Migraine ICYMI

PHILADELPHIA – Among patients with episodic cluster headache, the use of acute medications is high, but the use of preventive medications is low, according to an analysis presented at the annual meeting of the American Headache Society.

Although consensus treatment guidelines do not exist for episodic cluster headache, treatment of this disorder did not follow many established recommendations that call for the use of preventive medications (e.g., MacGregor et al., 2010; Sarchielli et al., 2012; and May et al., 2006). Additional preventive medication options may be needed.

Patients with episodic cluster headache have several unilateral headache attacks per day. Little information is available to guide the selection of treatments for this population, and little is known about how available treatments are used in routine practice.
 

Analyzing cross-sectional survey data

To address this paucity of evidence, Jeffrey Scott Andrews, PharmD, a senior research scientist at Eli Lilly in Indianapolis, and colleagues examined data from the Adelphi 2017 Cluster Headache Disease Specific Programme, a large, international, cross-sectional survey. Physicians and patients in Germany, the United Kingdom, and the United States responded to the survey. Eligible physicians consulted with at least four patients with cluster headache per month, and eligible patients had a diagnosis of episodic cluster headache that was consistent with ICHD-3 beta criteria. Additional data were collected from all participants through questionnaires.

The analysis included 309 patients in Germany, 328 in the United Kingdom, and 375 in the United States. The average age of the patients was 40 years, and most of the patients were male. Less than 70% of patients reported working full time, which may indicate “the impact of this condition on work status,” said Dr. Andrews. Patients’ average number of attacks per day within an active period was 2.4. The two most commonly reported comorbidities were anxiety and depression. About 40% of cases of depression were reported to have occurred after the receipt of a diagnosis of cluster headache.
 

Use of inhaled oxygen was low

Most patients received acute treatments. The proportion of patients who received acute therapy only was 53% in Germany, 48% in the United Kingdom, and 43% in the United States. Approximately 34% of patients in Germany received a combination of acute and preventive therapy, compared with 37% in the United Kingdom and 42% in the United States. The proportion of patients who received preventive therapy only was 10% in Germany, 8% in the United Kingdom, and 12% in the United States.

The most commonly prescribed acute treatment, regardless of formulation, was sumatriptan. About 60% of patients received this medication. Less than one-third of patients used inhaled oxygen. Oxygen was prescribed more often in Germany (45%) and the United Kingdom (33%), compared with the United States (19%). U.S. patients face well-known obstacles in getting access to, and reimbursement for, oxygen, said Dr. Andrews. “That’s an area that deserves increased attention.” Zolmitriptan was the third most commonly prescribed acute medication.

Among prescriptions for sumatriptan, oral and injectable formulations were approximately equally common. Recommendations, however, indicate formulations with potentially fast onset of action. “The average duration of one of these attacks is between 15 and 180 minutes, so that certainly suggests that a formulation that gives you a faster onset of action might improve outcomes,” said Dr. Andrews. The use of injectable sumatriptan was lowest in the United States and highest in the United Kingdom.

“The most common decision regarding preventive treatment was [to give] no preventive treatment,” said Dr. Andrews. Verapamil was the most commonly prescribed preventive therapy (34% in Germany, 29% in the United States, and 25% in the United Kingdom), followed by topiramate, lithium, and valproate.
 

Nonadherence and noncompliance was common

Fewer U.K. patients (32%) reported taking their preventive therapy as advised, compared with German patients (60%) and U.S. patients (80%). Common reasons for noncompliance, regardless of location, were forgetfulness, the belief that a dose was not needed, and side effects. Most patients in the United Kingdom (60%) and the United States (54%) reported the need to take an extra dose of their acute medication to relieve pain symptoms, compared with 30% in Germany. Furthermore, 13% of U.S. patients indicated that they took extra doses all the time or nearly all the time, compared with 2% in Germany and 7% in the United Kingdom. Among patients who had discontinued a preventive treatment in the past, the most common reasons for discontinuation were lack of efficacy and problems with tolerability.

One limitation of the study was that the survey was not designed to represent the general cluster headache or treating physician populations fully. The data may reflect selection bias in favor of physicians who treat high volumes of patients and in favor of patients who frequently seek health care. In addition, the data were based on self-reports.

“Increased awareness and educational efforts that aim at promoting the need and benefit of the preventive treatment for these patients is warranted,” Dr. Andrews concluded.

Dr. Andrews is an employee of Eli Lilly, which funded the study.

[email protected]

SOURCE: Nichols R et al. AHS 2019. Abstract OR04.

PHILADELPHIA – Among patients with episodic cluster headache, the use of acute medications is high, but the use of preventive medications is low, according to an analysis presented at the annual meeting of the American Headache Society.

Although consensus treatment guidelines do not exist for episodic cluster headache, treatment of this disorder did not follow many established recommendations that call for the use of preventive medications (e.g., MacGregor et al., 2010; Sarchielli et al., 2012; and May et al., 2006). Additional preventive medication options may be needed.

Patients with episodic cluster headache have several unilateral headache attacks per day. Little information is available to guide the selection of treatments for this population, and little is known about how available treatments are used in routine practice.
 

Analyzing cross-sectional survey data

To address this paucity of evidence, Jeffrey Scott Andrews, PharmD, a senior research scientist at Eli Lilly in Indianapolis, and colleagues examined data from the Adelphi 2017 Cluster Headache Disease Specific Programme, a large, international, cross-sectional survey. Physicians and patients in Germany, the United Kingdom, and the United States responded to the survey. Eligible physicians consulted with at least four patients with cluster headache per month, and eligible patients had a diagnosis of episodic cluster headache that was consistent with ICHD-3 beta criteria. Additional data were collected from all participants through questionnaires.

The analysis included 309 patients in Germany, 328 in the United Kingdom, and 375 in the United States. The average age of the patients was 40 years, and most of the patients were male. Less than 70% of patients reported working full time, which may indicate “the impact of this condition on work status,” said Dr. Andrews. Patients’ average number of attacks per day within an active period was 2.4. The two most commonly reported comorbidities were anxiety and depression. About 40% of cases of depression were reported to have occurred after the receipt of a diagnosis of cluster headache.
 

Use of inhaled oxygen was low

Most patients received acute treatments. The proportion of patients who received acute therapy only was 53% in Germany, 48% in the United Kingdom, and 43% in the United States. Approximately 34% of patients in Germany received a combination of acute and preventive therapy, compared with 37% in the United Kingdom and 42% in the United States. The proportion of patients who received preventive therapy only was 10% in Germany, 8% in the United Kingdom, and 12% in the United States.

The most commonly prescribed acute treatment, regardless of formulation, was sumatriptan. About 60% of patients received this medication. Less than one-third of patients used inhaled oxygen. Oxygen was prescribed more often in Germany (45%) and the United Kingdom (33%), compared with the United States (19%). U.S. patients face well-known obstacles in getting access to, and reimbursement for, oxygen, said Dr. Andrews. “That’s an area that deserves increased attention.” Zolmitriptan was the third most commonly prescribed acute medication.

Among prescriptions for sumatriptan, oral and injectable formulations were approximately equally common. Recommendations, however, indicate formulations with potentially fast onset of action. “The average duration of one of these attacks is between 15 and 180 minutes, so that certainly suggests that a formulation that gives you a faster onset of action might improve outcomes,” said Dr. Andrews. The use of injectable sumatriptan was lowest in the United States and highest in the United Kingdom.

“The most common decision regarding preventive treatment was [to give] no preventive treatment,” said Dr. Andrews. Verapamil was the most commonly prescribed preventive therapy (34% in Germany, 29% in the United States, and 25% in the United Kingdom), followed by topiramate, lithium, and valproate.
 

Nonadherence and noncompliance was common

Fewer U.K. patients (32%) reported taking their preventive therapy as advised, compared with German patients (60%) and U.S. patients (80%). Common reasons for noncompliance, regardless of location, were forgetfulness, the belief that a dose was not needed, and side effects. Most patients in the United Kingdom (60%) and the United States (54%) reported the need to take an extra dose of their acute medication to relieve pain symptoms, compared with 30% in Germany. Furthermore, 13% of U.S. patients indicated that they took extra doses all the time or nearly all the time, compared with 2% in Germany and 7% in the United Kingdom. Among patients who had discontinued a preventive treatment in the past, the most common reasons for discontinuation were lack of efficacy and problems with tolerability.

One limitation of the study was that the survey was not designed to represent the general cluster headache or treating physician populations fully. The data may reflect selection bias in favor of physicians who treat high volumes of patients and in favor of patients who frequently seek health care. In addition, the data were based on self-reports.

“Increased awareness and educational efforts that aim at promoting the need and benefit of the preventive treatment for these patients is warranted,” Dr. Andrews concluded.

Dr. Andrews is an employee of Eli Lilly, which funded the study.

[email protected]

SOURCE: Nichols R et al. AHS 2019. Abstract OR04.

PHILADELPHIA – Among patients with episodic cluster headache, the use of acute medications is high, but the use of preventive medications is low, according to an analysis presented at the annual meeting of the American Headache Society.

Although consensus treatment guidelines do not exist for episodic cluster headache, treatment of this disorder did not follow many established recommendations that call for the use of preventive medications (e.g., MacGregor et al., 2010; Sarchielli et al., 2012; and May et al., 2006). Additional preventive medication options may be needed.

Patients with episodic cluster headache have several unilateral headache attacks per day. Little information is available to guide the selection of treatments for this population, and little is known about how available treatments are used in routine practice.
 

Analyzing cross-sectional survey data

To address this paucity of evidence, Jeffrey Scott Andrews, PharmD, a senior research scientist at Eli Lilly in Indianapolis, and colleagues examined data from the Adelphi 2017 Cluster Headache Disease Specific Programme, a large, international, cross-sectional survey. Physicians and patients in Germany, the United Kingdom, and the United States responded to the survey. Eligible physicians consulted with at least four patients with cluster headache per month, and eligible patients had a diagnosis of episodic cluster headache that was consistent with ICHD-3 beta criteria. Additional data were collected from all participants through questionnaires.

The analysis included 309 patients in Germany, 328 in the United Kingdom, and 375 in the United States. The average age of the patients was 40 years, and most of the patients were male. Less than 70% of patients reported working full time, which may indicate “the impact of this condition on work status,” said Dr. Andrews. Patients’ average number of attacks per day within an active period was 2.4. The two most commonly reported comorbidities were anxiety and depression. About 40% of cases of depression were reported to have occurred after the receipt of a diagnosis of cluster headache.
 

Use of inhaled oxygen was low

Most patients received acute treatments. The proportion of patients who received acute therapy only was 53% in Germany, 48% in the United Kingdom, and 43% in the United States. Approximately 34% of patients in Germany received a combination of acute and preventive therapy, compared with 37% in the United Kingdom and 42% in the United States. The proportion of patients who received preventive therapy only was 10% in Germany, 8% in the United Kingdom, and 12% in the United States.

The most commonly prescribed acute treatment, regardless of formulation, was sumatriptan. About 60% of patients received this medication. Less than one-third of patients used inhaled oxygen. Oxygen was prescribed more often in Germany (45%) and the United Kingdom (33%), compared with the United States (19%). U.S. patients face well-known obstacles in getting access to, and reimbursement for, oxygen, said Dr. Andrews. “That’s an area that deserves increased attention.” Zolmitriptan was the third most commonly prescribed acute medication.

Among prescriptions for sumatriptan, oral and injectable formulations were approximately equally common. Recommendations, however, indicate formulations with potentially fast onset of action. “The average duration of one of these attacks is between 15 and 180 minutes, so that certainly suggests that a formulation that gives you a faster onset of action might improve outcomes,” said Dr. Andrews. The use of injectable sumatriptan was lowest in the United States and highest in the United Kingdom.

“The most common decision regarding preventive treatment was [to give] no preventive treatment,” said Dr. Andrews. Verapamil was the most commonly prescribed preventive therapy (34% in Germany, 29% in the United States, and 25% in the United Kingdom), followed by topiramate, lithium, and valproate.
 

Nonadherence and noncompliance was common

Fewer U.K. patients (32%) reported taking their preventive therapy as advised, compared with German patients (60%) and U.S. patients (80%). Common reasons for noncompliance, regardless of location, were forgetfulness, the belief that a dose was not needed, and side effects. Most patients in the United Kingdom (60%) and the United States (54%) reported the need to take an extra dose of their acute medication to relieve pain symptoms, compared with 30% in Germany. Furthermore, 13% of U.S. patients indicated that they took extra doses all the time or nearly all the time, compared with 2% in Germany and 7% in the United Kingdom. Among patients who had discontinued a preventive treatment in the past, the most common reasons for discontinuation were lack of efficacy and problems with tolerability.

One limitation of the study was that the survey was not designed to represent the general cluster headache or treating physician populations fully. The data may reflect selection bias in favor of physicians who treat high volumes of patients and in favor of patients who frequently seek health care. In addition, the data were based on self-reports.

“Increased awareness and educational efforts that aim at promoting the need and benefit of the preventive treatment for these patients is warranted,” Dr. Andrews concluded.

Dr. Andrews is an employee of Eli Lilly, which funded the study.

[email protected]

SOURCE: Nichols R et al. AHS 2019. Abstract OR04.

Remote Electrical Neuromodulation (REN) may provide relief of migraine pain and most bothersome symptoms compared to placebo, a new study found. The efficacy and safety of a REN device for acute treatment of migraine was assessed. The randomized, double-blind, multicenter study was conducted at 7 sites in the United States and 5 sites in Israel. The study included 252 adults meeting the International Classification of Headache Disorders criteria for migraine with 2 to 8 migraine headaches per month, and the patients were randomized 1:1 to active or sham stimulation. Among the findings:

• Active stimulation was more effective than sham stimulation in achieving pain relief, pain-free, and MBS relief at 2 hours post-treatment.
• The pain relief of the active treatment was sustained 48 hours post-treatment.
• Incidence of device-related adverse events was low and similar between treatment groups.

Yarnitsky D, et al. Remote electrical neuromodulation (REN) relieves acute migraine: A randomized, double-blind, placebo-controlled, multicenter trial. [Published online ahead of print May 9, 2019]. Headache. doi: 10.1111/head.13551.

Remote Electrical Neuromodulation (REN) may provide relief of migraine pain and most bothersome symptoms compared to placebo, a new study found. The efficacy and safety of a REN device for acute treatment of migraine was assessed. The randomized, double-blind, multicenter study was conducted at 7 sites in the United States and 5 sites in Israel. The study included 252 adults meeting the International Classification of Headache Disorders criteria for migraine with 2 to 8 migraine headaches per month, and the patients were randomized 1:1 to active or sham stimulation. Among the findings:

• Active stimulation was more effective than sham stimulation in achieving pain relief, pain-free, and MBS relief at 2 hours post-treatment.
• The pain relief of the active treatment was sustained 48 hours post-treatment.
• Incidence of device-related adverse events was low and similar between treatment groups.

Yarnitsky D, et al. Remote electrical neuromodulation (REN) relieves acute migraine: A randomized, double-blind, placebo-controlled, multicenter trial. [Published online ahead of print May 9, 2019]. Headache. doi: 10.1111/head.13551.

Remote Electrical Neuromodulation (REN) may provide relief of migraine pain and most bothersome symptoms compared to placebo, a new study found. The efficacy and safety of a REN device for acute treatment of migraine was assessed. The randomized, double-blind, multicenter study was conducted at 7 sites in the United States and 5 sites in Israel. The study included 252 adults meeting the International Classification of Headache Disorders criteria for migraine with 2 to 8 migraine headaches per month, and the patients were randomized 1:1 to active or sham stimulation. Among the findings:

• Active stimulation was more effective than sham stimulation in achieving pain relief, pain-free, and MBS relief at 2 hours post-treatment.
• The pain relief of the active treatment was sustained 48 hours post-treatment.
• Incidence of device-related adverse events was low and similar between treatment groups.

Yarnitsky D, et al. Remote electrical neuromodulation (REN) relieves acute migraine: A randomized, double-blind, placebo-controlled, multicenter trial. [Published online ahead of print May 9, 2019]. Headache. doi: 10.1111/head.13551.

Multiple cranial nerve blocks may provide an efficacious, well tolerated and reproducible transitional treatment for chronic headache disorders, a new study found. The uncontrolled, open-label study included 119 patients with chronic cluster headache, chronic migraine, short-lasting unilateral neuralgiform attack disorders, new daily persistent headaches, hemicrania continua and chronic paroxysmal hemicrania. All had failed to respond to greater occipital nerve blocks. Researchers found:

• Response rate for the entire cohort was 55.4%: Chronic cluster headache (69.2%), chronic migraine (49%), short-lasting unilateral neuralgiform attack disorders (56.3%), new daily persistent headache (10%), hemicrania continua (83.3%), and chronic paroxysmal hemicrania (25%).
• Time to benefit was between 0.5 and 33.58 hours.
• Benefit was maintained up to 4 weeks in over half of responders in all groups except chronic migraine and paroxysmal hemicrania.

Miller S, et al. Multiple cranial nerve blocks for the transitional treatment of chronic headaches. [Published online ahead of print May 13, 2019]. Cephalalgia. doi: 10.1177/0333102419848121. 

Multiple cranial nerve blocks may provide an efficacious, well tolerated and reproducible transitional treatment for chronic headache disorders, a new study found. The uncontrolled, open-label study included 119 patients with chronic cluster headache, chronic migraine, short-lasting unilateral neuralgiform attack disorders, new daily persistent headaches, hemicrania continua and chronic paroxysmal hemicrania. All had failed to respond to greater occipital nerve blocks. Researchers found:

• Response rate for the entire cohort was 55.4%: Chronic cluster headache (69.2%), chronic migraine (49%), short-lasting unilateral neuralgiform attack disorders (56.3%), new daily persistent headache (10%), hemicrania continua (83.3%), and chronic paroxysmal hemicrania (25%).
• Time to benefit was between 0.5 and 33.58 hours.
• Benefit was maintained up to 4 weeks in over half of responders in all groups except chronic migraine and paroxysmal hemicrania.

Miller S, et al. Multiple cranial nerve blocks for the transitional treatment of chronic headaches. [Published online ahead of print May 13, 2019]. Cephalalgia. doi: 10.1177/0333102419848121. 

Multiple cranial nerve blocks may provide an efficacious, well tolerated and reproducible transitional treatment for chronic headache disorders, a new study found. The uncontrolled, open-label study included 119 patients with chronic cluster headache, chronic migraine, short-lasting unilateral neuralgiform attack disorders, new daily persistent headaches, hemicrania continua and chronic paroxysmal hemicrania. All had failed to respond to greater occipital nerve blocks. Researchers found:

• Response rate for the entire cohort was 55.4%: Chronic cluster headache (69.2%), chronic migraine (49%), short-lasting unilateral neuralgiform attack disorders (56.3%), new daily persistent headache (10%), hemicrania continua (83.3%), and chronic paroxysmal hemicrania (25%).
• Time to benefit was between 0.5 and 33.58 hours.
• Benefit was maintained up to 4 weeks in over half of responders in all groups except chronic migraine and paroxysmal hemicrania.

Miller S, et al. Multiple cranial nerve blocks for the transitional treatment of chronic headaches. [Published online ahead of print May 13, 2019]. Cephalalgia. doi: 10.1177/0333102419848121. 

Transcranial sonography (TCS) signal alteration of brainstem raphe (BR) can be a biomarker for depression in migraine but is not associated with migraine headache itself, a new study found. Forty-two patients who had migraine without aura and 40 healthy controls were recruited for the study. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and BR, width of the frontal horns of the lateral ventricles, and the third ventricle were assessed with TCS. Researchers found:

• There were no significant differences between migraineurs and controls in the width of front horn of the lateral ventricle, width of third ventricle, as well as in the echogenicity of SN, CN, LN and BR.
• More patients with migraine were detected with increased echogenicity of CN and LN compared with controls.
• Patients with hypoechogenic BR had significantly higher Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D) scores than those with normal BR signal.

Tao WW, et al. Hypoechogenicity of brainstem raphe correlates with depression in migraine patients. [Published online ahead of print May 15, 2019]. J Headache Pain. doi: 10.1186/s10194-019-1011-2.

Transcranial sonography (TCS) signal alteration of brainstem raphe (BR) can be a biomarker for depression in migraine but is not associated with migraine headache itself, a new study found. Forty-two patients who had migraine without aura and 40 healthy controls were recruited for the study. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and BR, width of the frontal horns of the lateral ventricles, and the third ventricle were assessed with TCS. Researchers found:

• There were no significant differences between migraineurs and controls in the width of front horn of the lateral ventricle, width of third ventricle, as well as in the echogenicity of SN, CN, LN and BR.
• More patients with migraine were detected with increased echogenicity of CN and LN compared with controls.
• Patients with hypoechogenic BR had significantly higher Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D) scores than those with normal BR signal.

Tao WW, et al. Hypoechogenicity of brainstem raphe correlates with depression in migraine patients. [Published online ahead of print May 15, 2019]. J Headache Pain. doi: 10.1186/s10194-019-1011-2.

Transcranial sonography (TCS) signal alteration of brainstem raphe (BR) can be a biomarker for depression in migraine but is not associated with migraine headache itself, a new study found. Forty-two patients who had migraine without aura and 40 healthy controls were recruited for the study. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and BR, width of the frontal horns of the lateral ventricles, and the third ventricle were assessed with TCS. Researchers found:

• There were no significant differences between migraineurs and controls in the width of front horn of the lateral ventricle, width of third ventricle, as well as in the echogenicity of SN, CN, LN and BR.
• More patients with migraine were detected with increased echogenicity of CN and LN compared with controls.
• Patients with hypoechogenic BR had significantly higher Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D) scores than those with normal BR signal.

Tao WW, et al. Hypoechogenicity of brainstem raphe correlates with depression in migraine patients. [Published online ahead of print May 15, 2019]. J Headache Pain. doi: 10.1186/s10194-019-1011-2.

PHILADELPHIA – Among patients with episodic migraine, 4.5 years of preventive treatment with erenumab is effective, safe, and well tolerated, according to interim data from an open-label extension study. “Erenumab was well tolerated and safe, with no safety signals detected over this period,” said Messoud Ashina, MD, PhD, professor of neurology at the University of Copenhagen. Dr. Ashina presented the interim data from a 5-year, open-label extension study of erenumab at the annual meeting of the American Headache Society.

Erenumab is a monoclonal antibody that targets and blocks the calcitonin gene-related peptide (CGRP) receptor. In May 2018, the Food and Drug Administration approved erenumab for the preventive treatment of migraine in adults. The treatment, marketed as Aimovig, is administered once monthly by self-injection.

During the open-label study, patients initially received 70 mg of erenumab monthly. After approximately 2 years, patients switched to 140 mg of erenumab monthly. The researchers’ interim efficacy analysis included all patients on 140 mg of erenumab with data about monthly migraine days after more than 4 years of treatment. The safety analysis included all patients who enrolled in the open-label treatment period and received at least one dose of erenumab.

Of 250 patients who increased the erenumab dose from 70 mg to 140 mg, a total of 221 (88%) completed the open-label treatment period or remained on 140 mg after more than 4 years. Patients’ average number of monthly migraine days at study baseline was 8.7, and the average change from baseline to the most recent month in the interim analysis was –5.8.

During the most recent month of assessment, 77% of patients had at least a 50% reduction in monthly migraine days from baseline, 56% had at least a 75% reduction, and 33% had a 100% reduction.

Mean change from baseline in acute migraine‐specific medication treatment days was –4.6, from a baseline of 6.1.

Among the 383 patients who entered the open-label treatment period and received at least one dose of erenumab (mean age, 41.3; 79% female), the median erenumab exposure was 58.5 months. The exposure‐adjusted incidence of adverse events per 100 patient‐years was 124.9, and the three most frequent adverse events (per 100 patient-years) were nasopharyngitis (10.9), upper respiratory tract infection (6.8), and influenza (4.7). The exposure‐adjusted incidence rate per 100 patient‐years for constipation was 1.3 (9/383) for 70-mg erenumab and 2.6 (15/250) for 140-mg erenumab.

“The exposure‐adjusted incidence rate per 100 patient‐years of serious adverse events was 3.8, similar to the rate observed for erenumab and placebo during the placebo‐controlled periods of studies,” the researchers said.

The study was sponsored by Amgen, and several study authors are employees of Amgen or Novartis, the companies that market erenumab. Dr. Ashina is a consultant for Amgen, Novartis, and other companies.

[email protected]

SOURCE: Ashina M et al. AHS 2019, Abstract IOR10.

PHILADELPHIA – Among patients with episodic migraine, 4.5 years of preventive treatment with erenumab is effective, safe, and well tolerated, according to interim data from an open-label extension study. “Erenumab was well tolerated and safe, with no safety signals detected over this period,” said Messoud Ashina, MD, PhD, professor of neurology at the University of Copenhagen. Dr. Ashina presented the interim data from a 5-year, open-label extension study of erenumab at the annual meeting of the American Headache Society.

Erenumab is a monoclonal antibody that targets and blocks the calcitonin gene-related peptide (CGRP) receptor. In May 2018, the Food and Drug Administration approved erenumab for the preventive treatment of migraine in adults. The treatment, marketed as Aimovig, is administered once monthly by self-injection.

During the open-label study, patients initially received 70 mg of erenumab monthly. After approximately 2 years, patients switched to 140 mg of erenumab monthly. The researchers’ interim efficacy analysis included all patients on 140 mg of erenumab with data about monthly migraine days after more than 4 years of treatment. The safety analysis included all patients who enrolled in the open-label treatment period and received at least one dose of erenumab.

Of 250 patients who increased the erenumab dose from 70 mg to 140 mg, a total of 221 (88%) completed the open-label treatment period or remained on 140 mg after more than 4 years. Patients’ average number of monthly migraine days at study baseline was 8.7, and the average change from baseline to the most recent month in the interim analysis was –5.8.

During the most recent month of assessment, 77% of patients had at least a 50% reduction in monthly migraine days from baseline, 56% had at least a 75% reduction, and 33% had a 100% reduction.

Mean change from baseline in acute migraine‐specific medication treatment days was –4.6, from a baseline of 6.1.

Among the 383 patients who entered the open-label treatment period and received at least one dose of erenumab (mean age, 41.3; 79% female), the median erenumab exposure was 58.5 months. The exposure‐adjusted incidence of adverse events per 100 patient‐years was 124.9, and the three most frequent adverse events (per 100 patient-years) were nasopharyngitis (10.9), upper respiratory tract infection (6.8), and influenza (4.7). The exposure‐adjusted incidence rate per 100 patient‐years for constipation was 1.3 (9/383) for 70-mg erenumab and 2.6 (15/250) for 140-mg erenumab.

“The exposure‐adjusted incidence rate per 100 patient‐years of serious adverse events was 3.8, similar to the rate observed for erenumab and placebo during the placebo‐controlled periods of studies,” the researchers said.

The study was sponsored by Amgen, and several study authors are employees of Amgen or Novartis, the companies that market erenumab. Dr. Ashina is a consultant for Amgen, Novartis, and other companies.

[email protected]

SOURCE: Ashina M et al. AHS 2019, Abstract IOR10.

PHILADELPHIA – Among patients with episodic migraine, 4.5 years of preventive treatment with erenumab is effective, safe, and well tolerated, according to interim data from an open-label extension study. “Erenumab was well tolerated and safe, with no safety signals detected over this period,” said Messoud Ashina, MD, PhD, professor of neurology at the University of Copenhagen. Dr. Ashina presented the interim data from a 5-year, open-label extension study of erenumab at the annual meeting of the American Headache Society.

Erenumab is a monoclonal antibody that targets and blocks the calcitonin gene-related peptide (CGRP) receptor. In May 2018, the Food and Drug Administration approved erenumab for the preventive treatment of migraine in adults. The treatment, marketed as Aimovig, is administered once monthly by self-injection.

During the open-label study, patients initially received 70 mg of erenumab monthly. After approximately 2 years, patients switched to 140 mg of erenumab monthly. The researchers’ interim efficacy analysis included all patients on 140 mg of erenumab with data about monthly migraine days after more than 4 years of treatment. The safety analysis included all patients who enrolled in the open-label treatment period and received at least one dose of erenumab.

Of 250 patients who increased the erenumab dose from 70 mg to 140 mg, a total of 221 (88%) completed the open-label treatment period or remained on 140 mg after more than 4 years. Patients’ average number of monthly migraine days at study baseline was 8.7, and the average change from baseline to the most recent month in the interim analysis was –5.8.

During the most recent month of assessment, 77% of patients had at least a 50% reduction in monthly migraine days from baseline, 56% had at least a 75% reduction, and 33% had a 100% reduction.

Mean change from baseline in acute migraine‐specific medication treatment days was –4.6, from a baseline of 6.1.

Among the 383 patients who entered the open-label treatment period and received at least one dose of erenumab (mean age, 41.3; 79% female), the median erenumab exposure was 58.5 months. The exposure‐adjusted incidence of adverse events per 100 patient‐years was 124.9, and the three most frequent adverse events (per 100 patient-years) were nasopharyngitis (10.9), upper respiratory tract infection (6.8), and influenza (4.7). The exposure‐adjusted incidence rate per 100 patient‐years for constipation was 1.3 (9/383) for 70-mg erenumab and 2.6 (15/250) for 140-mg erenumab.

“The exposure‐adjusted incidence rate per 100 patient‐years of serious adverse events was 3.8, similar to the rate observed for erenumab and placebo during the placebo‐controlled periods of studies,” the researchers said.

The study was sponsored by Amgen, and several study authors are employees of Amgen or Novartis, the companies that market erenumab. Dr. Ashina is a consultant for Amgen, Novartis, and other companies.

[email protected]

SOURCE: Ashina M et al. AHS 2019, Abstract IOR10.

Philadelphia – The more exposure that a person without migraine has to people with the disorder, the more likely he or she is to have potentially stigmatizing attitudes toward migraine, according to an analysis presented at the annual meeting of the American Headache Society.

“We need to understand why this is true,” said Robert Shapiro, MD, PhD, professor of neurological sciences at the University of Vermont in Burlington. The finding also raises questions about which measures could successfully mitigate these stigmatizing attitudes.
 

An examination of data from OVERCOME

Stigma is a social process by which people are excluded from society because of particular traits that they have. The process encompasses stereotypes, prejudice, and discrimination. Data suggest that the level of stigma that people with migraine experience is similar to that experienced by people with epilepsy. Other data indicate that people without migraine are equally likely to hold stigmatizing attitudes toward people with migraine and people with epilepsy.

Dr. Shapiro and colleagues examined data from the Observational Survey of the Epidemiology, Treatment, and Care of Migraine (OVERCOME) study to better understand the attitudes that people without migraine have toward those who have the disorder. The data were gathered in fall 2018 through a web-based survey of a representative U.S. sample population. The researchers focused on a random sample of 2,000 people without migraine who responded to 11 questions about their attitudes toward patients with migraine. Responses described the frequency of holding attitudes and were scored on a 5-point Likert scale. The researchers categorized the responses “don’t know,” “never,” and “rarely” as “no” answers, and “sometimes,” “often,” and “very often” as “yes” answers. In addition, Dr. Shapiro and colleagues characterized each responder’s proximity to migraine according to the number of people with migraine that he or she knew (0, 1, or 2 or more) and the type of relationship (none, coworker, friend, or family member).
 

Sample was demographically representative

The demographic and socioeconomic characteristics of the study sample were similar to those of the most recent U.S. census data. The population’s mean age was 48, and 51% were female. Approximately 65% of respondents were non-Hispanic white, 14% were Hispanic, 11% were non-Hispanic black, 5% were Asian, and 5% were “other.” Approximately 45% of respondents reported that they had never known anyone with migraine. “Given the prevalence of migraine, it’s extraordinary that only 13% acknowledged that they had known two or more people with migraine,” said Dr. Shapiro. The finding raises questions about whether people with migraine have received adequate diagnoses and are aware of their disorder, he added. About 5% of the sample reported knowing only a coworker with migraine, and 37% reported knowing only one person with migraine.

About 31% of respondents thought that people with migraine use the disorder to avoid school or work commitments, and 33% thought that patients used migraine to avoid family or social commitments. Approximately 27% of respondents thought that people with migraine used it to get attention. About 45% of respondents thought that migraine should be treated easily, and 36% thought that people have migraine because of their own unhealthy behavior.

Individuals who knew people with migraine consistently held more negative attitudes toward those people, compared with those who did not know anyone with migraine. “These data are a little alarming,” said Dr. Shapiro. “They point to the difficulties that people with disabling migraine often encounter in having their experiences with the disease receive validation and understanding.”

Among the study’s strengths is the fact that it examined a large, population-based sample. The survey was conducted before many of the newer medications for migraine were available, and respondents were not likely to have been influenced by commercials that raised awareness of migraine, said Dr. Shapiro. The sample was not random, however, and the survey questions were based on the investigators’ interests, rather than on objective data. The generalizability of the results is in question, he added.

Dr. Shapiro consults for Eli Lilly, which sponsored the OVERCOME study.

[email protected]

SOURCE: Shapiro R et al. AHS 2019. Abstract OR15.

Philadelphia – The more exposure that a person without migraine has to people with the disorder, the more likely he or she is to have potentially stigmatizing attitudes toward migraine, according to an analysis presented at the annual meeting of the American Headache Society.

“We need to understand why this is true,” said Robert Shapiro, MD, PhD, professor of neurological sciences at the University of Vermont in Burlington. The finding also raises questions about which measures could successfully mitigate these stigmatizing attitudes.
 

An examination of data from OVERCOME

Stigma is a social process by which people are excluded from society because of particular traits that they have. The process encompasses stereotypes, prejudice, and discrimination. Data suggest that the level of stigma that people with migraine experience is similar to that experienced by people with epilepsy. Other data indicate that people without migraine are equally likely to hold stigmatizing attitudes toward people with migraine and people with epilepsy.

Dr. Shapiro and colleagues examined data from the Observational Survey of the Epidemiology, Treatment, and Care of Migraine (OVERCOME) study to better understand the attitudes that people without migraine have toward those who have the disorder. The data were gathered in fall 2018 through a web-based survey of a representative U.S. sample population. The researchers focused on a random sample of 2,000 people without migraine who responded to 11 questions about their attitudes toward patients with migraine. Responses described the frequency of holding attitudes and were scored on a 5-point Likert scale. The researchers categorized the responses “don’t know,” “never,” and “rarely” as “no” answers, and “sometimes,” “often,” and “very often” as “yes” answers. In addition, Dr. Shapiro and colleagues characterized each responder’s proximity to migraine according to the number of people with migraine that he or she knew (0, 1, or 2 or more) and the type of relationship (none, coworker, friend, or family member).
 

Sample was demographically representative

The demographic and socioeconomic characteristics of the study sample were similar to those of the most recent U.S. census data. The population’s mean age was 48, and 51% were female. Approximately 65% of respondents were non-Hispanic white, 14% were Hispanic, 11% were non-Hispanic black, 5% were Asian, and 5% were “other.” Approximately 45% of respondents reported that they had never known anyone with migraine. “Given the prevalence of migraine, it’s extraordinary that only 13% acknowledged that they had known two or more people with migraine,” said Dr. Shapiro. The finding raises questions about whether people with migraine have received adequate diagnoses and are aware of their disorder, he added. About 5% of the sample reported knowing only a coworker with migraine, and 37% reported knowing only one person with migraine.

About 31% of respondents thought that people with migraine use the disorder to avoid school or work commitments, and 33% thought that patients used migraine to avoid family or social commitments. Approximately 27% of respondents thought that people with migraine used it to get attention. About 45% of respondents thought that migraine should be treated easily, and 36% thought that people have migraine because of their own unhealthy behavior.

Individuals who knew people with migraine consistently held more negative attitudes toward those people, compared with those who did not know anyone with migraine. “These data are a little alarming,” said Dr. Shapiro. “They point to the difficulties that people with disabling migraine often encounter in having their experiences with the disease receive validation and understanding.”

Among the study’s strengths is the fact that it examined a large, population-based sample. The survey was conducted before many of the newer medications for migraine were available, and respondents were not likely to have been influenced by commercials that raised awareness of migraine, said Dr. Shapiro. The sample was not random, however, and the survey questions were based on the investigators’ interests, rather than on objective data. The generalizability of the results is in question, he added.

Dr. Shapiro consults for Eli Lilly, which sponsored the OVERCOME study.

[email protected]

SOURCE: Shapiro R et al. AHS 2019. Abstract OR15.

Philadelphia – The more exposure that a person without migraine has to people with the disorder, the more likely he or she is to have potentially stigmatizing attitudes toward migraine, according to an analysis presented at the annual meeting of the American Headache Society.

“We need to understand why this is true,” said Robert Shapiro, MD, PhD, professor of neurological sciences at the University of Vermont in Burlington. The finding also raises questions about which measures could successfully mitigate these stigmatizing attitudes.
 

An examination of data from OVERCOME

Stigma is a social process by which people are excluded from society because of particular traits that they have. The process encompasses stereotypes, prejudice, and discrimination. Data suggest that the level of stigma that people with migraine experience is similar to that experienced by people with epilepsy. Other data indicate that people without migraine are equally likely to hold stigmatizing attitudes toward people with migraine and people with epilepsy.

Dr. Shapiro and colleagues examined data from the Observational Survey of the Epidemiology, Treatment, and Care of Migraine (OVERCOME) study to better understand the attitudes that people without migraine have toward those who have the disorder. The data were gathered in fall 2018 through a web-based survey of a representative U.S. sample population. The researchers focused on a random sample of 2,000 people without migraine who responded to 11 questions about their attitudes toward patients with migraine. Responses described the frequency of holding attitudes and were scored on a 5-point Likert scale. The researchers categorized the responses “don’t know,” “never,” and “rarely” as “no” answers, and “sometimes,” “often,” and “very often” as “yes” answers. In addition, Dr. Shapiro and colleagues characterized each responder’s proximity to migraine according to the number of people with migraine that he or she knew (0, 1, or 2 or more) and the type of relationship (none, coworker, friend, or family member).
 

Sample was demographically representative

The demographic and socioeconomic characteristics of the study sample were similar to those of the most recent U.S. census data. The population’s mean age was 48, and 51% were female. Approximately 65% of respondents were non-Hispanic white, 14% were Hispanic, 11% were non-Hispanic black, 5% were Asian, and 5% were “other.” Approximately 45% of respondents reported that they had never known anyone with migraine. “Given the prevalence of migraine, it’s extraordinary that only 13% acknowledged that they had known two or more people with migraine,” said Dr. Shapiro. The finding raises questions about whether people with migraine have received adequate diagnoses and are aware of their disorder, he added. About 5% of the sample reported knowing only a coworker with migraine, and 37% reported knowing only one person with migraine.

About 31% of respondents thought that people with migraine use the disorder to avoid school or work commitments, and 33% thought that patients used migraine to avoid family or social commitments. Approximately 27% of respondents thought that people with migraine used it to get attention. About 45% of respondents thought that migraine should be treated easily, and 36% thought that people have migraine because of their own unhealthy behavior.

Individuals who knew people with migraine consistently held more negative attitudes toward those people, compared with those who did not know anyone with migraine. “These data are a little alarming,” said Dr. Shapiro. “They point to the difficulties that people with disabling migraine often encounter in having their experiences with the disease receive validation and understanding.”

Among the study’s strengths is the fact that it examined a large, population-based sample. The survey was conducted before many of the newer medications for migraine were available, and respondents were not likely to have been influenced by commercials that raised awareness of migraine, said Dr. Shapiro. The sample was not random, however, and the survey questions were based on the investigators’ interests, rather than on objective data. The generalizability of the results is in question, he added.

Dr. Shapiro consults for Eli Lilly, which sponsored the OVERCOME study.

[email protected]

SOURCE: Shapiro R et al. AHS 2019. Abstract OR15.

PHILADELPHIA – Atogepant, an oral small-molecule migraine drug from the “gepant” class, showed safety and efficacy for preventing migraine headaches in a phase 2/3, dose-ranging trial with 825 evaluable patients.

Mitchel L. Zoler/MDedge News

Atogepant is the first drug from this novel class to undergo efficacy testing in an advanced-phase trial for prevention of migraine headaches, David W. Dodick, MD, said at the annual meeting of the American Headache Society. Two other agents from the gepant class, rimegepant and ubrogepant, have undergone phase 3 testing for acute treatment of migraine headache, and both drugs are now under Food and Drug Administration consideration for an acute-treatment indication.

Three monoclonal antibodies to the calcitonin gene–related peptide (CGRP) receptor have received FDA marketing approval since 2018 for migraine headache prevention. The small-molecule antagonists to the CGRP receptor in the gepant class have an effect similar to the monoclonal antibodies, but with different dosage schedules, an oral route of administration, and with half-lives measured in hours, compared with days and weeks.

“Historically the [gepant] class of drugs was designed for acute treatment, and a couple of drugs from this class didn’t make it because of liver toxicity, but the liver toxicity is not a class effect.” The more recent candidate agents – atogepant, ubrogepant, and rimegepant – have shown hepatic safety as well as overall safety, noted Dr. Dodick, a neurologist and headache specialist at the Mayo Clinic in Phoenix.

If these gepant agents eventually receive FDA approval, which seems likely based on the evidence collected so far, they would collectively form “the only class to have both acute and preventive indications” for migraine, Dr. Dodick said in an interview. The preventive efficacy seen with atogepant in the current study is likely a class effect that has not yet been tested in ubrogepant and rimegepant.

In the multicenter study he reported, 834 patients, 86% of them women, were randomized to placebo or to any of five dosages of atogepant, ranging from 10 mg once daily to 60 mg b.i.d. Study participants had a history of episodic migraine with an average of nearly eight migraine-headache days per month and an average disease duration of about 19 years. The patients’ average age was about 40 years, and 72% had never before used a migraine-preventive treatment. Half had migraine without aura, about a quarter had migraine with aura, and a quarter had migraines of both types.


The researchers had safety data for 825 patients, and efficacy data for 795.

The study’s primary efficacy endpoint was the reduction from baseline in average migraine headache days per month after 12 weeks on treatment. Average migraine headache days fell by 2.85 days in the placebo group and by 3.55-4.23 days in the atogepant treatment groups, a significant difference. The reduction depended on the dosage patients received, but there was no clear dose-response relationship.

At least a 50% drop in average monthly headache day totals was seen in 40% of the placebo patients and in 52%-62% of the patients on atogepant, depending on their dosage. In this case, a signal appeared for a dose-response relationship as only the two subgroups with the patients who received the largest atogepant dosages showed statistically significant improvements in response, compared with placebo.

All patients on atogepant, regardless of their dosage, also had statistically significant reductions in their use of acute migraine medications, compared with placebo patients.

The level of benefit beyond placebo seen in these results was “clinically meaningful,” and roughly comparable with the preventive benefit seen with both the CGRP receptor antagonist monoclonal antibodies, as well as with the three conventional agents most commonly used for migraine headache prevention in current U.S. practice: topiramate, amitriptyline, and propranolol, Dr. Dodick said. Amitriptyline is not approved for this indication.

The adverse event profile among patients who received atogepant was about the same as it was among the placebo recipients. Seven study patients had serious treatment-related adverse effects; two of these patients were in the placebo arm of 186 patients. The most common adverse events were nausea, constipation, and fatigue, and were seen mostly at the highest dosage of atogepant. The incidence of elevated liver enzymes was low and similar in the placebo and drug-treated patients. Two patients, one on placebo and one on atogepant, had their liver enzymes reach at least five times the upper limit of normal. None had their enzymes reach at least 10 times the upper limit of normal, and no patients in the study had a response that fulfilled “Hy’s law,” which flags drug-induced liver injury as patients who develop the combination of elevated liver enzymes, elevated bilirubin, and depressed alkaline phosphatase.

The study was sponsored by Allergan, the company developing atogepant and ubrogepant. Dr. Dodick has been a consultant to Allergan and to several other drug companies.

[email protected]

PHILADELPHIA – Atogepant, an oral small-molecule migraine drug from the “gepant” class, showed safety and efficacy for preventing migraine headaches in a phase 2/3, dose-ranging trial with 825 evaluable patients.

Mitchel L. Zoler/MDedge News

Atogepant is the first drug from this novel class to undergo efficacy testing in an advanced-phase trial for prevention of migraine headaches, David W. Dodick, MD, said at the annual meeting of the American Headache Society. Two other agents from the gepant class, rimegepant and ubrogepant, have undergone phase 3 testing for acute treatment of migraine headache, and both drugs are now under Food and Drug Administration consideration for an acute-treatment indication.

Three monoclonal antibodies to the calcitonin gene–related peptide (CGRP) receptor have received FDA marketing approval since 2018 for migraine headache prevention. The small-molecule antagonists to the CGRP receptor in the gepant class have an effect similar to the monoclonal antibodies, but with different dosage schedules, an oral route of administration, and with half-lives measured in hours, compared with days and weeks.

“Historically the [gepant] class of drugs was designed for acute treatment, and a couple of drugs from this class didn’t make it because of liver toxicity, but the liver toxicity is not a class effect.” The more recent candidate agents – atogepant, ubrogepant, and rimegepant – have shown hepatic safety as well as overall safety, noted Dr. Dodick, a neurologist and headache specialist at the Mayo Clinic in Phoenix.

If these gepant agents eventually receive FDA approval, which seems likely based on the evidence collected so far, they would collectively form “the only class to have both acute and preventive indications” for migraine, Dr. Dodick said in an interview. The preventive efficacy seen with atogepant in the current study is likely a class effect that has not yet been tested in ubrogepant and rimegepant.

In the multicenter study he reported, 834 patients, 86% of them women, were randomized to placebo or to any of five dosages of atogepant, ranging from 10 mg once daily to 60 mg b.i.d. Study participants had a history of episodic migraine with an average of nearly eight migraine-headache days per month and an average disease duration of about 19 years. The patients’ average age was about 40 years, and 72% had never before used a migraine-preventive treatment. Half had migraine without aura, about a quarter had migraine with aura, and a quarter had migraines of both types.


The researchers had safety data for 825 patients, and efficacy data for 795.

The study’s primary efficacy endpoint was the reduction from baseline in average migraine headache days per month after 12 weeks on treatment. Average migraine headache days fell by 2.85 days in the placebo group and by 3.55-4.23 days in the atogepant treatment groups, a significant difference. The reduction depended on the dosage patients received, but there was no clear dose-response relationship.

At least a 50% drop in average monthly headache day totals was seen in 40% of the placebo patients and in 52%-62% of the patients on atogepant, depending on their dosage. In this case, a signal appeared for a dose-response relationship as only the two subgroups with the patients who received the largest atogepant dosages showed statistically significant improvements in response, compared with placebo.

All patients on atogepant, regardless of their dosage, also had statistically significant reductions in their use of acute migraine medications, compared with placebo patients.

The level of benefit beyond placebo seen in these results was “clinically meaningful,” and roughly comparable with the preventive benefit seen with both the CGRP receptor antagonist monoclonal antibodies, as well as with the three conventional agents most commonly used for migraine headache prevention in current U.S. practice: topiramate, amitriptyline, and propranolol, Dr. Dodick said. Amitriptyline is not approved for this indication.

The adverse event profile among patients who received atogepant was about the same as it was among the placebo recipients. Seven study patients had serious treatment-related adverse effects; two of these patients were in the placebo arm of 186 patients. The most common adverse events were nausea, constipation, and fatigue, and were seen mostly at the highest dosage of atogepant. The incidence of elevated liver enzymes was low and similar in the placebo and drug-treated patients. Two patients, one on placebo and one on atogepant, had their liver enzymes reach at least five times the upper limit of normal. None had their enzymes reach at least 10 times the upper limit of normal, and no patients in the study had a response that fulfilled “Hy’s law,” which flags drug-induced liver injury as patients who develop the combination of elevated liver enzymes, elevated bilirubin, and depressed alkaline phosphatase.

The study was sponsored by Allergan, the company developing atogepant and ubrogepant. Dr. Dodick has been a consultant to Allergan and to several other drug companies.

[email protected]

PHILADELPHIA – Atogepant, an oral small-molecule migraine drug from the “gepant” class, showed safety and efficacy for preventing migraine headaches in a phase 2/3, dose-ranging trial with 825 evaluable patients.

Mitchel L. Zoler/MDedge News

Atogepant is the first drug from this novel class to undergo efficacy testing in an advanced-phase trial for prevention of migraine headaches, David W. Dodick, MD, said at the annual meeting of the American Headache Society. Two other agents from the gepant class, rimegepant and ubrogepant, have undergone phase 3 testing for acute treatment of migraine headache, and both drugs are now under Food and Drug Administration consideration for an acute-treatment indication.

Three monoclonal antibodies to the calcitonin gene–related peptide (CGRP) receptor have received FDA marketing approval since 2018 for migraine headache prevention. The small-molecule antagonists to the CGRP receptor in the gepant class have an effect similar to the monoclonal antibodies, but with different dosage schedules, an oral route of administration, and with half-lives measured in hours, compared with days and weeks.

“Historically the [gepant] class of drugs was designed for acute treatment, and a couple of drugs from this class didn’t make it because of liver toxicity, but the liver toxicity is not a class effect.” The more recent candidate agents – atogepant, ubrogepant, and rimegepant – have shown hepatic safety as well as overall safety, noted Dr. Dodick, a neurologist and headache specialist at the Mayo Clinic in Phoenix.

If these gepant agents eventually receive FDA approval, which seems likely based on the evidence collected so far, they would collectively form “the only class to have both acute and preventive indications” for migraine, Dr. Dodick said in an interview. The preventive efficacy seen with atogepant in the current study is likely a class effect that has not yet been tested in ubrogepant and rimegepant.

In the multicenter study he reported, 834 patients, 86% of them women, were randomized to placebo or to any of five dosages of atogepant, ranging from 10 mg once daily to 60 mg b.i.d. Study participants had a history of episodic migraine with an average of nearly eight migraine-headache days per month and an average disease duration of about 19 years. The patients’ average age was about 40 years, and 72% had never before used a migraine-preventive treatment. Half had migraine without aura, about a quarter had migraine with aura, and a quarter had migraines of both types.


The researchers had safety data for 825 patients, and efficacy data for 795.

The study’s primary efficacy endpoint was the reduction from baseline in average migraine headache days per month after 12 weeks on treatment. Average migraine headache days fell by 2.85 days in the placebo group and by 3.55-4.23 days in the atogepant treatment groups, a significant difference. The reduction depended on the dosage patients received, but there was no clear dose-response relationship.

At least a 50% drop in average monthly headache day totals was seen in 40% of the placebo patients and in 52%-62% of the patients on atogepant, depending on their dosage. In this case, a signal appeared for a dose-response relationship as only the two subgroups with the patients who received the largest atogepant dosages showed statistically significant improvements in response, compared with placebo.

All patients on atogepant, regardless of their dosage, also had statistically significant reductions in their use of acute migraine medications, compared with placebo patients.

The level of benefit beyond placebo seen in these results was “clinically meaningful,” and roughly comparable with the preventive benefit seen with both the CGRP receptor antagonist monoclonal antibodies, as well as with the three conventional agents most commonly used for migraine headache prevention in current U.S. practice: topiramate, amitriptyline, and propranolol, Dr. Dodick said. Amitriptyline is not approved for this indication.

The adverse event profile among patients who received atogepant was about the same as it was among the placebo recipients. Seven study patients had serious treatment-related adverse effects; two of these patients were in the placebo arm of 186 patients. The most common adverse events were nausea, constipation, and fatigue, and were seen mostly at the highest dosage of atogepant. The incidence of elevated liver enzymes was low and similar in the placebo and drug-treated patients. Two patients, one on placebo and one on atogepant, had their liver enzymes reach at least five times the upper limit of normal. None had their enzymes reach at least 10 times the upper limit of normal, and no patients in the study had a response that fulfilled “Hy’s law,” which flags drug-induced liver injury as patients who develop the combination of elevated liver enzymes, elevated bilirubin, and depressed alkaline phosphatase.

The study was sponsored by Allergan, the company developing atogepant and ubrogepant. Dr. Dodick has been a consultant to Allergan and to several other drug companies.

[email protected]

PHILADELPHIA – Nineteen percent of patients with migraine use opioids to treat migraine, according to a survey of more than 21,000 patients in 2018. People with 4 or more migraine headache days per month are more likely to use opioids, compared with people with fewer migraine headache days per month, researchers said. Opioid use for migraine “remains alarmingly high,” the investigators said at the annual meeting of the American Headache Society.

Although opioid use for the treatment of migraine typically is discouraged, studies indicate that it is common. Evidence suggests that opioids may increase the risk of progression from episodic to chronic migraine.

To evaluate opioid use in people with migraine, Sait Ashina, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, and the research colleagues analyzed data from 21,143 people with migraine who participated in the OVERCOME (Observational Survey of the Epidemiology, Treatment and Care of Migraine), a Web-based study of a representative U.S. sample. OVERCOME enrolled participants in the fall of 2018.

The researchers classified self-reported opioid use for migraine as current use in the past 12 months, former use, or never. Participants had a mean age of 42 years, and 74% were female. The researchers used a multivariable logistic regression model adjusted for age and sex in their analyses.

“Strikingly, we were able to find 19% of people with migraine were reporting current use of opioids,” Dr. Ashina said.

Among 12,299 patients with 0-3 migraine headache days per month, 59% were never, 26% former, and 15% current users of opioids for migraine. Among 8,844 patients with 4 or more migraine headache days per month, 44.9% were never, 31.2% former, and 23.9% current users of opioids for migraine.

There was an increased likelihood of opioid use for migraine in people with pain comorbidities such as back pain, neck pain, and fibromyalgia and in people with anxiety and depression.

Approximately 30%-40% of those who used opioids for migraine were using strong opioids, as defined by the World Health Organization, Dr. Ashina noted. Preliminary analyses indicate that patients tended to receive opioids in a primary care setting, he said.

Eli Lilly funded the OVERCOME study. Dr. Ashina has consulted for Novartis, Amgen, Promius, Supernus, Satsuma, and Allergan. He is on the Editorial Advisory Board for Neurology Reviews.

[email protected]

PHILADELPHIA – Nineteen percent of patients with migraine use opioids to treat migraine, according to a survey of more than 21,000 patients in 2018. People with 4 or more migraine headache days per month are more likely to use opioids, compared with people with fewer migraine headache days per month, researchers said. Opioid use for migraine “remains alarmingly high,” the investigators said at the annual meeting of the American Headache Society.

Although opioid use for the treatment of migraine typically is discouraged, studies indicate that it is common. Evidence suggests that opioids may increase the risk of progression from episodic to chronic migraine.

To evaluate opioid use in people with migraine, Sait Ashina, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, and the research colleagues analyzed data from 21,143 people with migraine who participated in the OVERCOME (Observational Survey of the Epidemiology, Treatment and Care of Migraine), a Web-based study of a representative U.S. sample. OVERCOME enrolled participants in the fall of 2018.

The researchers classified self-reported opioid use for migraine as current use in the past 12 months, former use, or never. Participants had a mean age of 42 years, and 74% were female. The researchers used a multivariable logistic regression model adjusted for age and sex in their analyses.

“Strikingly, we were able to find 19% of people with migraine were reporting current use of opioids,” Dr. Ashina said.

Among 12,299 patients with 0-3 migraine headache days per month, 59% were never, 26% former, and 15% current users of opioids for migraine. Among 8,844 patients with 4 or more migraine headache days per month, 44.9% were never, 31.2% former, and 23.9% current users of opioids for migraine.

There was an increased likelihood of opioid use for migraine in people with pain comorbidities such as back pain, neck pain, and fibromyalgia and in people with anxiety and depression.

Approximately 30%-40% of those who used opioids for migraine were using strong opioids, as defined by the World Health Organization, Dr. Ashina noted. Preliminary analyses indicate that patients tended to receive opioids in a primary care setting, he said.

Eli Lilly funded the OVERCOME study. Dr. Ashina has consulted for Novartis, Amgen, Promius, Supernus, Satsuma, and Allergan. He is on the Editorial Advisory Board for Neurology Reviews.

[email protected]

PHILADELPHIA – Nineteen percent of patients with migraine use opioids to treat migraine, according to a survey of more than 21,000 patients in 2018. People with 4 or more migraine headache days per month are more likely to use opioids, compared with people with fewer migraine headache days per month, researchers said. Opioid use for migraine “remains alarmingly high,” the investigators said at the annual meeting of the American Headache Society.

Although opioid use for the treatment of migraine typically is discouraged, studies indicate that it is common. Evidence suggests that opioids may increase the risk of progression from episodic to chronic migraine.

To evaluate opioid use in people with migraine, Sait Ashina, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, and the research colleagues analyzed data from 21,143 people with migraine who participated in the OVERCOME (Observational Survey of the Epidemiology, Treatment and Care of Migraine), a Web-based study of a representative U.S. sample. OVERCOME enrolled participants in the fall of 2018.

The researchers classified self-reported opioid use for migraine as current use in the past 12 months, former use, or never. Participants had a mean age of 42 years, and 74% were female. The researchers used a multivariable logistic regression model adjusted for age and sex in their analyses.

“Strikingly, we were able to find 19% of people with migraine were reporting current use of opioids,” Dr. Ashina said.

Among 12,299 patients with 0-3 migraine headache days per month, 59% were never, 26% former, and 15% current users of opioids for migraine. Among 8,844 patients with 4 or more migraine headache days per month, 44.9% were never, 31.2% former, and 23.9% current users of opioids for migraine.

There was an increased likelihood of opioid use for migraine in people with pain comorbidities such as back pain, neck pain, and fibromyalgia and in people with anxiety and depression.

Approximately 30%-40% of those who used opioids for migraine were using strong opioids, as defined by the World Health Organization, Dr. Ashina noted. Preliminary analyses indicate that patients tended to receive opioids in a primary care setting, he said.

Eli Lilly funded the OVERCOME study. Dr. Ashina has consulted for Novartis, Amgen, Promius, Supernus, Satsuma, and Allergan. He is on the Editorial Advisory Board for Neurology Reviews.

[email protected]

PHILADELPHIA – A majority of migraineurs with 4 or more headache days per month have seen a health care professional for headache in the preceding 12 months, according to an investigation presented at the annual meeting of the American Headache Society.

The largest group of these patients consults primary care physicians. The acute and preventive migraine treatment that these patients receive vary according to the type of provider that they see. Nevertheless, treatment is generally suboptimal, compared with the standards of current guidelines, said the investigators.

Bruce Jancin/MDedge News

Migraine is underdiagnosed and undertreated, said Dawn C. Buse, PhD, clinical professor of neurology at Albert Einstein College of Medicine, New York, and colleagues. Recent changes in health care policy and the expanded array of treatments for migraine warrant an investigation of the current state of migraine care, they added. They examined survey data to understand where patients with migraine in the United States seek care, which characteristics are associated with seeking care in the previous 12 months, and which treatments are prescribed.

Dr. Buse and colleagues analyzed data from the OVERCOME (Observational Survey of the Epidemiology, Treatment, and Care of Migraine) study. These data were obtained in 2018 using a Web-based survey of a representative U.S. sample of 21,143 patients with migraine. The investigators focused on care seeking and medication use in a subsample of 8,844 patients with 4 or more migraine headache days per month to better understand those with the greatest care needs.

The mean age of this subsample was 42.0 years. Approximately 78% of participants were female, and 74.8% were white. In the preceding 12 months, 61.1% of the patients sought care for migraine; 38.3% sought care from more than two types of provider. Provider types included primary care physicians (45.5%), neurologists (20.2%), emergency medicine clinicians (19.2%), urgent care providers (14.4%), pain specialists (12.8%), headache specialists (12.0%), and retail (nonurgent) clinics (10.4%).

Dr. Buse and colleagues found that sociodemographic factors such as age, sex, education, income, and health insurance type influenced participants’ likelihood of seeking care. Seeking care was positively associated with the number of headache days, pain severity, allodynia, aura, and prodrome. When the researchers examined migraine characteristics, they found that nausea and vomiting (68.8%) was more likely to prompt a patient to seek care, compared with phonophobia and photophobia (64.3%). Participants who sought care from a headache specialist (55.0%) or a neurologist (50.1%) were most likely to be using migraine preventive medication. More than 20% of migraineurs seeking care from primary care, urgent care, or retail clinic professionals were undiagnosed.

Primary care doctors were most likely to prescribe triptans, followed by opioids and preventive medications. Neurologists and headache specialists were most likely to prescribe preventive medications and unlikely to prescribe opioids.

Eli Lilly funds the OVERCOME study. Dr. Buse consults for Lilly on this study, but she and her coauthors who do not work in the industry did not receive any funding for any work related to writing, publishing, or presenting any abstracts, posters, platforms, or manuscripts.

[email protected]

PHILADELPHIA – A majority of migraineurs with 4 or more headache days per month have seen a health care professional for headache in the preceding 12 months, according to an investigation presented at the annual meeting of the American Headache Society.

The largest group of these patients consults primary care physicians. The acute and preventive migraine treatment that these patients receive vary according to the type of provider that they see. Nevertheless, treatment is generally suboptimal, compared with the standards of current guidelines, said the investigators.

Bruce Jancin/MDedge News

Migraine is underdiagnosed and undertreated, said Dawn C. Buse, PhD, clinical professor of neurology at Albert Einstein College of Medicine, New York, and colleagues. Recent changes in health care policy and the expanded array of treatments for migraine warrant an investigation of the current state of migraine care, they added. They examined survey data to understand where patients with migraine in the United States seek care, which characteristics are associated with seeking care in the previous 12 months, and which treatments are prescribed.

Dr. Buse and colleagues analyzed data from the OVERCOME (Observational Survey of the Epidemiology, Treatment, and Care of Migraine) study. These data were obtained in 2018 using a Web-based survey of a representative U.S. sample of 21,143 patients with migraine. The investigators focused on care seeking and medication use in a subsample of 8,844 patients with 4 or more migraine headache days per month to better understand those with the greatest care needs.

The mean age of this subsample was 42.0 years. Approximately 78% of participants were female, and 74.8% were white. In the preceding 12 months, 61.1% of the patients sought care for migraine; 38.3% sought care from more than two types of provider. Provider types included primary care physicians (45.5%), neurologists (20.2%), emergency medicine clinicians (19.2%), urgent care providers (14.4%), pain specialists (12.8%), headache specialists (12.0%), and retail (nonurgent) clinics (10.4%).

Dr. Buse and colleagues found that sociodemographic factors such as age, sex, education, income, and health insurance type influenced participants’ likelihood of seeking care. Seeking care was positively associated with the number of headache days, pain severity, allodynia, aura, and prodrome. When the researchers examined migraine characteristics, they found that nausea and vomiting (68.8%) was more likely to prompt a patient to seek care, compared with phonophobia and photophobia (64.3%). Participants who sought care from a headache specialist (55.0%) or a neurologist (50.1%) were most likely to be using migraine preventive medication. More than 20% of migraineurs seeking care from primary care, urgent care, or retail clinic professionals were undiagnosed.

Primary care doctors were most likely to prescribe triptans, followed by opioids and preventive medications. Neurologists and headache specialists were most likely to prescribe preventive medications and unlikely to prescribe opioids.

Eli Lilly funds the OVERCOME study. Dr. Buse consults for Lilly on this study, but she and her coauthors who do not work in the industry did not receive any funding for any work related to writing, publishing, or presenting any abstracts, posters, platforms, or manuscripts.

[email protected]

PHILADELPHIA – A majority of migraineurs with 4 or more headache days per month have seen a health care professional for headache in the preceding 12 months, according to an investigation presented at the annual meeting of the American Headache Society.

The largest group of these patients consults primary care physicians. The acute and preventive migraine treatment that these patients receive vary according to the type of provider that they see. Nevertheless, treatment is generally suboptimal, compared with the standards of current guidelines, said the investigators.

Bruce Jancin/MDedge News

Migraine is underdiagnosed and undertreated, said Dawn C. Buse, PhD, clinical professor of neurology at Albert Einstein College of Medicine, New York, and colleagues. Recent changes in health care policy and the expanded array of treatments for migraine warrant an investigation of the current state of migraine care, they added. They examined survey data to understand where patients with migraine in the United States seek care, which characteristics are associated with seeking care in the previous 12 months, and which treatments are prescribed.

Dr. Buse and colleagues analyzed data from the OVERCOME (Observational Survey of the Epidemiology, Treatment, and Care of Migraine) study. These data were obtained in 2018 using a Web-based survey of a representative U.S. sample of 21,143 patients with migraine. The investigators focused on care seeking and medication use in a subsample of 8,844 patients with 4 or more migraine headache days per month to better understand those with the greatest care needs.

The mean age of this subsample was 42.0 years. Approximately 78% of participants were female, and 74.8% were white. In the preceding 12 months, 61.1% of the patients sought care for migraine; 38.3% sought care from more than two types of provider. Provider types included primary care physicians (45.5%), neurologists (20.2%), emergency medicine clinicians (19.2%), urgent care providers (14.4%), pain specialists (12.8%), headache specialists (12.0%), and retail (nonurgent) clinics (10.4%).

Dr. Buse and colleagues found that sociodemographic factors such as age, sex, education, income, and health insurance type influenced participants’ likelihood of seeking care. Seeking care was positively associated with the number of headache days, pain severity, allodynia, aura, and prodrome. When the researchers examined migraine characteristics, they found that nausea and vomiting (68.8%) was more likely to prompt a patient to seek care, compared with phonophobia and photophobia (64.3%). Participants who sought care from a headache specialist (55.0%) or a neurologist (50.1%) were most likely to be using migraine preventive medication. More than 20% of migraineurs seeking care from primary care, urgent care, or retail clinic professionals were undiagnosed.

Primary care doctors were most likely to prescribe triptans, followed by opioids and preventive medications. Neurologists and headache specialists were most likely to prescribe preventive medications and unlikely to prescribe opioids.

Eli Lilly funds the OVERCOME study. Dr. Buse consults for Lilly on this study, but she and her coauthors who do not work in the industry did not receive any funding for any work related to writing, publishing, or presenting any abstracts, posters, platforms, or manuscripts.

[email protected]

Periodontal inflammation is associated with increased circulating levels of calcitonin gene-related peptide (CGRP) in patients with chronic migraine, a new study found. The cohort included 102 chronic migraineurs and 77 age- and sex-matched individuals free of headache/migraine. Full-mouth periodontal parameters were recorded and the periodontal inflamed surface area (PISA) was calculated to quantify the periodontal inflammatory status for each participant. Researchers found:

• In the chronic migraine group, patients with periodontitis had greater levels of serum CGRP and IL-6, while nonsignificant differences were observed with IL-10 concentrations vs those without periodontitis.
• PISA was independently associated with CGRP in patients with chronic migraine.

Leira Y, et al. Periodontal inflammation is related to increased serum calcitonin gene-related peptide (CGRP) levels in patients with chronic migraine. [Published online ahead of print May 9, 2019]. J Periodontol. doi: 10.1002/JPER.19-0051.

Periodontal inflammation is associated with increased circulating levels of calcitonin gene-related peptide (CGRP) in patients with chronic migraine, a new study found. The cohort included 102 chronic migraineurs and 77 age- and sex-matched individuals free of headache/migraine. Full-mouth periodontal parameters were recorded and the periodontal inflamed surface area (PISA) was calculated to quantify the periodontal inflammatory status for each participant. Researchers found:

• In the chronic migraine group, patients with periodontitis had greater levels of serum CGRP and IL-6, while nonsignificant differences were observed with IL-10 concentrations vs those without periodontitis.
• PISA was independently associated with CGRP in patients with chronic migraine.

Leira Y, et al. Periodontal inflammation is related to increased serum calcitonin gene-related peptide (CGRP) levels in patients with chronic migraine. [Published online ahead of print May 9, 2019]. J Periodontol. doi: 10.1002/JPER.19-0051.

Periodontal inflammation is associated with increased circulating levels of calcitonin gene-related peptide (CGRP) in patients with chronic migraine, a new study found. The cohort included 102 chronic migraineurs and 77 age- and sex-matched individuals free of headache/migraine. Full-mouth periodontal parameters were recorded and the periodontal inflamed surface area (PISA) was calculated to quantify the periodontal inflammatory status for each participant. Researchers found:

• In the chronic migraine group, patients with periodontitis had greater levels of serum CGRP and IL-6, while nonsignificant differences were observed with IL-10 concentrations vs those without periodontitis.
• PISA was independently associated with CGRP in patients with chronic migraine.

Leira Y, et al. Periodontal inflammation is related to increased serum calcitonin gene-related peptide (CGRP) levels in patients with chronic migraine. [Published online ahead of print May 9, 2019]. J Periodontol. doi: 10.1002/JPER.19-0051.