Headache & Migraine

Key clinical point: High dietary acid load was associated with higher odds of migraine. Restricting dietary acid load could therefore reduce the odds of migraine in susceptible patients.

Major finding: The risk for migraine was higher among individuals in highest vs. lowest tertile of dietary acid load measures, including potential renal acid load (odds ratio [OR], 7.208; 95% confidence interval [95% CI], 3.33-15.55), net endogenous acid production (OR, 4.10; 95% CI, 1.92-8.77) scores, and the protein/potassium ratio (OR, 4.12; 95% CI, 1.93-8.81; all P_trend less than .001).

Study details: Findings are from a case-control study of 1,096 participants including those with migraine (n=514) and healthy volunteers (n=582).

Disclosures: The study was supported by the Iranian Centre of Neurological Research, Neuroscience Institute. All authors declared no conflicts of interest.

Source: Mousavi M et al. Neurol Ther. 2021 Apr 24. doi: 10.1007/s40120-021-00247-2.

Key clinical point: High dietary acid load was associated with higher odds of migraine. Restricting dietary acid load could therefore reduce the odds of migraine in susceptible patients.

Major finding: The risk for migraine was higher among individuals in highest vs. lowest tertile of dietary acid load measures, including potential renal acid load (odds ratio [OR], 7.208; 95% confidence interval [95% CI], 3.33-15.55), net endogenous acid production (OR, 4.10; 95% CI, 1.92-8.77) scores, and the protein/potassium ratio (OR, 4.12; 95% CI, 1.93-8.81; all P_trend less than .001).

Study details: Findings are from a case-control study of 1,096 participants including those with migraine (n=514) and healthy volunteers (n=582).

Disclosures: The study was supported by the Iranian Centre of Neurological Research, Neuroscience Institute. All authors declared no conflicts of interest.

Source: Mousavi M et al. Neurol Ther. 2021 Apr 24. doi: 10.1007/s40120-021-00247-2.

Key clinical point: High dietary acid load was associated with higher odds of migraine. Restricting dietary acid load could therefore reduce the odds of migraine in susceptible patients.

Major finding: The risk for migraine was higher among individuals in highest vs. lowest tertile of dietary acid load measures, including potential renal acid load (odds ratio [OR], 7.208; 95% confidence interval [95% CI], 3.33-15.55), net endogenous acid production (OR, 4.10; 95% CI, 1.92-8.77) scores, and the protein/potassium ratio (OR, 4.12; 95% CI, 1.93-8.81; all P_trend less than .001).

Study details: Findings are from a case-control study of 1,096 participants including those with migraine (n=514) and healthy volunteers (n=582).

Disclosures: The study was supported by the Iranian Centre of Neurological Research, Neuroscience Institute. All authors declared no conflicts of interest.

Source: Mousavi M et al. Neurol Ther. 2021 Apr 24. doi: 10.1007/s40120-021-00247-2.

Key clinical point: Menopausal women with migraine are at a higher risk for incident hypertension.

Major finding: Migraine was associated with an increased risk for incident hypertension (hazard ratio_migraine, 1.29; 95% confidence interval, 1.24-1.35) in menopausal women.

Study details: Findings are from a longitudinal cohort study of 56,202 menopausal women free of hypertension or cardiovascular disease at the age of menopause who participated in the French E3N cohort.

Disclosures: The authors reported no targeted funding. CJ MacDonald and T Kurth received funding and/or honoraria from multiple sources. Other authors had no disclosures relevant to the manuscript.

Source: MacDonald CJ et al. Neurology. 2021 Apr 21. doi: 10.1212/WNL.0000000000011986.

Key clinical point: Menopausal women with migraine are at a higher risk for incident hypertension.

Major finding: Migraine was associated with an increased risk for incident hypertension (hazard ratio_migraine, 1.29; 95% confidence interval, 1.24-1.35) in menopausal women.

Study details: Findings are from a longitudinal cohort study of 56,202 menopausal women free of hypertension or cardiovascular disease at the age of menopause who participated in the French E3N cohort.

Disclosures: The authors reported no targeted funding. CJ MacDonald and T Kurth received funding and/or honoraria from multiple sources. Other authors had no disclosures relevant to the manuscript.

Source: MacDonald CJ et al. Neurology. 2021 Apr 21. doi: 10.1212/WNL.0000000000011986.

Key clinical point: Menopausal women with migraine are at a higher risk for incident hypertension.

Major finding: Migraine was associated with an increased risk for incident hypertension (hazard ratio_migraine, 1.29; 95% confidence interval, 1.24-1.35) in menopausal women.

Study details: Findings are from a longitudinal cohort study of 56,202 menopausal women free of hypertension or cardiovascular disease at the age of menopause who participated in the French E3N cohort.

Disclosures: The authors reported no targeted funding. CJ MacDonald and T Kurth received funding and/or honoraria from multiple sources. Other authors had no disclosures relevant to the manuscript.

Source: MacDonald CJ et al. Neurology. 2021 Apr 21. doi: 10.1212/WNL.0000000000011986.

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

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

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

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

Prevalent, disabling

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

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

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

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

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

Retrospective database study

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

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

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

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

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

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

Unexpected finding

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Room for improvement

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Prevalent, disabling

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

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

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

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

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

Retrospective database study

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

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

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

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

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

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

Unexpected finding

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Room for improvement

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Prevalent, disabling

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

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

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

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

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

Retrospective database study

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

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

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

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

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

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

Unexpected finding

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Room for improvement

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Common questions

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

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

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

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

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

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

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

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

Migraine or vaccine reaction?

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

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

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

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

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

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

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

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

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

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

Continue to vaccinate

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

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

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

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

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

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

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

Common questions

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

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

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

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

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

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

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

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

Migraine or vaccine reaction?

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

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

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

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

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

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

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

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

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

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

Continue to vaccinate

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

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

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

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

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

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

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

Common questions

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

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

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

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

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

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

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

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

Migraine or vaccine reaction?

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

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

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

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

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

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

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

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

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

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

Continue to vaccinate

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

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

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

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

An in vitro study that used mouse endothelial cells to simulate the blood-brain barrier (BBB) suggests that specific proteins may be involved in destabilization of the protective barrier during a cortical spreading depression (CSD) event.

CSD has been linked to migraine aura, but a connection to pain symptoms is uncertain. “There’s just a lack of knowledge. We don’t understand migraine pathophysiology,” said Michael G. Harrington, MBChB, who was asked to comment on the study.

“The evidence for altered transport across the barrier in cortical spreading depression and the associated aura of migraine is pretty strong. The evidence for regular migraine, not so. In fact, there’s really no strong evidence for leakage in those people, and so it is still unresolved whether this initial cortical spreading depression that occurs in aura then triggers migraine afterwards, because it’s occurring during the aura. And in people who do not have the aura, is there a silent cortical spreading depression phenomenon with some leakage that triggers the migraine? That question is definitely not answered,” said Dr. Harrington, a research professor of neurology at the University of Southern California, Los Angeles.

Leakage of the BBB might allow passage of nociceptive compounds that could trigger migraine. Loss of BBB integrity has also been seen in other central nervous system pain disorders, suggesting that alterations to BBB functioning could have broader implications.

“In this model that we’re using, we’re seeing loss of overall barrier integrity, which lends itself to a whole cascade of further pathological possibilities,” Jared Wahl, a PhD candidate at the University of Arizona, Tucson, said in an interview. He presented the research at the American Headache Society’s 2021 annual meeting.

A leaky BBB could allow infiltration of a range of substances, but the potential for such a mechanism in migraine pathology is not well understood.

The researchers specifically investigated the potential role of claudin-5 in the tight junction (TJ) region of the BBB. The decision was made in part because the proteins involved in the BBB are difficult to study, and there is some familiarity with claudin-5, according to Mr. Wahl. ”Of all the proteins that are out there, for claudin-5 (there are) somewhat better techniques and products available to work with, and there’s been some previous research done to show that it’s implicated in blood brain barrier pathology. So it seemed like a good candidate to start with investigating this whole possible pathophysiological link between barrier disruption and migration of pronociceptive substances into the CNS during migraine attacks,” he said. The claudin proteins are also the major components of the tight junctions that seal off gaps between endothelial cells along the BBB.
 

Dynamic changes seen in the in vitro model

To simulate a CSD event, the researchers pulsed cultured cells for 5 minutes with astrocyte-conditioned media, artificial cerebrospinal fluid, KCl, glutamate, altered pH, or adenosine triphosphate (ATP). They used trans endothelial electrical resistance (TEER) to quickly and qualitatively screen for loss of barrier integrity, which is characterized by loss of electrical resistance. To quantify the magnitude of a breach, the researchers applied carbon-14 (C14)–labeled sucrose to one side of the barrier, and determined the amount of labeled sucrose transmitted to the other side of the barrier.

ATP and pH pulses that were outside normal physiological limits led to permeability. The team then used immunocytochemistry assays to visualize the condition of the model BBB, and found discontinuity of the tight junction membranes. Imaging of claudin-5 showed organizational changes within the tight junction, but there was no change in expression level, suggesting that the alterations were due to dynamic reorganization, according to Mr. Wahl.

Transient openings could allow passage of molecules such as bradykinin, calcitonin gene-related peptide (CGRP), and substance P, which could go on to affect the trigeminal nerve complex and trigger a migraine. “That’s sort of the crux of a lot of this migraine research, is gluing this physiological (mechanism) to how it is actually activating the CNS. And this is sort of where we’re going with it at the moment,” said Mr. Wahl.
 

Next steps

The researchers next plan to generate a cell line with claudin-5 linked to green fluorescent protein, then use confocal microscopy to image claudin-5 in real time as the BBB model responds to a simulated CSD.

Another important step will be to link physiological findings like those presented by Mr. Wahl to migraine-specific mechanisms. The results from this model will need to be expanded to include more than endothelial cells, especially astrocytes, pericytes, and neurons, as well as organoids, brain slices, or in vivo animal models, according to Dr. Harrington. “I think you could try and block the changes in occludin [another protein in the tight junction] or claudin-5 to see if, under the same provocation, that prevented the changes in a migraine model. That would be a direct way of connecting from CSD to migraine,” said Dr. Harrington.

If BBB disruption is confirmed to play an important role in migraine, and claudin-5 or other specific proteins are confirmed to be the cause, it could have clinical implications. A drug that could prevent those changes in the proteins and prevent a leak in the BBB could be a migraine preventative. “That could help prevent things like nociceptive substances migrating into the CNS, and could possibly be a well-tolerated drug target that doesn’t have the side effects or the overuse problems that a lot of stuff on the market has today,” said Mr. Wahl.

An in vitro study that used mouse endothelial cells to simulate the blood-brain barrier (BBB) suggests that specific proteins may be involved in destabilization of the protective barrier during a cortical spreading depression (CSD) event.

CSD has been linked to migraine aura, but a connection to pain symptoms is uncertain. “There’s just a lack of knowledge. We don’t understand migraine pathophysiology,” said Michael G. Harrington, MBChB, who was asked to comment on the study.

“The evidence for altered transport across the barrier in cortical spreading depression and the associated aura of migraine is pretty strong. The evidence for regular migraine, not so. In fact, there’s really no strong evidence for leakage in those people, and so it is still unresolved whether this initial cortical spreading depression that occurs in aura then triggers migraine afterwards, because it’s occurring during the aura. And in people who do not have the aura, is there a silent cortical spreading depression phenomenon with some leakage that triggers the migraine? That question is definitely not answered,” said Dr. Harrington, a research professor of neurology at the University of Southern California, Los Angeles.

Leakage of the BBB might allow passage of nociceptive compounds that could trigger migraine. Loss of BBB integrity has also been seen in other central nervous system pain disorders, suggesting that alterations to BBB functioning could have broader implications.

“In this model that we’re using, we’re seeing loss of overall barrier integrity, which lends itself to a whole cascade of further pathological possibilities,” Jared Wahl, a PhD candidate at the University of Arizona, Tucson, said in an interview. He presented the research at the American Headache Society’s 2021 annual meeting.

A leaky BBB could allow infiltration of a range of substances, but the potential for such a mechanism in migraine pathology is not well understood.

The researchers specifically investigated the potential role of claudin-5 in the tight junction (TJ) region of the BBB. The decision was made in part because the proteins involved in the BBB are difficult to study, and there is some familiarity with claudin-5, according to Mr. Wahl. ”Of all the proteins that are out there, for claudin-5 (there are) somewhat better techniques and products available to work with, and there’s been some previous research done to show that it’s implicated in blood brain barrier pathology. So it seemed like a good candidate to start with investigating this whole possible pathophysiological link between barrier disruption and migration of pronociceptive substances into the CNS during migraine attacks,” he said. The claudin proteins are also the major components of the tight junctions that seal off gaps between endothelial cells along the BBB.
 

Dynamic changes seen in the in vitro model

To simulate a CSD event, the researchers pulsed cultured cells for 5 minutes with astrocyte-conditioned media, artificial cerebrospinal fluid, KCl, glutamate, altered pH, or adenosine triphosphate (ATP). They used trans endothelial electrical resistance (TEER) to quickly and qualitatively screen for loss of barrier integrity, which is characterized by loss of electrical resistance. To quantify the magnitude of a breach, the researchers applied carbon-14 (C14)–labeled sucrose to one side of the barrier, and determined the amount of labeled sucrose transmitted to the other side of the barrier.

ATP and pH pulses that were outside normal physiological limits led to permeability. The team then used immunocytochemistry assays to visualize the condition of the model BBB, and found discontinuity of the tight junction membranes. Imaging of claudin-5 showed organizational changes within the tight junction, but there was no change in expression level, suggesting that the alterations were due to dynamic reorganization, according to Mr. Wahl.

Transient openings could allow passage of molecules such as bradykinin, calcitonin gene-related peptide (CGRP), and substance P, which could go on to affect the trigeminal nerve complex and trigger a migraine. “That’s sort of the crux of a lot of this migraine research, is gluing this physiological (mechanism) to how it is actually activating the CNS. And this is sort of where we’re going with it at the moment,” said Mr. Wahl.
 

Next steps

The researchers next plan to generate a cell line with claudin-5 linked to green fluorescent protein, then use confocal microscopy to image claudin-5 in real time as the BBB model responds to a simulated CSD.

Another important step will be to link physiological findings like those presented by Mr. Wahl to migraine-specific mechanisms. The results from this model will need to be expanded to include more than endothelial cells, especially astrocytes, pericytes, and neurons, as well as organoids, brain slices, or in vivo animal models, according to Dr. Harrington. “I think you could try and block the changes in occludin [another protein in the tight junction] or claudin-5 to see if, under the same provocation, that prevented the changes in a migraine model. That would be a direct way of connecting from CSD to migraine,” said Dr. Harrington.

If BBB disruption is confirmed to play an important role in migraine, and claudin-5 or other specific proteins are confirmed to be the cause, it could have clinical implications. A drug that could prevent those changes in the proteins and prevent a leak in the BBB could be a migraine preventative. “That could help prevent things like nociceptive substances migrating into the CNS, and could possibly be a well-tolerated drug target that doesn’t have the side effects or the overuse problems that a lot of stuff on the market has today,” said Mr. Wahl.

An in vitro study that used mouse endothelial cells to simulate the blood-brain barrier (BBB) suggests that specific proteins may be involved in destabilization of the protective barrier during a cortical spreading depression (CSD) event.

CSD has been linked to migraine aura, but a connection to pain symptoms is uncertain. “There’s just a lack of knowledge. We don’t understand migraine pathophysiology,” said Michael G. Harrington, MBChB, who was asked to comment on the study.

“The evidence for altered transport across the barrier in cortical spreading depression and the associated aura of migraine is pretty strong. The evidence for regular migraine, not so. In fact, there’s really no strong evidence for leakage in those people, and so it is still unresolved whether this initial cortical spreading depression that occurs in aura then triggers migraine afterwards, because it’s occurring during the aura. And in people who do not have the aura, is there a silent cortical spreading depression phenomenon with some leakage that triggers the migraine? That question is definitely not answered,” said Dr. Harrington, a research professor of neurology at the University of Southern California, Los Angeles.

Leakage of the BBB might allow passage of nociceptive compounds that could trigger migraine. Loss of BBB integrity has also been seen in other central nervous system pain disorders, suggesting that alterations to BBB functioning could have broader implications.

“In this model that we’re using, we’re seeing loss of overall barrier integrity, which lends itself to a whole cascade of further pathological possibilities,” Jared Wahl, a PhD candidate at the University of Arizona, Tucson, said in an interview. He presented the research at the American Headache Society’s 2021 annual meeting.

A leaky BBB could allow infiltration of a range of substances, but the potential for such a mechanism in migraine pathology is not well understood.

The researchers specifically investigated the potential role of claudin-5 in the tight junction (TJ) region of the BBB. The decision was made in part because the proteins involved in the BBB are difficult to study, and there is some familiarity with claudin-5, according to Mr. Wahl. ”Of all the proteins that are out there, for claudin-5 (there are) somewhat better techniques and products available to work with, and there’s been some previous research done to show that it’s implicated in blood brain barrier pathology. So it seemed like a good candidate to start with investigating this whole possible pathophysiological link between barrier disruption and migration of pronociceptive substances into the CNS during migraine attacks,” he said. The claudin proteins are also the major components of the tight junctions that seal off gaps between endothelial cells along the BBB.
 

Dynamic changes seen in the in vitro model

To simulate a CSD event, the researchers pulsed cultured cells for 5 minutes with astrocyte-conditioned media, artificial cerebrospinal fluid, KCl, glutamate, altered pH, or adenosine triphosphate (ATP). They used trans endothelial electrical resistance (TEER) to quickly and qualitatively screen for loss of barrier integrity, which is characterized by loss of electrical resistance. To quantify the magnitude of a breach, the researchers applied carbon-14 (C14)–labeled sucrose to one side of the barrier, and determined the amount of labeled sucrose transmitted to the other side of the barrier.

ATP and pH pulses that were outside normal physiological limits led to permeability. The team then used immunocytochemistry assays to visualize the condition of the model BBB, and found discontinuity of the tight junction membranes. Imaging of claudin-5 showed organizational changes within the tight junction, but there was no change in expression level, suggesting that the alterations were due to dynamic reorganization, according to Mr. Wahl.

Transient openings could allow passage of molecules such as bradykinin, calcitonin gene-related peptide (CGRP), and substance P, which could go on to affect the trigeminal nerve complex and trigger a migraine. “That’s sort of the crux of a lot of this migraine research, is gluing this physiological (mechanism) to how it is actually activating the CNS. And this is sort of where we’re going with it at the moment,” said Mr. Wahl.
 

Next steps

The researchers next plan to generate a cell line with claudin-5 linked to green fluorescent protein, then use confocal microscopy to image claudin-5 in real time as the BBB model responds to a simulated CSD.

Another important step will be to link physiological findings like those presented by Mr. Wahl to migraine-specific mechanisms. The results from this model will need to be expanded to include more than endothelial cells, especially astrocytes, pericytes, and neurons, as well as organoids, brain slices, or in vivo animal models, according to Dr. Harrington. “I think you could try and block the changes in occludin [another protein in the tight junction] or claudin-5 to see if, under the same provocation, that prevented the changes in a migraine model. That would be a direct way of connecting from CSD to migraine,” said Dr. Harrington.

If BBB disruption is confirmed to play an important role in migraine, and claudin-5 or other specific proteins are confirmed to be the cause, it could have clinical implications. A drug that could prevent those changes in the proteins and prevent a leak in the BBB could be a migraine preventative. “That could help prevent things like nociceptive substances migrating into the CNS, and could possibly be a well-tolerated drug target that doesn’t have the side effects or the overuse problems that a lot of stuff on the market has today,” said Mr. Wahl.

The migraine medication erenumab appears to pose no increased risk of hypertension, easing earlier concerns that this may be one of the drug’s adverse events, an analysis of postmarketing data shows. Nevertheless, investigators noted that more research is needed to confirm that this is the case.

While randomized clinical trials have shown no increased risk of hypertension related to the drug, it has been reported in postmarketing data. However, many of these events occurred in patients with previously documented hypertension or risk factors for the disorder, the investigators noted.

The rate of hypertension adverse events in postmarketing data was 0.144 per 100 person-years. Most such reports described only one instance of elevated blood pressure. In April 2020, the prescribing information for the drug was updated to include a mention of the risk of hypertension.

“Given the limitations of postmarketing reports, including incomplete information, lack of a control arm, and others, additional data are certainly needed to fully characterize the nature, the timing, and the extent to which hypertension is a risk associated with erenumab, and indeed other [calcitonin-gene-related peptide (CGRP)] pathway antagonists,” said study investigator David W. Dodick, MD, professor of neurology at the Mayo Clinic College of Medicine, Phoenix.

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

No increased risk over time

A monoclonal antibody and CGRP antagonist, erenumab is approved in the United States for migraine prevention in adults. CGRP medications are vasodilators, and, therefore, migraine treatments that target this pathway could theoretically have hypertensive effects.

To assess the risk of hypertension in migraine patients treated with erenumab, investigators examined clinical trial and postmarketing data. The analysis included cases with limited information and patients with a different etiology for the development of hypertension.

Using Amgen Clinical Trial data, the researchers performed a pooled safety analysis of four placebo-controlled, double-blind phase 2 or 3 studies of the drug. Participants had episodic or chronic migraine and were between ages 18 and 60 years or age 65 years. The doses studied were 70 mg and 140 mg.

In these studies, blood pressure data for each patient were based on an average of at least two measurements taken after patients were in rested state for at least 5 minutes. The position used for blood pressure measurement for each patient was consistent throughout the study.

The investigators also analyzed postmarketing reports of hypertension from May 17, 2018, to Jan. 31, 2020, identified in Amgen Global Safety data.

The pooled studies included 1,043 participants receiving placebo, 893 receiving 70 mg of erenumab, and 507 receiving 140 mg of the drug. During the treatment phase, the incidence of hypertension was 0.9% among controls, 0.8% in the 70-mg group, and 0.2% in the 140-mg group. The proportion of patients who started a new antihypertensive medication was 1.2% in controls, 0.8% in the 70-mg group, and 0.2% in the 140-mg group.

In a long-term, open-label study, patients with episodic migraine received erenumab treatment for up to 5 years. The incidence of hypertension did not increase with time in this population.

The postmarketing data encompassed 245,682 person-years of erenumab exposure. The researchers identified 362 hypertension events (355 cases). The rate of these events was 0.144 per 100 person-years. The exposure-adjusted incidence of hypertension was 1.9 per 100 patient-years for erenumab.

Of the 362 hypertensive events, 158 (43.6%) were in patients with a medical history of hypertension or risk factors for hypertension. Information about the time to onset of hypertension was available for 121 (33.4%) adverse events.

Of this group, 56 (46.2%) occurred within 1 week of erenumab initiation, including 43 (35.5%) that occurred within 1 day. This rapid time to hypertension onset “is inconsistent with the pharmacokinetic profile of once-monthly erenumab 70 mg or 140 mg, which has a peak serum concentration in approximately 6 days,” said Dr. Dodick.
 

Hypertension ‘not a barrier’ to treatment

Commenting on the findings, Richard B. Lipton, MD, Edwin S. Lowe professor and vice chair of neurology at Albert Einstein College of Medicine, New York, noted that in theory blocking CGRP could increase blood pressure. However, he noted that the data and clinical experience do not suggest erenumab poses a serious risk.

“I have rarely seen new-onset hypertension with erenumab in the patients treated at our medical center. The few cases I have seen were in older adults with pre-existing hypertension,” he said.

The investigators’ review of clinical trial data together with global safety databases was a strength of their study, said Dr. Lipton. In clinical trials, patients are monitored carefully, and a placebo control group aids in the determination of background rates.

“In the trials, the incidence of new-onset hypertension or hypertension exacerbation was 0.9%, while the placebo rate was 0.2%,” said Dr. Lipton. “The absolute increase in the risk of hypertension was 0.6% or six cases per thousand: A low rate.” But clinical trials enroll carefully selected patients who do not represent the broad group of people treated with erenumab in clinical practice, he added.

The global safety data are more representative of patients who receive erenumab in real-world settings. The weaknesses of these data, though, are the lack of a control group and the incomplete ascertainment of data associated with spontaneous reporting.

Yet both types of studies, with their complementary strengths and weaknesses, indicated low rates of hypertension.

“The low incidence of hypertension, in my view, is not a barrier to the use of erenumab, though checking blood pressure after starting any new migraine therapy is prudent,” Dr. Lipton concluded.

The study was funded by Amgen. Dr. Dodick had no relevant disclosures. Dr. Lipton has consulted for and conducted studies funded by Amgen and by other companies that manufacture CGRP drugs. He has stock options in Biohaven.

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

The migraine medication erenumab appears to pose no increased risk of hypertension, easing earlier concerns that this may be one of the drug’s adverse events, an analysis of postmarketing data shows. Nevertheless, investigators noted that more research is needed to confirm that this is the case.

While randomized clinical trials have shown no increased risk of hypertension related to the drug, it has been reported in postmarketing data. However, many of these events occurred in patients with previously documented hypertension or risk factors for the disorder, the investigators noted.

The rate of hypertension adverse events in postmarketing data was 0.144 per 100 person-years. Most such reports described only one instance of elevated blood pressure. In April 2020, the prescribing information for the drug was updated to include a mention of the risk of hypertension.

“Given the limitations of postmarketing reports, including incomplete information, lack of a control arm, and others, additional data are certainly needed to fully characterize the nature, the timing, and the extent to which hypertension is a risk associated with erenumab, and indeed other [calcitonin-gene-related peptide (CGRP)] pathway antagonists,” said study investigator David W. Dodick, MD, professor of neurology at the Mayo Clinic College of Medicine, Phoenix.

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

No increased risk over time

A monoclonal antibody and CGRP antagonist, erenumab is approved in the United States for migraine prevention in adults. CGRP medications are vasodilators, and, therefore, migraine treatments that target this pathway could theoretically have hypertensive effects.

To assess the risk of hypertension in migraine patients treated with erenumab, investigators examined clinical trial and postmarketing data. The analysis included cases with limited information and patients with a different etiology for the development of hypertension.

Using Amgen Clinical Trial data, the researchers performed a pooled safety analysis of four placebo-controlled, double-blind phase 2 or 3 studies of the drug. Participants had episodic or chronic migraine and were between ages 18 and 60 years or age 65 years. The doses studied were 70 mg and 140 mg.

In these studies, blood pressure data for each patient were based on an average of at least two measurements taken after patients were in rested state for at least 5 minutes. The position used for blood pressure measurement for each patient was consistent throughout the study.

The investigators also analyzed postmarketing reports of hypertension from May 17, 2018, to Jan. 31, 2020, identified in Amgen Global Safety data.

The pooled studies included 1,043 participants receiving placebo, 893 receiving 70 mg of erenumab, and 507 receiving 140 mg of the drug. During the treatment phase, the incidence of hypertension was 0.9% among controls, 0.8% in the 70-mg group, and 0.2% in the 140-mg group. The proportion of patients who started a new antihypertensive medication was 1.2% in controls, 0.8% in the 70-mg group, and 0.2% in the 140-mg group.

In a long-term, open-label study, patients with episodic migraine received erenumab treatment for up to 5 years. The incidence of hypertension did not increase with time in this population.

The postmarketing data encompassed 245,682 person-years of erenumab exposure. The researchers identified 362 hypertension events (355 cases). The rate of these events was 0.144 per 100 person-years. The exposure-adjusted incidence of hypertension was 1.9 per 100 patient-years for erenumab.

Of the 362 hypertensive events, 158 (43.6%) were in patients with a medical history of hypertension or risk factors for hypertension. Information about the time to onset of hypertension was available for 121 (33.4%) adverse events.

Of this group, 56 (46.2%) occurred within 1 week of erenumab initiation, including 43 (35.5%) that occurred within 1 day. This rapid time to hypertension onset “is inconsistent with the pharmacokinetic profile of once-monthly erenumab 70 mg or 140 mg, which has a peak serum concentration in approximately 6 days,” said Dr. Dodick.
 

Hypertension ‘not a barrier’ to treatment

Commenting on the findings, Richard B. Lipton, MD, Edwin S. Lowe professor and vice chair of neurology at Albert Einstein College of Medicine, New York, noted that in theory blocking CGRP could increase blood pressure. However, he noted that the data and clinical experience do not suggest erenumab poses a serious risk.

“I have rarely seen new-onset hypertension with erenumab in the patients treated at our medical center. The few cases I have seen were in older adults with pre-existing hypertension,” he said.

The investigators’ review of clinical trial data together with global safety databases was a strength of their study, said Dr. Lipton. In clinical trials, patients are monitored carefully, and a placebo control group aids in the determination of background rates.

“In the trials, the incidence of new-onset hypertension or hypertension exacerbation was 0.9%, while the placebo rate was 0.2%,” said Dr. Lipton. “The absolute increase in the risk of hypertension was 0.6% or six cases per thousand: A low rate.” But clinical trials enroll carefully selected patients who do not represent the broad group of people treated with erenumab in clinical practice, he added.

The global safety data are more representative of patients who receive erenumab in real-world settings. The weaknesses of these data, though, are the lack of a control group and the incomplete ascertainment of data associated with spontaneous reporting.

Yet both types of studies, with their complementary strengths and weaknesses, indicated low rates of hypertension.

“The low incidence of hypertension, in my view, is not a barrier to the use of erenumab, though checking blood pressure after starting any new migraine therapy is prudent,” Dr. Lipton concluded.

The study was funded by Amgen. Dr. Dodick had no relevant disclosures. Dr. Lipton has consulted for and conducted studies funded by Amgen and by other companies that manufacture CGRP drugs. He has stock options in Biohaven.

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

The migraine medication erenumab appears to pose no increased risk of hypertension, easing earlier concerns that this may be one of the drug’s adverse events, an analysis of postmarketing data shows. Nevertheless, investigators noted that more research is needed to confirm that this is the case.

While randomized clinical trials have shown no increased risk of hypertension related to the drug, it has been reported in postmarketing data. However, many of these events occurred in patients with previously documented hypertension or risk factors for the disorder, the investigators noted.

The rate of hypertension adverse events in postmarketing data was 0.144 per 100 person-years. Most such reports described only one instance of elevated blood pressure. In April 2020, the prescribing information for the drug was updated to include a mention of the risk of hypertension.

“Given the limitations of postmarketing reports, including incomplete information, lack of a control arm, and others, additional data are certainly needed to fully characterize the nature, the timing, and the extent to which hypertension is a risk associated with erenumab, and indeed other [calcitonin-gene-related peptide (CGRP)] pathway antagonists,” said study investigator David W. Dodick, MD, professor of neurology at the Mayo Clinic College of Medicine, Phoenix.

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

No increased risk over time

A monoclonal antibody and CGRP antagonist, erenumab is approved in the United States for migraine prevention in adults. CGRP medications are vasodilators, and, therefore, migraine treatments that target this pathway could theoretically have hypertensive effects.

To assess the risk of hypertension in migraine patients treated with erenumab, investigators examined clinical trial and postmarketing data. The analysis included cases with limited information and patients with a different etiology for the development of hypertension.

Using Amgen Clinical Trial data, the researchers performed a pooled safety analysis of four placebo-controlled, double-blind phase 2 or 3 studies of the drug. Participants had episodic or chronic migraine and were between ages 18 and 60 years or age 65 years. The doses studied were 70 mg and 140 mg.

In these studies, blood pressure data for each patient were based on an average of at least two measurements taken after patients were in rested state for at least 5 minutes. The position used for blood pressure measurement for each patient was consistent throughout the study.

The investigators also analyzed postmarketing reports of hypertension from May 17, 2018, to Jan. 31, 2020, identified in Amgen Global Safety data.

The pooled studies included 1,043 participants receiving placebo, 893 receiving 70 mg of erenumab, and 507 receiving 140 mg of the drug. During the treatment phase, the incidence of hypertension was 0.9% among controls, 0.8% in the 70-mg group, and 0.2% in the 140-mg group. The proportion of patients who started a new antihypertensive medication was 1.2% in controls, 0.8% in the 70-mg group, and 0.2% in the 140-mg group.

In a long-term, open-label study, patients with episodic migraine received erenumab treatment for up to 5 years. The incidence of hypertension did not increase with time in this population.

The postmarketing data encompassed 245,682 person-years of erenumab exposure. The researchers identified 362 hypertension events (355 cases). The rate of these events was 0.144 per 100 person-years. The exposure-adjusted incidence of hypertension was 1.9 per 100 patient-years for erenumab.

Of the 362 hypertensive events, 158 (43.6%) were in patients with a medical history of hypertension or risk factors for hypertension. Information about the time to onset of hypertension was available for 121 (33.4%) adverse events.

Of this group, 56 (46.2%) occurred within 1 week of erenumab initiation, including 43 (35.5%) that occurred within 1 day. This rapid time to hypertension onset “is inconsistent with the pharmacokinetic profile of once-monthly erenumab 70 mg or 140 mg, which has a peak serum concentration in approximately 6 days,” said Dr. Dodick.
 

Hypertension ‘not a barrier’ to treatment

Commenting on the findings, Richard B. Lipton, MD, Edwin S. Lowe professor and vice chair of neurology at Albert Einstein College of Medicine, New York, noted that in theory blocking CGRP could increase blood pressure. However, he noted that the data and clinical experience do not suggest erenumab poses a serious risk.

“I have rarely seen new-onset hypertension with erenumab in the patients treated at our medical center. The few cases I have seen were in older adults with pre-existing hypertension,” he said.

The investigators’ review of clinical trial data together with global safety databases was a strength of their study, said Dr. Lipton. In clinical trials, patients are monitored carefully, and a placebo control group aids in the determination of background rates.

“In the trials, the incidence of new-onset hypertension or hypertension exacerbation was 0.9%, while the placebo rate was 0.2%,” said Dr. Lipton. “The absolute increase in the risk of hypertension was 0.6% or six cases per thousand: A low rate.” But clinical trials enroll carefully selected patients who do not represent the broad group of people treated with erenumab in clinical practice, he added.

The global safety data are more representative of patients who receive erenumab in real-world settings. The weaknesses of these data, though, are the lack of a control group and the incomplete ascertainment of data associated with spontaneous reporting.

Yet both types of studies, with their complementary strengths and weaknesses, indicated low rates of hypertension.

“The low incidence of hypertension, in my view, is not a barrier to the use of erenumab, though checking blood pressure after starting any new migraine therapy is prudent,” Dr. Lipton concluded.

The study was funded by Amgen. Dr. Dodick had no relevant disclosures. Dr. Lipton has consulted for and conducted studies funded by Amgen and by other companies that manufacture CGRP drugs. He has stock options in Biohaven.

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

Key clinical point: Galcanezumab effectively reduced monthly migraine headache days (MMHD) in patients with migraine who did not benefit from commonly prescribed preventive treatments.

Major finding: Patients treated with galcanezumab vs. placebo had a greater mean reduction in MMHD across months 1-3 (all P less than .01) and improved quality of life at month 3 (P less than .01). A greater proportion of patients treated with galcanezumab vs. placebo experienced 50% or more reduction in MMHD from baseline (all P less than .05).

Study details: Data come from a post hoc analysis of phase 3b CONQUER study which included patients with chronic or episodic migraine who were not benefited from 2-4 classes of migraine preventive treatments and were randomly allocated to receive placebo (n=230) or galcanezumab 120 mg/month (n=232).

Disclosures: This study was funded by Eli Lilly and Company. DK Kuruppu, Y Dong, and LY Medina declared being full-time employees of and/or minor stockholders of Eli Lilly and Company. J Tobin and AL Green reported receiving compensation from Eli Lilly and Company.

Source: Kuruppu DK et al. BMC Neurol. 2021 Apr 23. doi: 10.1186/s12883-021-02196-7.

Key clinical point: Galcanezumab effectively reduced monthly migraine headache days (MMHD) in patients with migraine who did not benefit from commonly prescribed preventive treatments.

Major finding: Patients treated with galcanezumab vs. placebo had a greater mean reduction in MMHD across months 1-3 (all P less than .01) and improved quality of life at month 3 (P less than .01). A greater proportion of patients treated with galcanezumab vs. placebo experienced 50% or more reduction in MMHD from baseline (all P less than .05).

Study details: Data come from a post hoc analysis of phase 3b CONQUER study which included patients with chronic or episodic migraine who were not benefited from 2-4 classes of migraine preventive treatments and were randomly allocated to receive placebo (n=230) or galcanezumab 120 mg/month (n=232).

Disclosures: This study was funded by Eli Lilly and Company. DK Kuruppu, Y Dong, and LY Medina declared being full-time employees of and/or minor stockholders of Eli Lilly and Company. J Tobin and AL Green reported receiving compensation from Eli Lilly and Company.

Source: Kuruppu DK et al. BMC Neurol. 2021 Apr 23. doi: 10.1186/s12883-021-02196-7.

Key clinical point: Galcanezumab effectively reduced monthly migraine headache days (MMHD) in patients with migraine who did not benefit from commonly prescribed preventive treatments.

Major finding: Patients treated with galcanezumab vs. placebo had a greater mean reduction in MMHD across months 1-3 (all P less than .01) and improved quality of life at month 3 (P less than .01). A greater proportion of patients treated with galcanezumab vs. placebo experienced 50% or more reduction in MMHD from baseline (all P less than .05).

Study details: Data come from a post hoc analysis of phase 3b CONQUER study which included patients with chronic or episodic migraine who were not benefited from 2-4 classes of migraine preventive treatments and were randomly allocated to receive placebo (n=230) or galcanezumab 120 mg/month (n=232).

Disclosures: This study was funded by Eli Lilly and Company. DK Kuruppu, Y Dong, and LY Medina declared being full-time employees of and/or minor stockholders of Eli Lilly and Company. J Tobin and AL Green reported receiving compensation from Eli Lilly and Company.

Source: Kuruppu DK et al. BMC Neurol. 2021 Apr 23. doi: 10.1186/s12883-021-02196-7.

Key clinical point: Medication-overuse headache (MOH) was associated with an increased risk for suicidal ideation and prior suicide attempt in patients with chronic migraine (CM).

Major finding: The presence of MOH increased the risks for suicidal ideation (odds ratio [OR], 1.75; P = .004) and prior suicide attempt (OR, 1.88; P = .024) in patients with CM.

Study details: Findings are from a cross-sectional study of 603 patients with CM with (n=320) or without (n=283) coexisting MOH.

Disclosures: The study was supported in part by the Taiwan Ministry of Science and Technology, Taipei Veterans General Hospital, and others. YF Wang and SJ Wang reported receiving honoraria and/or research grants from and serving on advisory boards for multiple sources. Three other authors had no disclosures.

Source: Wang YF et al. J Headache Pain. 2021 May 10. doi: 10.1186/s10194-021-01248-0.

Key clinical point: Medication-overuse headache (MOH) was associated with an increased risk for suicidal ideation and prior suicide attempt in patients with chronic migraine (CM).

Major finding: The presence of MOH increased the risks for suicidal ideation (odds ratio [OR], 1.75; P = .004) and prior suicide attempt (OR, 1.88; P = .024) in patients with CM.

Study details: Findings are from a cross-sectional study of 603 patients with CM with (n=320) or without (n=283) coexisting MOH.

Disclosures: The study was supported in part by the Taiwan Ministry of Science and Technology, Taipei Veterans General Hospital, and others. YF Wang and SJ Wang reported receiving honoraria and/or research grants from and serving on advisory boards for multiple sources. Three other authors had no disclosures.

Source: Wang YF et al. J Headache Pain. 2021 May 10. doi: 10.1186/s10194-021-01248-0.

Key clinical point: Medication-overuse headache (MOH) was associated with an increased risk for suicidal ideation and prior suicide attempt in patients with chronic migraine (CM).

Major finding: The presence of MOH increased the risks for suicidal ideation (odds ratio [OR], 1.75; P = .004) and prior suicide attempt (OR, 1.88; P = .024) in patients with CM.

Study details: Findings are from a cross-sectional study of 603 patients with CM with (n=320) or without (n=283) coexisting MOH.

Disclosures: The study was supported in part by the Taiwan Ministry of Science and Technology, Taipei Veterans General Hospital, and others. YF Wang and SJ Wang reported receiving honoraria and/or research grants from and serving on advisory boards for multiple sources. Three other authors had no disclosures.

Source: Wang YF et al. J Headache Pain. 2021 May 10. doi: 10.1186/s10194-021-01248-0.

Key clinical point: In a real-life cohort of patients with chronic migraine (CM) and high-frequency episodic migraine (HFEM), galcanezumab was safe, well tolerated, and seemed to be more effective compared with that in randomized control trials.

Major finding: After 6 months of therapy, galcanezumab reduced monthly migraine days by 8 days in patients with HFEM and monthly headache days by 13 days in patients with CM (both P less than .001). Overall, galcanezumab was well tolerated with no serious adverse events reported.

Study details: Data come from a real-life, prospective cohort study (GARLIT) of 163 patients with HFEM and CM treated with subcutaneous galcanezumab 120 mg monthly.

Disclosures: The study was funded by Campus Bio-Medico University. Lead author F Vernieri along with other authors reported receiving travel grants, honoraria, and/or grants from various pharma companies. N Brunelli, CM Costa, and M Albanese had nothing to disclose.

Source: Vernieri F et al. J Headache Pain. 2021 May 3. doi: 10.1186/s10194-021-01247-1.

Key clinical point: In a real-life cohort of patients with chronic migraine (CM) and high-frequency episodic migraine (HFEM), galcanezumab was safe, well tolerated, and seemed to be more effective compared with that in randomized control trials.

Major finding: After 6 months of therapy, galcanezumab reduced monthly migraine days by 8 days in patients with HFEM and monthly headache days by 13 days in patients with CM (both P less than .001). Overall, galcanezumab was well tolerated with no serious adverse events reported.

Study details: Data come from a real-life, prospective cohort study (GARLIT) of 163 patients with HFEM and CM treated with subcutaneous galcanezumab 120 mg monthly.

Disclosures: The study was funded by Campus Bio-Medico University. Lead author F Vernieri along with other authors reported receiving travel grants, honoraria, and/or grants from various pharma companies. N Brunelli, CM Costa, and M Albanese had nothing to disclose.

Source: Vernieri F et al. J Headache Pain. 2021 May 3. doi: 10.1186/s10194-021-01247-1.

Key clinical point: In a real-life cohort of patients with chronic migraine (CM) and high-frequency episodic migraine (HFEM), galcanezumab was safe, well tolerated, and seemed to be more effective compared with that in randomized control trials.

Major finding: After 6 months of therapy, galcanezumab reduced monthly migraine days by 8 days in patients with HFEM and monthly headache days by 13 days in patients with CM (both P less than .001). Overall, galcanezumab was well tolerated with no serious adverse events reported.

Study details: Data come from a real-life, prospective cohort study (GARLIT) of 163 patients with HFEM and CM treated with subcutaneous galcanezumab 120 mg monthly.

Disclosures: The study was funded by Campus Bio-Medico University. Lead author F Vernieri along with other authors reported receiving travel grants, honoraria, and/or grants from various pharma companies. N Brunelli, CM Costa, and M Albanese had nothing to disclose.

Source: Vernieri F et al. J Headache Pain. 2021 May 3. doi: 10.1186/s10194-021-01247-1.

Key clinical point: Fremanezumab was significantly more efficacious than placebo in reducing the average number of monthly headache days (MHDs) and monthly migraine days (MMDs) in patients with chronic migraine (CM) and comorbid moderate-to-severe depression.

Major finding: At week 12, the average number of MHDs of at least moderate severity was significantly reduced in fremanezumab quarterly (least-squares mean change [LSM], −5.3) and monthly (LSM, −5.5) dose regimens vs. placebo (LSM, −2.2; both P less than .001). Similarly, MMDs were significantly reduced with fremanezumab quarterly (LSM, −5.4; P = .002) and monthly (LSM, −5.5; P less than .001) dose regimens vs. placebo (LSM, −2.4).

Study details: Findings are from a post hoc analysis of phase 3 HALO trial that included 1,130 patients with CM randomly allocated to receive fremanezumab quarterly, fremanezumab monthly, or placebo.

Disclosures: The study was funded by Teva Pharmaceutical Industries Ltd. Some of the authors declared serving as consultant, advisory board member, and/or receiving research support and honoraria from multiple sources. Some of the authors declared being current/former employees of Teva Branded Pharmaceutical Products R&D, Inc. (USA).

Source: Lipton RB et al. Headache. 2021 Apr 23. doi: 10.1111/head.14097.

Key clinical point: Fremanezumab was significantly more efficacious than placebo in reducing the average number of monthly headache days (MHDs) and monthly migraine days (MMDs) in patients with chronic migraine (CM) and comorbid moderate-to-severe depression.

Major finding: At week 12, the average number of MHDs of at least moderate severity was significantly reduced in fremanezumab quarterly (least-squares mean change [LSM], −5.3) and monthly (LSM, −5.5) dose regimens vs. placebo (LSM, −2.2; both P less than .001). Similarly, MMDs were significantly reduced with fremanezumab quarterly (LSM, −5.4; P = .002) and monthly (LSM, −5.5; P less than .001) dose regimens vs. placebo (LSM, −2.4).

Study details: Findings are from a post hoc analysis of phase 3 HALO trial that included 1,130 patients with CM randomly allocated to receive fremanezumab quarterly, fremanezumab monthly, or placebo.

Disclosures: The study was funded by Teva Pharmaceutical Industries Ltd. Some of the authors declared serving as consultant, advisory board member, and/or receiving research support and honoraria from multiple sources. Some of the authors declared being current/former employees of Teva Branded Pharmaceutical Products R&D, Inc. (USA).

Source: Lipton RB et al. Headache. 2021 Apr 23. doi: 10.1111/head.14097.

Key clinical point: Fremanezumab was significantly more efficacious than placebo in reducing the average number of monthly headache days (MHDs) and monthly migraine days (MMDs) in patients with chronic migraine (CM) and comorbid moderate-to-severe depression.

Major finding: At week 12, the average number of MHDs of at least moderate severity was significantly reduced in fremanezumab quarterly (least-squares mean change [LSM], −5.3) and monthly (LSM, −5.5) dose regimens vs. placebo (LSM, −2.2; both P less than .001). Similarly, MMDs were significantly reduced with fremanezumab quarterly (LSM, −5.4; P = .002) and monthly (LSM, −5.5; P less than .001) dose regimens vs. placebo (LSM, −2.4).

Study details: Findings are from a post hoc analysis of phase 3 HALO trial that included 1,130 patients with CM randomly allocated to receive fremanezumab quarterly, fremanezumab monthly, or placebo.

Disclosures: The study was funded by Teva Pharmaceutical Industries Ltd. Some of the authors declared serving as consultant, advisory board member, and/or receiving research support and honoraria from multiple sources. Some of the authors declared being current/former employees of Teva Branded Pharmaceutical Products R&D, Inc. (USA).

Source: Lipton RB et al. Headache. 2021 Apr 23. doi: 10.1111/head.14097.