Headache & Migraine

Key clinical point: Repetitive intravenous dihydroergotamine (DHE) administration using an inpatient protocol seemed effective and tolerable in patients with refractory chronic migraine (rCM), even in those at an elevated risk for atherosclerotic cardiovascular disease (ASCVD).

Major finding: The elevated-ASCVD vs low-ASCVD risk group had fewer patients receiving the maximum dose of DHE (42.2% vs 64.4%; P = .002) and lower median doses of DHE on discharge (0.75 vs 1.00 mg; P < .001). Both groups experienced significant pain reduction, but it was more pronounced in the low-ASCVD risk group (P = .037). No significant cardiovascular adverse events or electrocardiogram abnormalities were reported in either group.

Study details: This single-center retrospective cohort study included 347 patients with rCM who received inpatient intravenous DHE, of whom 64 and 163 patients had elevated and low ASCVD risk, respectively.

Disclosures: This study was partially funded by Impel Pharmaceuticals, Inc. Two authors declared being full-time employees and stockowners of Impel Pharmaceuticals. Some authors declared ties with various sources, including Impel Pharmaceuticals.

Source: Wang VS et al. Safety, tolerability, and effectiveness of repetitive intravenous dihydroergotamine for refractory chronic migraine with cardiovascular risk factors: A retrospective study. Headache. 2023;63(9):1251-1258 (Sep 23). doi: 10.1111/head.14636

Key clinical point: Repetitive intravenous dihydroergotamine (DHE) administration using an inpatient protocol seemed effective and tolerable in patients with refractory chronic migraine (rCM), even in those at an elevated risk for atherosclerotic cardiovascular disease (ASCVD).

Major finding: The elevated-ASCVD vs low-ASCVD risk group had fewer patients receiving the maximum dose of DHE (42.2% vs 64.4%; P = .002) and lower median doses of DHE on discharge (0.75 vs 1.00 mg; P < .001). Both groups experienced significant pain reduction, but it was more pronounced in the low-ASCVD risk group (P = .037). No significant cardiovascular adverse events or electrocardiogram abnormalities were reported in either group.

Study details: This single-center retrospective cohort study included 347 patients with rCM who received inpatient intravenous DHE, of whom 64 and 163 patients had elevated and low ASCVD risk, respectively.

Disclosures: This study was partially funded by Impel Pharmaceuticals, Inc. Two authors declared being full-time employees and stockowners of Impel Pharmaceuticals. Some authors declared ties with various sources, including Impel Pharmaceuticals.

Source: Wang VS et al. Safety, tolerability, and effectiveness of repetitive intravenous dihydroergotamine for refractory chronic migraine with cardiovascular risk factors: A retrospective study. Headache. 2023;63(9):1251-1258 (Sep 23). doi: 10.1111/head.14636

Key clinical point: Repetitive intravenous dihydroergotamine (DHE) administration using an inpatient protocol seemed effective and tolerable in patients with refractory chronic migraine (rCM), even in those at an elevated risk for atherosclerotic cardiovascular disease (ASCVD).

Major finding: The elevated-ASCVD vs low-ASCVD risk group had fewer patients receiving the maximum dose of DHE (42.2% vs 64.4%; P = .002) and lower median doses of DHE on discharge (0.75 vs 1.00 mg; P < .001). Both groups experienced significant pain reduction, but it was more pronounced in the low-ASCVD risk group (P = .037). No significant cardiovascular adverse events or electrocardiogram abnormalities were reported in either group.

Study details: This single-center retrospective cohort study included 347 patients with rCM who received inpatient intravenous DHE, of whom 64 and 163 patients had elevated and low ASCVD risk, respectively.

Disclosures: This study was partially funded by Impel Pharmaceuticals, Inc. Two authors declared being full-time employees and stockowners of Impel Pharmaceuticals. Some authors declared ties with various sources, including Impel Pharmaceuticals.

Source: Wang VS et al. Safety, tolerability, and effectiveness of repetitive intravenous dihydroergotamine for refractory chronic migraine with cardiovascular risk factors: A retrospective study. Headache. 2023;63(9):1251-1258 (Sep 23). doi: 10.1111/head.14636

TOPLINE:

Childhood trauma increases the risk of developing a primary headache disorder in adulthood, with more early adverse experiences raising the risk even more, a new study found.

METHODOLOGY:

• The meta-analysis included 28 observational studies with 154,739 persons in 19 countries that assessed the relationship between at least one adverse childhood experience (ACE) and primary headache (including migraine, tension-type headache, cluster headache, and chronic/severe headache) at age 21 years or older.
• From each study, researchers extracted outcome point estimates and corresponding 95% confidence intervals, number of events in each group, and covariates included in the model. They subcategorized ACEs according to those involving threat (for example, physical, emotional, or sexual abuse) and deprivation (for example, neglect, household substance misuse).
• For the primary analysis, the researchers calculated the odds ratios and hazard ratios of headache among persons with at least one ACE, compared with those with no ACEs.
• They also tested an underlying biological theory that threat and deprivation ACEs may manifest differently in neurodevelopment, with distinct impacts on primary headaches.
•  

TAKEAWAY:

• The most commonly reported ACEs were physical abuse (77%), sexual abuse (73%), and exposure to family violence (38%).
• Compared with having experienced no ACEs, experiencing at least one was associated with primary headaches (pooled OR, 1.48; 95% confidence interval, 1.36-1.61).
• As the number of ACEs increased, the strength of the association with primary headaches increased in a dose-response relationship (P for trend < .0001).
• Both threat and deprivation were independently associated with primary headaches; the pooled main effect was consistent for threat (OR, 1.46; 95% CI, 1.32-1.60) and for deprivation (OR, 1.35; 95% CI, 1.23-1.49), suggesting possible distinct pathways of early adversity.
•  

IN PRACTICE:

Clinicians who treat primary headaches in adults “should routinely screen for ACEs, educate patients on the connection between ACEs and health, and provide referrals for treatment strategies,” the investigators write. Strategies such as trauma-informed or attachment-based therapy may help rewire parts of the brain that have been dysregulated, they add.

SOURCE:

The study was led by Claudia Sikorski, department of health research methods, evidence, and impact, McMaster University, Hamilton, Ont. It was published online in Neurology.

LIMITATIONS:

The findings reflect a conservative estimate of the true impact of ACEs on primary headaches, because ACEs are commonly underreported. The analysis could not statistically disentangle younger adults with developing brains (age 21-26 years) from older adults. Not all included studies adjusted for age and sex, which are known risk factors for headaches. The study did not explore the relationship between ACEs and primary headache disorders in childhood and adolescence. Owing to the inherent nature of studies investigating ACEs, causation cannot be inferred.

DISCLOSURES:

The authors report no targeted funding and no relevant conflicts of interest.

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

TOPLINE:

Childhood trauma increases the risk of developing a primary headache disorder in adulthood, with more early adverse experiences raising the risk even more, a new study found.

METHODOLOGY:

• The meta-analysis included 28 observational studies with 154,739 persons in 19 countries that assessed the relationship between at least one adverse childhood experience (ACE) and primary headache (including migraine, tension-type headache, cluster headache, and chronic/severe headache) at age 21 years or older.
• From each study, researchers extracted outcome point estimates and corresponding 95% confidence intervals, number of events in each group, and covariates included in the model. They subcategorized ACEs according to those involving threat (for example, physical, emotional, or sexual abuse) and deprivation (for example, neglect, household substance misuse).
• For the primary analysis, the researchers calculated the odds ratios and hazard ratios of headache among persons with at least one ACE, compared with those with no ACEs.
• They also tested an underlying biological theory that threat and deprivation ACEs may manifest differently in neurodevelopment, with distinct impacts on primary headaches.
•  

TAKEAWAY:

• The most commonly reported ACEs were physical abuse (77%), sexual abuse (73%), and exposure to family violence (38%).
• Compared with having experienced no ACEs, experiencing at least one was associated with primary headaches (pooled OR, 1.48; 95% confidence interval, 1.36-1.61).
• As the number of ACEs increased, the strength of the association with primary headaches increased in a dose-response relationship (P for trend < .0001).
• Both threat and deprivation were independently associated with primary headaches; the pooled main effect was consistent for threat (OR, 1.46; 95% CI, 1.32-1.60) and for deprivation (OR, 1.35; 95% CI, 1.23-1.49), suggesting possible distinct pathways of early adversity.
•  

IN PRACTICE:

Clinicians who treat primary headaches in adults “should routinely screen for ACEs, educate patients on the connection between ACEs and health, and provide referrals for treatment strategies,” the investigators write. Strategies such as trauma-informed or attachment-based therapy may help rewire parts of the brain that have been dysregulated, they add.

SOURCE:

The study was led by Claudia Sikorski, department of health research methods, evidence, and impact, McMaster University, Hamilton, Ont. It was published online in Neurology.

LIMITATIONS:

The findings reflect a conservative estimate of the true impact of ACEs on primary headaches, because ACEs are commonly underreported. The analysis could not statistically disentangle younger adults with developing brains (age 21-26 years) from older adults. Not all included studies adjusted for age and sex, which are known risk factors for headaches. The study did not explore the relationship between ACEs and primary headache disorders in childhood and adolescence. Owing to the inherent nature of studies investigating ACEs, causation cannot be inferred.

DISCLOSURES:

The authors report no targeted funding and no relevant conflicts of interest.

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

TOPLINE:

Childhood trauma increases the risk of developing a primary headache disorder in adulthood, with more early adverse experiences raising the risk even more, a new study found.

METHODOLOGY:

• The meta-analysis included 28 observational studies with 154,739 persons in 19 countries that assessed the relationship between at least one adverse childhood experience (ACE) and primary headache (including migraine, tension-type headache, cluster headache, and chronic/severe headache) at age 21 years or older.
• From each study, researchers extracted outcome point estimates and corresponding 95% confidence intervals, number of events in each group, and covariates included in the model. They subcategorized ACEs according to those involving threat (for example, physical, emotional, or sexual abuse) and deprivation (for example, neglect, household substance misuse).
• For the primary analysis, the researchers calculated the odds ratios and hazard ratios of headache among persons with at least one ACE, compared with those with no ACEs.
• They also tested an underlying biological theory that threat and deprivation ACEs may manifest differently in neurodevelopment, with distinct impacts on primary headaches.
•  

TAKEAWAY:

• The most commonly reported ACEs were physical abuse (77%), sexual abuse (73%), and exposure to family violence (38%).
• Compared with having experienced no ACEs, experiencing at least one was associated with primary headaches (pooled OR, 1.48; 95% confidence interval, 1.36-1.61).
• As the number of ACEs increased, the strength of the association with primary headaches increased in a dose-response relationship (P for trend < .0001).
• Both threat and deprivation were independently associated with primary headaches; the pooled main effect was consistent for threat (OR, 1.46; 95% CI, 1.32-1.60) and for deprivation (OR, 1.35; 95% CI, 1.23-1.49), suggesting possible distinct pathways of early adversity.
•  

IN PRACTICE:

Clinicians who treat primary headaches in adults “should routinely screen for ACEs, educate patients on the connection between ACEs and health, and provide referrals for treatment strategies,” the investigators write. Strategies such as trauma-informed or attachment-based therapy may help rewire parts of the brain that have been dysregulated, they add.

SOURCE:

The study was led by Claudia Sikorski, department of health research methods, evidence, and impact, McMaster University, Hamilton, Ont. It was published online in Neurology.

LIMITATIONS:

The findings reflect a conservative estimate of the true impact of ACEs on primary headaches, because ACEs are commonly underreported. The analysis could not statistically disentangle younger adults with developing brains (age 21-26 years) from older adults. Not all included studies adjusted for age and sex, which are known risk factors for headaches. The study did not explore the relationship between ACEs and primary headache disorders in childhood and adolescence. Owing to the inherent nature of studies investigating ACEs, causation cannot be inferred.

DISCLOSURES:

The authors report no targeted funding and no relevant conflicts of interest.

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

This transcript has been edited for clarity.

Dear colleagues, I’m Hans-Christoph Diener from the Faculty of Medicine at the University of Duisburg-Essen in Germany. I would like to give you an update on what was reported during the International Headache Congress in Seoul in September.
 

CGRP receptor agonists

Let me start with the treatment of acute migraine attacks. Until recently, we had analgesics, nonsteroidal anti-inflammatory drugs like ibuprofen, ergot alkaloids, and triptans. There are new developments, which are small molecules that are antagonists at the calcitonin gene-related peptide (CGRP) receptor. At the moment, we have three of them: rimegepant 75 mg, ubrogepant 50 mg or 100 mg, and zavegepant (a nasal spray) 10 mg.

These are all effective and superior to placebo. The 2-hour pain-free rate is somewhere between 25% and 30%. They have very few side effects; these include a little bit of nausea, somnolence, nasopharyngitis, and for zavegepant, the nasal spray, taste disturbance. In indirect comparisons, the so-called gepants are about as effective as ibuprofen and aspirin, and they seem to be less effective than sumatriptan 100 mg.

Unfortunately, until now, we have no direct comparison with triptans and we have no data demonstrating whether they are effective in people where triptans do not work. The major shortcoming is the cost in the United States. The cost per tablet or nasal spray is somewhere between $80 and $200. This means we definitely need more studies for these gepants.
 

Migraine prophylaxis

Let me move to the prophylaxis of migraine with drugs. Previously and still, we have all medications like beta-blockers, flunarizine, topiramate, valproic acid, amitriptyline, and candesartan, and for chronic migraine, onabotulinumtoxinA. We have now 5 years’ experience with the monoclonal antibodies against CGRP or the CGRP receptor like eptinezumab, erenumab, fremanezumab, and galcanezumab.

These are all equally effective. They reduce migraine-days between 3 and 7 per month. They are effective both in episodic and chronic migraine, and most importantly, they are effective in people with medication overuse headaches. The 50% responder rates are somewhere between 40% and 60%, and there are no significant differences between the four monoclonal antibodies.

The major advantage is a very good tolerability profile; very few patients terminate treatment because of adverse events. There has been, with one exception, no direct comparison of the monoclonal antibodies with traditional migraine preventive drugs or onabotulinumtoxinA. The only exception is a trial that compared topiramate and erenumab, showing that erenumab was definitely more effective and better tolerated.

At the moment, the recommendation is to use these monoclonal antibodies for 12 months in episodic migraine and 24 months in chronic migraine and then pause. It usually turns out that between 50% and 70% of these patients need to continue the treatment. If they are not working, there is a possibility to switch between the monoclonal antibodies, and the success rate after this is somewhere between 15% and 30%.

Gepants were also developed for the prevention of migraine. Here, we have rimegepant 75 mg every other day or atogepant 60 mg daily. They are effective, but in indirect comparisons, they are less effective than the monoclonal antibodies. At present, we have no comparative trials with monoclonal antibodies or the traditional migraine preventive drugs.

Potential patients are those who have needle phobia or patients who do not respond to monoclonal antibodies. Again, the biggest shortcoming is cost in the United States. The cost per year for migraine prevention or prophylaxis is between $12,000 and $20,000.

Finally, we also had very exciting news. There is a new therapeutic approach via PACAP. PACAP is pituitary adenylate cyclase-activating polypeptide, which has similar biological actions as CGRP but with additional actions. It could very well be that people who do not respond to a monoclonal antibody would respond to a monoclonal antibody against PACAP.

At the congress, the first randomized, placebo-controlled trial with a monoclonal antibody against PACAP was presented. This monoclonal antibody was effective in a population of people in whom prior preventive therapy had failed. A phase 3 study is planned, and most probably the PACAP monoclonal could work in people who do not respond to monoclonal antibodies against CGRP.

Dear colleagues, we have now many choices for the acute treatment of migraine and migraine prophylaxis. We have new kids on the block, and we have to learn more about how to use these drugs, their benefits, and their shortcomings.

He has disclosed the following relevant financial relationships:Received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Abbott; Addex Pharma; Alder; Allergan; Almirall; Amgen; Autonomic Technology; AstraZeneca; Bayer Vital; Berlin Chemie; Bristol-Myers Squibb; Boehringer Ingelheim; Chordate; CoAxia; Corimmun; Covidien; Coherex; CoLucid; Daiichi-Sankyo; D-Pharm; Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 3M Medica; MSD; Medtronic; Menarini; MindFrame; Minster; Neuroscore; Neurobiological Technologies; Novartis; Novo Nordisk; Johnson & Johnson; Knoll; Paion; Parke-Davis; Pierre Fabre; Pfizer; Schaper and Brummer; Sanofi-Aventis; Schering-Plough; Servier; Solvay; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.

Dr. Diener is professor, department of neurology, Stroke Center-Headache Center, University Duisburg-Essen (Germany).

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Dear colleagues, I’m Hans-Christoph Diener from the Faculty of Medicine at the University of Duisburg-Essen in Germany. I would like to give you an update on what was reported during the International Headache Congress in Seoul in September.
 

CGRP receptor agonists

Let me start with the treatment of acute migraine attacks. Until recently, we had analgesics, nonsteroidal anti-inflammatory drugs like ibuprofen, ergot alkaloids, and triptans. There are new developments, which are small molecules that are antagonists at the calcitonin gene-related peptide (CGRP) receptor. At the moment, we have three of them: rimegepant 75 mg, ubrogepant 50 mg or 100 mg, and zavegepant (a nasal spray) 10 mg.

These are all effective and superior to placebo. The 2-hour pain-free rate is somewhere between 25% and 30%. They have very few side effects; these include a little bit of nausea, somnolence, nasopharyngitis, and for zavegepant, the nasal spray, taste disturbance. In indirect comparisons, the so-called gepants are about as effective as ibuprofen and aspirin, and they seem to be less effective than sumatriptan 100 mg.

Unfortunately, until now, we have no direct comparison with triptans and we have no data demonstrating whether they are effective in people where triptans do not work. The major shortcoming is the cost in the United States. The cost per tablet or nasal spray is somewhere between $80 and $200. This means we definitely need more studies for these gepants.
 

Migraine prophylaxis

Let me move to the prophylaxis of migraine with drugs. Previously and still, we have all medications like beta-blockers, flunarizine, topiramate, valproic acid, amitriptyline, and candesartan, and for chronic migraine, onabotulinumtoxinA. We have now 5 years’ experience with the monoclonal antibodies against CGRP or the CGRP receptor like eptinezumab, erenumab, fremanezumab, and galcanezumab.

These are all equally effective. They reduce migraine-days between 3 and 7 per month. They are effective both in episodic and chronic migraine, and most importantly, they are effective in people with medication overuse headaches. The 50% responder rates are somewhere between 40% and 60%, and there are no significant differences between the four monoclonal antibodies.

The major advantage is a very good tolerability profile; very few patients terminate treatment because of adverse events. There has been, with one exception, no direct comparison of the monoclonal antibodies with traditional migraine preventive drugs or onabotulinumtoxinA. The only exception is a trial that compared topiramate and erenumab, showing that erenumab was definitely more effective and better tolerated.

At the moment, the recommendation is to use these monoclonal antibodies for 12 months in episodic migraine and 24 months in chronic migraine and then pause. It usually turns out that between 50% and 70% of these patients need to continue the treatment. If they are not working, there is a possibility to switch between the monoclonal antibodies, and the success rate after this is somewhere between 15% and 30%.

Gepants were also developed for the prevention of migraine. Here, we have rimegepant 75 mg every other day or atogepant 60 mg daily. They are effective, but in indirect comparisons, they are less effective than the monoclonal antibodies. At present, we have no comparative trials with monoclonal antibodies or the traditional migraine preventive drugs.

Potential patients are those who have needle phobia or patients who do not respond to monoclonal antibodies. Again, the biggest shortcoming is cost in the United States. The cost per year for migraine prevention or prophylaxis is between $12,000 and $20,000.

Finally, we also had very exciting news. There is a new therapeutic approach via PACAP. PACAP is pituitary adenylate cyclase-activating polypeptide, which has similar biological actions as CGRP but with additional actions. It could very well be that people who do not respond to a monoclonal antibody would respond to a monoclonal antibody against PACAP.

At the congress, the first randomized, placebo-controlled trial with a monoclonal antibody against PACAP was presented. This monoclonal antibody was effective in a population of people in whom prior preventive therapy had failed. A phase 3 study is planned, and most probably the PACAP monoclonal could work in people who do not respond to monoclonal antibodies against CGRP.

Dear colleagues, we have now many choices for the acute treatment of migraine and migraine prophylaxis. We have new kids on the block, and we have to learn more about how to use these drugs, their benefits, and their shortcomings.

He has disclosed the following relevant financial relationships:Received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Abbott; Addex Pharma; Alder; Allergan; Almirall; Amgen; Autonomic Technology; AstraZeneca; Bayer Vital; Berlin Chemie; Bristol-Myers Squibb; Boehringer Ingelheim; Chordate; CoAxia; Corimmun; Covidien; Coherex; CoLucid; Daiichi-Sankyo; D-Pharm; Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 3M Medica; MSD; Medtronic; Menarini; MindFrame; Minster; Neuroscore; Neurobiological Technologies; Novartis; Novo Nordisk; Johnson & Johnson; Knoll; Paion; Parke-Davis; Pierre Fabre; Pfizer; Schaper and Brummer; Sanofi-Aventis; Schering-Plough; Servier; Solvay; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.

Dr. Diener is professor, department of neurology, Stroke Center-Headache Center, University Duisburg-Essen (Germany).

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Dear colleagues, I’m Hans-Christoph Diener from the Faculty of Medicine at the University of Duisburg-Essen in Germany. I would like to give you an update on what was reported during the International Headache Congress in Seoul in September.
 

CGRP receptor agonists

Let me start with the treatment of acute migraine attacks. Until recently, we had analgesics, nonsteroidal anti-inflammatory drugs like ibuprofen, ergot alkaloids, and triptans. There are new developments, which are small molecules that are antagonists at the calcitonin gene-related peptide (CGRP) receptor. At the moment, we have three of them: rimegepant 75 mg, ubrogepant 50 mg or 100 mg, and zavegepant (a nasal spray) 10 mg.

These are all effective and superior to placebo. The 2-hour pain-free rate is somewhere between 25% and 30%. They have very few side effects; these include a little bit of nausea, somnolence, nasopharyngitis, and for zavegepant, the nasal spray, taste disturbance. In indirect comparisons, the so-called gepants are about as effective as ibuprofen and aspirin, and they seem to be less effective than sumatriptan 100 mg.

Unfortunately, until now, we have no direct comparison with triptans and we have no data demonstrating whether they are effective in people where triptans do not work. The major shortcoming is the cost in the United States. The cost per tablet or nasal spray is somewhere between $80 and $200. This means we definitely need more studies for these gepants.
 

Migraine prophylaxis

Let me move to the prophylaxis of migraine with drugs. Previously and still, we have all medications like beta-blockers, flunarizine, topiramate, valproic acid, amitriptyline, and candesartan, and for chronic migraine, onabotulinumtoxinA. We have now 5 years’ experience with the monoclonal antibodies against CGRP or the CGRP receptor like eptinezumab, erenumab, fremanezumab, and galcanezumab.

These are all equally effective. They reduce migraine-days between 3 and 7 per month. They are effective both in episodic and chronic migraine, and most importantly, they are effective in people with medication overuse headaches. The 50% responder rates are somewhere between 40% and 60%, and there are no significant differences between the four monoclonal antibodies.

The major advantage is a very good tolerability profile; very few patients terminate treatment because of adverse events. There has been, with one exception, no direct comparison of the monoclonal antibodies with traditional migraine preventive drugs or onabotulinumtoxinA. The only exception is a trial that compared topiramate and erenumab, showing that erenumab was definitely more effective and better tolerated.

At the moment, the recommendation is to use these monoclonal antibodies for 12 months in episodic migraine and 24 months in chronic migraine and then pause. It usually turns out that between 50% and 70% of these patients need to continue the treatment. If they are not working, there is a possibility to switch between the monoclonal antibodies, and the success rate after this is somewhere between 15% and 30%.

Gepants were also developed for the prevention of migraine. Here, we have rimegepant 75 mg every other day or atogepant 60 mg daily. They are effective, but in indirect comparisons, they are less effective than the monoclonal antibodies. At present, we have no comparative trials with monoclonal antibodies or the traditional migraine preventive drugs.

Potential patients are those who have needle phobia or patients who do not respond to monoclonal antibodies. Again, the biggest shortcoming is cost in the United States. The cost per year for migraine prevention or prophylaxis is between $12,000 and $20,000.

Finally, we also had very exciting news. There is a new therapeutic approach via PACAP. PACAP is pituitary adenylate cyclase-activating polypeptide, which has similar biological actions as CGRP but with additional actions. It could very well be that people who do not respond to a monoclonal antibody would respond to a monoclonal antibody against PACAP.

At the congress, the first randomized, placebo-controlled trial with a monoclonal antibody against PACAP was presented. This monoclonal antibody was effective in a population of people in whom prior preventive therapy had failed. A phase 3 study is planned, and most probably the PACAP monoclonal could work in people who do not respond to monoclonal antibodies against CGRP.

Dear colleagues, we have now many choices for the acute treatment of migraine and migraine prophylaxis. We have new kids on the block, and we have to learn more about how to use these drugs, their benefits, and their shortcomings.

He has disclosed the following relevant financial relationships:Received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Abbott; Addex Pharma; Alder; Allergan; Almirall; Amgen; Autonomic Technology; AstraZeneca; Bayer Vital; Berlin Chemie; Bristol-Myers Squibb; Boehringer Ingelheim; Chordate; CoAxia; Corimmun; Covidien; Coherex; CoLucid; Daiichi-Sankyo; D-Pharm; Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 3M Medica; MSD; Medtronic; Menarini; MindFrame; Minster; Neuroscore; Neurobiological Technologies; Novartis; Novo Nordisk; Johnson & Johnson; Knoll; Paion; Parke-Davis; Pierre Fabre; Pfizer; Schaper and Brummer; Sanofi-Aventis; Schering-Plough; Servier; Solvay; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.

Dr. Diener is professor, department of neurology, Stroke Center-Headache Center, University Duisburg-Essen (Germany).

A version of this article appeared on Medscape.com.

Prescribing patterns of preventive migraine medications for young adults do not appear to vary based on whether the provider is a pediatric or adult neurologist, but researchers say preventive medications may be underused for this group, according to recent research published in the journal Headache.

“Approximately two-fifths of young adults with migraine were prescribed preventive medications, and this did not differ between pediatric and adult neurologists,” Hannah F. J. Shapiro MD, of the department of neurology at the University of California, San Francisco, and the UCSF Benioff Children’s Hospitals, and colleagues wrote in their study. “This finding suggests that pediatric neurologists are providing comparable care to adult neurologists for young adults with migraine; however, this may represent the underuse of preventive medications in this patient population.”

Dr. Shapiro and colleagues conducted a retrospective study of 767 patients (mean age 20.3 years) at Mass General Brigham Hospital in Boston between 2017 and 2021 who received care from a pediatric or adult neurologist for episodic migraine. The majority of patients in the study were white (72.2%), non-Hispanic (82.1%) women (80.3%) with episodic migraine (72.8%), some of whom experienced a psychiatric comorbidity (12.7%), and had a 3.88 mean clinic visits for migraine. Researchers assessed prescription of migraine preventive medication as a primary outcome, with a secondary outcome of comparing the rate of migraine preventive prescriptions written by pediatric and adult neurologists.

Overall, 290 patients (37.8%) received care from a pediatric neurologist, and 131 of those 290 patients (45.2%) received preventive medications (95% confidence interval, 39.5%-51.0%). The remaining 477 patients received care from an adult neurologist; of these, 206 patients (43.2%) received preventive medications (95% CI, 39.0%-47.7%; P = .591). The most common preventive medication prescribed was topiramate, which was prescribed in 19.1% of cases by adult neurologists and 15.2% of cases by pediatric neurologists. Other preventive medications included tricyclic antidepressants such as amitriptyline and nortriptyline; pediatric neurologists prescribed amitriptyline more often than adult neurologists (14.5% vs. 5.5%; P <  .001), and adult neurologists prescribed nortriptyline more often than pediatric neurologists (12.8% vs. 2.4%; P < .001).

Dr. Shapiro and colleagues performed a mixed effects logistic regression analysis of potential confounders, and found no significant association between clinician specialty and use of preventive medication (adjusted odds ratio, 1.20; 95% CI, 0.62­-2.31), while factors such as female sex (aOR, 1.69; 95% CI, 1.07-2.66) and number of visits (aOR, 1.64; 95% CI, 1.49-1.80) carried associations with preventive medication use.

The finding that pediatric and adult neurologists use similar preventive medications is a positive one because “patients who continue care into adulthood with a pediatric neurologist should receive comparable care to the care they would receive with an adult neurologist,” Dr. Shapiro and colleagues said. “It is even more pertinent now for pediatric neurologists to have comfort prescribing preventive medication to young adults, as the newer calcitonin gene-related peptide (CGRP) pathway antagonists are currently only FDA approved for use in patients aged 18 years or older.”
 

Roadblocks may prevent adoption

M. Cristina Victorio, MD, a pediatric neurologist and director of the headache program at Akron (Ohio) Children’s, said in an interview that the study is well-designed, but the results cannot be generalized as the study is retrospective, was conducted at a single institution, and data about nutraceuticals and drug-free neuromodulation devices were excluded from the analysis.

Another aspect of the study to consider is that episodic migraine, defined as between 0 and 14 migraine days per month, comprised most of the diagnoses in this study, while preventive medication is usually considered in patients with migraines occurring at least 6 days per month. “[I]f migraine is only once every other month or once a month, preventive treatment may not be recommended,” she said.

There is also the element of patient preference, which is “difficult to obtain” in a retrospective study, she noted.

Citing the authors’ comments about pediatric neurologists’ comfortability prescribing preventive medications, including CGRP antagonists, Dr. Victorio said she offers CGRP antagonists to “young adult patients who have failed at least two of the guideline-recommended preventive medications.”

However, pediatric neurologists may encounter roadblocks to prescribing these medications. “A big challenge is access, as it requires prior authorization as well as writing a letter of appeal or medical necessity, which can be a nuisance for clinicians who are already inundated with clinical responsibilities,” she said.
 

More education is needed

“As a pediatric headache specialist and knowing the results of this study, my colleagues and I have a role in educating all clinicians as well as trainees on headache management to improve and provide optimal care for young adult patients with migraine,” Dr. Victorio said.

In her experience, more clinic visits usually mean a need for preventative medication, and psychiatric morbidities are common. “I differ in the sense that as a headache specialist I am comfortable offering various preventive treatment options when indicated, so I do not believe I am underutilizing,” she said.

Dr. Victorio said she prescribes topiramate, amitriptyline, and propranolol as migraine preventatives for adolescents and young adults, but recommends cyproheptadine for younger children “due to lesser side effects, tolerability, and convenience of formulation (both liquid and tablet forms are available), which can be challenging for younger children who are unable to swallow pills.”

“Cognizant that there are patients who are reluctant to take daily prescription medication and that consideration for preventive treatment includes patient’s preference, I include the use of nutraceuticals and drug-free neuromodulation devices when discussing preventive treatment options,” she added, noting that children and adolescents “[m]ore often than not” prefer nutraceuticals like magnesium and vitamin B2.

“I think the bottom line is that all clinicians managing young adults with migraine should know when to consider starting preventive migraine medication,” Dr. Victorio said. “Not offering preventive treatment to young adults specifically for those who have frequent migraine attacks, or those who have severe migraine despite adequate acute treatment, or those with significant adverse reactions to acute medications will only put these patients at risk to progression to chronic migraine (meaning having migraine more often than not – at least 15 days per month), and increases headache-related disability and reduces quality of life.”

The authors report no relevant financial disclosures. This study was supported by Harvard University and an award from the National Institutes of Health. Dr. Victorio reports being on the advisory board for Theranica Bio-electronics, has received honorarium serving as an author of the Merck Manual, and is involved in industry-sponsored clinical trials through Akron Children’s Hospital.

Prescribing patterns of preventive migraine medications for young adults do not appear to vary based on whether the provider is a pediatric or adult neurologist, but researchers say preventive medications may be underused for this group, according to recent research published in the journal Headache.

“Approximately two-fifths of young adults with migraine were prescribed preventive medications, and this did not differ between pediatric and adult neurologists,” Hannah F. J. Shapiro MD, of the department of neurology at the University of California, San Francisco, and the UCSF Benioff Children’s Hospitals, and colleagues wrote in their study. “This finding suggests that pediatric neurologists are providing comparable care to adult neurologists for young adults with migraine; however, this may represent the underuse of preventive medications in this patient population.”

Dr. Shapiro and colleagues conducted a retrospective study of 767 patients (mean age 20.3 years) at Mass General Brigham Hospital in Boston between 2017 and 2021 who received care from a pediatric or adult neurologist for episodic migraine. The majority of patients in the study were white (72.2%), non-Hispanic (82.1%) women (80.3%) with episodic migraine (72.8%), some of whom experienced a psychiatric comorbidity (12.7%), and had a 3.88 mean clinic visits for migraine. Researchers assessed prescription of migraine preventive medication as a primary outcome, with a secondary outcome of comparing the rate of migraine preventive prescriptions written by pediatric and adult neurologists.

Overall, 290 patients (37.8%) received care from a pediatric neurologist, and 131 of those 290 patients (45.2%) received preventive medications (95% confidence interval, 39.5%-51.0%). The remaining 477 patients received care from an adult neurologist; of these, 206 patients (43.2%) received preventive medications (95% CI, 39.0%-47.7%; P = .591). The most common preventive medication prescribed was topiramate, which was prescribed in 19.1% of cases by adult neurologists and 15.2% of cases by pediatric neurologists. Other preventive medications included tricyclic antidepressants such as amitriptyline and nortriptyline; pediatric neurologists prescribed amitriptyline more often than adult neurologists (14.5% vs. 5.5%; P <  .001), and adult neurologists prescribed nortriptyline more often than pediatric neurologists (12.8% vs. 2.4%; P < .001).

Dr. Shapiro and colleagues performed a mixed effects logistic regression analysis of potential confounders, and found no significant association between clinician specialty and use of preventive medication (adjusted odds ratio, 1.20; 95% CI, 0.62­-2.31), while factors such as female sex (aOR, 1.69; 95% CI, 1.07-2.66) and number of visits (aOR, 1.64; 95% CI, 1.49-1.80) carried associations with preventive medication use.

The finding that pediatric and adult neurologists use similar preventive medications is a positive one because “patients who continue care into adulthood with a pediatric neurologist should receive comparable care to the care they would receive with an adult neurologist,” Dr. Shapiro and colleagues said. “It is even more pertinent now for pediatric neurologists to have comfort prescribing preventive medication to young adults, as the newer calcitonin gene-related peptide (CGRP) pathway antagonists are currently only FDA approved for use in patients aged 18 years or older.”
 

Roadblocks may prevent adoption

M. Cristina Victorio, MD, a pediatric neurologist and director of the headache program at Akron (Ohio) Children’s, said in an interview that the study is well-designed, but the results cannot be generalized as the study is retrospective, was conducted at a single institution, and data about nutraceuticals and drug-free neuromodulation devices were excluded from the analysis.

Another aspect of the study to consider is that episodic migraine, defined as between 0 and 14 migraine days per month, comprised most of the diagnoses in this study, while preventive medication is usually considered in patients with migraines occurring at least 6 days per month. “[I]f migraine is only once every other month or once a month, preventive treatment may not be recommended,” she said.

There is also the element of patient preference, which is “difficult to obtain” in a retrospective study, she noted.

Citing the authors’ comments about pediatric neurologists’ comfortability prescribing preventive medications, including CGRP antagonists, Dr. Victorio said she offers CGRP antagonists to “young adult patients who have failed at least two of the guideline-recommended preventive medications.”

However, pediatric neurologists may encounter roadblocks to prescribing these medications. “A big challenge is access, as it requires prior authorization as well as writing a letter of appeal or medical necessity, which can be a nuisance for clinicians who are already inundated with clinical responsibilities,” she said.
 

More education is needed

“As a pediatric headache specialist and knowing the results of this study, my colleagues and I have a role in educating all clinicians as well as trainees on headache management to improve and provide optimal care for young adult patients with migraine,” Dr. Victorio said.

In her experience, more clinic visits usually mean a need for preventative medication, and psychiatric morbidities are common. “I differ in the sense that as a headache specialist I am comfortable offering various preventive treatment options when indicated, so I do not believe I am underutilizing,” she said.

Dr. Victorio said she prescribes topiramate, amitriptyline, and propranolol as migraine preventatives for adolescents and young adults, but recommends cyproheptadine for younger children “due to lesser side effects, tolerability, and convenience of formulation (both liquid and tablet forms are available), which can be challenging for younger children who are unable to swallow pills.”

“Cognizant that there are patients who are reluctant to take daily prescription medication and that consideration for preventive treatment includes patient’s preference, I include the use of nutraceuticals and drug-free neuromodulation devices when discussing preventive treatment options,” she added, noting that children and adolescents “[m]ore often than not” prefer nutraceuticals like magnesium and vitamin B2.

“I think the bottom line is that all clinicians managing young adults with migraine should know when to consider starting preventive migraine medication,” Dr. Victorio said. “Not offering preventive treatment to young adults specifically for those who have frequent migraine attacks, or those who have severe migraine despite adequate acute treatment, or those with significant adverse reactions to acute medications will only put these patients at risk to progression to chronic migraine (meaning having migraine more often than not – at least 15 days per month), and increases headache-related disability and reduces quality of life.”

The authors report no relevant financial disclosures. This study was supported by Harvard University and an award from the National Institutes of Health. Dr. Victorio reports being on the advisory board for Theranica Bio-electronics, has received honorarium serving as an author of the Merck Manual, and is involved in industry-sponsored clinical trials through Akron Children’s Hospital.

Prescribing patterns of preventive migraine medications for young adults do not appear to vary based on whether the provider is a pediatric or adult neurologist, but researchers say preventive medications may be underused for this group, according to recent research published in the journal Headache.

“Approximately two-fifths of young adults with migraine were prescribed preventive medications, and this did not differ between pediatric and adult neurologists,” Hannah F. J. Shapiro MD, of the department of neurology at the University of California, San Francisco, and the UCSF Benioff Children’s Hospitals, and colleagues wrote in their study. “This finding suggests that pediatric neurologists are providing comparable care to adult neurologists for young adults with migraine; however, this may represent the underuse of preventive medications in this patient population.”

Dr. Shapiro and colleagues conducted a retrospective study of 767 patients (mean age 20.3 years) at Mass General Brigham Hospital in Boston between 2017 and 2021 who received care from a pediatric or adult neurologist for episodic migraine. The majority of patients in the study were white (72.2%), non-Hispanic (82.1%) women (80.3%) with episodic migraine (72.8%), some of whom experienced a psychiatric comorbidity (12.7%), and had a 3.88 mean clinic visits for migraine. Researchers assessed prescription of migraine preventive medication as a primary outcome, with a secondary outcome of comparing the rate of migraine preventive prescriptions written by pediatric and adult neurologists.

Overall, 290 patients (37.8%) received care from a pediatric neurologist, and 131 of those 290 patients (45.2%) received preventive medications (95% confidence interval, 39.5%-51.0%). The remaining 477 patients received care from an adult neurologist; of these, 206 patients (43.2%) received preventive medications (95% CI, 39.0%-47.7%; P = .591). The most common preventive medication prescribed was topiramate, which was prescribed in 19.1% of cases by adult neurologists and 15.2% of cases by pediatric neurologists. Other preventive medications included tricyclic antidepressants such as amitriptyline and nortriptyline; pediatric neurologists prescribed amitriptyline more often than adult neurologists (14.5% vs. 5.5%; P <  .001), and adult neurologists prescribed nortriptyline more often than pediatric neurologists (12.8% vs. 2.4%; P < .001).

Dr. Shapiro and colleagues performed a mixed effects logistic regression analysis of potential confounders, and found no significant association between clinician specialty and use of preventive medication (adjusted odds ratio, 1.20; 95% CI, 0.62­-2.31), while factors such as female sex (aOR, 1.69; 95% CI, 1.07-2.66) and number of visits (aOR, 1.64; 95% CI, 1.49-1.80) carried associations with preventive medication use.

The finding that pediatric and adult neurologists use similar preventive medications is a positive one because “patients who continue care into adulthood with a pediatric neurologist should receive comparable care to the care they would receive with an adult neurologist,” Dr. Shapiro and colleagues said. “It is even more pertinent now for pediatric neurologists to have comfort prescribing preventive medication to young adults, as the newer calcitonin gene-related peptide (CGRP) pathway antagonists are currently only FDA approved for use in patients aged 18 years or older.”
 

Roadblocks may prevent adoption

M. Cristina Victorio, MD, a pediatric neurologist and director of the headache program at Akron (Ohio) Children’s, said in an interview that the study is well-designed, but the results cannot be generalized as the study is retrospective, was conducted at a single institution, and data about nutraceuticals and drug-free neuromodulation devices were excluded from the analysis.

Another aspect of the study to consider is that episodic migraine, defined as between 0 and 14 migraine days per month, comprised most of the diagnoses in this study, while preventive medication is usually considered in patients with migraines occurring at least 6 days per month. “[I]f migraine is only once every other month or once a month, preventive treatment may not be recommended,” she said.

There is also the element of patient preference, which is “difficult to obtain” in a retrospective study, she noted.

Citing the authors’ comments about pediatric neurologists’ comfortability prescribing preventive medications, including CGRP antagonists, Dr. Victorio said she offers CGRP antagonists to “young adult patients who have failed at least two of the guideline-recommended preventive medications.”

However, pediatric neurologists may encounter roadblocks to prescribing these medications. “A big challenge is access, as it requires prior authorization as well as writing a letter of appeal or medical necessity, which can be a nuisance for clinicians who are already inundated with clinical responsibilities,” she said.
 

More education is needed

“As a pediatric headache specialist and knowing the results of this study, my colleagues and I have a role in educating all clinicians as well as trainees on headache management to improve and provide optimal care for young adult patients with migraine,” Dr. Victorio said.

In her experience, more clinic visits usually mean a need for preventative medication, and psychiatric morbidities are common. “I differ in the sense that as a headache specialist I am comfortable offering various preventive treatment options when indicated, so I do not believe I am underutilizing,” she said.

Dr. Victorio said she prescribes topiramate, amitriptyline, and propranolol as migraine preventatives for adolescents and young adults, but recommends cyproheptadine for younger children “due to lesser side effects, tolerability, and convenience of formulation (both liquid and tablet forms are available), which can be challenging for younger children who are unable to swallow pills.”

“Cognizant that there are patients who are reluctant to take daily prescription medication and that consideration for preventive treatment includes patient’s preference, I include the use of nutraceuticals and drug-free neuromodulation devices when discussing preventive treatment options,” she added, noting that children and adolescents “[m]ore often than not” prefer nutraceuticals like magnesium and vitamin B2.

“I think the bottom line is that all clinicians managing young adults with migraine should know when to consider starting preventive migraine medication,” Dr. Victorio said. “Not offering preventive treatment to young adults specifically for those who have frequent migraine attacks, or those who have severe migraine despite adequate acute treatment, or those with significant adverse reactions to acute medications will only put these patients at risk to progression to chronic migraine (meaning having migraine more often than not – at least 15 days per month), and increases headache-related disability and reduces quality of life.”

The authors report no relevant financial disclosures. This study was supported by Harvard University and an award from the National Institutes of Health. Dr. Victorio reports being on the advisory board for Theranica Bio-electronics, has received honorarium serving as an author of the Merck Manual, and is involved in industry-sponsored clinical trials through Akron Children’s Hospital.

This month we will discuss "migraine plus" conditions: menstrual migraine as well as migraine-associated symptoms, including allodynia, photophobia, and nausea.

Migraine is one of the most common and disabling conditions worldwide, and it is three times more likely to be found in women than men. This is even more so during reproductive years, where many women experience hormonally triggered migraine attacks. Although some women will experience migraine exclusively perimenstrually, most women who experience menstrual migraine attacks also will have migraine attacks that are not hormonally triggered. It is often challenging to find the correct acute treatment for specific kinds of migraine attacks, and many women will describe specific acute medications as more effective for their nonmenstrual or "regular" migraine attacks compared with their perimenstrual attacks. The study by MacGregor and colleagues investigated the use of ubrogepant and compared its effect between these two subtypes of attacks.

This trial was an extension of the initial phase 3 trial of ubrogepant, called ACHIEVE II. Initial investigators enrolled over 700 patients into an open-label extension, and the participants were randomly assigned 1:1:1 to their "usual care," 50 mg ubrogepant, or 100 mg ubrogepant. Participants were blinded to the dose of ubrogepant even though they knew that they were taking ubrogepant or their standard acute medication. The purpose of the "usual care" arm was not to collect efficacy results; rather, it was for safety, specifically to evaluate the long-term hepatic safety with ubrogepant.

Participants were allowed to treat up to eight migraine attacks per 4-week interval. The duration of the trial was 52 weeks, and a second dose of medication was allowed, identical to the initial dose. Women in this trial recorded their menstrual start date and whether they treated menstrually related attacks. An attack was considered menstrually related if the headache was within a 5-day window of the onset of menstruation. Of the 734 women enrolled in the intention-to-treat population, 354 reported at least one menstrual cycle start date with a headache day. Efficacy outcome measures included pain freedom at 2 hours post-dose, pain relief at 2 hours post-dose, absence of photophobia, phonophobia, and nausea at 2 hours post-dose, normal function at 2 hours post-dose, and use of rescue medication within 24 hours of the initial dose. All information was collected via an electronic diary.

There was no statistically significant difference between 2-hour pain freedom outcomes of menstrual and nonmenstrual migraine attacks, although there was a numerically higher mean percentage of menstrual attacks that was not statistically significant. This was noted for both doses of ubrogepant. This was also the case for 2-hour pain relief; the migraine-associated symptoms of photophobia, phonophobia, and nausea; for functional disability; and the use of a rescue medication. Among all outcomes it appears that both doses of ubrogepant are equally effective for both menstrual and nonmenstrual migraine attacks. On the basis of this evidence, clinicians may be able to consolidate different acute medications for different migraine subtypes and consider the use of this calcitonin gene-related peptide (CGRP) antagonist for all the patient's attacks.

Allodynia is a condition whereby a nonpainful stimulus is perceived as painful. In the context of migraine, this often will occur in the head and neck region and as a result of the chronification of migraine — headache frequency increasing to > 15 days per month. One significant risk factor for the development of chronic migraine is medication overuse, when an acute medication for migraine is used more often than its recommended use. Pijpers and colleagues sought to determine whether the presence of allodynia was predictive for the prognosis of chronic migraine complicated by medication overuse.

This study was a subset of the Chronification And Reversibility of Migraine (CHARM) study, a randomized, double-blind, placebo-controlled trial that aimed to investigate whether treatment with botulinum toxin A was of added value in addition to withdrawal therapy in chronic migraine patients with medication overuse headache. Diagnoses were made in consultation with headache experts and confirmed by a headache diary. Exclusion criteria were: (1) other primary headache or neurologic disorders; (2) other chronic pain disorders with medium to high pain intensity or requiring pain medication; (3) major psychiatric disorders other than depression; (4) major cognitive, behavioral, or oncologic disorders; (5) contraindications for treatment or inability to adhere to the study protocol; (6) (planned) pregnancy or breastfeeding; (7) use of ergots, opioids, or barbiturates; or (8) abuse of drugs in the past 12 months. Allodynia was determined by the Allodynia Symptom Checklist (ASC) .

The primary outcome was reversion from chronic to episodic migraine; secondary outcomes were > 50% reduction in monthly migraine days and reduction in number of monthly headache days. A total of 173 participants in the CHARM trial provided baseline allodynia data and were included in this current study. Participants with cutaneous allodynia were mainly women and did not differ significantly in age, number of monthly migraine or headache days, age of onset, use of acute or prophylactic treatment, or being treated with botulinum toxin.

The absence of cutaneous allodynia was predictive for good outcome after 12 weeks. For the primary endpoint, the odds for reversion from chronic migraine to episodic migraine were 2.5 times higher for participants without allodynia vs with allodynia. In all, 75.0% of participants without allodynia vs 57.4% of participants with allodynia reverted to episodic migraine. These helpful data will allow us to better predict accurately the disease process and better set expectations for our patients with chronic migraine.

In the earlier days of headache treatment, the focus for both acute and preventive medications was a decrease in the severity or frequency of pain. As time has progressed and our understanding of migraine has broadened, we now consider pain one of the many features of migraine, albeit usually the most prominent feature. The CGRP antagonist class of migraine medications has revolutionized how migraine is treated, both acutely and preventively; however, the initial studies all focused on pain-related outcomes. Alpuente and colleagues sought to better determine the effect of CGRP monoclonal antibody medications on other migraine-associated symptoms, specifically photophobia, photophobia, nausea, dizziness, and aura.

All injectable CGRP antibody medications were studied. Responses were recorded in an electronic diary. Patients were followed at 3 and 6 months and were excluded if their diary was < 80% complete; a total of 158 patients were included in this study. At 3 months, groups of patients were further divided between those who had > 50% decrease in monthly headache days and those that had < 50% reduction.

The > 50% group showed statistically significant reductions in the ratios of photophobia, phonophobia, and aura after 6 months of treatment, and, of note, these symptoms decreased at a higher rate than the reduction in headache days per month after 6 months. Rates of nausea and dizziness only reduced proportionally to the monthly headache days. For the < 50% group, there was a rebound of dizziness in between months 3 and 6, but all other outcomes decreased in proportion to the monthly headache days.

Our patients all experience symptoms other than headache pain as part of their migraine attacks. When we discuss the risks and benefits of a new treatment, we can now more accurately address many of the other associated symptoms and explain what our patients are likely to expect when starting a new medication. Similar studies have described these findings with the oral CGRP antagonists as well, and most acute migraine studies now use "most bothersome symptom" rather than pain severity as their primary outcome.

This month we will discuss "migraine plus" conditions: menstrual migraine as well as migraine-associated symptoms, including allodynia, photophobia, and nausea.

Migraine is one of the most common and disabling conditions worldwide, and it is three times more likely to be found in women than men. This is even more so during reproductive years, where many women experience hormonally triggered migraine attacks. Although some women will experience migraine exclusively perimenstrually, most women who experience menstrual migraine attacks also will have migraine attacks that are not hormonally triggered. It is often challenging to find the correct acute treatment for specific kinds of migraine attacks, and many women will describe specific acute medications as more effective for their nonmenstrual or "regular" migraine attacks compared with their perimenstrual attacks. The study by MacGregor and colleagues investigated the use of ubrogepant and compared its effect between these two subtypes of attacks.

This trial was an extension of the initial phase 3 trial of ubrogepant, called ACHIEVE II. Initial investigators enrolled over 700 patients into an open-label extension, and the participants were randomly assigned 1:1:1 to their "usual care," 50 mg ubrogepant, or 100 mg ubrogepant. Participants were blinded to the dose of ubrogepant even though they knew that they were taking ubrogepant or their standard acute medication. The purpose of the "usual care" arm was not to collect efficacy results; rather, it was for safety, specifically to evaluate the long-term hepatic safety with ubrogepant.

Participants were allowed to treat up to eight migraine attacks per 4-week interval. The duration of the trial was 52 weeks, and a second dose of medication was allowed, identical to the initial dose. Women in this trial recorded their menstrual start date and whether they treated menstrually related attacks. An attack was considered menstrually related if the headache was within a 5-day window of the onset of menstruation. Of the 734 women enrolled in the intention-to-treat population, 354 reported at least one menstrual cycle start date with a headache day. Efficacy outcome measures included pain freedom at 2 hours post-dose, pain relief at 2 hours post-dose, absence of photophobia, phonophobia, and nausea at 2 hours post-dose, normal function at 2 hours post-dose, and use of rescue medication within 24 hours of the initial dose. All information was collected via an electronic diary.

There was no statistically significant difference between 2-hour pain freedom outcomes of menstrual and nonmenstrual migraine attacks, although there was a numerically higher mean percentage of menstrual attacks that was not statistically significant. This was noted for both doses of ubrogepant. This was also the case for 2-hour pain relief; the migraine-associated symptoms of photophobia, phonophobia, and nausea; for functional disability; and the use of a rescue medication. Among all outcomes it appears that both doses of ubrogepant are equally effective for both menstrual and nonmenstrual migraine attacks. On the basis of this evidence, clinicians may be able to consolidate different acute medications for different migraine subtypes and consider the use of this calcitonin gene-related peptide (CGRP) antagonist for all the patient's attacks.

Allodynia is a condition whereby a nonpainful stimulus is perceived as painful. In the context of migraine, this often will occur in the head and neck region and as a result of the chronification of migraine — headache frequency increasing to > 15 days per month. One significant risk factor for the development of chronic migraine is medication overuse, when an acute medication for migraine is used more often than its recommended use. Pijpers and colleagues sought to determine whether the presence of allodynia was predictive for the prognosis of chronic migraine complicated by medication overuse.

This study was a subset of the Chronification And Reversibility of Migraine (CHARM) study, a randomized, double-blind, placebo-controlled trial that aimed to investigate whether treatment with botulinum toxin A was of added value in addition to withdrawal therapy in chronic migraine patients with medication overuse headache. Diagnoses were made in consultation with headache experts and confirmed by a headache diary. Exclusion criteria were: (1) other primary headache or neurologic disorders; (2) other chronic pain disorders with medium to high pain intensity or requiring pain medication; (3) major psychiatric disorders other than depression; (4) major cognitive, behavioral, or oncologic disorders; (5) contraindications for treatment or inability to adhere to the study protocol; (6) (planned) pregnancy or breastfeeding; (7) use of ergots, opioids, or barbiturates; or (8) abuse of drugs in the past 12 months. Allodynia was determined by the Allodynia Symptom Checklist (ASC) .

The primary outcome was reversion from chronic to episodic migraine; secondary outcomes were > 50% reduction in monthly migraine days and reduction in number of monthly headache days. A total of 173 participants in the CHARM trial provided baseline allodynia data and were included in this current study. Participants with cutaneous allodynia were mainly women and did not differ significantly in age, number of monthly migraine or headache days, age of onset, use of acute or prophylactic treatment, or being treated with botulinum toxin.

The absence of cutaneous allodynia was predictive for good outcome after 12 weeks. For the primary endpoint, the odds for reversion from chronic migraine to episodic migraine were 2.5 times higher for participants without allodynia vs with allodynia. In all, 75.0% of participants without allodynia vs 57.4% of participants with allodynia reverted to episodic migraine. These helpful data will allow us to better predict accurately the disease process and better set expectations for our patients with chronic migraine.

In the earlier days of headache treatment, the focus for both acute and preventive medications was a decrease in the severity or frequency of pain. As time has progressed and our understanding of migraine has broadened, we now consider pain one of the many features of migraine, albeit usually the most prominent feature. The CGRP antagonist class of migraine medications has revolutionized how migraine is treated, both acutely and preventively; however, the initial studies all focused on pain-related outcomes. Alpuente and colleagues sought to better determine the effect of CGRP monoclonal antibody medications on other migraine-associated symptoms, specifically photophobia, photophobia, nausea, dizziness, and aura.

All injectable CGRP antibody medications were studied. Responses were recorded in an electronic diary. Patients were followed at 3 and 6 months and were excluded if their diary was < 80% complete; a total of 158 patients were included in this study. At 3 months, groups of patients were further divided between those who had > 50% decrease in monthly headache days and those that had < 50% reduction.

The > 50% group showed statistically significant reductions in the ratios of photophobia, phonophobia, and aura after 6 months of treatment, and, of note, these symptoms decreased at a higher rate than the reduction in headache days per month after 6 months. Rates of nausea and dizziness only reduced proportionally to the monthly headache days. For the < 50% group, there was a rebound of dizziness in between months 3 and 6, but all other outcomes decreased in proportion to the monthly headache days.

Our patients all experience symptoms other than headache pain as part of their migraine attacks. When we discuss the risks and benefits of a new treatment, we can now more accurately address many of the other associated symptoms and explain what our patients are likely to expect when starting a new medication. Similar studies have described these findings with the oral CGRP antagonists as well, and most acute migraine studies now use "most bothersome symptom" rather than pain severity as their primary outcome.

This month we will discuss "migraine plus" conditions: menstrual migraine as well as migraine-associated symptoms, including allodynia, photophobia, and nausea.

Migraine is one of the most common and disabling conditions worldwide, and it is three times more likely to be found in women than men. This is even more so during reproductive years, where many women experience hormonally triggered migraine attacks. Although some women will experience migraine exclusively perimenstrually, most women who experience menstrual migraine attacks also will have migraine attacks that are not hormonally triggered. It is often challenging to find the correct acute treatment for specific kinds of migraine attacks, and many women will describe specific acute medications as more effective for their nonmenstrual or "regular" migraine attacks compared with their perimenstrual attacks. The study by MacGregor and colleagues investigated the use of ubrogepant and compared its effect between these two subtypes of attacks.

This trial was an extension of the initial phase 3 trial of ubrogepant, called ACHIEVE II. Initial investigators enrolled over 700 patients into an open-label extension, and the participants were randomly assigned 1:1:1 to their "usual care," 50 mg ubrogepant, or 100 mg ubrogepant. Participants were blinded to the dose of ubrogepant even though they knew that they were taking ubrogepant or their standard acute medication. The purpose of the "usual care" arm was not to collect efficacy results; rather, it was for safety, specifically to evaluate the long-term hepatic safety with ubrogepant.

Participants were allowed to treat up to eight migraine attacks per 4-week interval. The duration of the trial was 52 weeks, and a second dose of medication was allowed, identical to the initial dose. Women in this trial recorded their menstrual start date and whether they treated menstrually related attacks. An attack was considered menstrually related if the headache was within a 5-day window of the onset of menstruation. Of the 734 women enrolled in the intention-to-treat population, 354 reported at least one menstrual cycle start date with a headache day. Efficacy outcome measures included pain freedom at 2 hours post-dose, pain relief at 2 hours post-dose, absence of photophobia, phonophobia, and nausea at 2 hours post-dose, normal function at 2 hours post-dose, and use of rescue medication within 24 hours of the initial dose. All information was collected via an electronic diary.

There was no statistically significant difference between 2-hour pain freedom outcomes of menstrual and nonmenstrual migraine attacks, although there was a numerically higher mean percentage of menstrual attacks that was not statistically significant. This was noted for both doses of ubrogepant. This was also the case for 2-hour pain relief; the migraine-associated symptoms of photophobia, phonophobia, and nausea; for functional disability; and the use of a rescue medication. Among all outcomes it appears that both doses of ubrogepant are equally effective for both menstrual and nonmenstrual migraine attacks. On the basis of this evidence, clinicians may be able to consolidate different acute medications for different migraine subtypes and consider the use of this calcitonin gene-related peptide (CGRP) antagonist for all the patient's attacks.

Allodynia is a condition whereby a nonpainful stimulus is perceived as painful. In the context of migraine, this often will occur in the head and neck region and as a result of the chronification of migraine — headache frequency increasing to > 15 days per month. One significant risk factor for the development of chronic migraine is medication overuse, when an acute medication for migraine is used more often than its recommended use. Pijpers and colleagues sought to determine whether the presence of allodynia was predictive for the prognosis of chronic migraine complicated by medication overuse.

This study was a subset of the Chronification And Reversibility of Migraine (CHARM) study, a randomized, double-blind, placebo-controlled trial that aimed to investigate whether treatment with botulinum toxin A was of added value in addition to withdrawal therapy in chronic migraine patients with medication overuse headache. Diagnoses were made in consultation with headache experts and confirmed by a headache diary. Exclusion criteria were: (1) other primary headache or neurologic disorders; (2) other chronic pain disorders with medium to high pain intensity or requiring pain medication; (3) major psychiatric disorders other than depression; (4) major cognitive, behavioral, or oncologic disorders; (5) contraindications for treatment or inability to adhere to the study protocol; (6) (planned) pregnancy or breastfeeding; (7) use of ergots, opioids, or barbiturates; or (8) abuse of drugs in the past 12 months. Allodynia was determined by the Allodynia Symptom Checklist (ASC) .

The primary outcome was reversion from chronic to episodic migraine; secondary outcomes were > 50% reduction in monthly migraine days and reduction in number of monthly headache days. A total of 173 participants in the CHARM trial provided baseline allodynia data and were included in this current study. Participants with cutaneous allodynia were mainly women and did not differ significantly in age, number of monthly migraine or headache days, age of onset, use of acute or prophylactic treatment, or being treated with botulinum toxin.

The absence of cutaneous allodynia was predictive for good outcome after 12 weeks. For the primary endpoint, the odds for reversion from chronic migraine to episodic migraine were 2.5 times higher for participants without allodynia vs with allodynia. In all, 75.0% of participants without allodynia vs 57.4% of participants with allodynia reverted to episodic migraine. These helpful data will allow us to better predict accurately the disease process and better set expectations for our patients with chronic migraine.

In the earlier days of headache treatment, the focus for both acute and preventive medications was a decrease in the severity or frequency of pain. As time has progressed and our understanding of migraine has broadened, we now consider pain one of the many features of migraine, albeit usually the most prominent feature. The CGRP antagonist class of migraine medications has revolutionized how migraine is treated, both acutely and preventively; however, the initial studies all focused on pain-related outcomes. Alpuente and colleagues sought to better determine the effect of CGRP monoclonal antibody medications on other migraine-associated symptoms, specifically photophobia, photophobia, nausea, dizziness, and aura.

All injectable CGRP antibody medications were studied. Responses were recorded in an electronic diary. Patients were followed at 3 and 6 months and were excluded if their diary was < 80% complete; a total of 158 patients were included in this study. At 3 months, groups of patients were further divided between those who had > 50% decrease in monthly headache days and those that had < 50% reduction.

The > 50% group showed statistically significant reductions in the ratios of photophobia, phonophobia, and aura after 6 months of treatment, and, of note, these symptoms decreased at a higher rate than the reduction in headache days per month after 6 months. Rates of nausea and dizziness only reduced proportionally to the monthly headache days. For the < 50% group, there was a rebound of dizziness in between months 3 and 6, but all other outcomes decreased in proportion to the monthly headache days.

Our patients all experience symptoms other than headache pain as part of their migraine attacks. When we discuss the risks and benefits of a new treatment, we can now more accurately address many of the other associated symptoms and explain what our patients are likely to expect when starting a new medication. Similar studies have described these findings with the oral CGRP antagonists as well, and most acute migraine studies now use "most bothersome symptom" rather than pain severity as their primary outcome.

Key clinical point: Fremanezumab was effective as a preventive treatment in patients with chronic migraine (CM) with or without medication overuse (MO) and showed potential benefits in reducing MO.

Major finding: During a 12-week follow-up period, the administration of monthly and quarterly fremanezumab vs placebo led to significantly reduced average number of monthly headache days of moderate or greater severity in patients with MO (monthly: mean change [∆] −2.0, P = .0012; and quarterly: ∆ −1.8, P = .0042) and without MO (monthly: ∆ −1.6, P = .0437; and quarterly: ∆ −1.5, P = .0441). A greater proportion of patients receiving fremanezumab vs placebo reverted to no MO (P ≤ .05).

Study details: This post hoc analysis of a phase 2b/3 trial included 479 Japanese patients with CM who were randomly assigned to receive monthly fremanezumab (n = 159), quarterly fremanezumab (n = 159), or placebo (n = 161), and of whom 320 patients reported MO.

Disclosures: This study was funded by Otsuka Pharmaceutical Co., Ltd. Several authors declared being full-time employees of Otsuka Pharmaceutical Co., Ltd., and N Imai declared ties with various other sources.

Source: Imai N et al. Effects of fremanezumab on medication overuse in Japanese chronic migraine patients: Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial. Neurol Ther. 2023 (Sep 11). doi: 10.1007/s40120-023-00531-3

Key clinical point: Fremanezumab was effective as a preventive treatment in patients with chronic migraine (CM) with or without medication overuse (MO) and showed potential benefits in reducing MO.

Major finding: During a 12-week follow-up period, the administration of monthly and quarterly fremanezumab vs placebo led to significantly reduced average number of monthly headache days of moderate or greater severity in patients with MO (monthly: mean change [∆] −2.0, P = .0012; and quarterly: ∆ −1.8, P = .0042) and without MO (monthly: ∆ −1.6, P = .0437; and quarterly: ∆ −1.5, P = .0441). A greater proportion of patients receiving fremanezumab vs placebo reverted to no MO (P ≤ .05).

Study details: This post hoc analysis of a phase 2b/3 trial included 479 Japanese patients with CM who were randomly assigned to receive monthly fremanezumab (n = 159), quarterly fremanezumab (n = 159), or placebo (n = 161), and of whom 320 patients reported MO.

Disclosures: This study was funded by Otsuka Pharmaceutical Co., Ltd. Several authors declared being full-time employees of Otsuka Pharmaceutical Co., Ltd., and N Imai declared ties with various other sources.

Source: Imai N et al. Effects of fremanezumab on medication overuse in Japanese chronic migraine patients: Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial. Neurol Ther. 2023 (Sep 11). doi: 10.1007/s40120-023-00531-3

Key clinical point: Fremanezumab was effective as a preventive treatment in patients with chronic migraine (CM) with or without medication overuse (MO) and showed potential benefits in reducing MO.

Major finding: During a 12-week follow-up period, the administration of monthly and quarterly fremanezumab vs placebo led to significantly reduced average number of monthly headache days of moderate or greater severity in patients with MO (monthly: mean change [∆] −2.0, P = .0012; and quarterly: ∆ −1.8, P = .0042) and without MO (monthly: ∆ −1.6, P = .0437; and quarterly: ∆ −1.5, P = .0441). A greater proportion of patients receiving fremanezumab vs placebo reverted to no MO (P ≤ .05).

Study details: This post hoc analysis of a phase 2b/3 trial included 479 Japanese patients with CM who were randomly assigned to receive monthly fremanezumab (n = 159), quarterly fremanezumab (n = 159), or placebo (n = 161), and of whom 320 patients reported MO.

Disclosures: This study was funded by Otsuka Pharmaceutical Co., Ltd. Several authors declared being full-time employees of Otsuka Pharmaceutical Co., Ltd., and N Imai declared ties with various other sources.

Source: Imai N et al. Effects of fremanezumab on medication overuse in Japanese chronic migraine patients: Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial. Neurol Ther. 2023 (Sep 11). doi: 10.1007/s40120-023-00531-3

Key clinical point: Patients with migraine who achieved ≥ 50% reduction in headache days at 6 months (responders) with anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) showed an even greater reduction in the number of days per month with photophobia, phonophobia, and aura ratios.

Major finding: Monthly headache days reduced significantly by 9.4 days/month (P < .001) and 2.2 days/month (P = .004) among responders and non-responders, respectively, with responders having additional significant reductions in photophobia (−19.5%; P < .001), phonophobia (−12.1%; P = .010), and aura (−25.1%; P = .008) ratios. Higher basal photophobia ratios were predictors of increased response rates between months 3 and 6 (incidence risk ratio 0.928; P = .040).

Study details: This prospective observational study included 158 patients with migraine treated with anti-CGRP mAb, of whom 43.7% were responders.

Disclosures: This study did not receive any funding. A Alpuente, E Caronna, M Torres-Ferrús, and P Pozo-Rosich declared receiving honoraria as consultants or speakers from various sources.

Source: Alpuente A et al. Impact of anti-CGRP monoclonal antibodies on migraine attack accompanying symptoms: A real-world evidence study. Cephalalgia. 2023;43(8):3331024231177636 (Aug 9). doi: 10.1177/03331024231177636

Key clinical point: Patients with migraine who achieved ≥ 50% reduction in headache days at 6 months (responders) with anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) showed an even greater reduction in the number of days per month with photophobia, phonophobia, and aura ratios.

Major finding: Monthly headache days reduced significantly by 9.4 days/month (P < .001) and 2.2 days/month (P = .004) among responders and non-responders, respectively, with responders having additional significant reductions in photophobia (−19.5%; P < .001), phonophobia (−12.1%; P = .010), and aura (−25.1%; P = .008) ratios. Higher basal photophobia ratios were predictors of increased response rates between months 3 and 6 (incidence risk ratio 0.928; P = .040).

Study details: This prospective observational study included 158 patients with migraine treated with anti-CGRP mAb, of whom 43.7% were responders.

Disclosures: This study did not receive any funding. A Alpuente, E Caronna, M Torres-Ferrús, and P Pozo-Rosich declared receiving honoraria as consultants or speakers from various sources.

Source: Alpuente A et al. Impact of anti-CGRP monoclonal antibodies on migraine attack accompanying symptoms: A real-world evidence study. Cephalalgia. 2023;43(8):3331024231177636 (Aug 9). doi: 10.1177/03331024231177636

Key clinical point: Patients with migraine who achieved ≥ 50% reduction in headache days at 6 months (responders) with anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) showed an even greater reduction in the number of days per month with photophobia, phonophobia, and aura ratios.

Major finding: Monthly headache days reduced significantly by 9.4 days/month (P < .001) and 2.2 days/month (P = .004) among responders and non-responders, respectively, with responders having additional significant reductions in photophobia (−19.5%; P < .001), phonophobia (−12.1%; P = .010), and aura (−25.1%; P = .008) ratios. Higher basal photophobia ratios were predictors of increased response rates between months 3 and 6 (incidence risk ratio 0.928; P = .040).

Study details: This prospective observational study included 158 patients with migraine treated with anti-CGRP mAb, of whom 43.7% were responders.

Disclosures: This study did not receive any funding. A Alpuente, E Caronna, M Torres-Ferrús, and P Pozo-Rosich declared receiving honoraria as consultants or speakers from various sources.

Source: Alpuente A et al. Impact of anti-CGRP monoclonal antibodies on migraine attack accompanying symptoms: A real-world evidence study. Cephalalgia. 2023;43(8):3331024231177636 (Aug 9). doi: 10.1177/03331024231177636

Key clinical point: No appreciable association was observed between a history of migraine or its subtypes and an increase in the risk for COVID-19, including hospitalization for COVID-19, in older women.

Major finding: No significant association was observed between a history of migraine and the risk of developing COVID-19 (odds ratio [OR] 1.08; 95% CI 0.95-1.22) or being hospitalized for COVID-19 (OR 1.20; 95% CI 0.86-1.68) among older women. Similarly, other migraine statuses, including migraine with aura, showed no association with the risk for COVID-19.

Study details: This prospective cohort study included 16,492 women (age ≥ 45 years) enrolled in the Women’s Health Study, of whom 28.9% had a history of migraine and 7.7% reported positive SARS-CoV-2 test results, a diagnosis of COVID-19, or hospitalization for COVID-19.

Disclosures: The Women’s Health Study was funded by grants from the US National Cancer Institute and the US National Heart, Lung, and Blood Institute. T Kurth declared receiving research grants and personal compensation from various sources. The other authors declared no conflicts of interest.

Source: Rist PM et al. History of migraine and risk of COVID-19: A cohort study. Am J Med. 2023 (Aug 18). doi: 10.1016/j.amjmed.2023.07.021

Key clinical point: No appreciable association was observed between a history of migraine or its subtypes and an increase in the risk for COVID-19, including hospitalization for COVID-19, in older women.

Major finding: No significant association was observed between a history of migraine and the risk of developing COVID-19 (odds ratio [OR] 1.08; 95% CI 0.95-1.22) or being hospitalized for COVID-19 (OR 1.20; 95% CI 0.86-1.68) among older women. Similarly, other migraine statuses, including migraine with aura, showed no association with the risk for COVID-19.

Study details: This prospective cohort study included 16,492 women (age ≥ 45 years) enrolled in the Women’s Health Study, of whom 28.9% had a history of migraine and 7.7% reported positive SARS-CoV-2 test results, a diagnosis of COVID-19, or hospitalization for COVID-19.

Disclosures: The Women’s Health Study was funded by grants from the US National Cancer Institute and the US National Heart, Lung, and Blood Institute. T Kurth declared receiving research grants and personal compensation from various sources. The other authors declared no conflicts of interest.

Source: Rist PM et al. History of migraine and risk of COVID-19: A cohort study. Am J Med. 2023 (Aug 18). doi: 10.1016/j.amjmed.2023.07.021

Key clinical point: No appreciable association was observed between a history of migraine or its subtypes and an increase in the risk for COVID-19, including hospitalization for COVID-19, in older women.

Major finding: No significant association was observed between a history of migraine and the risk of developing COVID-19 (odds ratio [OR] 1.08; 95% CI 0.95-1.22) or being hospitalized for COVID-19 (OR 1.20; 95% CI 0.86-1.68) among older women. Similarly, other migraine statuses, including migraine with aura, showed no association with the risk for COVID-19.

Study details: This prospective cohort study included 16,492 women (age ≥ 45 years) enrolled in the Women’s Health Study, of whom 28.9% had a history of migraine and 7.7% reported positive SARS-CoV-2 test results, a diagnosis of COVID-19, or hospitalization for COVID-19.

Disclosures: The Women’s Health Study was funded by grants from the US National Cancer Institute and the US National Heart, Lung, and Blood Institute. T Kurth declared receiving research grants and personal compensation from various sources. The other authors declared no conflicts of interest.

Source: Rist PM et al. History of migraine and risk of COVID-19: A cohort study. Am J Med. 2023 (Aug 18). doi: 10.1016/j.amjmed.2023.07.021

Key clinical point: Nearly 24% of patients with multiple sclerosis (MS) experience migraine, with the odds of migraine occurrence being approximately 2-fold higher in patients with MS compared with control individuals.

Major finding: The overall prevalence rate of migraine among patients with MS was 0.24 (95% CI 0.21-0.28). Moreover, patients with MS vs control participants without MS had a ~2-fold greater risk of experiencing migraine (odds ratio 1.96; 95% CI 1.20-3.20).

Study details: This meta-analysis of 35 studies included 279,620 patients with MS and 279,603 control participants without MS.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Mohammadi M et al. The association between multiple sclerosis and migraine: A meta-analysis. Mult Scler Relat Disord. 2023;79:104954 (Aug 30). doi: 10.1016/j.msard.2023.104954

Key clinical point: Nearly 24% of patients with multiple sclerosis (MS) experience migraine, with the odds of migraine occurrence being approximately 2-fold higher in patients with MS compared with control individuals.

Major finding: The overall prevalence rate of migraine among patients with MS was 0.24 (95% CI 0.21-0.28). Moreover, patients with MS vs control participants without MS had a ~2-fold greater risk of experiencing migraine (odds ratio 1.96; 95% CI 1.20-3.20).

Study details: This meta-analysis of 35 studies included 279,620 patients with MS and 279,603 control participants without MS.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Mohammadi M et al. The association between multiple sclerosis and migraine: A meta-analysis. Mult Scler Relat Disord. 2023;79:104954 (Aug 30). doi: 10.1016/j.msard.2023.104954

Key clinical point: Nearly 24% of patients with multiple sclerosis (MS) experience migraine, with the odds of migraine occurrence being approximately 2-fold higher in patients with MS compared with control individuals.

Major finding: The overall prevalence rate of migraine among patients with MS was 0.24 (95% CI 0.21-0.28). Moreover, patients with MS vs control participants without MS had a ~2-fold greater risk of experiencing migraine (odds ratio 1.96; 95% CI 1.20-3.20).

Study details: This meta-analysis of 35 studies included 279,620 patients with MS and 279,603 control participants without MS.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Mohammadi M et al. The association between multiple sclerosis and migraine: A meta-analysis. Mult Scler Relat Disord. 2023;79:104954 (Aug 30). doi: 10.1016/j.msard.2023.104954

Key clinical point: Absence of cutaneous allodynia was a predictor of treatment response following withdrawal therapy in patients with chronic migraine and medication overuse, with the predictive value being even more pronounced when compared with cephalic or extracephalic allodynia.

Major finding: The chances of reversion from chronic to episodic migraine were ~2.5 times higher in patients without vs with cutaneous allodynia (odds ratio [OR] 2.45; P = .042), with the predictive values of absence of allodynia being even more pronounced when compared with patients having cephalic (OR 4.16; P = .024) or extracephalic (OR 7.32; P = .003) allodynia.

Study details: This study, conducted as part of the Chronification And Reversibility of Migraine study, included 173 patients with chronic migraine and medication overuse, of whom 129 had cutaneous allodynia.

Disclosures: This study was supported by grants from the Netherlands Organization for Scientific Research and the Dutch Brain Foundation. I de Boer and GM Terwindt declared receiving independent support, consultancy support, or both from various sources.

Source: Pijpers JA et al. Cutaneous allodynia as predictor for treatment response in chronic migraine: A cohort study. J Headache Pain. 2023;24:118 (Aug 30). Doi: 10.1186/s10194-023-01651-9.

Key clinical point: Absence of cutaneous allodynia was a predictor of treatment response following withdrawal therapy in patients with chronic migraine and medication overuse, with the predictive value being even more pronounced when compared with cephalic or extracephalic allodynia.

Major finding: The chances of reversion from chronic to episodic migraine were ~2.5 times higher in patients without vs with cutaneous allodynia (odds ratio [OR] 2.45; P = .042), with the predictive values of absence of allodynia being even more pronounced when compared with patients having cephalic (OR 4.16; P = .024) or extracephalic (OR 7.32; P = .003) allodynia.

Study details: This study, conducted as part of the Chronification And Reversibility of Migraine study, included 173 patients with chronic migraine and medication overuse, of whom 129 had cutaneous allodynia.

Disclosures: This study was supported by grants from the Netherlands Organization for Scientific Research and the Dutch Brain Foundation. I de Boer and GM Terwindt declared receiving independent support, consultancy support, or both from various sources.

Source: Pijpers JA et al. Cutaneous allodynia as predictor for treatment response in chronic migraine: A cohort study. J Headache Pain. 2023;24:118 (Aug 30). Doi: 10.1186/s10194-023-01651-9.

Key clinical point: Absence of cutaneous allodynia was a predictor of treatment response following withdrawal therapy in patients with chronic migraine and medication overuse, with the predictive value being even more pronounced when compared with cephalic or extracephalic allodynia.

Major finding: The chances of reversion from chronic to episodic migraine were ~2.5 times higher in patients without vs with cutaneous allodynia (odds ratio [OR] 2.45; P = .042), with the predictive values of absence of allodynia being even more pronounced when compared with patients having cephalic (OR 4.16; P = .024) or extracephalic (OR 7.32; P = .003) allodynia.

Study details: This study, conducted as part of the Chronification And Reversibility of Migraine study, included 173 patients with chronic migraine and medication overuse, of whom 129 had cutaneous allodynia.

Disclosures: This study was supported by grants from the Netherlands Organization for Scientific Research and the Dutch Brain Foundation. I de Boer and GM Terwindt declared receiving independent support, consultancy support, or both from various sources.

Source: Pijpers JA et al. Cutaneous allodynia as predictor for treatment response in chronic migraine: A cohort study. J Headache Pain. 2023;24:118 (Aug 30). Doi: 10.1186/s10194-023-01651-9.