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Dual treatment may boost efficacy in chronic migraine
, possibly owing to the synergistic mechanism of action of the two agents, a new study suggests.
“People with chronic migraine may be the toughest to treat. They have the greatest disability, and often insurance companies would prefer monotherapy, but in these patients, sometimes using a multifaceted approach and using different drugs that target different pathophysiologies of migraine can probably provide greater benefit in terms of reducing the frequency and severity of the headaches,” study investigator MaryAnn Mays, MD, staff neurologist at the Headache and Facial Pain Clinic in the Neurologic Institute, Cleveland Clinic, Cleveland, Ohio, said in an interview.
The findings were presented at the annual meeting of the American Headache Society.
Fewer Migraine Days
OnabotulinumtodxinA (onabot) has been shown to selectively inhibit unmyelinated C-fibers but not A-delta-meningeal nociceptors. Anti-CGRP mAb therapies have been shown to prevent the activation of A-delta-fibers but not C-fibers, said Dr. Mays.
For the study, the investigators reviewed the electronic medical records of 194 patients who had been concurrently treated with anti-CGRP mAbs and onabot. Most (86.6%) were women; ages ranged from 36 to 65 years, and at baseline, they had been having an average of 28 (+4.6) monthly migraine days (MMDs).
The number of MMDs were assessed at two periods: 3 months after monotherapy with an anti-CGRP mAb or onabot injections, and 3 months after combined therapy.
Monotherapy reduced the average number of MMDs from 28 to 18.6, for a reduction of 9.4 days (P > .0001).
After initiation of combined therapy, the average number of MMDs decreased further, from 18.6 MMDs to 12.1 MMDs (P > .0001).
In all, the combination of onabot and anti-CGRP mAbs resulted in a total MMD reduction of 15.8 (P > .0001).
In addition, most patients (68%) reported a 50% or greater reduction in MMDs, and 46.4% reported a 75% or greater reduction.
Great News for Patients
Commenting for this article, Rashmi B. Halker Singh, MD, associate professor of neurology at Mayo Clinic, Scottsdale, Arizona, said the study findings “support what we see in clinical practice and what we suspected from preclinical data.”
Single-agent treatment is not sufficient for many patients. Data confirming the benefit of dual therapy will provide more evidence to insurance companies of the need for coverage.
“We have lots of individuals for whom single treatment is not sufficient and who need this combination of treatment, and it is often denied by insurance. There are preclinical data suggesting synergy, but insurance says it is experimental, so the claims get denied. This leaves patients having to choose which drug they want to continue with, and that’s really heartbreaking,” Dr. Halker Singh said.
The importance of this study is that it adds more data to support evidence-based therapies for migraine and to help patients get the treatment they need, she added.
Dr. Mays reports financial relationships with AbbVie, Amgen, and Teva. Dr. Halker Singh reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
, possibly owing to the synergistic mechanism of action of the two agents, a new study suggests.
“People with chronic migraine may be the toughest to treat. They have the greatest disability, and often insurance companies would prefer monotherapy, but in these patients, sometimes using a multifaceted approach and using different drugs that target different pathophysiologies of migraine can probably provide greater benefit in terms of reducing the frequency and severity of the headaches,” study investigator MaryAnn Mays, MD, staff neurologist at the Headache and Facial Pain Clinic in the Neurologic Institute, Cleveland Clinic, Cleveland, Ohio, said in an interview.
The findings were presented at the annual meeting of the American Headache Society.
Fewer Migraine Days
OnabotulinumtodxinA (onabot) has been shown to selectively inhibit unmyelinated C-fibers but not A-delta-meningeal nociceptors. Anti-CGRP mAb therapies have been shown to prevent the activation of A-delta-fibers but not C-fibers, said Dr. Mays.
For the study, the investigators reviewed the electronic medical records of 194 patients who had been concurrently treated with anti-CGRP mAbs and onabot. Most (86.6%) were women; ages ranged from 36 to 65 years, and at baseline, they had been having an average of 28 (+4.6) monthly migraine days (MMDs).
The number of MMDs were assessed at two periods: 3 months after monotherapy with an anti-CGRP mAb or onabot injections, and 3 months after combined therapy.
Monotherapy reduced the average number of MMDs from 28 to 18.6, for a reduction of 9.4 days (P > .0001).
After initiation of combined therapy, the average number of MMDs decreased further, from 18.6 MMDs to 12.1 MMDs (P > .0001).
In all, the combination of onabot and anti-CGRP mAbs resulted in a total MMD reduction of 15.8 (P > .0001).
In addition, most patients (68%) reported a 50% or greater reduction in MMDs, and 46.4% reported a 75% or greater reduction.
Great News for Patients
Commenting for this article, Rashmi B. Halker Singh, MD, associate professor of neurology at Mayo Clinic, Scottsdale, Arizona, said the study findings “support what we see in clinical practice and what we suspected from preclinical data.”
Single-agent treatment is not sufficient for many patients. Data confirming the benefit of dual therapy will provide more evidence to insurance companies of the need for coverage.
“We have lots of individuals for whom single treatment is not sufficient and who need this combination of treatment, and it is often denied by insurance. There are preclinical data suggesting synergy, but insurance says it is experimental, so the claims get denied. This leaves patients having to choose which drug they want to continue with, and that’s really heartbreaking,” Dr. Halker Singh said.
The importance of this study is that it adds more data to support evidence-based therapies for migraine and to help patients get the treatment they need, she added.
Dr. Mays reports financial relationships with AbbVie, Amgen, and Teva. Dr. Halker Singh reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
, possibly owing to the synergistic mechanism of action of the two agents, a new study suggests.
“People with chronic migraine may be the toughest to treat. They have the greatest disability, and often insurance companies would prefer monotherapy, but in these patients, sometimes using a multifaceted approach and using different drugs that target different pathophysiologies of migraine can probably provide greater benefit in terms of reducing the frequency and severity of the headaches,” study investigator MaryAnn Mays, MD, staff neurologist at the Headache and Facial Pain Clinic in the Neurologic Institute, Cleveland Clinic, Cleveland, Ohio, said in an interview.
The findings were presented at the annual meeting of the American Headache Society.
Fewer Migraine Days
OnabotulinumtodxinA (onabot) has been shown to selectively inhibit unmyelinated C-fibers but not A-delta-meningeal nociceptors. Anti-CGRP mAb therapies have been shown to prevent the activation of A-delta-fibers but not C-fibers, said Dr. Mays.
For the study, the investigators reviewed the electronic medical records of 194 patients who had been concurrently treated with anti-CGRP mAbs and onabot. Most (86.6%) were women; ages ranged from 36 to 65 years, and at baseline, they had been having an average of 28 (+4.6) monthly migraine days (MMDs).
The number of MMDs were assessed at two periods: 3 months after monotherapy with an anti-CGRP mAb or onabot injections, and 3 months after combined therapy.
Monotherapy reduced the average number of MMDs from 28 to 18.6, for a reduction of 9.4 days (P > .0001).
After initiation of combined therapy, the average number of MMDs decreased further, from 18.6 MMDs to 12.1 MMDs (P > .0001).
In all, the combination of onabot and anti-CGRP mAbs resulted in a total MMD reduction of 15.8 (P > .0001).
In addition, most patients (68%) reported a 50% or greater reduction in MMDs, and 46.4% reported a 75% or greater reduction.
Great News for Patients
Commenting for this article, Rashmi B. Halker Singh, MD, associate professor of neurology at Mayo Clinic, Scottsdale, Arizona, said the study findings “support what we see in clinical practice and what we suspected from preclinical data.”
Single-agent treatment is not sufficient for many patients. Data confirming the benefit of dual therapy will provide more evidence to insurance companies of the need for coverage.
“We have lots of individuals for whom single treatment is not sufficient and who need this combination of treatment, and it is often denied by insurance. There are preclinical data suggesting synergy, but insurance says it is experimental, so the claims get denied. This leaves patients having to choose which drug they want to continue with, and that’s really heartbreaking,” Dr. Halker Singh said.
The importance of this study is that it adds more data to support evidence-based therapies for migraine and to help patients get the treatment they need, she added.
Dr. Mays reports financial relationships with AbbVie, Amgen, and Teva. Dr. Halker Singh reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM AHS 2023
Medication overuse headache a pain to treat
BARCELONA, SPAIN — Around half of all patients with chronic headache or migraine overuse their medication, leading to aggravated or new types of headaches. “Medication overuse headache” is the third most frequent type of headache, affecting some 60 million people or around 1% of the world’s population.
“It’s a big problem,” Sait Ashina, MD, of Beth Israel Deaconess Medical Center, Boston, Massachusetts, told the audience in an opening plenary at the 17th European Headache Congress in Barcelona.
Medication overuse headache is characterized by an increasing headache frequency and progressive use of short-term medication and is recognized as a major factor in the shift from episodic to chronic headache.
It is often underrecognized; however, educating doctors and patients is a crucial element of effective treatment. Recognition that headache medication is being overused is a crucial first step to treatment, followed by advising the patient to discontinue the medication. But this poses its own problems, as it can cause withdrawal symptoms.
According to a longitudinal population-based study published in 2008, most patients overuse acetaminophen or paracetamol, followed by nonsteroidal anti-inflammatory drugs and 5-hydroxytriptamine agonists (triptans) and, in the United States, barbiturates and opioids.
What’s the Best Treatment Strategy?
Medication overuse headache is often treated by complete withdrawal from medication, but the withdrawal symptoms can be severe. They include nausea and vomiting, arterial hypertension, tachycardia, sleep disturbances, anxiety, and restlessness, with their duration and severity depending solely on the type of headache medication that has been overused.
There is, however, no consensus on how best to treat medication overuse headache — withdrawal plus preventive treatment, preventive treatment without withdrawal, and withdrawal with optional preventive treatment 2 months after withdrawal. The findings showed that all three strategies were effective. But the research team concluded that withdrawal combined with preventive medication from the start of withdrawal was the recommended approach.
The electronic headache diary has proved to be very useful, as it can aid accurate diagnosis by providing clear insights into a patient’s condition. Information from the diary is more reliable than self-reports because patients often underestimate the frequency of their headaches, migraines, and use of medication.
Patients who are treated for medication overuse headache tend to have a high relapse rate. So, the electronic headache diary can also be very useful for follow-up by alerting patients and clinicians when headaches and medication overuse are increasing again.
“After diagnosing medication overuse or medication overuse headache, we advise our patients to discontinue the medication,” said Judith Pijpers of Leiden University Medical School, the Netherlands. “This provides clinically relevant improvements in headache frequency in a majority of patients and a significant reduction in headache days.”
In 2019, Dr. Pijpers and her colleagues published the results of a double-blind randomized controlled trial showing that botulinum toxin A, which is widely used to treat chronic migraine, has no additional benefit over acute withdrawal in patients with chronic migraine and medication overuse.
“We saw no difference between the groups during both the double-blind and the open label phase,” said Dr. Pijpers. “And that is why we do not give patients botulinum toxin A during withdrawal.”
A further trial within the botox study showed modest benefits for behavioral intervention by a headache nurse comprising education, motivational interviewing, and value-based activity planning during withdrawal therapy.
Patients can be stratified to some extent based on the type of headache they have and the medication they are taking for it.
“You can predict [a patient’s response] to some extent from the type of medication they overuse and the type of underlying primary headache,” Dr. Pijpers said in an interview.
“Those with underlying tension-type headache have different withdrawal symptoms than those with underlying migraine, and the withdrawal symptoms tend to be somewhat shorter if a patient overuses triptans compared to analgesics.”
Predicting Patients’ Responses to Migraine Medication
Dr. Pijpers and her colleagues recently published the results of a cohort study suggesting that cutaneous allodynia may predict how patients with migraine respond to withdrawal therapy. Nearly 75% of the 173 patients enrolled in the study reported experiencing allodynia — pain caused by a stimulus that does not normally cause pain. The study showed that absence of allodynia was predictive of a good outcome for patients after withdrawal therapy and of reversion from chronic to episodic migraine.
The ability to accurately predict patients’ responses could pave the way for personalized treatments of medication overuse headache.
A version of this article appeared in Medscape.com.
BARCELONA, SPAIN — Around half of all patients with chronic headache or migraine overuse their medication, leading to aggravated or new types of headaches. “Medication overuse headache” is the third most frequent type of headache, affecting some 60 million people or around 1% of the world’s population.
“It’s a big problem,” Sait Ashina, MD, of Beth Israel Deaconess Medical Center, Boston, Massachusetts, told the audience in an opening plenary at the 17th European Headache Congress in Barcelona.
Medication overuse headache is characterized by an increasing headache frequency and progressive use of short-term medication and is recognized as a major factor in the shift from episodic to chronic headache.
It is often underrecognized; however, educating doctors and patients is a crucial element of effective treatment. Recognition that headache medication is being overused is a crucial first step to treatment, followed by advising the patient to discontinue the medication. But this poses its own problems, as it can cause withdrawal symptoms.
According to a longitudinal population-based study published in 2008, most patients overuse acetaminophen or paracetamol, followed by nonsteroidal anti-inflammatory drugs and 5-hydroxytriptamine agonists (triptans) and, in the United States, barbiturates and opioids.
What’s the Best Treatment Strategy?
Medication overuse headache is often treated by complete withdrawal from medication, but the withdrawal symptoms can be severe. They include nausea and vomiting, arterial hypertension, tachycardia, sleep disturbances, anxiety, and restlessness, with their duration and severity depending solely on the type of headache medication that has been overused.
There is, however, no consensus on how best to treat medication overuse headache — withdrawal plus preventive treatment, preventive treatment without withdrawal, and withdrawal with optional preventive treatment 2 months after withdrawal. The findings showed that all three strategies were effective. But the research team concluded that withdrawal combined with preventive medication from the start of withdrawal was the recommended approach.
The electronic headache diary has proved to be very useful, as it can aid accurate diagnosis by providing clear insights into a patient’s condition. Information from the diary is more reliable than self-reports because patients often underestimate the frequency of their headaches, migraines, and use of medication.
Patients who are treated for medication overuse headache tend to have a high relapse rate. So, the electronic headache diary can also be very useful for follow-up by alerting patients and clinicians when headaches and medication overuse are increasing again.
“After diagnosing medication overuse or medication overuse headache, we advise our patients to discontinue the medication,” said Judith Pijpers of Leiden University Medical School, the Netherlands. “This provides clinically relevant improvements in headache frequency in a majority of patients and a significant reduction in headache days.”
In 2019, Dr. Pijpers and her colleagues published the results of a double-blind randomized controlled trial showing that botulinum toxin A, which is widely used to treat chronic migraine, has no additional benefit over acute withdrawal in patients with chronic migraine and medication overuse.
“We saw no difference between the groups during both the double-blind and the open label phase,” said Dr. Pijpers. “And that is why we do not give patients botulinum toxin A during withdrawal.”
A further trial within the botox study showed modest benefits for behavioral intervention by a headache nurse comprising education, motivational interviewing, and value-based activity planning during withdrawal therapy.
Patients can be stratified to some extent based on the type of headache they have and the medication they are taking for it.
“You can predict [a patient’s response] to some extent from the type of medication they overuse and the type of underlying primary headache,” Dr. Pijpers said in an interview.
“Those with underlying tension-type headache have different withdrawal symptoms than those with underlying migraine, and the withdrawal symptoms tend to be somewhat shorter if a patient overuses triptans compared to analgesics.”
Predicting Patients’ Responses to Migraine Medication
Dr. Pijpers and her colleagues recently published the results of a cohort study suggesting that cutaneous allodynia may predict how patients with migraine respond to withdrawal therapy. Nearly 75% of the 173 patients enrolled in the study reported experiencing allodynia — pain caused by a stimulus that does not normally cause pain. The study showed that absence of allodynia was predictive of a good outcome for patients after withdrawal therapy and of reversion from chronic to episodic migraine.
The ability to accurately predict patients’ responses could pave the way for personalized treatments of medication overuse headache.
A version of this article appeared in Medscape.com.
BARCELONA, SPAIN — Around half of all patients with chronic headache or migraine overuse their medication, leading to aggravated or new types of headaches. “Medication overuse headache” is the third most frequent type of headache, affecting some 60 million people or around 1% of the world’s population.
“It’s a big problem,” Sait Ashina, MD, of Beth Israel Deaconess Medical Center, Boston, Massachusetts, told the audience in an opening plenary at the 17th European Headache Congress in Barcelona.
Medication overuse headache is characterized by an increasing headache frequency and progressive use of short-term medication and is recognized as a major factor in the shift from episodic to chronic headache.
It is often underrecognized; however, educating doctors and patients is a crucial element of effective treatment. Recognition that headache medication is being overused is a crucial first step to treatment, followed by advising the patient to discontinue the medication. But this poses its own problems, as it can cause withdrawal symptoms.
According to a longitudinal population-based study published in 2008, most patients overuse acetaminophen or paracetamol, followed by nonsteroidal anti-inflammatory drugs and 5-hydroxytriptamine agonists (triptans) and, in the United States, barbiturates and opioids.
What’s the Best Treatment Strategy?
Medication overuse headache is often treated by complete withdrawal from medication, but the withdrawal symptoms can be severe. They include nausea and vomiting, arterial hypertension, tachycardia, sleep disturbances, anxiety, and restlessness, with their duration and severity depending solely on the type of headache medication that has been overused.
There is, however, no consensus on how best to treat medication overuse headache — withdrawal plus preventive treatment, preventive treatment without withdrawal, and withdrawal with optional preventive treatment 2 months after withdrawal. The findings showed that all three strategies were effective. But the research team concluded that withdrawal combined with preventive medication from the start of withdrawal was the recommended approach.
The electronic headache diary has proved to be very useful, as it can aid accurate diagnosis by providing clear insights into a patient’s condition. Information from the diary is more reliable than self-reports because patients often underestimate the frequency of their headaches, migraines, and use of medication.
Patients who are treated for medication overuse headache tend to have a high relapse rate. So, the electronic headache diary can also be very useful for follow-up by alerting patients and clinicians when headaches and medication overuse are increasing again.
“After diagnosing medication overuse or medication overuse headache, we advise our patients to discontinue the medication,” said Judith Pijpers of Leiden University Medical School, the Netherlands. “This provides clinically relevant improvements in headache frequency in a majority of patients and a significant reduction in headache days.”
In 2019, Dr. Pijpers and her colleagues published the results of a double-blind randomized controlled trial showing that botulinum toxin A, which is widely used to treat chronic migraine, has no additional benefit over acute withdrawal in patients with chronic migraine and medication overuse.
“We saw no difference between the groups during both the double-blind and the open label phase,” said Dr. Pijpers. “And that is why we do not give patients botulinum toxin A during withdrawal.”
A further trial within the botox study showed modest benefits for behavioral intervention by a headache nurse comprising education, motivational interviewing, and value-based activity planning during withdrawal therapy.
Patients can be stratified to some extent based on the type of headache they have and the medication they are taking for it.
“You can predict [a patient’s response] to some extent from the type of medication they overuse and the type of underlying primary headache,” Dr. Pijpers said in an interview.
“Those with underlying tension-type headache have different withdrawal symptoms than those with underlying migraine, and the withdrawal symptoms tend to be somewhat shorter if a patient overuses triptans compared to analgesics.”
Predicting Patients’ Responses to Migraine Medication
Dr. Pijpers and her colleagues recently published the results of a cohort study suggesting that cutaneous allodynia may predict how patients with migraine respond to withdrawal therapy. Nearly 75% of the 173 patients enrolled in the study reported experiencing allodynia — pain caused by a stimulus that does not normally cause pain. The study showed that absence of allodynia was predictive of a good outcome for patients after withdrawal therapy and of reversion from chronic to episodic migraine.
The ability to accurately predict patients’ responses could pave the way for personalized treatments of medication overuse headache.
A version of this article appeared in Medscape.com.
FROM EHC 2023
PFO closure may reduce migraine days and prevent stroke
, according to a discussion at the 2023 Scottsdale Headache Symposium.
In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.
Other right-to-left shunt defects have also been associated with both migraine and stroke, leading Dr. Charles to suggest these defects are more a common denominator.
“Stroke during a migraine is, in fact, very uncommon,” Dr. Charles said. “This raises the possibility that it is not the migraine causing the stroke but rather there is a shared risk factor for stroke and migraine,” said Dr. Charles, referring to PFO as well as other right-to-left shunt defects, such as hereditary hemorrhaging telangiectasia in the lungs.
One Intervention, Two Potential Benefits
Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.
Use of oral contraceptives, which produce a hypercoagulable state, is an example.
“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.
The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
Primary Endpoint Missed in Clinical Trials
The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.
In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).
A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.
There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.
Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.
“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
Migraine Days Might Be a Better Endpoint
For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.
“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.
He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.
One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.
Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.
Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.
“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.
Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”
In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).
The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”
As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.
“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.
Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.
, according to a discussion at the 2023 Scottsdale Headache Symposium.
In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.
Other right-to-left shunt defects have also been associated with both migraine and stroke, leading Dr. Charles to suggest these defects are more a common denominator.
“Stroke during a migraine is, in fact, very uncommon,” Dr. Charles said. “This raises the possibility that it is not the migraine causing the stroke but rather there is a shared risk factor for stroke and migraine,” said Dr. Charles, referring to PFO as well as other right-to-left shunt defects, such as hereditary hemorrhaging telangiectasia in the lungs.
One Intervention, Two Potential Benefits
Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.
Use of oral contraceptives, which produce a hypercoagulable state, is an example.
“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.
The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
Primary Endpoint Missed in Clinical Trials
The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.
In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).
A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.
There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.
Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.
“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
Migraine Days Might Be a Better Endpoint
For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.
“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.
He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.
One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.
Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.
Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.
“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.
Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”
In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).
The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”
As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.
“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.
Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.
, according to a discussion at the 2023 Scottsdale Headache Symposium.
In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.
Other right-to-left shunt defects have also been associated with both migraine and stroke, leading Dr. Charles to suggest these defects are more a common denominator.
“Stroke during a migraine is, in fact, very uncommon,” Dr. Charles said. “This raises the possibility that it is not the migraine causing the stroke but rather there is a shared risk factor for stroke and migraine,” said Dr. Charles, referring to PFO as well as other right-to-left shunt defects, such as hereditary hemorrhaging telangiectasia in the lungs.
One Intervention, Two Potential Benefits
Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.
Use of oral contraceptives, which produce a hypercoagulable state, is an example.
“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.
The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
Primary Endpoint Missed in Clinical Trials
The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.
In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).
A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.
There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.
Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.
“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
Migraine Days Might Be a Better Endpoint
For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.
“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.
He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.
One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.
Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.
Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.
“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.
Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”
In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).
The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”
As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.
“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.
Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.
FROM THE 2023 SCOTTSDALE HEADACHE SYMPOSIUM
Secondhand smoke exposure linked to migraine, severe headache
TOPLINE:
, with effects of exposure varying depending on body mass index (BMI) and level of physical activity, new research shows.
METHODOLOGY:
Investigators analyzed data on 4,560 participants (median age, 43 years; 60% female; 71.5% White) from the 1999-2004 National Health and Nutrition Examination Survey.
Participants were aged 20 years or older and had never smoked.
Migraine headache status was determined by asking whether participants experienced severe headaches or migraines during the previous 3 months.
SHS exposure was categorized as unexposed (serum cotinine levels <0.05 ng/mL and no smoker in the home), low (0.05 ng/mL ≤ serum cotinine level <1 ng/mL), or heavy (1 ng/mL ≤ serum cotinine level ≤ 10 ng/mL).
TAKEAWAY:
In all, 919 (20%) participants had severe headaches or migraines.
After adjustment for demographic and lifestyle factors (including medication use), heavy SHS exposure was positively associated with severe headache or migraine (adjusted odds ratio [aOR], 2.02; 95% CI, 1.19-3.43).
No significant association was found between low SHS exposure and severe headaches or migraine (aOR, 1.15; 95% CI, 0.91-1.47).
In participants who were sedentary (P=.016) and those with a BMI <25 (P=.001), significant associations between SHS and severe headache or migraine were observed.
IN PRACTICE:
Noting a linear dose-response relationship between cotinine and severe headaches or migraine, the investigators write, “These findings underscore the need for stronger regulation of tobacco exposure, particularly in homes and public places.”
SOURCE:
Junpeng Wu, MMc, and Haitang Wang, MD, of Southern Medical University in Guangzhou, China, and their colleagues conducted the study. It was published online in Headache.
LIMITATIONS:
The study could not establish causal relationships between SHS and migraine or severe headache. In addition, the half-life of serum cotinine is 15-40 hours and thus this measure can reflect only recent SHS exposure.
DISCLOSURES:
The study was not funded. The investigators reported no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
, with effects of exposure varying depending on body mass index (BMI) and level of physical activity, new research shows.
METHODOLOGY:
Investigators analyzed data on 4,560 participants (median age, 43 years; 60% female; 71.5% White) from the 1999-2004 National Health and Nutrition Examination Survey.
Participants were aged 20 years or older and had never smoked.
Migraine headache status was determined by asking whether participants experienced severe headaches or migraines during the previous 3 months.
SHS exposure was categorized as unexposed (serum cotinine levels <0.05 ng/mL and no smoker in the home), low (0.05 ng/mL ≤ serum cotinine level <1 ng/mL), or heavy (1 ng/mL ≤ serum cotinine level ≤ 10 ng/mL).
TAKEAWAY:
In all, 919 (20%) participants had severe headaches or migraines.
After adjustment for demographic and lifestyle factors (including medication use), heavy SHS exposure was positively associated with severe headache or migraine (adjusted odds ratio [aOR], 2.02; 95% CI, 1.19-3.43).
No significant association was found between low SHS exposure and severe headaches or migraine (aOR, 1.15; 95% CI, 0.91-1.47).
In participants who were sedentary (P=.016) and those with a BMI <25 (P=.001), significant associations between SHS and severe headache or migraine were observed.
IN PRACTICE:
Noting a linear dose-response relationship between cotinine and severe headaches or migraine, the investigators write, “These findings underscore the need for stronger regulation of tobacco exposure, particularly in homes and public places.”
SOURCE:
Junpeng Wu, MMc, and Haitang Wang, MD, of Southern Medical University in Guangzhou, China, and their colleagues conducted the study. It was published online in Headache.
LIMITATIONS:
The study could not establish causal relationships between SHS and migraine or severe headache. In addition, the half-life of serum cotinine is 15-40 hours and thus this measure can reflect only recent SHS exposure.
DISCLOSURES:
The study was not funded. The investigators reported no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
, with effects of exposure varying depending on body mass index (BMI) and level of physical activity, new research shows.
METHODOLOGY:
Investigators analyzed data on 4,560 participants (median age, 43 years; 60% female; 71.5% White) from the 1999-2004 National Health and Nutrition Examination Survey.
Participants were aged 20 years or older and had never smoked.
Migraine headache status was determined by asking whether participants experienced severe headaches or migraines during the previous 3 months.
SHS exposure was categorized as unexposed (serum cotinine levels <0.05 ng/mL and no smoker in the home), low (0.05 ng/mL ≤ serum cotinine level <1 ng/mL), or heavy (1 ng/mL ≤ serum cotinine level ≤ 10 ng/mL).
TAKEAWAY:
In all, 919 (20%) participants had severe headaches or migraines.
After adjustment for demographic and lifestyle factors (including medication use), heavy SHS exposure was positively associated with severe headache or migraine (adjusted odds ratio [aOR], 2.02; 95% CI, 1.19-3.43).
No significant association was found between low SHS exposure and severe headaches or migraine (aOR, 1.15; 95% CI, 0.91-1.47).
In participants who were sedentary (P=.016) and those with a BMI <25 (P=.001), significant associations between SHS and severe headache or migraine were observed.
IN PRACTICE:
Noting a linear dose-response relationship between cotinine and severe headaches or migraine, the investigators write, “These findings underscore the need for stronger regulation of tobacco exposure, particularly in homes and public places.”
SOURCE:
Junpeng Wu, MMc, and Haitang Wang, MD, of Southern Medical University in Guangzhou, China, and their colleagues conducted the study. It was published online in Headache.
LIMITATIONS:
The study could not establish causal relationships between SHS and migraine or severe headache. In addition, the half-life of serum cotinine is 15-40 hours and thus this measure can reflect only recent SHS exposure.
DISCLOSURES:
The study was not funded. The investigators reported no disclosures.
A version of this article appeared on Medscape.com.
Drugs to prevent versus those to treat migraine might not share targets
, according to experts attempting to put these puzzle pieces together at the 2023 Scottsdale Headache Symposium.
As the details of the complex chain of molecular events become better understood, there is reason to believe that the targets for aborting events early in the process are not necessarily therapeutic at later stages or vice versa, according to Peter Goadsby, MBBS, MD, PhD, director of the National Institute for Health Research and professor of neurology, King’s College, London.
“I think this explains some of the frustration at trigger modulation. I think we are often trying to modulate a process that has already got started,” he said. The analogy might be closing the barn door after the animals have escaped.
Migraine phases might explain pathology
Given the progress in understanding each step that leads from one phase to the next in migraine onset, this premise is not surprising. Increased blood flow, trigeminal activation, and release of calcitonin gene–related peptide (CGRP) are early events in this process, according to Dr. Goadsby, but there is still uncertainty about the triggers of brainstem stimulation and cranial blood flow that precedes these events.
In his talk about the advances that led to the development of CGRP-targeted therapy, Dr. Goadsby explained how and why CGRP inhibition, along with triptans, pituitary adenylate cyclase–activating polypeptide (PACAP) inhibitors, and ditans, have been developed as treatment targets in migraine, while other once-promising targets, such as substance P inhibition and inducible nitric oxide synthase (INOS) inhibition, have not.
Much of this progress has been by trial and error through clinical studies in which efficacy has or has not been seen. Despite the progress in mapping the release of CGRP and its activity, Dr. Goadsby acknowledged that there is still much about its participation in migraine pathophysiology that remains poorly defined.
“Anyone who tells you that they know how CGRP works I think is blowing smoke, frankly,” Dr. Goadsby said. “Clearly these things are complex.”
CGRP is active in the CSF
This includes the site of action. Dr. Goadsby said that it is widely believed that CGRP inhibitors are active in the dura and not in the cerebrospinal fluid (CSF). However, Dr. Goadsby said that a study undertaken with monoclonal antibodies targeting CGRP have produced compelling evidence that CGRP is reduced in the CSF.
“They clearly get into the CSF,” said Dr. Goadsby, noting that the barrier between peripheral blood and the CSF “is different from the blood-brain barrier.”
Widely regarded as playing a pivotal role in the development of CGRP as a therapeutic target in migraine, Dr. Goadsby spent some time speculating about its potential for preventing the earliest steps in the process that leads from the premonitory state to allodynia, prodromal symptoms, migraine, and postdromal recovery.
Of triggers, “light is my favorite example,” he said. He noted that many patients are convinced that light initiates the subsequent steps that end in a migraine. This is fair assumption for those who have seen a sequence of events in which light in the absence of any other symptom always precedes prodromal symptoms and migraine.
“Why would you not think that?” he asked. “Unless you point out that the attack had already started and the reason that you are noticing the light is because of photophobia that started during the premonitory phase.”
It is increasingly clear that CGRP inhibition does have clinical benefit when started at early signs of a coming migraine, according to Dr. Goadsby. He cited a phase 3 study published just days before he spoke at the Scottsdale Headache Symposium. Called PRODROME, the study associated the CGRP receptor antagonist ubrogepant, which is already approved for treatment of migraine, with a significant reduction in the risk of moderate to severe headache relative to placebo when measured 24 hours after randomization (46% vs. 29%; P < .0001).
Brain activity monitoring supports phases
Citing imaging studies in his own laboratory, Todd J. Schwedt, MD, chair of neurology research, Mayo Clinic, Phoenix, substantiated several of the points made by Dr. Goadsby in a separate talk he made on migraine phases. By monitoring brain activity during each phase of migraine, he suggested his data support the role of CGRP in producing an inflammatory response as well as sensitizing the trigeminal cervical system in steps that appear to be important to the pain process.
Dr. Schwedt showed several pieces of evidence suggesting that CGRP is an early mediator even if it is not necessarily the first step in a process for every patient. However, like Dr. Goadsby, Dr. Schwedt also acknowledged that the interplay between events is complex and might differ between patients.
Yet, he says that brain activity on imaging is not the only evidence of the role of CGRP activation early in the process leading toward migraine.
“I am a little biased towards imaging, but it’s not just about imaging,” Dr. Schwedt said.
“If we look at preictal salivary CGRP levels and then follow them into the headache phase, we see the levels increase, but they go back to normal a couple of hours into the attack and then stay normal, presumably, until the patient gets closer to the next attack,” Dr. Schwedt said.
Despite progress there is more to be done to determine why CGRP is released and whether it can be inhibited early to abort migraine before the headache phase, but both Dr. Goadsby and Dr. Schwedt pointed to this as a very early event. This is not to say that others, such as cortical spreading depression, do not have an equally important role in the evolution of migraine, but each expert considers migraine phases to be useful divisions for tracing the sequence of pathogenic events.
The phase of a migraine attack and their corresponding symptoms “can be mapped to altered brain function and release of neuropeptides and neurotransmitters,” Dr. Schwedt said. The implication is that better targets for blocking migraine before it reaches the headache phase might be discovered in these early phases.
Dr. Goadsby and Dr. Schwedt listed more than 10 pharmaceutical companies to which they have financial relationships, but both claimed that none of these relationships posed a potential conflict of interest.
, according to experts attempting to put these puzzle pieces together at the 2023 Scottsdale Headache Symposium.
As the details of the complex chain of molecular events become better understood, there is reason to believe that the targets for aborting events early in the process are not necessarily therapeutic at later stages or vice versa, according to Peter Goadsby, MBBS, MD, PhD, director of the National Institute for Health Research and professor of neurology, King’s College, London.
“I think this explains some of the frustration at trigger modulation. I think we are often trying to modulate a process that has already got started,” he said. The analogy might be closing the barn door after the animals have escaped.
Migraine phases might explain pathology
Given the progress in understanding each step that leads from one phase to the next in migraine onset, this premise is not surprising. Increased blood flow, trigeminal activation, and release of calcitonin gene–related peptide (CGRP) are early events in this process, according to Dr. Goadsby, but there is still uncertainty about the triggers of brainstem stimulation and cranial blood flow that precedes these events.
In his talk about the advances that led to the development of CGRP-targeted therapy, Dr. Goadsby explained how and why CGRP inhibition, along with triptans, pituitary adenylate cyclase–activating polypeptide (PACAP) inhibitors, and ditans, have been developed as treatment targets in migraine, while other once-promising targets, such as substance P inhibition and inducible nitric oxide synthase (INOS) inhibition, have not.
Much of this progress has been by trial and error through clinical studies in which efficacy has or has not been seen. Despite the progress in mapping the release of CGRP and its activity, Dr. Goadsby acknowledged that there is still much about its participation in migraine pathophysiology that remains poorly defined.
“Anyone who tells you that they know how CGRP works I think is blowing smoke, frankly,” Dr. Goadsby said. “Clearly these things are complex.”
CGRP is active in the CSF
This includes the site of action. Dr. Goadsby said that it is widely believed that CGRP inhibitors are active in the dura and not in the cerebrospinal fluid (CSF). However, Dr. Goadsby said that a study undertaken with monoclonal antibodies targeting CGRP have produced compelling evidence that CGRP is reduced in the CSF.
“They clearly get into the CSF,” said Dr. Goadsby, noting that the barrier between peripheral blood and the CSF “is different from the blood-brain barrier.”
Widely regarded as playing a pivotal role in the development of CGRP as a therapeutic target in migraine, Dr. Goadsby spent some time speculating about its potential for preventing the earliest steps in the process that leads from the premonitory state to allodynia, prodromal symptoms, migraine, and postdromal recovery.
Of triggers, “light is my favorite example,” he said. He noted that many patients are convinced that light initiates the subsequent steps that end in a migraine. This is fair assumption for those who have seen a sequence of events in which light in the absence of any other symptom always precedes prodromal symptoms and migraine.
“Why would you not think that?” he asked. “Unless you point out that the attack had already started and the reason that you are noticing the light is because of photophobia that started during the premonitory phase.”
It is increasingly clear that CGRP inhibition does have clinical benefit when started at early signs of a coming migraine, according to Dr. Goadsby. He cited a phase 3 study published just days before he spoke at the Scottsdale Headache Symposium. Called PRODROME, the study associated the CGRP receptor antagonist ubrogepant, which is already approved for treatment of migraine, with a significant reduction in the risk of moderate to severe headache relative to placebo when measured 24 hours after randomization (46% vs. 29%; P < .0001).
Brain activity monitoring supports phases
Citing imaging studies in his own laboratory, Todd J. Schwedt, MD, chair of neurology research, Mayo Clinic, Phoenix, substantiated several of the points made by Dr. Goadsby in a separate talk he made on migraine phases. By monitoring brain activity during each phase of migraine, he suggested his data support the role of CGRP in producing an inflammatory response as well as sensitizing the trigeminal cervical system in steps that appear to be important to the pain process.
Dr. Schwedt showed several pieces of evidence suggesting that CGRP is an early mediator even if it is not necessarily the first step in a process for every patient. However, like Dr. Goadsby, Dr. Schwedt also acknowledged that the interplay between events is complex and might differ between patients.
Yet, he says that brain activity on imaging is not the only evidence of the role of CGRP activation early in the process leading toward migraine.
“I am a little biased towards imaging, but it’s not just about imaging,” Dr. Schwedt said.
“If we look at preictal salivary CGRP levels and then follow them into the headache phase, we see the levels increase, but they go back to normal a couple of hours into the attack and then stay normal, presumably, until the patient gets closer to the next attack,” Dr. Schwedt said.
Despite progress there is more to be done to determine why CGRP is released and whether it can be inhibited early to abort migraine before the headache phase, but both Dr. Goadsby and Dr. Schwedt pointed to this as a very early event. This is not to say that others, such as cortical spreading depression, do not have an equally important role in the evolution of migraine, but each expert considers migraine phases to be useful divisions for tracing the sequence of pathogenic events.
The phase of a migraine attack and their corresponding symptoms “can be mapped to altered brain function and release of neuropeptides and neurotransmitters,” Dr. Schwedt said. The implication is that better targets for blocking migraine before it reaches the headache phase might be discovered in these early phases.
Dr. Goadsby and Dr. Schwedt listed more than 10 pharmaceutical companies to which they have financial relationships, but both claimed that none of these relationships posed a potential conflict of interest.
, according to experts attempting to put these puzzle pieces together at the 2023 Scottsdale Headache Symposium.
As the details of the complex chain of molecular events become better understood, there is reason to believe that the targets for aborting events early in the process are not necessarily therapeutic at later stages or vice versa, according to Peter Goadsby, MBBS, MD, PhD, director of the National Institute for Health Research and professor of neurology, King’s College, London.
“I think this explains some of the frustration at trigger modulation. I think we are often trying to modulate a process that has already got started,” he said. The analogy might be closing the barn door after the animals have escaped.
Migraine phases might explain pathology
Given the progress in understanding each step that leads from one phase to the next in migraine onset, this premise is not surprising. Increased blood flow, trigeminal activation, and release of calcitonin gene–related peptide (CGRP) are early events in this process, according to Dr. Goadsby, but there is still uncertainty about the triggers of brainstem stimulation and cranial blood flow that precedes these events.
In his talk about the advances that led to the development of CGRP-targeted therapy, Dr. Goadsby explained how and why CGRP inhibition, along with triptans, pituitary adenylate cyclase–activating polypeptide (PACAP) inhibitors, and ditans, have been developed as treatment targets in migraine, while other once-promising targets, such as substance P inhibition and inducible nitric oxide synthase (INOS) inhibition, have not.
Much of this progress has been by trial and error through clinical studies in which efficacy has or has not been seen. Despite the progress in mapping the release of CGRP and its activity, Dr. Goadsby acknowledged that there is still much about its participation in migraine pathophysiology that remains poorly defined.
“Anyone who tells you that they know how CGRP works I think is blowing smoke, frankly,” Dr. Goadsby said. “Clearly these things are complex.”
CGRP is active in the CSF
This includes the site of action. Dr. Goadsby said that it is widely believed that CGRP inhibitors are active in the dura and not in the cerebrospinal fluid (CSF). However, Dr. Goadsby said that a study undertaken with monoclonal antibodies targeting CGRP have produced compelling evidence that CGRP is reduced in the CSF.
“They clearly get into the CSF,” said Dr. Goadsby, noting that the barrier between peripheral blood and the CSF “is different from the blood-brain barrier.”
Widely regarded as playing a pivotal role in the development of CGRP as a therapeutic target in migraine, Dr. Goadsby spent some time speculating about its potential for preventing the earliest steps in the process that leads from the premonitory state to allodynia, prodromal symptoms, migraine, and postdromal recovery.
Of triggers, “light is my favorite example,” he said. He noted that many patients are convinced that light initiates the subsequent steps that end in a migraine. This is fair assumption for those who have seen a sequence of events in which light in the absence of any other symptom always precedes prodromal symptoms and migraine.
“Why would you not think that?” he asked. “Unless you point out that the attack had already started and the reason that you are noticing the light is because of photophobia that started during the premonitory phase.”
It is increasingly clear that CGRP inhibition does have clinical benefit when started at early signs of a coming migraine, according to Dr. Goadsby. He cited a phase 3 study published just days before he spoke at the Scottsdale Headache Symposium. Called PRODROME, the study associated the CGRP receptor antagonist ubrogepant, which is already approved for treatment of migraine, with a significant reduction in the risk of moderate to severe headache relative to placebo when measured 24 hours after randomization (46% vs. 29%; P < .0001).
Brain activity monitoring supports phases
Citing imaging studies in his own laboratory, Todd J. Schwedt, MD, chair of neurology research, Mayo Clinic, Phoenix, substantiated several of the points made by Dr. Goadsby in a separate talk he made on migraine phases. By monitoring brain activity during each phase of migraine, he suggested his data support the role of CGRP in producing an inflammatory response as well as sensitizing the trigeminal cervical system in steps that appear to be important to the pain process.
Dr. Schwedt showed several pieces of evidence suggesting that CGRP is an early mediator even if it is not necessarily the first step in a process for every patient. However, like Dr. Goadsby, Dr. Schwedt also acknowledged that the interplay between events is complex and might differ between patients.
Yet, he says that brain activity on imaging is not the only evidence of the role of CGRP activation early in the process leading toward migraine.
“I am a little biased towards imaging, but it’s not just about imaging,” Dr. Schwedt said.
“If we look at preictal salivary CGRP levels and then follow them into the headache phase, we see the levels increase, but they go back to normal a couple of hours into the attack and then stay normal, presumably, until the patient gets closer to the next attack,” Dr. Schwedt said.
Despite progress there is more to be done to determine why CGRP is released and whether it can be inhibited early to abort migraine before the headache phase, but both Dr. Goadsby and Dr. Schwedt pointed to this as a very early event. This is not to say that others, such as cortical spreading depression, do not have an equally important role in the evolution of migraine, but each expert considers migraine phases to be useful divisions for tracing the sequence of pathogenic events.
The phase of a migraine attack and their corresponding symptoms “can be mapped to altered brain function and release of neuropeptides and neurotransmitters,” Dr. Schwedt said. The implication is that better targets for blocking migraine before it reaches the headache phase might be discovered in these early phases.
Dr. Goadsby and Dr. Schwedt listed more than 10 pharmaceutical companies to which they have financial relationships, but both claimed that none of these relationships posed a potential conflict of interest.
FROM THE 2023 SCOTTSDALE HEADACHE SYMPOSIUM
Real-world study confirms benefits of erenumab for migraine prevention
Key clinical point: This real-world study confirms the efficacy and safety of erenumab in patients with migraine associated with extreme unmet needs.
Major finding: Overall, 52.9%, 58.5%, 57.0%, and 58.8% of patients receiving erenumab achieved ≥50% reduction in monthly migraine days at 3, 6, 9, and 12 months, respectively, with significant reductions in the proportion of patients with chronic migraine at all time points compared with baseline (P < .001). At month 3, 57.3% of patients changed from chronic migraine to episodic migraine. No treatment-related serious adverse events were reported.
Study details: Findings are from a 1-year prospective, real-word study including 140 patients with migraine and previous migraine preventive treatment failures who received ≥1 dose of erenumab.
Disclosures: This study did not receive funding from any source. Several authors declared receiving personal fees for consultancy activities or research support from various sources, and some authors declared no conflicts of interest.
Source: Lanteri-Minet M et al. One-year prospective real-world assessment of effectiveness and safety of erenumab in migraine prevention: Results of the French FHU INOVPAIN registry study. J Headache Pain. 2023;24:152 (Nov 8). doi: 10.1186/s10194-023-01680-4
Key clinical point: This real-world study confirms the efficacy and safety of erenumab in patients with migraine associated with extreme unmet needs.
Major finding: Overall, 52.9%, 58.5%, 57.0%, and 58.8% of patients receiving erenumab achieved ≥50% reduction in monthly migraine days at 3, 6, 9, and 12 months, respectively, with significant reductions in the proportion of patients with chronic migraine at all time points compared with baseline (P < .001). At month 3, 57.3% of patients changed from chronic migraine to episodic migraine. No treatment-related serious adverse events were reported.
Study details: Findings are from a 1-year prospective, real-word study including 140 patients with migraine and previous migraine preventive treatment failures who received ≥1 dose of erenumab.
Disclosures: This study did not receive funding from any source. Several authors declared receiving personal fees for consultancy activities or research support from various sources, and some authors declared no conflicts of interest.
Source: Lanteri-Minet M et al. One-year prospective real-world assessment of effectiveness and safety of erenumab in migraine prevention: Results of the French FHU INOVPAIN registry study. J Headache Pain. 2023;24:152 (Nov 8). doi: 10.1186/s10194-023-01680-4
Key clinical point: This real-world study confirms the efficacy and safety of erenumab in patients with migraine associated with extreme unmet needs.
Major finding: Overall, 52.9%, 58.5%, 57.0%, and 58.8% of patients receiving erenumab achieved ≥50% reduction in monthly migraine days at 3, 6, 9, and 12 months, respectively, with significant reductions in the proportion of patients with chronic migraine at all time points compared with baseline (P < .001). At month 3, 57.3% of patients changed from chronic migraine to episodic migraine. No treatment-related serious adverse events were reported.
Study details: Findings are from a 1-year prospective, real-word study including 140 patients with migraine and previous migraine preventive treatment failures who received ≥1 dose of erenumab.
Disclosures: This study did not receive funding from any source. Several authors declared receiving personal fees for consultancy activities or research support from various sources, and some authors declared no conflicts of interest.
Source: Lanteri-Minet M et al. One-year prospective real-world assessment of effectiveness and safety of erenumab in migraine prevention: Results of the French FHU INOVPAIN registry study. J Headache Pain. 2023;24:152 (Nov 8). doi: 10.1186/s10194-023-01680-4
Heavy secondhand smoke exposure tied to higher risk for severe headaches or migraine
Key clinical point: Heavy secondhand smoke (SHS) exposure was positively associated with a higher risk for severe headaches or migraine in adults who never smoked.
Major finding: Heavy SHS exposure (serum cotinine level 1-10 ng/mL) was positively associated with severe headaches or migraine (adjusted odds ratio 2.02; P = .011). No significant association was observed between low SHS exposure (serum cotinine level 0.05-0.99 ng/mL) and headaches or migraine (P = .226).
Study details: This nationwide cross-sectional study included 4560 adults who had never smoked, of which 20% had severe headaches or migraine.
Disclosures: This study did not receive any funding from external sources. The authors declared no conflicts of interest.
Source: Wu J, Yang P, et al. Association between secondhand smoke exposure and severe headaches or migraine in never-smoking adults. Headache. 2023 (Nov 8). doi: 10.1111/head.14640
Key clinical point: Heavy secondhand smoke (SHS) exposure was positively associated with a higher risk for severe headaches or migraine in adults who never smoked.
Major finding: Heavy SHS exposure (serum cotinine level 1-10 ng/mL) was positively associated with severe headaches or migraine (adjusted odds ratio 2.02; P = .011). No significant association was observed between low SHS exposure (serum cotinine level 0.05-0.99 ng/mL) and headaches or migraine (P = .226).
Study details: This nationwide cross-sectional study included 4560 adults who had never smoked, of which 20% had severe headaches or migraine.
Disclosures: This study did not receive any funding from external sources. The authors declared no conflicts of interest.
Source: Wu J, Yang P, et al. Association between secondhand smoke exposure and severe headaches or migraine in never-smoking adults. Headache. 2023 (Nov 8). doi: 10.1111/head.14640
Key clinical point: Heavy secondhand smoke (SHS) exposure was positively associated with a higher risk for severe headaches or migraine in adults who never smoked.
Major finding: Heavy SHS exposure (serum cotinine level 1-10 ng/mL) was positively associated with severe headaches or migraine (adjusted odds ratio 2.02; P = .011). No significant association was observed between low SHS exposure (serum cotinine level 0.05-0.99 ng/mL) and headaches or migraine (P = .226).
Study details: This nationwide cross-sectional study included 4560 adults who had never smoked, of which 20% had severe headaches or migraine.
Disclosures: This study did not receive any funding from external sources. The authors declared no conflicts of interest.
Source: Wu J, Yang P, et al. Association between secondhand smoke exposure and severe headaches or migraine in never-smoking adults. Headache. 2023 (Nov 8). doi: 10.1111/head.14640
Heart rate variability may help predict treatment response in chronic migraine
Key clinical point: Patients with chronic migraine have autonomic dysfunction, the extent of which is evaluated using heart rate variability (HRV) analysis, and a preserved function is associated with a superior response to flunarizine preventive treatment.
Major finding: Most heart-rate variability (HRV) parameters, except the ratios of low-frequency (LF) band and LF/high-frequency band, were significantly lower in patients with migraine vs control individuals (P < .001). The response to flunarizine treatment was superior in patients with normal HRV, as exemplified by higher reductions in monthly headache days after 3 months in those with normal vs lower HRV (─9.7 days vs ─6.2 days; P = .026).
Study details: This cross-sectional, prospective study included 81 prophylaxis-naive patients with chronic migraine and 58 age- and gender-matched control individuals. Patients with migraine initiated flunarizine as a preventive treatment for 12 weeks.
Disclosures: This study was supported by grants from the National Science and Technology Council, Taiwan, and others. SJ Wang declared being a principal investigator and receiving personal fees as an advisor or speaker from various sources.
Source: Chuang CH et al. Abnormal heart rate variability and its application in predicting treatment efficacy in patients with chronic migraine: An exploratory study. Cephalalgia. 2023 (Oct 18). doi: 10.1177/03331024231206781
Key clinical point: Patients with chronic migraine have autonomic dysfunction, the extent of which is evaluated using heart rate variability (HRV) analysis, and a preserved function is associated with a superior response to flunarizine preventive treatment.
Major finding: Most heart-rate variability (HRV) parameters, except the ratios of low-frequency (LF) band and LF/high-frequency band, were significantly lower in patients with migraine vs control individuals (P < .001). The response to flunarizine treatment was superior in patients with normal HRV, as exemplified by higher reductions in monthly headache days after 3 months in those with normal vs lower HRV (─9.7 days vs ─6.2 days; P = .026).
Study details: This cross-sectional, prospective study included 81 prophylaxis-naive patients with chronic migraine and 58 age- and gender-matched control individuals. Patients with migraine initiated flunarizine as a preventive treatment for 12 weeks.
Disclosures: This study was supported by grants from the National Science and Technology Council, Taiwan, and others. SJ Wang declared being a principal investigator and receiving personal fees as an advisor or speaker from various sources.
Source: Chuang CH et al. Abnormal heart rate variability and its application in predicting treatment efficacy in patients with chronic migraine: An exploratory study. Cephalalgia. 2023 (Oct 18). doi: 10.1177/03331024231206781
Key clinical point: Patients with chronic migraine have autonomic dysfunction, the extent of which is evaluated using heart rate variability (HRV) analysis, and a preserved function is associated with a superior response to flunarizine preventive treatment.
Major finding: Most heart-rate variability (HRV) parameters, except the ratios of low-frequency (LF) band and LF/high-frequency band, were significantly lower in patients with migraine vs control individuals (P < .001). The response to flunarizine treatment was superior in patients with normal HRV, as exemplified by higher reductions in monthly headache days after 3 months in those with normal vs lower HRV (─9.7 days vs ─6.2 days; P = .026).
Study details: This cross-sectional, prospective study included 81 prophylaxis-naive patients with chronic migraine and 58 age- and gender-matched control individuals. Patients with migraine initiated flunarizine as a preventive treatment for 12 weeks.
Disclosures: This study was supported by grants from the National Science and Technology Council, Taiwan, and others. SJ Wang declared being a principal investigator and receiving personal fees as an advisor or speaker from various sources.
Source: Chuang CH et al. Abnormal heart rate variability and its application in predicting treatment efficacy in patients with chronic migraine: An exploratory study. Cephalalgia. 2023 (Oct 18). doi: 10.1177/03331024231206781
Remote electrical neuromodulation: A pill-free, needle-free option for long-term migraine management
Key clinical point: This real-world study confirms the safety, efficacy, and tolerability of remote electrical neuromodulation (REN) for long-term management of acute migraine, thus establishing REN as a valuable comprehensive treatment for this chronic disease.
Major finding: Overall, 74.1% and 26.0% of patients achieved consistent pain relief and pain freedom with REN, respectively, and 70.2% and 33.7% achieved functional disability relief and functional disability freedom, respectively. The incidence of device-related adverse events (dAE) was low, ie, 1.96%, which included 0.49% negligible, 1.22% moderate, and 0.24% mild AE. No severe AE were reported, and all patients continued treatment despite dAE.
Study details: This real-world evidence study included 409 patients with migraine treated for 12 consecutive months with REN, a self-administered device used at the onset of migraine headache or aura for acute treatment.
Disclosures: This study was funded by Theranica Bio-Electronics Ltd. M Weinstein and A Synowiec declared serving as consultants for Theranica. A Stark-Inbar and A Ironi declared being employees of and hold stock options in Theranica. A Mauskop had no conflicts of interest to disclose.
Source: Synowiec A et al. One-year consistent safety, utilization, and efficacy assessment of remote electrical neuromodulation (REN) for migraine treatment. Adv Ther. 2023 (Oct 19). doi: 10.1007/s12325-023-02697-6
Key clinical point: This real-world study confirms the safety, efficacy, and tolerability of remote electrical neuromodulation (REN) for long-term management of acute migraine, thus establishing REN as a valuable comprehensive treatment for this chronic disease.
Major finding: Overall, 74.1% and 26.0% of patients achieved consistent pain relief and pain freedom with REN, respectively, and 70.2% and 33.7% achieved functional disability relief and functional disability freedom, respectively. The incidence of device-related adverse events (dAE) was low, ie, 1.96%, which included 0.49% negligible, 1.22% moderate, and 0.24% mild AE. No severe AE were reported, and all patients continued treatment despite dAE.
Study details: This real-world evidence study included 409 patients with migraine treated for 12 consecutive months with REN, a self-administered device used at the onset of migraine headache or aura for acute treatment.
Disclosures: This study was funded by Theranica Bio-Electronics Ltd. M Weinstein and A Synowiec declared serving as consultants for Theranica. A Stark-Inbar and A Ironi declared being employees of and hold stock options in Theranica. A Mauskop had no conflicts of interest to disclose.
Source: Synowiec A et al. One-year consistent safety, utilization, and efficacy assessment of remote electrical neuromodulation (REN) for migraine treatment. Adv Ther. 2023 (Oct 19). doi: 10.1007/s12325-023-02697-6
Key clinical point: This real-world study confirms the safety, efficacy, and tolerability of remote electrical neuromodulation (REN) for long-term management of acute migraine, thus establishing REN as a valuable comprehensive treatment for this chronic disease.
Major finding: Overall, 74.1% and 26.0% of patients achieved consistent pain relief and pain freedom with REN, respectively, and 70.2% and 33.7% achieved functional disability relief and functional disability freedom, respectively. The incidence of device-related adverse events (dAE) was low, ie, 1.96%, which included 0.49% negligible, 1.22% moderate, and 0.24% mild AE. No severe AE were reported, and all patients continued treatment despite dAE.
Study details: This real-world evidence study included 409 patients with migraine treated for 12 consecutive months with REN, a self-administered device used at the onset of migraine headache or aura for acute treatment.
Disclosures: This study was funded by Theranica Bio-Electronics Ltd. M Weinstein and A Synowiec declared serving as consultants for Theranica. A Stark-Inbar and A Ironi declared being employees of and hold stock options in Theranica. A Mauskop had no conflicts of interest to disclose.
Source: Synowiec A et al. One-year consistent safety, utilization, and efficacy assessment of remote electrical neuromodulation (REN) for migraine treatment. Adv Ther. 2023 (Oct 19). doi: 10.1007/s12325-023-02697-6
Ubrogepant and anti-CGRP mAb combo is effective for acute treatment of migraine
Key clinical point: The use of ubrogepant in combination with anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) leads to meaningful pain relief (MPR), return to normal function (RNF), treatment satisfaction, and acute treatment optimization in patients with migraine.
Major finding: Following the first treated attack, 61.6% and 80.4% of patients achieved MPR and 34.7% and 55.5% of patients achieved RNF at 2 hours and 4 hours post-dose, respectively, in the ubrogepant plus anti-CGRP mAb arm. Moreover, 72.7% of patients reported being satisfied with ubrogepant when used in combination with anti-CGRP mAb, and 79.7% of patients achieved acute treatment optimization at 30 days.
Study details: Findings are from a prospective, observational study that included 245 patients with migraine who were treated with ubrogepant combined with anti-CGRP mAb, onabotulinumtoxinA, or both, for migraine prevention.
Disclosures: This study was funded by Allergan (prior to its acquisition by AbbVie). RB Lipton declared receiving research support, honoraria, and royalties from, and serving as a consultant and advisory board member for various sources, including AbbVie or Allergan.
Source: Lipton RB et al. Real-world use of ubrogepant as acute treatment for migraine with an anti-calcitonin gene-related peptide monoclonal antibody: Results from COURAGE. Neurol Ther. 2023 (Nov 1). doi: 10.1007/s40120-023-00556-8
Key clinical point: The use of ubrogepant in combination with anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) leads to meaningful pain relief (MPR), return to normal function (RNF), treatment satisfaction, and acute treatment optimization in patients with migraine.
Major finding: Following the first treated attack, 61.6% and 80.4% of patients achieved MPR and 34.7% and 55.5% of patients achieved RNF at 2 hours and 4 hours post-dose, respectively, in the ubrogepant plus anti-CGRP mAb arm. Moreover, 72.7% of patients reported being satisfied with ubrogepant when used in combination with anti-CGRP mAb, and 79.7% of patients achieved acute treatment optimization at 30 days.
Study details: Findings are from a prospective, observational study that included 245 patients with migraine who were treated with ubrogepant combined with anti-CGRP mAb, onabotulinumtoxinA, or both, for migraine prevention.
Disclosures: This study was funded by Allergan (prior to its acquisition by AbbVie). RB Lipton declared receiving research support, honoraria, and royalties from, and serving as a consultant and advisory board member for various sources, including AbbVie or Allergan.
Source: Lipton RB et al. Real-world use of ubrogepant as acute treatment for migraine with an anti-calcitonin gene-related peptide monoclonal antibody: Results from COURAGE. Neurol Ther. 2023 (Nov 1). doi: 10.1007/s40120-023-00556-8
Key clinical point: The use of ubrogepant in combination with anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) leads to meaningful pain relief (MPR), return to normal function (RNF), treatment satisfaction, and acute treatment optimization in patients with migraine.
Major finding: Following the first treated attack, 61.6% and 80.4% of patients achieved MPR and 34.7% and 55.5% of patients achieved RNF at 2 hours and 4 hours post-dose, respectively, in the ubrogepant plus anti-CGRP mAb arm. Moreover, 72.7% of patients reported being satisfied with ubrogepant when used in combination with anti-CGRP mAb, and 79.7% of patients achieved acute treatment optimization at 30 days.
Study details: Findings are from a prospective, observational study that included 245 patients with migraine who were treated with ubrogepant combined with anti-CGRP mAb, onabotulinumtoxinA, or both, for migraine prevention.
Disclosures: This study was funded by Allergan (prior to its acquisition by AbbVie). RB Lipton declared receiving research support, honoraria, and royalties from, and serving as a consultant and advisory board member for various sources, including AbbVie or Allergan.
Source: Lipton RB et al. Real-world use of ubrogepant as acute treatment for migraine with an anti-calcitonin gene-related peptide monoclonal antibody: Results from COURAGE. Neurol Ther. 2023 (Nov 1). doi: 10.1007/s40120-023-00556-8