Migraine ICYMI

Key clinical point: Eptinezumab, particularly at a dosage of 300 mg, has significant efficacy and an acceptable safety profile for treatment of migraine.

Major finding: Eptinezumab significantly reduced the mean monthly migraine days (MMDs) compared with placebo at week 12 at a dosage of 30 mg (change in MMDs, −0.29; P = .0001), 100 mg (change in MMDs, −0.31; P less than .00001), and 300 mg (change in MMDs, −0.41; P less than .00001). Treatment-emergent adverse events were not significantly different between eptinezumab and placebo.

Study details: This was a meta-analysis of 4 randomized controlled trials including 2,739 patients with migraine.

Disclosures: This work was supported by the Suzhou Health Talents Training Project. The authors declared no competing interests.

Source: Yan Z et al. J Headache Pain. 2021 Mar 6. doi: 10.1186/s10194-021-01220-y.

Key clinical point: Eptinezumab, particularly at a dosage of 300 mg, has significant efficacy and an acceptable safety profile for treatment of migraine.

Major finding: Eptinezumab significantly reduced the mean monthly migraine days (MMDs) compared with placebo at week 12 at a dosage of 30 mg (change in MMDs, −0.29; P = .0001), 100 mg (change in MMDs, −0.31; P less than .00001), and 300 mg (change in MMDs, −0.41; P less than .00001). Treatment-emergent adverse events were not significantly different between eptinezumab and placebo.

Study details: This was a meta-analysis of 4 randomized controlled trials including 2,739 patients with migraine.

Disclosures: This work was supported by the Suzhou Health Talents Training Project. The authors declared no competing interests.

Source: Yan Z et al. J Headache Pain. 2021 Mar 6. doi: 10.1186/s10194-021-01220-y.

Key clinical point: Eptinezumab, particularly at a dosage of 300 mg, has significant efficacy and an acceptable safety profile for treatment of migraine.

Major finding: Eptinezumab significantly reduced the mean monthly migraine days (MMDs) compared with placebo at week 12 at a dosage of 30 mg (change in MMDs, −0.29; P = .0001), 100 mg (change in MMDs, −0.31; P less than .00001), and 300 mg (change in MMDs, −0.41; P less than .00001). Treatment-emergent adverse events were not significantly different between eptinezumab and placebo.

Study details: This was a meta-analysis of 4 randomized controlled trials including 2,739 patients with migraine.

Disclosures: This work was supported by the Suzhou Health Talents Training Project. The authors declared no competing interests.

Source: Yan Z et al. J Headache Pain. 2021 Mar 6. doi: 10.1186/s10194-021-01220-y.

Key clinical point: Components of nonpharmacological interventions are effective for treatment of pediatric migraine.

Major finding: Short-term self-administered treatments (standardized mean difference [SMD], 1.44; 95% confidence interval [95% CI], 0.26-2.62), biofeedback (SMD, 1.41; 95% CI, 0.64-2.17), relaxation (SMD, 1.38; 95% CI, 0.61-2.14), and psychological treatments (SMD, 1.36; 95% CI, 0.15-2.57) were more effective than the waiting list, with findings being similar for long-term treatments.

Study details: A network meta-analysis of 12 randomized clinical trials that evaluated nonpharmacological treatments for pediatric migraine in 576 children and adolescents with episodic migraine.

Disclosures: The study was supported in part by the Sara Page Mayo Endowment for Pediatric Pain Research, Education, and Treatment. The authors reported no potential conflicts of interest.

Source: Koechlin H et al. Pediatrics. 2021 Mar 9. doi: 10.1542/peds.2019-4107.

Key clinical point: Components of nonpharmacological interventions are effective for treatment of pediatric migraine.

Major finding: Short-term self-administered treatments (standardized mean difference [SMD], 1.44; 95% confidence interval [95% CI], 0.26-2.62), biofeedback (SMD, 1.41; 95% CI, 0.64-2.17), relaxation (SMD, 1.38; 95% CI, 0.61-2.14), and psychological treatments (SMD, 1.36; 95% CI, 0.15-2.57) were more effective than the waiting list, with findings being similar for long-term treatments.

Study details: A network meta-analysis of 12 randomized clinical trials that evaluated nonpharmacological treatments for pediatric migraine in 576 children and adolescents with episodic migraine.

Disclosures: The study was supported in part by the Sara Page Mayo Endowment for Pediatric Pain Research, Education, and Treatment. The authors reported no potential conflicts of interest.

Source: Koechlin H et al. Pediatrics. 2021 Mar 9. doi: 10.1542/peds.2019-4107.

Key clinical point: Components of nonpharmacological interventions are effective for treatment of pediatric migraine.

Major finding: Short-term self-administered treatments (standardized mean difference [SMD], 1.44; 95% confidence interval [95% CI], 0.26-2.62), biofeedback (SMD, 1.41; 95% CI, 0.64-2.17), relaxation (SMD, 1.38; 95% CI, 0.61-2.14), and psychological treatments (SMD, 1.36; 95% CI, 0.15-2.57) were more effective than the waiting list, with findings being similar for long-term treatments.

Study details: A network meta-analysis of 12 randomized clinical trials that evaluated nonpharmacological treatments for pediatric migraine in 576 children and adolescents with episodic migraine.

Disclosures: The study was supported in part by the Sara Page Mayo Endowment for Pediatric Pain Research, Education, and Treatment. The authors reported no potential conflicts of interest.

Source: Koechlin H et al. Pediatrics. 2021 Mar 9. doi: 10.1542/peds.2019-4107.

Intranasal zavegepant, a third-generation calcitonin gene-related peptide (CGRP) receptor agonist, is effective and well tolerated in the treatment of acute migraine, new research shows. In a randomized dose-ranging, placebo-controlled, phase 2/3 trial, investigators found both the 10- and 20-mg doses of the drug were associated with pain freedom in more than 20% of patients and alleviated the most bothersome symptom, defined as photophobia, phonophobia, or nausea, in more than 40% of patients.

Most adverse events associated with zavegepant were mild or moderate. The drug is not associated with liver toxicity.

Three doses

Zavegepant is the only intranasal CGRP receptor antagonist undergoing late-stage development for the acute treatment of migraine. A previous single ascending dose study suggested the drug provided systemic exposure and had potentially therapeutic effects.

The study included participants age 18 years or older who had a diagnosis of migraine for at least 1 year, had two to eight migraine attacks of moderate or severe intensity and fewer than 15 monthly headache days over the previous 3 months.

The investigators randomly assigned participants in this phase 2/3 trial to placebo or a 5-mg, 10-mg, or 20-mg dose of intranasal zavegepant. Participants treated a single attack of moderate to severe pain with their assigned treatment.

The study’s two primary endpoints were freedom from pain and freedom from the most bothersome symptom at 2 hours after dosing.

The investigators randomly assigned 1,673 participants to treatment. Of this group, 1,588 treated an attack with study medication. The researchers also included 1,581 participants in the modified intention-to-treat population. Of this group, 387 received the 5-mg dose, 391 received the 10-mg dose, 402 received the 20-mg dose, and 401 received placebo.
 

Pain freedom

The population’s median age was approximately 41 years, 86% of participants were female, and 14% were taking preventive migraine medication. Participants’ mean number of moderate or severe attacks per month was 4.9 overall. The most common most bothersome symptom was photophobia.

The researchers observed a difference in outcome between the active and placebo arms as early as 15 minutes post-dose, but this difference was not statistically significant. At 2 hours, the rate of pain freedom was 15.5% in the placebo group, 22.5% in the 10-mg group (P = .0113), and 23.1% in the 20-mg group (P = .0055). The result for the 5-mg group (19.6%) was not significantly different from that of the placebo group.

The rate of freedom from the most bothersome symptom was 33.7% in the placebo group, 41.9% in the 10-mg group (P = .0155), and 42.5% in the 20-mg group (P = .0094). For this endpoint as well, the result of the 5-mg group (39%) was not significantly different from that among controls.

The most common adverse events were dysgeusia (impaired sense of taste) and nasal discomfort. The rate of dysgeusia ranged from 13.5% to 16.1% in the zavegepant groups, compared with 3.5% among controls. The rate of nasal discomfort ranged from 1.3% to 5.2% in the zavegepant groups, compared with 0.2% among controls. The investigators concluded that intranasal zavegepant had a favorable safety profile.
 

‘Exciting potential addition’

Commenting on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said: “Zavegepant is an exciting potential addition to rimegepant for the acute care of migraine.”

Many patients like the orally dissolving tablet formulation of rimegepant (Nurtec), but some have nausea and do not absorb oral preparations well, said Dr. Rapoport, who is editor-in-chief of Neurology Reviews and a past president of the International Headache Society. “So, it makes sense to have a gepant, which is not a vasoconstrictor and has few adverse events, developed as a nasal spray.” Nasal preparations often work more quickly than oral preparations, he added.

Other intranasal treatments available for migraine include dihydroergotamine (Migranal), zolmitriptan (Zomig), sumatriptan (Imitrex), and ketorolac (Sprix). It is not possible to compare zavegepant with these medications, or with other CGRP receptor antagonists, because they have not been studied in head-to-head trials, said Dr. Rapoport, who was not involved in the study but has previously consulted for Biohaven Pharmaceuticals, the drug’s manufacturer.

“I would predict a nasal spray would work somewhat faster and better in some patients with nausea or poor absorption, so I would be happy to have it approved and available.”

The current study uses endpoints typically prescribed by the U.S. Food and Drug Administration and includes a large sample size, said Dr. Rapoport.

“During the informed consent [stage], the patients in this trial would be told that there is a 3-in-4 chance that they would be getting an active drug versus placebo, and that often increases the placebo response,” he added. “In this trial, a placebo response of 15.5% is slightly high, but not atypical,” he added.

This study raises the question of whether other acute-care migraine medications should be studied as nasal preparations. “I think the answer is yes,” said Dr. Rapoport. “Fast-acting, effective nasal preparations that are easy to use and cause few adverse events [are] what we need.”

Biohaven Pharmaceuticals sponsored the study. Dr. Lipton has been a consultant for Biohaven, has conducted studies funded by the company, and has stock in the company. Dr. Rapoport has consulted and spoken for Biohaven, but did not participate in the current study.

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

Intranasal zavegepant, a third-generation calcitonin gene-related peptide (CGRP) receptor agonist, is effective and well tolerated in the treatment of acute migraine, new research shows. In a randomized dose-ranging, placebo-controlled, phase 2/3 trial, investigators found both the 10- and 20-mg doses of the drug were associated with pain freedom in more than 20% of patients and alleviated the most bothersome symptom, defined as photophobia, phonophobia, or nausea, in more than 40% of patients.

Most adverse events associated with zavegepant were mild or moderate. The drug is not associated with liver toxicity.

Three doses

Zavegepant is the only intranasal CGRP receptor antagonist undergoing late-stage development for the acute treatment of migraine. A previous single ascending dose study suggested the drug provided systemic exposure and had potentially therapeutic effects.

The study included participants age 18 years or older who had a diagnosis of migraine for at least 1 year, had two to eight migraine attacks of moderate or severe intensity and fewer than 15 monthly headache days over the previous 3 months.

The investigators randomly assigned participants in this phase 2/3 trial to placebo or a 5-mg, 10-mg, or 20-mg dose of intranasal zavegepant. Participants treated a single attack of moderate to severe pain with their assigned treatment.

The study’s two primary endpoints were freedom from pain and freedom from the most bothersome symptom at 2 hours after dosing.

The investigators randomly assigned 1,673 participants to treatment. Of this group, 1,588 treated an attack with study medication. The researchers also included 1,581 participants in the modified intention-to-treat population. Of this group, 387 received the 5-mg dose, 391 received the 10-mg dose, 402 received the 20-mg dose, and 401 received placebo.
 

Pain freedom

The population’s median age was approximately 41 years, 86% of participants were female, and 14% were taking preventive migraine medication. Participants’ mean number of moderate or severe attacks per month was 4.9 overall. The most common most bothersome symptom was photophobia.

The researchers observed a difference in outcome between the active and placebo arms as early as 15 minutes post-dose, but this difference was not statistically significant. At 2 hours, the rate of pain freedom was 15.5% in the placebo group, 22.5% in the 10-mg group (P = .0113), and 23.1% in the 20-mg group (P = .0055). The result for the 5-mg group (19.6%) was not significantly different from that of the placebo group.

The rate of freedom from the most bothersome symptom was 33.7% in the placebo group, 41.9% in the 10-mg group (P = .0155), and 42.5% in the 20-mg group (P = .0094). For this endpoint as well, the result of the 5-mg group (39%) was not significantly different from that among controls.

The most common adverse events were dysgeusia (impaired sense of taste) and nasal discomfort. The rate of dysgeusia ranged from 13.5% to 16.1% in the zavegepant groups, compared with 3.5% among controls. The rate of nasal discomfort ranged from 1.3% to 5.2% in the zavegepant groups, compared with 0.2% among controls. The investigators concluded that intranasal zavegepant had a favorable safety profile.
 

‘Exciting potential addition’

Commenting on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said: “Zavegepant is an exciting potential addition to rimegepant for the acute care of migraine.”

Many patients like the orally dissolving tablet formulation of rimegepant (Nurtec), but some have nausea and do not absorb oral preparations well, said Dr. Rapoport, who is editor-in-chief of Neurology Reviews and a past president of the International Headache Society. “So, it makes sense to have a gepant, which is not a vasoconstrictor and has few adverse events, developed as a nasal spray.” Nasal preparations often work more quickly than oral preparations, he added.

Other intranasal treatments available for migraine include dihydroergotamine (Migranal), zolmitriptan (Zomig), sumatriptan (Imitrex), and ketorolac (Sprix). It is not possible to compare zavegepant with these medications, or with other CGRP receptor antagonists, because they have not been studied in head-to-head trials, said Dr. Rapoport, who was not involved in the study but has previously consulted for Biohaven Pharmaceuticals, the drug’s manufacturer.

“I would predict a nasal spray would work somewhat faster and better in some patients with nausea or poor absorption, so I would be happy to have it approved and available.”

The current study uses endpoints typically prescribed by the U.S. Food and Drug Administration and includes a large sample size, said Dr. Rapoport.

“During the informed consent [stage], the patients in this trial would be told that there is a 3-in-4 chance that they would be getting an active drug versus placebo, and that often increases the placebo response,” he added. “In this trial, a placebo response of 15.5% is slightly high, but not atypical,” he added.

This study raises the question of whether other acute-care migraine medications should be studied as nasal preparations. “I think the answer is yes,” said Dr. Rapoport. “Fast-acting, effective nasal preparations that are easy to use and cause few adverse events [are] what we need.”

Biohaven Pharmaceuticals sponsored the study. Dr. Lipton has been a consultant for Biohaven, has conducted studies funded by the company, and has stock in the company. Dr. Rapoport has consulted and spoken for Biohaven, but did not participate in the current study.

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

Intranasal zavegepant, a third-generation calcitonin gene-related peptide (CGRP) receptor agonist, is effective and well tolerated in the treatment of acute migraine, new research shows. In a randomized dose-ranging, placebo-controlled, phase 2/3 trial, investigators found both the 10- and 20-mg doses of the drug were associated with pain freedom in more than 20% of patients and alleviated the most bothersome symptom, defined as photophobia, phonophobia, or nausea, in more than 40% of patients.

Most adverse events associated with zavegepant were mild or moderate. The drug is not associated with liver toxicity.

Three doses

Zavegepant is the only intranasal CGRP receptor antagonist undergoing late-stage development for the acute treatment of migraine. A previous single ascending dose study suggested the drug provided systemic exposure and had potentially therapeutic effects.

The study included participants age 18 years or older who had a diagnosis of migraine for at least 1 year, had two to eight migraine attacks of moderate or severe intensity and fewer than 15 monthly headache days over the previous 3 months.

The investigators randomly assigned participants in this phase 2/3 trial to placebo or a 5-mg, 10-mg, or 20-mg dose of intranasal zavegepant. Participants treated a single attack of moderate to severe pain with their assigned treatment.

The study’s two primary endpoints were freedom from pain and freedom from the most bothersome symptom at 2 hours after dosing.

The investigators randomly assigned 1,673 participants to treatment. Of this group, 1,588 treated an attack with study medication. The researchers also included 1,581 participants in the modified intention-to-treat population. Of this group, 387 received the 5-mg dose, 391 received the 10-mg dose, 402 received the 20-mg dose, and 401 received placebo.
 

Pain freedom

The population’s median age was approximately 41 years, 86% of participants were female, and 14% were taking preventive migraine medication. Participants’ mean number of moderate or severe attacks per month was 4.9 overall. The most common most bothersome symptom was photophobia.

The researchers observed a difference in outcome between the active and placebo arms as early as 15 minutes post-dose, but this difference was not statistically significant. At 2 hours, the rate of pain freedom was 15.5% in the placebo group, 22.5% in the 10-mg group (P = .0113), and 23.1% in the 20-mg group (P = .0055). The result for the 5-mg group (19.6%) was not significantly different from that of the placebo group.

The rate of freedom from the most bothersome symptom was 33.7% in the placebo group, 41.9% in the 10-mg group (P = .0155), and 42.5% in the 20-mg group (P = .0094). For this endpoint as well, the result of the 5-mg group (39%) was not significantly different from that among controls.

The most common adverse events were dysgeusia (impaired sense of taste) and nasal discomfort. The rate of dysgeusia ranged from 13.5% to 16.1% in the zavegepant groups, compared with 3.5% among controls. The rate of nasal discomfort ranged from 1.3% to 5.2% in the zavegepant groups, compared with 0.2% among controls. The investigators concluded that intranasal zavegepant had a favorable safety profile.
 

‘Exciting potential addition’

Commenting on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said: “Zavegepant is an exciting potential addition to rimegepant for the acute care of migraine.”

Many patients like the orally dissolving tablet formulation of rimegepant (Nurtec), but some have nausea and do not absorb oral preparations well, said Dr. Rapoport, who is editor-in-chief of Neurology Reviews and a past president of the International Headache Society. “So, it makes sense to have a gepant, which is not a vasoconstrictor and has few adverse events, developed as a nasal spray.” Nasal preparations often work more quickly than oral preparations, he added.

Other intranasal treatments available for migraine include dihydroergotamine (Migranal), zolmitriptan (Zomig), sumatriptan (Imitrex), and ketorolac (Sprix). It is not possible to compare zavegepant with these medications, or with other CGRP receptor antagonists, because they have not been studied in head-to-head trials, said Dr. Rapoport, who was not involved in the study but has previously consulted for Biohaven Pharmaceuticals, the drug’s manufacturer.

“I would predict a nasal spray would work somewhat faster and better in some patients with nausea or poor absorption, so I would be happy to have it approved and available.”

The current study uses endpoints typically prescribed by the U.S. Food and Drug Administration and includes a large sample size, said Dr. Rapoport.

“During the informed consent [stage], the patients in this trial would be told that there is a 3-in-4 chance that they would be getting an active drug versus placebo, and that often increases the placebo response,” he added. “In this trial, a placebo response of 15.5% is slightly high, but not atypical,” he added.

This study raises the question of whether other acute-care migraine medications should be studied as nasal preparations. “I think the answer is yes,” said Dr. Rapoport. “Fast-acting, effective nasal preparations that are easy to use and cause few adverse events [are] what we need.”

Biohaven Pharmaceuticals sponsored the study. Dr. Lipton has been a consultant for Biohaven, has conducted studies funded by the company, and has stock in the company. Dr. Rapoport has consulted and spoken for Biohaven, but did not participate in the current study.

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

Patients with chronic migraine who turn to cannabis to relieve headache pain may be setting themselves up for medication overuse headache, preliminary research suggests, although the direction of the relationship is unclear. Researchers at Stanford (Calif.) University found a significant increase in the likelihood of medication overuse headache (rebound headache) in chronic migraine patients who use cannabis.

“This study shows that there is some kind of association between cannabis use and medication overuse headache in people with chronic migraine,” said lead investigator Niushen Zhang, MD, a clinical assistant professor at Stanford.

“But it is unclear at this time whether patients are using cannabis to treat medication overuse headache or if cannabis is contributing to the development medication overuse headache, or both,” she said.

The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
 

Sixfold increase

“Medication overuse occurs in about 1% to 3% of the general population. It affects nearly one-third of the patients (mostly patients with chronic migraine) seen at tertiary care centers such as the Stanford Headache Center,” Dr. Zhang said.

From clinical observations, patients with chronic migraine and medication overuse headache appear to be concomitantly using cannabis products, yet there is currently very little research on this topic, she added.

To investigate, the researchers reviewed the records of 368 adults who experienced chronic migraine (15 or more migraine days per month) for at least 1 year. Of the 368 patients, 150 were using cannabis, and 218 were not. In addition, 212 had medication overuse headache, and 156 did not.

Results showed that patients who used cannabis were nearly six times more likely to have medication overuse headache than those who did not use cannabis (odds ratio, 5.99; 95% confidence interval, 3.45-10.43; P < .0001).

There were significant bidirectional relationships between current cannabis use, opioid use, and medication overuse headache.
 

Jury out on cannabis for migraine

Commenting on the findings, Teshamae Monteith, MD, of the University of Miami, noted, “With increased legalization, greater access, and less stigmatization, there are more individuals using cannabis for migraine, but there is no solid evidence to suggest that cannabis is effective for acute or preventive treatment of migraine.”

The study is “interesting,” Dr. Monteith said, but, owing to methodologic limitations, it is not clear that cannabis contributes to medication overuse headache. “Patients with medication overuse headaches may have more comorbidities, such as anxiety, depression, and sleep disorders, that are driving the cannabis use. The patients on cannabis also had higher rates of opiate use, which itself is a stronger contributor to medication overuse headache and may indicate the presence of other pain disorders,” Dr. Monteith said.

“It is not clear if these patients were appropriately treated with migraine prevention; patients that use cannabis sometimes report that they prefer to avoid pharmaceutical treatments, such as antidepressants, etc., used for migraine,” Dr. Monteith noted.

She said that at this point, she would advise clinicians to ask about cannabis use “and let patients know that we do not know enough about the long-term effects of cannabis on the migraine brain.”

Most importantly, Dr. Monteith said, she would “encourage clinicians to be sensitive to the high prevalence of migraine, chronic migraine, and medication overuse. If we can treat more effectively and prevent migraine progression, which includes addressing comorbidities, there would be a lot less medication overuse headache.”

Also weighing in on the study, Jessica Ailani, MD, director, Medstar Georgetown Headache Center, Washington, D.C., noted that there is no conclusive evidence that cannabis is an effective acute or preventive treatment for migraine. “There is a suggestion that cannabis can help treat a migraine attack, but there is uncertainty about concentration of cannabidiol (CBD) to tetrahydrocannabinol (THC) needed to achieve pain freedom,” Dr. Ailani said.

“There has also been some concern about interactions between CBD and other medications used to treat migraine and that CBD can cause a condition known as reversible cerebral vasoconstrictive syndrome. These are reasons to be cautious with CBD,” Dr. Ailani added.

“At this time there is limited advice we can give our patients except that more studies need to be done. If cannabis is used, it should be reported, and medications that may interact with cannabis should be avoided. A headache calendar should be kept to ensure frequency of migraine and headache attacks do not go up,” said Dr. Ailani.

The study had no specific funding. Dr. Zhang, Dr. Monteith, and Dr. Ailani have disclosed no relevant financial relationships.

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

Patients with chronic migraine who turn to cannabis to relieve headache pain may be setting themselves up for medication overuse headache, preliminary research suggests, although the direction of the relationship is unclear. Researchers at Stanford (Calif.) University found a significant increase in the likelihood of medication overuse headache (rebound headache) in chronic migraine patients who use cannabis.

“This study shows that there is some kind of association between cannabis use and medication overuse headache in people with chronic migraine,” said lead investigator Niushen Zhang, MD, a clinical assistant professor at Stanford.

“But it is unclear at this time whether patients are using cannabis to treat medication overuse headache or if cannabis is contributing to the development medication overuse headache, or both,” she said.

The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
 

Sixfold increase

“Medication overuse occurs in about 1% to 3% of the general population. It affects nearly one-third of the patients (mostly patients with chronic migraine) seen at tertiary care centers such as the Stanford Headache Center,” Dr. Zhang said.

From clinical observations, patients with chronic migraine and medication overuse headache appear to be concomitantly using cannabis products, yet there is currently very little research on this topic, she added.

To investigate, the researchers reviewed the records of 368 adults who experienced chronic migraine (15 or more migraine days per month) for at least 1 year. Of the 368 patients, 150 were using cannabis, and 218 were not. In addition, 212 had medication overuse headache, and 156 did not.

Results showed that patients who used cannabis were nearly six times more likely to have medication overuse headache than those who did not use cannabis (odds ratio, 5.99; 95% confidence interval, 3.45-10.43; P < .0001).

There were significant bidirectional relationships between current cannabis use, opioid use, and medication overuse headache.
 

Jury out on cannabis for migraine

Commenting on the findings, Teshamae Monteith, MD, of the University of Miami, noted, “With increased legalization, greater access, and less stigmatization, there are more individuals using cannabis for migraine, but there is no solid evidence to suggest that cannabis is effective for acute or preventive treatment of migraine.”

The study is “interesting,” Dr. Monteith said, but, owing to methodologic limitations, it is not clear that cannabis contributes to medication overuse headache. “Patients with medication overuse headaches may have more comorbidities, such as anxiety, depression, and sleep disorders, that are driving the cannabis use. The patients on cannabis also had higher rates of opiate use, which itself is a stronger contributor to medication overuse headache and may indicate the presence of other pain disorders,” Dr. Monteith said.

“It is not clear if these patients were appropriately treated with migraine prevention; patients that use cannabis sometimes report that they prefer to avoid pharmaceutical treatments, such as antidepressants, etc., used for migraine,” Dr. Monteith noted.

She said that at this point, she would advise clinicians to ask about cannabis use “and let patients know that we do not know enough about the long-term effects of cannabis on the migraine brain.”

Most importantly, Dr. Monteith said, she would “encourage clinicians to be sensitive to the high prevalence of migraine, chronic migraine, and medication overuse. If we can treat more effectively and prevent migraine progression, which includes addressing comorbidities, there would be a lot less medication overuse headache.”

Also weighing in on the study, Jessica Ailani, MD, director, Medstar Georgetown Headache Center, Washington, D.C., noted that there is no conclusive evidence that cannabis is an effective acute or preventive treatment for migraine. “There is a suggestion that cannabis can help treat a migraine attack, but there is uncertainty about concentration of cannabidiol (CBD) to tetrahydrocannabinol (THC) needed to achieve pain freedom,” Dr. Ailani said.

“There has also been some concern about interactions between CBD and other medications used to treat migraine and that CBD can cause a condition known as reversible cerebral vasoconstrictive syndrome. These are reasons to be cautious with CBD,” Dr. Ailani added.

“At this time there is limited advice we can give our patients except that more studies need to be done. If cannabis is used, it should be reported, and medications that may interact with cannabis should be avoided. A headache calendar should be kept to ensure frequency of migraine and headache attacks do not go up,” said Dr. Ailani.

The study had no specific funding. Dr. Zhang, Dr. Monteith, and Dr. Ailani have disclosed no relevant financial relationships.

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

Patients with chronic migraine who turn to cannabis to relieve headache pain may be setting themselves up for medication overuse headache, preliminary research suggests, although the direction of the relationship is unclear. Researchers at Stanford (Calif.) University found a significant increase in the likelihood of medication overuse headache (rebound headache) in chronic migraine patients who use cannabis.

“This study shows that there is some kind of association between cannabis use and medication overuse headache in people with chronic migraine,” said lead investigator Niushen Zhang, MD, a clinical assistant professor at Stanford.

“But it is unclear at this time whether patients are using cannabis to treat medication overuse headache or if cannabis is contributing to the development medication overuse headache, or both,” she said.

The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
 

Sixfold increase

“Medication overuse occurs in about 1% to 3% of the general population. It affects nearly one-third of the patients (mostly patients with chronic migraine) seen at tertiary care centers such as the Stanford Headache Center,” Dr. Zhang said.

From clinical observations, patients with chronic migraine and medication overuse headache appear to be concomitantly using cannabis products, yet there is currently very little research on this topic, she added.

To investigate, the researchers reviewed the records of 368 adults who experienced chronic migraine (15 or more migraine days per month) for at least 1 year. Of the 368 patients, 150 were using cannabis, and 218 were not. In addition, 212 had medication overuse headache, and 156 did not.

Results showed that patients who used cannabis were nearly six times more likely to have medication overuse headache than those who did not use cannabis (odds ratio, 5.99; 95% confidence interval, 3.45-10.43; P < .0001).

There were significant bidirectional relationships between current cannabis use, opioid use, and medication overuse headache.
 

Jury out on cannabis for migraine

Commenting on the findings, Teshamae Monteith, MD, of the University of Miami, noted, “With increased legalization, greater access, and less stigmatization, there are more individuals using cannabis for migraine, but there is no solid evidence to suggest that cannabis is effective for acute or preventive treatment of migraine.”

The study is “interesting,” Dr. Monteith said, but, owing to methodologic limitations, it is not clear that cannabis contributes to medication overuse headache. “Patients with medication overuse headaches may have more comorbidities, such as anxiety, depression, and sleep disorders, that are driving the cannabis use. The patients on cannabis also had higher rates of opiate use, which itself is a stronger contributor to medication overuse headache and may indicate the presence of other pain disorders,” Dr. Monteith said.

“It is not clear if these patients were appropriately treated with migraine prevention; patients that use cannabis sometimes report that they prefer to avoid pharmaceutical treatments, such as antidepressants, etc., used for migraine,” Dr. Monteith noted.

She said that at this point, she would advise clinicians to ask about cannabis use “and let patients know that we do not know enough about the long-term effects of cannabis on the migraine brain.”

Most importantly, Dr. Monteith said, she would “encourage clinicians to be sensitive to the high prevalence of migraine, chronic migraine, and medication overuse. If we can treat more effectively and prevent migraine progression, which includes addressing comorbidities, there would be a lot less medication overuse headache.”

Also weighing in on the study, Jessica Ailani, MD, director, Medstar Georgetown Headache Center, Washington, D.C., noted that there is no conclusive evidence that cannabis is an effective acute or preventive treatment for migraine. “There is a suggestion that cannabis can help treat a migraine attack, but there is uncertainty about concentration of cannabidiol (CBD) to tetrahydrocannabinol (THC) needed to achieve pain freedom,” Dr. Ailani said.

“There has also been some concern about interactions between CBD and other medications used to treat migraine and that CBD can cause a condition known as reversible cerebral vasoconstrictive syndrome. These are reasons to be cautious with CBD,” Dr. Ailani added.

“At this time there is limited advice we can give our patients except that more studies need to be done. If cannabis is used, it should be reported, and medications that may interact with cannabis should be avoided. A headache calendar should be kept to ensure frequency of migraine and headache attacks do not go up,” said Dr. Ailani.

The study had no specific funding. Dr. Zhang, Dr. Monteith, and Dr. Ailani have disclosed no relevant financial relationships.

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

Atogepant, an oral, small-molecule, calcitonin gene–related peptide receptor antagonist that’s been in development as a preventive treatment for chronic migraine, has been found to have fewer side effects and similar hepatic function profile to standard of care oral treatment after 1 year of use, according to results of a multicenter, open-label trial presented at the 2021 annual meeting of the American Academy of Neurology.

The trial included 739 patients, 543 of whom were randomized to daily oral atogepant with the remainder assigned to the existing standard of care oral migraine prevention medication, said Messoud Ashina, MD, PhD, of the Danish Headache Center at the University of Copenhagen. Initially, 67% (n = 364) of the atogepant patients reported treatment-emergent adverse events (TEAEs). However, he noted, the rate of TEAEs related to treatment was actually 18% (n = 98), and the rate of serious AEs was 4.4% (n = 24); 31 patients (5.7%) discontinued therapy because of TEAEs.

Those rates compared favorably with the standard of care group, Dr. Ashina said. In that group, the rate of TEAEs was 78.6% (154/196), and the rate of treatment-related TEAEs was 36.2% (n = 71).

In the atogepant group, the most common TEAEs were upper respiratory tract infection (10.3%, n = 56), constipation (7.2%, n = 39) and nausea (6.3%, n = 34). “With constipation in particular most cases were mild to moderate,” Dr. Ashina said. “Only one case was considered severe and it resolved before the end of the trial.” One patient discontinued treatment because of constipation.

Most significantly, said Dr. Ashina, “No hepatic safety issues were identified.” In the atogepant group, 2.4% of patients (n = 13) had ALT/AST levels at three times the upper limit of normal versus 3.2% (n = 6) in the standard of care group.

During question-and-answer, Dr. Ashina was pressed on the rate or urinary tract infections in the atogepant patients – 5.2% (n = 28), a measure not reported in the standard of care group – but he said there was no indication the UTIs resulted from atogepant itself. “I assume if there was some problems with urinary tract infections because of the kidneys then you would expect to see the lab data showing that,” he added in an interview. “There were no differences in lab abnormalities between the two groups.”

While Dr. Ashina said “I don’t think it’s something of concern” with regard to the UTI risk, he added: “It doesn’t mean that we don’t have to be careful. As physicians, we have to exhibit pharmacovigilance all the time, especially with the new drugs coming out over the next 5 years. But don’t panic.”

Atogepant, an oral, small-molecule, calcitonin gene–related peptide receptor antagonist that’s been in development as a preventive treatment for chronic migraine, has been found to have fewer side effects and similar hepatic function profile to standard of care oral treatment after 1 year of use, according to results of a multicenter, open-label trial presented at the 2021 annual meeting of the American Academy of Neurology.

The trial included 739 patients, 543 of whom were randomized to daily oral atogepant with the remainder assigned to the existing standard of care oral migraine prevention medication, said Messoud Ashina, MD, PhD, of the Danish Headache Center at the University of Copenhagen. Initially, 67% (n = 364) of the atogepant patients reported treatment-emergent adverse events (TEAEs). However, he noted, the rate of TEAEs related to treatment was actually 18% (n = 98), and the rate of serious AEs was 4.4% (n = 24); 31 patients (5.7%) discontinued therapy because of TEAEs.

Those rates compared favorably with the standard of care group, Dr. Ashina said. In that group, the rate of TEAEs was 78.6% (154/196), and the rate of treatment-related TEAEs was 36.2% (n = 71).

In the atogepant group, the most common TEAEs were upper respiratory tract infection (10.3%, n = 56), constipation (7.2%, n = 39) and nausea (6.3%, n = 34). “With constipation in particular most cases were mild to moderate,” Dr. Ashina said. “Only one case was considered severe and it resolved before the end of the trial.” One patient discontinued treatment because of constipation.

Most significantly, said Dr. Ashina, “No hepatic safety issues were identified.” In the atogepant group, 2.4% of patients (n = 13) had ALT/AST levels at three times the upper limit of normal versus 3.2% (n = 6) in the standard of care group.

During question-and-answer, Dr. Ashina was pressed on the rate or urinary tract infections in the atogepant patients – 5.2% (n = 28), a measure not reported in the standard of care group – but he said there was no indication the UTIs resulted from atogepant itself. “I assume if there was some problems with urinary tract infections because of the kidneys then you would expect to see the lab data showing that,” he added in an interview. “There were no differences in lab abnormalities between the two groups.”

While Dr. Ashina said “I don’t think it’s something of concern” with regard to the UTI risk, he added: “It doesn’t mean that we don’t have to be careful. As physicians, we have to exhibit pharmacovigilance all the time, especially with the new drugs coming out over the next 5 years. But don’t panic.”

Atogepant, an oral, small-molecule, calcitonin gene–related peptide receptor antagonist that’s been in development as a preventive treatment for chronic migraine, has been found to have fewer side effects and similar hepatic function profile to standard of care oral treatment after 1 year of use, according to results of a multicenter, open-label trial presented at the 2021 annual meeting of the American Academy of Neurology.

The trial included 739 patients, 543 of whom were randomized to daily oral atogepant with the remainder assigned to the existing standard of care oral migraine prevention medication, said Messoud Ashina, MD, PhD, of the Danish Headache Center at the University of Copenhagen. Initially, 67% (n = 364) of the atogepant patients reported treatment-emergent adverse events (TEAEs). However, he noted, the rate of TEAEs related to treatment was actually 18% (n = 98), and the rate of serious AEs was 4.4% (n = 24); 31 patients (5.7%) discontinued therapy because of TEAEs.

Those rates compared favorably with the standard of care group, Dr. Ashina said. In that group, the rate of TEAEs was 78.6% (154/196), and the rate of treatment-related TEAEs was 36.2% (n = 71).

In the atogepant group, the most common TEAEs were upper respiratory tract infection (10.3%, n = 56), constipation (7.2%, n = 39) and nausea (6.3%, n = 34). “With constipation in particular most cases were mild to moderate,” Dr. Ashina said. “Only one case was considered severe and it resolved before the end of the trial.” One patient discontinued treatment because of constipation.

Most significantly, said Dr. Ashina, “No hepatic safety issues were identified.” In the atogepant group, 2.4% of patients (n = 13) had ALT/AST levels at three times the upper limit of normal versus 3.2% (n = 6) in the standard of care group.

During question-and-answer, Dr. Ashina was pressed on the rate or urinary tract infections in the atogepant patients – 5.2% (n = 28), a measure not reported in the standard of care group – but he said there was no indication the UTIs resulted from atogepant itself. “I assume if there was some problems with urinary tract infections because of the kidneys then you would expect to see the lab data showing that,” he added in an interview. “There were no differences in lab abnormalities between the two groups.”

While Dr. Ashina said “I don’t think it’s something of concern” with regard to the UTI risk, he added: “It doesn’t mean that we don’t have to be careful. As physicians, we have to exhibit pharmacovigilance all the time, especially with the new drugs coming out over the next 5 years. But don’t panic.”

Results from a 1-year, open-label safety study suggest that the oral migraine prevention drug rimegepant is safe and effective in patients with cardiovascular risk factors. Patients who fall into this category may be ineligible for treatment with triptans.

There are mechanistic concerns with rimegepant and related CGRP receptor antagonists. They block CGRP’s effect in the central nervous system, but CGRP is also active in blood vessels and the heart, leading to the possibility that countering its vasodilating effect could expose organs to risk of ischemia.

The Food and Drug Administration approved rimegepant in 2020 for treatment of acute migraine attacks. Sponsor Biohaven is also seeking approval for migraine prevention after a successful phase 3 study published January 2021 in The Lancet.

Susan Hutchinson, MD, who is a headache specialist at Orange County Migraine & Headache Center in Irvine, Calif., presented the results at the American Academy of Neurology’s 2021 annual meeting. The open-label study suggested that rimegepant is generally safe. “The proportion of subjects reporting at least one adverse event was similar among subjects whether they had zero, one, or two or more cardiovascular disease risk factors, and also among those with low and moderate to high 10-year cardiovascular risk, as determined by the Framingham Risk Score,” said Dr. Hutchinson during her presentation.

Still, there was one concerning case: A 53-year-old man experienced an attack of angina. But he already had angina prior to the study, was being treated for hypercholesterolemia, and had current or former exposure to statins. “This adverse event was deemed by the investigator to not be related to rimegepant,” said Dr. Hutchinson.

During the following question-and-answer session, an attendee pressed Dr. Hutchinson about the case, and she admitted to some initial doubts. “That was my concern when I saw those slides. I’m like, ‘oh, my goodness.’ ” She clarified that the man’s angina history dated to 2016, which was several years before the trial, and the episode of angina occurred 7 months after the first dose of rimegepant. “He was treated with nitroglycerin and taken out of the trial,” said Dr. Hutchinson.
 

Proper patient selection is key

The research adds to the literature on rimegepant by providing data on multiple uses, as opposed to the phase 3 study, which only looked at single use, according to Olivia Begasse de Dhaem, MD, who is a neurology attending physician at Stamford (Conn.) Health and was the session moderator. Rimegepant and other oral CGRP receptor antagonists, including the FDA-approved ubrogepant and the investigative drug atogepant, will help fill the gap of patients who don’t tolerate or are ineligible for triptans, she said.

Dr. Begasse de Dhaem pointed out that patient selection remains important. “I think the main thing for patient care is to look at whether the patient we are treating would fit within the inclusion criteria, or would have been excluded from this study,” said Dr. Begasse de Dhaem. Specifically, according to its clinicaltrials.gov page, the trial excluded patients with hemiplegic and basilar migraine, as well as patients with uncontrolled, unstable, or recently diagnosed cardiovascular disease, those with a body mass index of 30 kg/m² or higher, and hemoglobin A1c levels of 6.5% or higher. “This also looked at people with less than 15 migraine days per month, so it’s limited in how much we can extrapolate to people with chronic migraine who may take more than 7.7 rimegepant [doses, the mean value taken by trial participants] per month,” Dr. Begasse de Dhaem added.

She also applauded the inclusion of older patients in the study, noting that most migraine studies have an upper age limit.

The study included subjects who experienced 2-14 moderate or severe migraine attacks per month, and they were allowed to take other migraine medications. Cardiovascular risk factors did not prevent entry to the trial and, like the previous pivotal trial, the long-term safety study admitted subjects older than 65. Among the study cohort, 1,514 participants were told to treat migraine pain of any intensity with 75 mg rimegepant up to once per day on an as-needed basis (PRN), and a second group of 286 were told to take 75 mg rimegepant every other day for 12 weeks, along with PRN dosing on nonscheduled treatment days.

Nearly 90% of subjects were female, the mean age was 43.1 years, and 3.7% were age 65 or older. Among the study participants, 40.8% had cardiovascular risk factors, including 28.8% with one risk factor, and 12.1% with two or more. About 7% had a moderate to high (≥10%) 10-year cardiovascular risk by Framingham Risk Score, 23.6% had a family history of coronary artery disease, 11.7% were being treated for hypertension, 10.4% smoked, 8.3% were being treated with a statin, and 3.0% had a history of diabetes.

In total, subjects were exposed to 112,014 doses of rimegepant, a mean of 7.7 doses per 4-week period. The exposure was similar across all risk groups, which included zero risk factors, one risk factor, and two or more risk factors; FRS of less than 10%; and FRS of 10% or greater. The most common adverse events were upper respiratory tract infection (8.8%), nasopharyngitis (6.8%), and sinusitis (5.1%). The frequency of one or more adverse events was similar among those with zero cardiovascular risk factors (59.6%), one risk factor (61.4%), two or more risk factors (62.2%), FRS less than 10% (59.9%), and FRS of 10% or greater (59.9%).

The study was funded by Biohaven Pharmaceuticals. Dr. Hutchinson has been a consultant or advisory board member for Biohaven, Alder, Allergan, Amgen, Avanir, electroCore, Lilly, Novartis, Promius, Supernus, and Teva. She has been on the speaker’s bureau for Allergan, Amgen, Avanir, electroCore, Lilly, Novartis, Promius, Supernus, and Teva. Dr. Begasse de Dhaem has no relevant financial disclosures.

Results from a 1-year, open-label safety study suggest that the oral migraine prevention drug rimegepant is safe and effective in patients with cardiovascular risk factors. Patients who fall into this category may be ineligible for treatment with triptans.

There are mechanistic concerns with rimegepant and related CGRP receptor antagonists. They block CGRP’s effect in the central nervous system, but CGRP is also active in blood vessels and the heart, leading to the possibility that countering its vasodilating effect could expose organs to risk of ischemia.

The Food and Drug Administration approved rimegepant in 2020 for treatment of acute migraine attacks. Sponsor Biohaven is also seeking approval for migraine prevention after a successful phase 3 study published January 2021 in The Lancet.

Susan Hutchinson, MD, who is a headache specialist at Orange County Migraine & Headache Center in Irvine, Calif., presented the results at the American Academy of Neurology’s 2021 annual meeting. The open-label study suggested that rimegepant is generally safe. “The proportion of subjects reporting at least one adverse event was similar among subjects whether they had zero, one, or two or more cardiovascular disease risk factors, and also among those with low and moderate to high 10-year cardiovascular risk, as determined by the Framingham Risk Score,” said Dr. Hutchinson during her presentation.

Still, there was one concerning case: A 53-year-old man experienced an attack of angina. But he already had angina prior to the study, was being treated for hypercholesterolemia, and had current or former exposure to statins. “This adverse event was deemed by the investigator to not be related to rimegepant,” said Dr. Hutchinson.

During the following question-and-answer session, an attendee pressed Dr. Hutchinson about the case, and she admitted to some initial doubts. “That was my concern when I saw those slides. I’m like, ‘oh, my goodness.’ ” She clarified that the man’s angina history dated to 2016, which was several years before the trial, and the episode of angina occurred 7 months after the first dose of rimegepant. “He was treated with nitroglycerin and taken out of the trial,” said Dr. Hutchinson.
 

Proper patient selection is key

The research adds to the literature on rimegepant by providing data on multiple uses, as opposed to the phase 3 study, which only looked at single use, according to Olivia Begasse de Dhaem, MD, who is a neurology attending physician at Stamford (Conn.) Health and was the session moderator. Rimegepant and other oral CGRP receptor antagonists, including the FDA-approved ubrogepant and the investigative drug atogepant, will help fill the gap of patients who don’t tolerate or are ineligible for triptans, she said.

Dr. Begasse de Dhaem pointed out that patient selection remains important. “I think the main thing for patient care is to look at whether the patient we are treating would fit within the inclusion criteria, or would have been excluded from this study,” said Dr. Begasse de Dhaem. Specifically, according to its clinicaltrials.gov page, the trial excluded patients with hemiplegic and basilar migraine, as well as patients with uncontrolled, unstable, or recently diagnosed cardiovascular disease, those with a body mass index of 30 kg/m² or higher, and hemoglobin A1c levels of 6.5% or higher. “This also looked at people with less than 15 migraine days per month, so it’s limited in how much we can extrapolate to people with chronic migraine who may take more than 7.7 rimegepant [doses, the mean value taken by trial participants] per month,” Dr. Begasse de Dhaem added.

She also applauded the inclusion of older patients in the study, noting that most migraine studies have an upper age limit.

The study included subjects who experienced 2-14 moderate or severe migraine attacks per month, and they were allowed to take other migraine medications. Cardiovascular risk factors did not prevent entry to the trial and, like the previous pivotal trial, the long-term safety study admitted subjects older than 65. Among the study cohort, 1,514 participants were told to treat migraine pain of any intensity with 75 mg rimegepant up to once per day on an as-needed basis (PRN), and a second group of 286 were told to take 75 mg rimegepant every other day for 12 weeks, along with PRN dosing on nonscheduled treatment days.

Nearly 90% of subjects were female, the mean age was 43.1 years, and 3.7% were age 65 or older. Among the study participants, 40.8% had cardiovascular risk factors, including 28.8% with one risk factor, and 12.1% with two or more. About 7% had a moderate to high (≥10%) 10-year cardiovascular risk by Framingham Risk Score, 23.6% had a family history of coronary artery disease, 11.7% were being treated for hypertension, 10.4% smoked, 8.3% were being treated with a statin, and 3.0% had a history of diabetes.

In total, subjects were exposed to 112,014 doses of rimegepant, a mean of 7.7 doses per 4-week period. The exposure was similar across all risk groups, which included zero risk factors, one risk factor, and two or more risk factors; FRS of less than 10%; and FRS of 10% or greater. The most common adverse events were upper respiratory tract infection (8.8%), nasopharyngitis (6.8%), and sinusitis (5.1%). The frequency of one or more adverse events was similar among those with zero cardiovascular risk factors (59.6%), one risk factor (61.4%), two or more risk factors (62.2%), FRS less than 10% (59.9%), and FRS of 10% or greater (59.9%).

The study was funded by Biohaven Pharmaceuticals. Dr. Hutchinson has been a consultant or advisory board member for Biohaven, Alder, Allergan, Amgen, Avanir, electroCore, Lilly, Novartis, Promius, Supernus, and Teva. She has been on the speaker’s bureau for Allergan, Amgen, Avanir, electroCore, Lilly, Novartis, Promius, Supernus, and Teva. Dr. Begasse de Dhaem has no relevant financial disclosures.

Results from a 1-year, open-label safety study suggest that the oral migraine prevention drug rimegepant is safe and effective in patients with cardiovascular risk factors. Patients who fall into this category may be ineligible for treatment with triptans.

There are mechanistic concerns with rimegepant and related CGRP receptor antagonists. They block CGRP’s effect in the central nervous system, but CGRP is also active in blood vessels and the heart, leading to the possibility that countering its vasodilating effect could expose organs to risk of ischemia.

The Food and Drug Administration approved rimegepant in 2020 for treatment of acute migraine attacks. Sponsor Biohaven is also seeking approval for migraine prevention after a successful phase 3 study published January 2021 in The Lancet.

Susan Hutchinson, MD, who is a headache specialist at Orange County Migraine & Headache Center in Irvine, Calif., presented the results at the American Academy of Neurology’s 2021 annual meeting. The open-label study suggested that rimegepant is generally safe. “The proportion of subjects reporting at least one adverse event was similar among subjects whether they had zero, one, or two or more cardiovascular disease risk factors, and also among those with low and moderate to high 10-year cardiovascular risk, as determined by the Framingham Risk Score,” said Dr. Hutchinson during her presentation.

Still, there was one concerning case: A 53-year-old man experienced an attack of angina. But he already had angina prior to the study, was being treated for hypercholesterolemia, and had current or former exposure to statins. “This adverse event was deemed by the investigator to not be related to rimegepant,” said Dr. Hutchinson.

During the following question-and-answer session, an attendee pressed Dr. Hutchinson about the case, and she admitted to some initial doubts. “That was my concern when I saw those slides. I’m like, ‘oh, my goodness.’ ” She clarified that the man’s angina history dated to 2016, which was several years before the trial, and the episode of angina occurred 7 months after the first dose of rimegepant. “He was treated with nitroglycerin and taken out of the trial,” said Dr. Hutchinson.
 

Proper patient selection is key

The research adds to the literature on rimegepant by providing data on multiple uses, as opposed to the phase 3 study, which only looked at single use, according to Olivia Begasse de Dhaem, MD, who is a neurology attending physician at Stamford (Conn.) Health and was the session moderator. Rimegepant and other oral CGRP receptor antagonists, including the FDA-approved ubrogepant and the investigative drug atogepant, will help fill the gap of patients who don’t tolerate or are ineligible for triptans, she said.

Dr. Begasse de Dhaem pointed out that patient selection remains important. “I think the main thing for patient care is to look at whether the patient we are treating would fit within the inclusion criteria, or would have been excluded from this study,” said Dr. Begasse de Dhaem. Specifically, according to its clinicaltrials.gov page, the trial excluded patients with hemiplegic and basilar migraine, as well as patients with uncontrolled, unstable, or recently diagnosed cardiovascular disease, those with a body mass index of 30 kg/m² or higher, and hemoglobin A1c levels of 6.5% or higher. “This also looked at people with less than 15 migraine days per month, so it’s limited in how much we can extrapolate to people with chronic migraine who may take more than 7.7 rimegepant [doses, the mean value taken by trial participants] per month,” Dr. Begasse de Dhaem added.

She also applauded the inclusion of older patients in the study, noting that most migraine studies have an upper age limit.

The study included subjects who experienced 2-14 moderate or severe migraine attacks per month, and they were allowed to take other migraine medications. Cardiovascular risk factors did not prevent entry to the trial and, like the previous pivotal trial, the long-term safety study admitted subjects older than 65. Among the study cohort, 1,514 participants were told to treat migraine pain of any intensity with 75 mg rimegepant up to once per day on an as-needed basis (PRN), and a second group of 286 were told to take 75 mg rimegepant every other day for 12 weeks, along with PRN dosing on nonscheduled treatment days.

Nearly 90% of subjects were female, the mean age was 43.1 years, and 3.7% were age 65 or older. Among the study participants, 40.8% had cardiovascular risk factors, including 28.8% with one risk factor, and 12.1% with two or more. About 7% had a moderate to high (≥10%) 10-year cardiovascular risk by Framingham Risk Score, 23.6% had a family history of coronary artery disease, 11.7% were being treated for hypertension, 10.4% smoked, 8.3% were being treated with a statin, and 3.0% had a history of diabetes.

In total, subjects were exposed to 112,014 doses of rimegepant, a mean of 7.7 doses per 4-week period. The exposure was similar across all risk groups, which included zero risk factors, one risk factor, and two or more risk factors; FRS of less than 10%; and FRS of 10% or greater. The most common adverse events were upper respiratory tract infection (8.8%), nasopharyngitis (6.8%), and sinusitis (5.1%). The frequency of one or more adverse events was similar among those with zero cardiovascular risk factors (59.6%), one risk factor (61.4%), two or more risk factors (62.2%), FRS less than 10% (59.9%), and FRS of 10% or greater (59.9%).

The study was funded by Biohaven Pharmaceuticals. Dr. Hutchinson has been a consultant or advisory board member for Biohaven, Alder, Allergan, Amgen, Avanir, electroCore, Lilly, Novartis, Promius, Supernus, and Teva. She has been on the speaker’s bureau for Allergan, Amgen, Avanir, electroCore, Lilly, Novartis, Promius, Supernus, and Teva. Dr. Begasse de Dhaem has no relevant financial disclosures.

The majority of patients with migraine do not get the recommended amount of weekly exercise, but those who do gain benefits that extend to fewer migraine days and reduced rates of triggers including stress, depression, and sleep problems, new research shows.

“This study adds to an ever-growing body of research that points to exercise as an effective way to promote general well-being and reduce monthly migraine days,” said study investigator Mason Dyess, DO, from the University of Washington, Seattle. “This study also highlights that exercise is an underutilized resource in migraine sufferers.”

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology..
 

An accessible prophylactic

Dr. Dyess said that the COVID-19 pandemic prompted him and his colleagues to investigate how many patients with migraine in their headache clinic were utilizing “one of the most accessible prevention tools for migraine – exercise.”

“The pandemic has restricted physical and financial access to care for patients in our community and across the country, so understanding how exercise is being used by our patients and its effect on monthly migraine days has never been more important,” Dr. Dyess said.

The study involved 4,647 people diagnosed with migraine. About three-fourths had chronic migraine (at least 15 migraine days a month) and about one-quarter had episodic migraine (up to 14 monthly migraine days).

The patients provided information via a questionnaire about their migraine characteristics, sleep, depression, stress, anxiety, and the amount of moderate to vigorous exercise they got each week.

Only 27% of patients reported getting at least 150 minutes of moderate to vigorous exercise each week, the minimum amount recommended by the World Health Organization.

Patients with migraine who did not achieve the minimum 2.5 hours of moderate to vigorous exercise recommended per week had increased rates of depression, anxiety, and sleep problems.
 

A word of caution

Depression was reported by 47% of patients who reported no exercise, compared with 25% of people who reported the recommended amount of weekly exercise.

Anxiety was reported by 39% of people who did not exercise, compared with 28% of those who got the recommended 150-plus minutes of exercise. Sleep problems were reported by 77% of the nonexercisers versus 61% of those who achieved the recommended exercise amount.

Exercise also appeared to reduce the risk for migraine attacks.

Among patients who did not exercise, 48% had high headache frequency (25-plus headache days per month), while only 5% had low headache frequency (0-4 headache days per month).

In contrast, of people who got the recommended 150-plus minutes of exercise per week, 28% had high headache frequency and 10% had low headache frequency.

“Exercise should be part of the discussion while counseling patients with migraines. This is a resource available across the socioeconomic spectrum that is easily integrated into the plan of care for many patients,” said Dr. Dyess. 

However, he cautioned that there is a subgroup of migraine patients for whom moderate to vigorous exercise is simply not tolerable. “In these patients, research points to the promotion of a healthy diet and lifestyle with gentle movement exercises like yoga rather than aggressively pursuing moderate or vigorous exercise regimens,” Dr. Dyess said.
 

A ‘puzzling’ relationship

Reached for comment, Shaheen Lakhan, MD, PhD, a neurologist in Newton, Mass., and executive director of Global Neuroscience Initiative Foundation, said the interaction of exercise and migraine is “puzzling.”

“First, it is well known that strenuous physical exercise may aggravate or even trigger migraine attacks. These are found even in the migraine diagnostic criteria,” said Dr. Lakhan. “Interestingly, there is a body of evidence that demonstrates a basic level of exercise as prophylactic treatment for migraine.”

Dr. Lakhan said that exercise is “definitely underutilized in clinical practice for migraine for these reasons: Migraineurs have fear avoidance behavior given the strenuous physical exercise as a potential trigger.”

Also weighing in on the study, Noah Rosen, MD, director of Northwell Health’s Headache Center in Great Neck, N.Y., said it’s a “useful reminder of the benefits that can be achieved without medication, but we need more information to give better guidance. I wish this study had given us more information as to what type of exercise was best for people with migraine, whether active group sports, running, swimming, or others.”

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

The majority of patients with migraine do not get the recommended amount of weekly exercise, but those who do gain benefits that extend to fewer migraine days and reduced rates of triggers including stress, depression, and sleep problems, new research shows.

“This study adds to an ever-growing body of research that points to exercise as an effective way to promote general well-being and reduce monthly migraine days,” said study investigator Mason Dyess, DO, from the University of Washington, Seattle. “This study also highlights that exercise is an underutilized resource in migraine sufferers.”

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology..
 

An accessible prophylactic

Dr. Dyess said that the COVID-19 pandemic prompted him and his colleagues to investigate how many patients with migraine in their headache clinic were utilizing “one of the most accessible prevention tools for migraine – exercise.”

“The pandemic has restricted physical and financial access to care for patients in our community and across the country, so understanding how exercise is being used by our patients and its effect on monthly migraine days has never been more important,” Dr. Dyess said.

The study involved 4,647 people diagnosed with migraine. About three-fourths had chronic migraine (at least 15 migraine days a month) and about one-quarter had episodic migraine (up to 14 monthly migraine days).

The patients provided information via a questionnaire about their migraine characteristics, sleep, depression, stress, anxiety, and the amount of moderate to vigorous exercise they got each week.

Only 27% of patients reported getting at least 150 minutes of moderate to vigorous exercise each week, the minimum amount recommended by the World Health Organization.

Patients with migraine who did not achieve the minimum 2.5 hours of moderate to vigorous exercise recommended per week had increased rates of depression, anxiety, and sleep problems.
 

A word of caution

Depression was reported by 47% of patients who reported no exercise, compared with 25% of people who reported the recommended amount of weekly exercise.

Anxiety was reported by 39% of people who did not exercise, compared with 28% of those who got the recommended 150-plus minutes of exercise. Sleep problems were reported by 77% of the nonexercisers versus 61% of those who achieved the recommended exercise amount.

Exercise also appeared to reduce the risk for migraine attacks.

Among patients who did not exercise, 48% had high headache frequency (25-plus headache days per month), while only 5% had low headache frequency (0-4 headache days per month).

In contrast, of people who got the recommended 150-plus minutes of exercise per week, 28% had high headache frequency and 10% had low headache frequency.

“Exercise should be part of the discussion while counseling patients with migraines. This is a resource available across the socioeconomic spectrum that is easily integrated into the plan of care for many patients,” said Dr. Dyess. 

However, he cautioned that there is a subgroup of migraine patients for whom moderate to vigorous exercise is simply not tolerable. “In these patients, research points to the promotion of a healthy diet and lifestyle with gentle movement exercises like yoga rather than aggressively pursuing moderate or vigorous exercise regimens,” Dr. Dyess said.
 

A ‘puzzling’ relationship

Reached for comment, Shaheen Lakhan, MD, PhD, a neurologist in Newton, Mass., and executive director of Global Neuroscience Initiative Foundation, said the interaction of exercise and migraine is “puzzling.”

“First, it is well known that strenuous physical exercise may aggravate or even trigger migraine attacks. These are found even in the migraine diagnostic criteria,” said Dr. Lakhan. “Interestingly, there is a body of evidence that demonstrates a basic level of exercise as prophylactic treatment for migraine.”

Dr. Lakhan said that exercise is “definitely underutilized in clinical practice for migraine for these reasons: Migraineurs have fear avoidance behavior given the strenuous physical exercise as a potential trigger.”

Also weighing in on the study, Noah Rosen, MD, director of Northwell Health’s Headache Center in Great Neck, N.Y., said it’s a “useful reminder of the benefits that can be achieved without medication, but we need more information to give better guidance. I wish this study had given us more information as to what type of exercise was best for people with migraine, whether active group sports, running, swimming, or others.”

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

The majority of patients with migraine do not get the recommended amount of weekly exercise, but those who do gain benefits that extend to fewer migraine days and reduced rates of triggers including stress, depression, and sleep problems, new research shows.

“This study adds to an ever-growing body of research that points to exercise as an effective way to promote general well-being and reduce monthly migraine days,” said study investigator Mason Dyess, DO, from the University of Washington, Seattle. “This study also highlights that exercise is an underutilized resource in migraine sufferers.”

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology..
 

An accessible prophylactic

Dr. Dyess said that the COVID-19 pandemic prompted him and his colleagues to investigate how many patients with migraine in their headache clinic were utilizing “one of the most accessible prevention tools for migraine – exercise.”

“The pandemic has restricted physical and financial access to care for patients in our community and across the country, so understanding how exercise is being used by our patients and its effect on monthly migraine days has never been more important,” Dr. Dyess said.

The study involved 4,647 people diagnosed with migraine. About three-fourths had chronic migraine (at least 15 migraine days a month) and about one-quarter had episodic migraine (up to 14 monthly migraine days).

The patients provided information via a questionnaire about their migraine characteristics, sleep, depression, stress, anxiety, and the amount of moderate to vigorous exercise they got each week.

Only 27% of patients reported getting at least 150 minutes of moderate to vigorous exercise each week, the minimum amount recommended by the World Health Organization.

Patients with migraine who did not achieve the minimum 2.5 hours of moderate to vigorous exercise recommended per week had increased rates of depression, anxiety, and sleep problems.
 

A word of caution

Depression was reported by 47% of patients who reported no exercise, compared with 25% of people who reported the recommended amount of weekly exercise.

Anxiety was reported by 39% of people who did not exercise, compared with 28% of those who got the recommended 150-plus minutes of exercise. Sleep problems were reported by 77% of the nonexercisers versus 61% of those who achieved the recommended exercise amount.

Exercise also appeared to reduce the risk for migraine attacks.

Among patients who did not exercise, 48% had high headache frequency (25-plus headache days per month), while only 5% had low headache frequency (0-4 headache days per month).

In contrast, of people who got the recommended 150-plus minutes of exercise per week, 28% had high headache frequency and 10% had low headache frequency.

“Exercise should be part of the discussion while counseling patients with migraines. This is a resource available across the socioeconomic spectrum that is easily integrated into the plan of care for many patients,” said Dr. Dyess. 

However, he cautioned that there is a subgroup of migraine patients for whom moderate to vigorous exercise is simply not tolerable. “In these patients, research points to the promotion of a healthy diet and lifestyle with gentle movement exercises like yoga rather than aggressively pursuing moderate or vigorous exercise regimens,” Dr. Dyess said.
 

A ‘puzzling’ relationship

Reached for comment, Shaheen Lakhan, MD, PhD, a neurologist in Newton, Mass., and executive director of Global Neuroscience Initiative Foundation, said the interaction of exercise and migraine is “puzzling.”

“First, it is well known that strenuous physical exercise may aggravate or even trigger migraine attacks. These are found even in the migraine diagnostic criteria,” said Dr. Lakhan. “Interestingly, there is a body of evidence that demonstrates a basic level of exercise as prophylactic treatment for migraine.”

Dr. Lakhan said that exercise is “definitely underutilized in clinical practice for migraine for these reasons: Migraineurs have fear avoidance behavior given the strenuous physical exercise as a potential trigger.”

Also weighing in on the study, Noah Rosen, MD, director of Northwell Health’s Headache Center in Great Neck, N.Y., said it’s a “useful reminder of the benefits that can be achieved without medication, but we need more information to give better guidance. I wish this study had given us more information as to what type of exercise was best for people with migraine, whether active group sports, running, swimming, or others.”

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

Key clinical point: Poor sleep and higher stress level is associated with a higher rate of headache recurrence over next 6 weeks in patients with episodic migraine.

Major finding: Poor sleep quality was associated with a 22% higher rate of headache recurrence (adjusted hazard ratio [aHR], 1.22; 95% confidence interval [95% CI], 1.02-1.46), and the combination of poor sleep and moderate/high stress vs. good sleep and low stress was associated with a 31% higher rate of headache recurrence (aHR, 1.31; 95% CI, 1.05-1.65).

Study details: Findings are from a priori secondary analysis of a prospective cohort study of 98 patients with episodic migraine.

Disclosures: The work was funded by the National Institute of Neurological Disorders and Stroke, the American Sleep Medicine Foundation, the Harvard Clinical and Translational Science Center, and Harvard University and its affiliated academic health care centers. Dr. SM Bertisch reported receiving research support from and serving as a consultant for various sources. All other authors declared no financial conflicts of interest.

Source: Vgontzas A et al. Headache. 2021 Mar 22. doi: 10.1111/head.14105.

Key clinical point: Poor sleep and higher stress level is associated with a higher rate of headache recurrence over next 6 weeks in patients with episodic migraine.

Major finding: Poor sleep quality was associated with a 22% higher rate of headache recurrence (adjusted hazard ratio [aHR], 1.22; 95% confidence interval [95% CI], 1.02-1.46), and the combination of poor sleep and moderate/high stress vs. good sleep and low stress was associated with a 31% higher rate of headache recurrence (aHR, 1.31; 95% CI, 1.05-1.65).

Study details: Findings are from a priori secondary analysis of a prospective cohort study of 98 patients with episodic migraine.

Disclosures: The work was funded by the National Institute of Neurological Disorders and Stroke, the American Sleep Medicine Foundation, the Harvard Clinical and Translational Science Center, and Harvard University and its affiliated academic health care centers. Dr. SM Bertisch reported receiving research support from and serving as a consultant for various sources. All other authors declared no financial conflicts of interest.

Source: Vgontzas A et al. Headache. 2021 Mar 22. doi: 10.1111/head.14105.

Key clinical point: Poor sleep and higher stress level is associated with a higher rate of headache recurrence over next 6 weeks in patients with episodic migraine.

Major finding: Poor sleep quality was associated with a 22% higher rate of headache recurrence (adjusted hazard ratio [aHR], 1.22; 95% confidence interval [95% CI], 1.02-1.46), and the combination of poor sleep and moderate/high stress vs. good sleep and low stress was associated with a 31% higher rate of headache recurrence (aHR, 1.31; 95% CI, 1.05-1.65).

Study details: Findings are from a priori secondary analysis of a prospective cohort study of 98 patients with episodic migraine.

Disclosures: The work was funded by the National Institute of Neurological Disorders and Stroke, the American Sleep Medicine Foundation, the Harvard Clinical and Translational Science Center, and Harvard University and its affiliated academic health care centers. Dr. SM Bertisch reported receiving research support from and serving as a consultant for various sources. All other authors declared no financial conflicts of interest.

Source: Vgontzas A et al. Headache. 2021 Mar 22. doi: 10.1111/head.14105.

Key clinical point: DFN-15- an oral, ready-made liquid solution of a selective cyclo-oxygenase-2 inhibitor celecoxib, was superior to placebo for acute treatment of a migraine attack of any pain intensity, along with a favorable safety and tolerability profile.

Major finding: Percentage of patients with freedom from pain (46.2% vs. 31.1%; P less than.001) and freedom from the most bothersome symptom (63.4% vs. 50.0%; P = .010) at 2 hours after dose was significantly higher for DFN-15 vs. placebo. No serious treatment-emergent adverse events or those leading to study drug termination were reported.

Study details: Data come from the second phase of a 2-phase, double-blind, multicenter trial, which re-randomized 535 patients with migraine to placebo or DFN-15 group.

Disclosures: This study was supported and funded by Dr. Reddy’s Laboratories group of companies, Princeton, NJ 08540, USA. The authors declared receiving funding, honoraria, and consulting from various sources. S Munjal reported being an employee and owning stocks and C Iaconangelo declared being a paid consultant of Dr. Reddy’s Laboratories.

Source: Lipton RB et al. J Pain Res. 2021 Feb 25. doi: 10.2147/JPR.S287571.

Key clinical point: DFN-15- an oral, ready-made liquid solution of a selective cyclo-oxygenase-2 inhibitor celecoxib, was superior to placebo for acute treatment of a migraine attack of any pain intensity, along with a favorable safety and tolerability profile.

Major finding: Percentage of patients with freedom from pain (46.2% vs. 31.1%; P less than.001) and freedom from the most bothersome symptom (63.4% vs. 50.0%; P = .010) at 2 hours after dose was significantly higher for DFN-15 vs. placebo. No serious treatment-emergent adverse events or those leading to study drug termination were reported.

Study details: Data come from the second phase of a 2-phase, double-blind, multicenter trial, which re-randomized 535 patients with migraine to placebo or DFN-15 group.

Disclosures: This study was supported and funded by Dr. Reddy’s Laboratories group of companies, Princeton, NJ 08540, USA. The authors declared receiving funding, honoraria, and consulting from various sources. S Munjal reported being an employee and owning stocks and C Iaconangelo declared being a paid consultant of Dr. Reddy’s Laboratories.

Source: Lipton RB et al. J Pain Res. 2021 Feb 25. doi: 10.2147/JPR.S287571.

Key clinical point: DFN-15- an oral, ready-made liquid solution of a selective cyclo-oxygenase-2 inhibitor celecoxib, was superior to placebo for acute treatment of a migraine attack of any pain intensity, along with a favorable safety and tolerability profile.

Major finding: Percentage of patients with freedom from pain (46.2% vs. 31.1%; P less than.001) and freedom from the most bothersome symptom (63.4% vs. 50.0%; P = .010) at 2 hours after dose was significantly higher for DFN-15 vs. placebo. No serious treatment-emergent adverse events or those leading to study drug termination were reported.

Study details: Data come from the second phase of a 2-phase, double-blind, multicenter trial, which re-randomized 535 patients with migraine to placebo or DFN-15 group.

Disclosures: This study was supported and funded by Dr. Reddy’s Laboratories group of companies, Princeton, NJ 08540, USA. The authors declared receiving funding, honoraria, and consulting from various sources. S Munjal reported being an employee and owning stocks and C Iaconangelo declared being a paid consultant of Dr. Reddy’s Laboratories.

Source: Lipton RB et al. J Pain Res. 2021 Feb 25. doi: 10.2147/JPR.S287571.

Key clinical point: Triptan historical responder status had no significant impact on the treatment effects of ubrogepant in patients with a history of migraine.

Major finding: Historical triptan responder status had no significant impact on the efficacy of ubrogepant for pain freedom (P_interaction based on odds ratio [OR] = .290) and absence of migraine-associated symptom (P_interaction based on OR = .705). The incidence of treatment-emergent adverse events (TEAEs) and treatment-related TEAEs was not significantly different across historical triptan experience subgroups.

Study details: This was a post hoc analysis of pooled data from ACHIEVE I and II phase 3 trials involving 1,799 adults with a history of migraine with/without aura randomly allocated to either placebo or ubrogepant to treat a single attack. Based on previous experience with triptans, participants were categorized as responders, insufficient responders, and naïve.

Disclosures: The study was sponsored by Allergan. Some authors including the lead author declared receiving grants and personal fees; being consultant, speaker, or contributing author; or being on advisory boards for various sources including AbbVie. Some authors declared being current/former employees and/or holding stocks at AbbVie.

Source: Blumenfeld AM et al. Headache. 2021 Mar 22. doi: 10.1111/head.14089.

Key clinical point: Triptan historical responder status had no significant impact on the treatment effects of ubrogepant in patients with a history of migraine.

Major finding: Historical triptan responder status had no significant impact on the efficacy of ubrogepant for pain freedom (P_interaction based on odds ratio [OR] = .290) and absence of migraine-associated symptom (P_interaction based on OR = .705). The incidence of treatment-emergent adverse events (TEAEs) and treatment-related TEAEs was not significantly different across historical triptan experience subgroups.

Study details: This was a post hoc analysis of pooled data from ACHIEVE I and II phase 3 trials involving 1,799 adults with a history of migraine with/without aura randomly allocated to either placebo or ubrogepant to treat a single attack. Based on previous experience with triptans, participants were categorized as responders, insufficient responders, and naïve.

Disclosures: The study was sponsored by Allergan. Some authors including the lead author declared receiving grants and personal fees; being consultant, speaker, or contributing author; or being on advisory boards for various sources including AbbVie. Some authors declared being current/former employees and/or holding stocks at AbbVie.

Source: Blumenfeld AM et al. Headache. 2021 Mar 22. doi: 10.1111/head.14089.

Key clinical point: Triptan historical responder status had no significant impact on the treatment effects of ubrogepant in patients with a history of migraine.

Major finding: Historical triptan responder status had no significant impact on the efficacy of ubrogepant for pain freedom (P_interaction based on odds ratio [OR] = .290) and absence of migraine-associated symptom (P_interaction based on OR = .705). The incidence of treatment-emergent adverse events (TEAEs) and treatment-related TEAEs was not significantly different across historical triptan experience subgroups.

Study details: This was a post hoc analysis of pooled data from ACHIEVE I and II phase 3 trials involving 1,799 adults with a history of migraine with/without aura randomly allocated to either placebo or ubrogepant to treat a single attack. Based on previous experience with triptans, participants were categorized as responders, insufficient responders, and naïve.

Disclosures: The study was sponsored by Allergan. Some authors including the lead author declared receiving grants and personal fees; being consultant, speaker, or contributing author; or being on advisory boards for various sources including AbbVie. Some authors declared being current/former employees and/or holding stocks at AbbVie.

Source: Blumenfeld AM et al. Headache. 2021 Mar 22. doi: 10.1111/head.14089.