day again.

So, I went back to review what happened to my HRV when I had COVID in 2023. My HRV was 14 msec and 12 msec on the first 2 days of symptoms, and then returned to the 20 msec range.

I received the RSV vaccine this year without adverse effects, and my HRV scores were 29 msec, 33 msec, and 32 msec on the first 3 days after vaccination. Finally, after receiving a pneumococcal vaccine in 2023, I had no adverse effects, and my HRV scores on the 5 days after vaccination were indeterminate: 19 msec, 14 msec, 18 msec, 13 msec, and 17 msec.

Of course, correlation is not causation. Cause and effect remain undetermined. But I find these observations interesting for a potentially useful screening test.

George D. Lundberg, MD, is the Editor in Chief of Cancer Commons.

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

A very long time ago, when I ran clinical labs, one of the most ordered tests was the “sed rate” (aka ESR, the erythrocyte sedimentation rate). Easy, quick, and low cost, with high sensitivity but very low specificity. If the sed rate was normal, the patient probably did not have an infectious or inflammatory disease. If it was elevated, they probably did, but no telling what. Later, the C-reactive protein (CRP) test came into common use. Same general inferences: If the CRP was low, the patient was unlikely to have an inflammatory process; if high, they were sick, but we didn’t know what with.

Could the heart rate variability (HRV) score come to be thought of similarly? Much as the sed rate and CRP are sensitivity indicators of infectious or inflammatory diseases, might the HRV score be a sensitivity indicator for nervous system (central and autonomic) and cardiovascular (especially heart rhythm) malfunctions?

A substantial and relatively old body of heart rhythm literature ties HRV alterations to posttraumatic stress disorder, physician occupational stress, sleep disorders, depression, autonomic nervous system derangements, various cardiac arrhythmias, fatigue, overexertion, medications, and age itself.

More than 100 million Americans are now believed to use smartwatches or personal fitness monitors. Some 30%-40% of these devices measure HRV. So what? Credible research about this huge mass of accumulating data from “wearables” is lacking.
 

What is HRV?

HRV is the variation in time between each heartbeat, in milliseconds. HRV is influenced by the autonomic nervous system, perhaps reflecting sympathetic-parasympathetic balance. Some devices measure HRV 24/7. My Fitbit Inspire 2 reports only nighttime measures during 3 hours of sustained sleep. Most trackers report averages; some calculate the root mean squares; others calculate standard deviations. All fitness trackers warn not to use the data for medical purposes.

Normal values (reference ranges) for HRV begin at an average of 100 msec in the first decade of life and decline by approximately 10 msec per decade lived. At age 30-40, the average is 70 msec; age 60-70, it’s 40 msec; and at age 90-100, it’s 10 msec.

As a long-time lab guy, I used to teach proper use of lab tests. Fitness trackers are “lab tests” of a sort. We taught never to do a lab test unless you know what you are going to do with the result, no matter what it is. We also taught “never do anything just because you can.” Curiosity, we know, is a frequent driver of lab test ordering.

That underlying philosophy gives me a hard time when it comes to wearables. I have been enamored of watching my step count, active zone minutes, resting heart rate, active heart rate, various sleep scores, and breathing rate (and, of course, a manually entered early morning daily body weight) for several years. I even check my “readiness score” (a calculation using resting heart rate, recent sleep, recent active zone minutes, and perhaps HRV) each morning and adjust my behaviors accordingly.
 

Why monitor HRV?

But what should we do with HRV scores? Ignore them? Try to understand them, perhaps as a screening tool? Or monitor HRV for consistency or change? “Monitoring” is a proper and common use of lab tests.

Some say we should improve the HRV score by managing stress, getting regular exercise, eating a healthy diet, getting enough sleep, and not smoking or consuming excess alcohol. Duh! I do all of that anyway.

The claims that HRV is a “simple but powerful tool that can be used to track overall health and well-being” might turn out to be true. Proper study and sharing of data will enable that determination.

To advance understanding, I offer an n-of-1, a real-world personal anecdote about HRV.

I did not request the HRV function on my Fitbit Inspire 2. It simply appeared, and I ignored it for some time.

A year or two ago, I started noticing my HRV score every morning. Initially, I did not like to see my “low” score, until I learned that the reference range was dramatically affected by age and I was in my late 80s at the time. The vast majority of my HRV readings were in the range of 17 msec to 27 msec.

Last week, I was administered the new Moderna COVID-19 Spikevax vaccine and the old folks’ influenza vaccine simultaneously. In my case, side effects from each vaccine have been modest in the past, but I never previously had both administered at the same time. My immune response was, shall we say, robust. Chills, muscle aches, headache, fatigue, deltoid swelling, fitful sleep, and increased resting heart rate.

My nightly average HRV had been running between 17 msec and 35 msec for many months. WHOA! After the shots, my overnight HRV score plummeted from 24 msec to 10 msec, my lowest ever. Instant worry. The next day, it rebounded to 28 msec, and it has been in the high teens or low 20s since then.

Off to PubMed. A recent study of HRV on the second and 10th days after administering the Pfizer mRNA vaccine to 75 healthy volunteers found that the HRV on day 2 was dramatically lower than prevaccination levels and by day 10, it had returned to prevaccination levels. Some comfort there.

Another review article has reported a rapid fall and rapid rebound of HRV after COVID-19 vaccination. A 2010 report demonstrated a significant but not dramatic short-term lowering of HRV after influenza A vaccination and correlated it with CRP changes.

Some believe that the decline in HRV after vaccination reflects an increased immune response and sympathetic nervous activity.

I don’t plan to receive my flu and COVID vaccines on the same day again.

So, I went back to review what happened to my HRV when I had COVID in 2023. My HRV was 14 msec and 12 msec on the first 2 days of symptoms, and then returned to the 20 msec range.

I received the RSV vaccine this year without adverse effects, and my HRV scores were 29 msec, 33 msec, and 32 msec on the first 3 days after vaccination. Finally, after receiving a pneumococcal vaccine in 2023, I had no adverse effects, and my HRV scores on the 5 days after vaccination were indeterminate: 19 msec, 14 msec, 18 msec, 13 msec, and 17 msec.

Of course, correlation is not causation. Cause and effect remain undetermined. But I find these observations interesting for a potentially useful screening test.

George D. Lundberg, MD, is the Editor in Chief of Cancer Commons.

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

BARCELONA – The typical lag between treatment initiation with selective serotonin reuptake inhibitors (SSRIs) for depression and enhanced mood may be because of the time it takes to increase brain synaptic density, new imaging data suggest.

In a double-blind study, more than 30 volunteers were randomly assigned to the SSRI escitalopram or placebo for 3-5 weeks. Using PET imaging, the investigators found that over time, synaptic density significantly increased significantly in the neocortex and hippocampus but only in patients taking the active drug.

The results point to two conclusions, said study investigator Gitta Moos Knudsen, MD, PhD, clinical professor and chief physician at the department of clinical medicine, neurology, psychiatry and sensory sciences at Copenhagen (Denmark) University Hospital.

First, they indicate that SSRIs increase synaptic density in brain areas critically involved in depression, a finding that would go some way to indicating that the synaptic density in the brain may be involved in how antidepressants function, “which would give us a target for developing novel drugs against depression,” said Dr. Knudsen.

“Secondly, our data suggest synapses build up over a period of weeks, which would explain why the effects of these drugs take time to kick in,” she added.

The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress and simultaneously published online in Molecular Psychiatry.
 

Marked increase in synaptic density

SSRIs are widely used for depression as well as anxiety and obsessive-compulsive disorder. It is thought that they act via neuroplasticity and synaptic remodeling to improve cognition and emotion processing. However, the investigators note clinical evidence is lacking.

For the study, the researchers randomly assigned healthy individuals to either 20-mg escitalopram or placebo for 3-5 weeks.

They performed PET with the 11C-UCB-J tracer, which allows imaging of the synaptic vesicle glycoprotein 2A (SV2A) in the brain, synaptic density, as well as changes in density over time, in the hippocampus and neocortex.

Between May 2020 and October 2021, 17 individuals were assigned to escitalopram and 15 to placebo. There were no significant differences between two groups in terms of age, sex, and PET-related variables. Serum escitalopram measurements confirmed that all participants in the active drug group were compliant.

When synaptic density was assessed at a single time point, an average of 29 days after the intervention, there were no significant differences between the escitalopram and placebo groups in either the neocortex (P = .41) or in the hippocampus (P = .26).

However, when they performed a secondary analysis of the time-dependent effect on SV2A levels, they found a marked difference between the two study groups.

Compared with the placebo group, participants taking escitalopram had a marked increase in synaptic density in both the neocortex (rp value, 0.58; P = .003) and the hippocampus (rp value, 0.41; P = .048).

In contrast, there were no significant changes in synaptic density in either the neocortex (rp value, –0.01; P = .95) or the hippocampus (rp value, –0.06; P = .62) in the hippocampus.

“That is consistent with our clinical observation that it takes time to evolve synaptic density, along with clinical improvement. Does that mean that the increase in synaptic density is a precondition for improvement in symptoms? We don’t know,” said Dr. Knudsen.
 

Exciting but not conclusive

Session co-chair Oliver Howes, MD, PhD, professor of molecular psychiatry, King’s College London, agreed that the results do not prove the gradual increase in synaptic density the treatment response lag with SSRIs.

“We definitely don’t yet have all the data to know one way or the other,” he said in an interview.

Another potential hypothesis, he said, is that SSRIs are causing shifts in underlying brain circuits that lead to cognitive changes before there is a discernable improvement in mood.

Indeed, Dr. Howes suggested that increases in synaptic density and cognitive changes related to SSRI use are not necessarily dependent on each other and could even be unrelated.

Also commenting on the research, David Nutt, MD, PhD, Edmond J. Safra professor of neuropsychopharmacology at Imperial College London, said that the “delay in therapeutic action of antidepressants has been a puzzle to psychiatrists ever since they were first discerned over 50 years ago. So, these new data in humans, that use cutting edge brain imaging to demonstrate an increase in brain connections developing over the period that the depression lifts, are very exciting.”

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

BARCELONA – The typical lag between treatment initiation with selective serotonin reuptake inhibitors (SSRIs) for depression and enhanced mood may be because of the time it takes to increase brain synaptic density, new imaging data suggest.

In a double-blind study, more than 30 volunteers were randomly assigned to the SSRI escitalopram or placebo for 3-5 weeks. Using PET imaging, the investigators found that over time, synaptic density significantly increased significantly in the neocortex and hippocampus but only in patients taking the active drug.

The results point to two conclusions, said study investigator Gitta Moos Knudsen, MD, PhD, clinical professor and chief physician at the department of clinical medicine, neurology, psychiatry and sensory sciences at Copenhagen (Denmark) University Hospital.

First, they indicate that SSRIs increase synaptic density in brain areas critically involved in depression, a finding that would go some way to indicating that the synaptic density in the brain may be involved in how antidepressants function, “which would give us a target for developing novel drugs against depression,” said Dr. Knudsen.

“Secondly, our data suggest synapses build up over a period of weeks, which would explain why the effects of these drugs take time to kick in,” she added.

The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress and simultaneously published online in Molecular Psychiatry.
 

Marked increase in synaptic density

SSRIs are widely used for depression as well as anxiety and obsessive-compulsive disorder. It is thought that they act via neuroplasticity and synaptic remodeling to improve cognition and emotion processing. However, the investigators note clinical evidence is lacking.

For the study, the researchers randomly assigned healthy individuals to either 20-mg escitalopram or placebo for 3-5 weeks.

They performed PET with the 11C-UCB-J tracer, which allows imaging of the synaptic vesicle glycoprotein 2A (SV2A) in the brain, synaptic density, as well as changes in density over time, in the hippocampus and neocortex.

Between May 2020 and October 2021, 17 individuals were assigned to escitalopram and 15 to placebo. There were no significant differences between two groups in terms of age, sex, and PET-related variables. Serum escitalopram measurements confirmed that all participants in the active drug group were compliant.

When synaptic density was assessed at a single time point, an average of 29 days after the intervention, there were no significant differences between the escitalopram and placebo groups in either the neocortex (P = .41) or in the hippocampus (P = .26).

However, when they performed a secondary analysis of the time-dependent effect on SV2A levels, they found a marked difference between the two study groups.

Compared with the placebo group, participants taking escitalopram had a marked increase in synaptic density in both the neocortex (rp value, 0.58; P = .003) and the hippocampus (rp value, 0.41; P = .048).

In contrast, there were no significant changes in synaptic density in either the neocortex (rp value, –0.01; P = .95) or the hippocampus (rp value, –0.06; P = .62) in the hippocampus.

“That is consistent with our clinical observation that it takes time to evolve synaptic density, along with clinical improvement. Does that mean that the increase in synaptic density is a precondition for improvement in symptoms? We don’t know,” said Dr. Knudsen.
 

Exciting but not conclusive

Session co-chair Oliver Howes, MD, PhD, professor of molecular psychiatry, King’s College London, agreed that the results do not prove the gradual increase in synaptic density the treatment response lag with SSRIs.

“We definitely don’t yet have all the data to know one way or the other,” he said in an interview.

Another potential hypothesis, he said, is that SSRIs are causing shifts in underlying brain circuits that lead to cognitive changes before there is a discernable improvement in mood.

Indeed, Dr. Howes suggested that increases in synaptic density and cognitive changes related to SSRI use are not necessarily dependent on each other and could even be unrelated.

Also commenting on the research, David Nutt, MD, PhD, Edmond J. Safra professor of neuropsychopharmacology at Imperial College London, said that the “delay in therapeutic action of antidepressants has been a puzzle to psychiatrists ever since they were first discerned over 50 years ago. So, these new data in humans, that use cutting edge brain imaging to demonstrate an increase in brain connections developing over the period that the depression lifts, are very exciting.”

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

BARCELONA – The typical lag between treatment initiation with selective serotonin reuptake inhibitors (SSRIs) for depression and enhanced mood may be because of the time it takes to increase brain synaptic density, new imaging data suggest.

In a double-blind study, more than 30 volunteers were randomly assigned to the SSRI escitalopram or placebo for 3-5 weeks. Using PET imaging, the investigators found that over time, synaptic density significantly increased significantly in the neocortex and hippocampus but only in patients taking the active drug.

The results point to two conclusions, said study investigator Gitta Moos Knudsen, MD, PhD, clinical professor and chief physician at the department of clinical medicine, neurology, psychiatry and sensory sciences at Copenhagen (Denmark) University Hospital.

First, they indicate that SSRIs increase synaptic density in brain areas critically involved in depression, a finding that would go some way to indicating that the synaptic density in the brain may be involved in how antidepressants function, “which would give us a target for developing novel drugs against depression,” said Dr. Knudsen.

“Secondly, our data suggest synapses build up over a period of weeks, which would explain why the effects of these drugs take time to kick in,” she added.

The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress and simultaneously published online in Molecular Psychiatry.
 

Marked increase in synaptic density

SSRIs are widely used for depression as well as anxiety and obsessive-compulsive disorder. It is thought that they act via neuroplasticity and synaptic remodeling to improve cognition and emotion processing. However, the investigators note clinical evidence is lacking.

For the study, the researchers randomly assigned healthy individuals to either 20-mg escitalopram or placebo for 3-5 weeks.

They performed PET with the 11C-UCB-J tracer, which allows imaging of the synaptic vesicle glycoprotein 2A (SV2A) in the brain, synaptic density, as well as changes in density over time, in the hippocampus and neocortex.

Between May 2020 and October 2021, 17 individuals were assigned to escitalopram and 15 to placebo. There were no significant differences between two groups in terms of age, sex, and PET-related variables. Serum escitalopram measurements confirmed that all participants in the active drug group were compliant.

When synaptic density was assessed at a single time point, an average of 29 days after the intervention, there were no significant differences between the escitalopram and placebo groups in either the neocortex (P = .41) or in the hippocampus (P = .26).

However, when they performed a secondary analysis of the time-dependent effect on SV2A levels, they found a marked difference between the two study groups.

Compared with the placebo group, participants taking escitalopram had a marked increase in synaptic density in both the neocortex (rp value, 0.58; P = .003) and the hippocampus (rp value, 0.41; P = .048).

In contrast, there were no significant changes in synaptic density in either the neocortex (rp value, –0.01; P = .95) or the hippocampus (rp value, –0.06; P = .62) in the hippocampus.

“That is consistent with our clinical observation that it takes time to evolve synaptic density, along with clinical improvement. Does that mean that the increase in synaptic density is a precondition for improvement in symptoms? We don’t know,” said Dr. Knudsen.
 

Exciting but not conclusive

Session co-chair Oliver Howes, MD, PhD, professor of molecular psychiatry, King’s College London, agreed that the results do not prove the gradual increase in synaptic density the treatment response lag with SSRIs.

“We definitely don’t yet have all the data to know one way or the other,” he said in an interview.

Another potential hypothesis, he said, is that SSRIs are causing shifts in underlying brain circuits that lead to cognitive changes before there is a discernable improvement in mood.

Indeed, Dr. Howes suggested that increases in synaptic density and cognitive changes related to SSRI use are not necessarily dependent on each other and could even be unrelated.

Also commenting on the research, David Nutt, MD, PhD, Edmond J. Safra professor of neuropsychopharmacology at Imperial College London, said that the “delay in therapeutic action of antidepressants has been a puzzle to psychiatrists ever since they were first discerned over 50 years ago. So, these new data in humans, that use cutting edge brain imaging to demonstrate an increase in brain connections developing over the period that the depression lifts, are very exciting.”

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

The U.S. Food and Drug Administration has approved a meningococcal vaccine against the five most common serogroups causing disease in children and young adults.

The new formulation called Penbraya is manufactured by Pfizer and combines the components from two existing meningococcal vaccines, Trumenba the group B vaccine and Nimenrix groups A, C, W-135, and Y conjugate vaccine.

This is the first pentavalent vaccine for meningococcal disease and is approved for use in people aged 10-25.

“Today marks an important step forward in the prevention of meningococcal disease in the U.S.,” Annaliesa Anderson, PhD, head of vaccine research and development at Pfizer, said in a news release. “In a single vaccine, Penbraya has the potential to protect more adolescents and young adults from this severe and unpredictable disease by providing the broadest meningococcal coverage in the fewest shots.”
 

One shot, five common types

“Incomplete protection against invasive meningococcal disease,” is common, added Jana Shaw, MD, MPH, a pediatric infectious diseases specialist from Upstate Golisano Children’s Hospital in Syracuse, N.Y. Reducing the number of shots is important because streamlining the vaccination process should help increase the number of young people who get fully vaccinated against meningococcal disease.

Rates are low in the United States, according to the Centers for Disease Control and Prevention, and in 2021 there were around 210 cases reported. But a statewide outbreak has been going on in Virginia since June 2022, with 29 confirmed cases and 6 deaths.

The FDA’s decision is based on the positive results from phase 2 and phase 3 trials, including a randomized, active-controlled and observer-blinded phase 3 trial assessing the safety, tolerability, and immunogenicity of the pentavalent vaccine candidate, compared with currently licensed meningococcal vaccines. The phase 3 trial evaluated more than 2,400 patients from the United States and Europe.

The CDC Advisory Committee on Immunization Practices is meeting on Oct. 25 to discuss recommendations for the appropriate use of Penbraya in young people.

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

The U.S. Food and Drug Administration has approved a meningococcal vaccine against the five most common serogroups causing disease in children and young adults.

The new formulation called Penbraya is manufactured by Pfizer and combines the components from two existing meningococcal vaccines, Trumenba the group B vaccine and Nimenrix groups A, C, W-135, and Y conjugate vaccine.

This is the first pentavalent vaccine for meningococcal disease and is approved for use in people aged 10-25.

“Today marks an important step forward in the prevention of meningococcal disease in the U.S.,” Annaliesa Anderson, PhD, head of vaccine research and development at Pfizer, said in a news release. “In a single vaccine, Penbraya has the potential to protect more adolescents and young adults from this severe and unpredictable disease by providing the broadest meningococcal coverage in the fewest shots.”
 

One shot, five common types

“Incomplete protection against invasive meningococcal disease,” is common, added Jana Shaw, MD, MPH, a pediatric infectious diseases specialist from Upstate Golisano Children’s Hospital in Syracuse, N.Y. Reducing the number of shots is important because streamlining the vaccination process should help increase the number of young people who get fully vaccinated against meningococcal disease.

Rates are low in the United States, according to the Centers for Disease Control and Prevention, and in 2021 there were around 210 cases reported. But a statewide outbreak has been going on in Virginia since June 2022, with 29 confirmed cases and 6 deaths.

The FDA’s decision is based on the positive results from phase 2 and phase 3 trials, including a randomized, active-controlled and observer-blinded phase 3 trial assessing the safety, tolerability, and immunogenicity of the pentavalent vaccine candidate, compared with currently licensed meningococcal vaccines. The phase 3 trial evaluated more than 2,400 patients from the United States and Europe.

The CDC Advisory Committee on Immunization Practices is meeting on Oct. 25 to discuss recommendations for the appropriate use of Penbraya in young people.

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

The U.S. Food and Drug Administration has approved a meningococcal vaccine against the five most common serogroups causing disease in children and young adults.

The new formulation called Penbraya is manufactured by Pfizer and combines the components from two existing meningococcal vaccines, Trumenba the group B vaccine and Nimenrix groups A, C, W-135, and Y conjugate vaccine.

This is the first pentavalent vaccine for meningococcal disease and is approved for use in people aged 10-25.

“Today marks an important step forward in the prevention of meningococcal disease in the U.S.,” Annaliesa Anderson, PhD, head of vaccine research and development at Pfizer, said in a news release. “In a single vaccine, Penbraya has the potential to protect more adolescents and young adults from this severe and unpredictable disease by providing the broadest meningococcal coverage in the fewest shots.”
 

One shot, five common types

“Incomplete protection against invasive meningococcal disease,” is common, added Jana Shaw, MD, MPH, a pediatric infectious diseases specialist from Upstate Golisano Children’s Hospital in Syracuse, N.Y. Reducing the number of shots is important because streamlining the vaccination process should help increase the number of young people who get fully vaccinated against meningococcal disease.

Rates are low in the United States, according to the Centers for Disease Control and Prevention, and in 2021 there were around 210 cases reported. But a statewide outbreak has been going on in Virginia since June 2022, with 29 confirmed cases and 6 deaths.

The FDA’s decision is based on the positive results from phase 2 and phase 3 trials, including a randomized, active-controlled and observer-blinded phase 3 trial assessing the safety, tolerability, and immunogenicity of the pentavalent vaccine candidate, compared with currently licensed meningococcal vaccines. The phase 3 trial evaluated more than 2,400 patients from the United States and Europe.

The CDC Advisory Committee on Immunization Practices is meeting on Oct. 25 to discuss recommendations for the appropriate use of Penbraya in young people.

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

Playing chess or other board games slows cognitive decline and improves quality of life in older patients, results of a new systematic review suggest.
 

“For patients who are elderly and suffer from social isolation and mild cognitive issues, I would definitely recommend board games,” study investigator Frederico Emanuele Pozzi, MD, a neurology resident at Fondazione IRCCS San Gerardo dei Tintori in Monza, Italy, told this news organization.

The findings were presented at the virtual XXVI World Congress of Neurology (WCN).

After searching the published literature, Dr. Pozzi and his colleagues selected 15 studies for the review. The studies assessed the impact of board games on older individuals at risk of or with cognitive impairment, or those with mild cognitive impairment (MCI) at any age.

The studies included different board games including chess, Mah-jongg, and Go, a two-player game popular in China, Japan, and Korea that involves moving board pieces to surround and capture as much territory as possible.

Most interventions lasted about an hour and were held once or twice per week for 3-4 months.
 

Which games are best?

Researchers found that board games improved cognitive function, as measured by improved scores on the Montreal Cognitive Assessment (P = .003) and Mini-Mental State Examination (P = .02).

Playing Go was linked with improved working memory, as measured by the Trail Making Test-A. Those who played Mah-jongg reported improved executive functioning and a temporary decrease in depressive symptoms. And chess players reported improved quality of life on the World Health Organization Quality of Life scale from playing chess (P < .00001).

In general, cognition improved across different populations. For example, some studies looked at unimpaired elderly while others looked at MCI, said Dr. Pozzi.

Playing board games in a social context appeared to be especially good at boosting brain power. One Japanese study included a control group that just did tai chi, a group that did Go alone on tablets, and another group that did Go in groups. Both Go groups improved cognitively, but participants who played together improved the most.

The results also seemed to suggest that Go and chess have different biological effects. “For example, Go increased [brain-derived neurotrophic factor] (BDNF) levels and metabolism in areas key for cognition like the middle temporal gyrus,” Dr. Pozzi said.

He noted that the methodology of the studies was generally “not bad,” although in some cases the analyses were per protocol and in others intention-to-treat. Outcomes varied across studies, there were a lot of dropouts, and some were not randomized, meaning reverse causality can’t be ruled out.

Dr. Pozzi has started a randomized controlled trial at a Go and chess club in Italy. He’s enrolling patients aged 60 and over with subjective cognitive decline or MCI and separating participants into a control group, a group that plays chess, another that plays Go, and another that plays both Go and chess.

In addition to the standard cognitive tests, and measures of depression and quality of life, Dr. Pozzi aims to assess cognitive reserve and is in the process of validating a questionnaire that will look at leisure activities and lifestyle.
 

Social and cognitive value

Commenting on the research for this news organization, Vladimir Hachinski, MD, a professor of clinical neurological sciences at Western University in London, Ont., said the results make sense.

Playing a board game involves concentration, strategy, and intermittent rewards – all of which are good for the brain and may involve the prefrontal cortex, he noted. Board games are also typically timed, which involves brain speed processing, and they have a winner and loser so emotions can run high, which also affects the brain, Dr. Hachinski added.

There may also be social value in playing a board game with someone else, added Dr. Hachinski.

“It’s encouraging that people can improve what they’re doing, and the longer they’re at it, the more of the brain they use,” he said. “There might be a long-term effect because players are building up networks.”

But Dr. Hachinski cautioned that playing a lot of chess does not necessarily make you a better thinker, just as learning to play one instrument doesn’t mean you can automatically play others.

“Learning one skill will translate only partially to another, and only if it’s related,” he said. “It increases cognition in the area you’re practicing in, but it doesn’t spread to other areas.”

Dr. Pozzi and Dr. Hachinski report no relevant financial relationships.

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

Playing chess or other board games slows cognitive decline and improves quality of life in older patients, results of a new systematic review suggest.
 

“For patients who are elderly and suffer from social isolation and mild cognitive issues, I would definitely recommend board games,” study investigator Frederico Emanuele Pozzi, MD, a neurology resident at Fondazione IRCCS San Gerardo dei Tintori in Monza, Italy, told this news organization.

The findings were presented at the virtual XXVI World Congress of Neurology (WCN).

After searching the published literature, Dr. Pozzi and his colleagues selected 15 studies for the review. The studies assessed the impact of board games on older individuals at risk of or with cognitive impairment, or those with mild cognitive impairment (MCI) at any age.

The studies included different board games including chess, Mah-jongg, and Go, a two-player game popular in China, Japan, and Korea that involves moving board pieces to surround and capture as much territory as possible.

Most interventions lasted about an hour and were held once or twice per week for 3-4 months.
 

Which games are best?

Researchers found that board games improved cognitive function, as measured by improved scores on the Montreal Cognitive Assessment (P = .003) and Mini-Mental State Examination (P = .02).

Playing Go was linked with improved working memory, as measured by the Trail Making Test-A. Those who played Mah-jongg reported improved executive functioning and a temporary decrease in depressive symptoms. And chess players reported improved quality of life on the World Health Organization Quality of Life scale from playing chess (P < .00001).

In general, cognition improved across different populations. For example, some studies looked at unimpaired elderly while others looked at MCI, said Dr. Pozzi.

Playing board games in a social context appeared to be especially good at boosting brain power. One Japanese study included a control group that just did tai chi, a group that did Go alone on tablets, and another group that did Go in groups. Both Go groups improved cognitively, but participants who played together improved the most.

The results also seemed to suggest that Go and chess have different biological effects. “For example, Go increased [brain-derived neurotrophic factor] (BDNF) levels and metabolism in areas key for cognition like the middle temporal gyrus,” Dr. Pozzi said.

He noted that the methodology of the studies was generally “not bad,” although in some cases the analyses were per protocol and in others intention-to-treat. Outcomes varied across studies, there were a lot of dropouts, and some were not randomized, meaning reverse causality can’t be ruled out.

Dr. Pozzi has started a randomized controlled trial at a Go and chess club in Italy. He’s enrolling patients aged 60 and over with subjective cognitive decline or MCI and separating participants into a control group, a group that plays chess, another that plays Go, and another that plays both Go and chess.

In addition to the standard cognitive tests, and measures of depression and quality of life, Dr. Pozzi aims to assess cognitive reserve and is in the process of validating a questionnaire that will look at leisure activities and lifestyle.
 

Social and cognitive value

Commenting on the research for this news organization, Vladimir Hachinski, MD, a professor of clinical neurological sciences at Western University in London, Ont., said the results make sense.

Playing a board game involves concentration, strategy, and intermittent rewards – all of which are good for the brain and may involve the prefrontal cortex, he noted. Board games are also typically timed, which involves brain speed processing, and they have a winner and loser so emotions can run high, which also affects the brain, Dr. Hachinski added.

There may also be social value in playing a board game with someone else, added Dr. Hachinski.

“It’s encouraging that people can improve what they’re doing, and the longer they’re at it, the more of the brain they use,” he said. “There might be a long-term effect because players are building up networks.”

But Dr. Hachinski cautioned that playing a lot of chess does not necessarily make you a better thinker, just as learning to play one instrument doesn’t mean you can automatically play others.

“Learning one skill will translate only partially to another, and only if it’s related,” he said. “It increases cognition in the area you’re practicing in, but it doesn’t spread to other areas.”

Dr. Pozzi and Dr. Hachinski report no relevant financial relationships.

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

Playing chess or other board games slows cognitive decline and improves quality of life in older patients, results of a new systematic review suggest.
 

“For patients who are elderly and suffer from social isolation and mild cognitive issues, I would definitely recommend board games,” study investigator Frederico Emanuele Pozzi, MD, a neurology resident at Fondazione IRCCS San Gerardo dei Tintori in Monza, Italy, told this news organization.

The findings were presented at the virtual XXVI World Congress of Neurology (WCN).

After searching the published literature, Dr. Pozzi and his colleagues selected 15 studies for the review. The studies assessed the impact of board games on older individuals at risk of or with cognitive impairment, or those with mild cognitive impairment (MCI) at any age.

The studies included different board games including chess, Mah-jongg, and Go, a two-player game popular in China, Japan, and Korea that involves moving board pieces to surround and capture as much territory as possible.

Most interventions lasted about an hour and were held once or twice per week for 3-4 months.
 

Which games are best?

Researchers found that board games improved cognitive function, as measured by improved scores on the Montreal Cognitive Assessment (P = .003) and Mini-Mental State Examination (P = .02).

Playing Go was linked with improved working memory, as measured by the Trail Making Test-A. Those who played Mah-jongg reported improved executive functioning and a temporary decrease in depressive symptoms. And chess players reported improved quality of life on the World Health Organization Quality of Life scale from playing chess (P < .00001).

In general, cognition improved across different populations. For example, some studies looked at unimpaired elderly while others looked at MCI, said Dr. Pozzi.

Playing board games in a social context appeared to be especially good at boosting brain power. One Japanese study included a control group that just did tai chi, a group that did Go alone on tablets, and another group that did Go in groups. Both Go groups improved cognitively, but participants who played together improved the most.

The results also seemed to suggest that Go and chess have different biological effects. “For example, Go increased [brain-derived neurotrophic factor] (BDNF) levels and metabolism in areas key for cognition like the middle temporal gyrus,” Dr. Pozzi said.

He noted that the methodology of the studies was generally “not bad,” although in some cases the analyses were per protocol and in others intention-to-treat. Outcomes varied across studies, there were a lot of dropouts, and some were not randomized, meaning reverse causality can’t be ruled out.

Dr. Pozzi has started a randomized controlled trial at a Go and chess club in Italy. He’s enrolling patients aged 60 and over with subjective cognitive decline or MCI and separating participants into a control group, a group that plays chess, another that plays Go, and another that plays both Go and chess.

In addition to the standard cognitive tests, and measures of depression and quality of life, Dr. Pozzi aims to assess cognitive reserve and is in the process of validating a questionnaire that will look at leisure activities and lifestyle.
 

Social and cognitive value

Commenting on the research for this news organization, Vladimir Hachinski, MD, a professor of clinical neurological sciences at Western University in London, Ont., said the results make sense.

Playing a board game involves concentration, strategy, and intermittent rewards – all of which are good for the brain and may involve the prefrontal cortex, he noted. Board games are also typically timed, which involves brain speed processing, and they have a winner and loser so emotions can run high, which also affects the brain, Dr. Hachinski added.

There may also be social value in playing a board game with someone else, added Dr. Hachinski.

“It’s encouraging that people can improve what they’re doing, and the longer they’re at it, the more of the brain they use,” he said. “There might be a long-term effect because players are building up networks.”

But Dr. Hachinski cautioned that playing a lot of chess does not necessarily make you a better thinker, just as learning to play one instrument doesn’t mean you can automatically play others.

“Learning one skill will translate only partially to another, and only if it’s related,” he said. “It increases cognition in the area you’re practicing in, but it doesn’t spread to other areas.”

Dr. Pozzi and Dr. Hachinski report no relevant financial relationships.

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