Headache & Migraine

In a large, nationally representative retrospective cohort study, migraine admission with aura was independently associated with transient ischemic attack (TIA) readmission, and status migrainosus was independently associated with subarachnoid hemorrhage. The Nationwide Readmissions Database was designed to analyze readmissions for all payers and uninsured, with data on more than 14 million US admissions in 2013. Researchers identified index migraine admissions with and without aura or status migrainosus, and readmissions for cerebrovascular events. Cox proportional hazards regression was performed for each outcome with aura and status migrainosus as main predictors, adjusting for age and vascular risk factors. They found:

• Out of 12,448 index admissions for migraine, 9972 (80.1%) were women, mean age was 45.5 ± 14.8 years, aura was present in 3038 (24.41%), and status migrainosus in 1798 (14.44%).
• The 30‐day readmission rate (per 100,000 index admissions) was 154 for ischemic stroke, 86 for TIA, 42 for subarachnoid hemorrhage, and 17 for intracranial hemorrhage.
• In unadjusted models, aura was significantly associated with TIA (hazard ratio 2.43), but not acute ischemic stroke (1.26), intracranial hemorrhage (1.86), or subarachnoid hemorrhage (1.85).

Velickovic Osotjic L, Liang JW, Sheikh HU, Dhamoon MS. Impact of aura and status migrainosus on readmissions for vascular events after migraine admission. [Published online ahead of print June 22, 2018]. Headache. doi:10.1111/head.13347.

In a large, nationally representative retrospective cohort study, migraine admission with aura was independently associated with transient ischemic attack (TIA) readmission, and status migrainosus was independently associated with subarachnoid hemorrhage. The Nationwide Readmissions Database was designed to analyze readmissions for all payers and uninsured, with data on more than 14 million US admissions in 2013. Researchers identified index migraine admissions with and without aura or status migrainosus, and readmissions for cerebrovascular events. Cox proportional hazards regression was performed for each outcome with aura and status migrainosus as main predictors, adjusting for age and vascular risk factors. They found:

• Out of 12,448 index admissions for migraine, 9972 (80.1%) were women, mean age was 45.5 ± 14.8 years, aura was present in 3038 (24.41%), and status migrainosus in 1798 (14.44%).
• The 30‐day readmission rate (per 100,000 index admissions) was 154 for ischemic stroke, 86 for TIA, 42 for subarachnoid hemorrhage, and 17 for intracranial hemorrhage.
• In unadjusted models, aura was significantly associated with TIA (hazard ratio 2.43), but not acute ischemic stroke (1.26), intracranial hemorrhage (1.86), or subarachnoid hemorrhage (1.85).

Velickovic Osotjic L, Liang JW, Sheikh HU, Dhamoon MS. Impact of aura and status migrainosus on readmissions for vascular events after migraine admission. [Published online ahead of print June 22, 2018]. Headache. doi:10.1111/head.13347.

In a large, nationally representative retrospective cohort study, migraine admission with aura was independently associated with transient ischemic attack (TIA) readmission, and status migrainosus was independently associated with subarachnoid hemorrhage. The Nationwide Readmissions Database was designed to analyze readmissions for all payers and uninsured, with data on more than 14 million US admissions in 2013. Researchers identified index migraine admissions with and without aura or status migrainosus, and readmissions for cerebrovascular events. Cox proportional hazards regression was performed for each outcome with aura and status migrainosus as main predictors, adjusting for age and vascular risk factors. They found:

• Out of 12,448 index admissions for migraine, 9972 (80.1%) were women, mean age was 45.5 ± 14.8 years, aura was present in 3038 (24.41%), and status migrainosus in 1798 (14.44%).
• The 30‐day readmission rate (per 100,000 index admissions) was 154 for ischemic stroke, 86 for TIA, 42 for subarachnoid hemorrhage, and 17 for intracranial hemorrhage.
• In unadjusted models, aura was significantly associated with TIA (hazard ratio 2.43), but not acute ischemic stroke (1.26), intracranial hemorrhage (1.86), or subarachnoid hemorrhage (1.85).

Velickovic Osotjic L, Liang JW, Sheikh HU, Dhamoon MS. Impact of aura and status migrainosus on readmissions for vascular events after migraine admission. [Published online ahead of print June 22, 2018]. Headache. doi:10.1111/head.13347.

Headache smartphone applications (apps) shared information with third parties, posing privacy risks partly because there are few legal protections against the sale or disclosure of data from medical apps to third parties. This is according to a recent study that sought to assess whether there are privacy issues surrounding apps and the potential privacy implications of how the app companies (and other third parties) might use that information. Researchers conducted a systematic search of the most popular “headache” and “migraine” apps and developed a database of the types of data the apps requested for input by the user, and whether the apps had clear privacy policies. They also examined the content of the privacy policies and found:

• Twenty-nine apps were examined (14 diary apps, 15 relaxation apps).
• Of the diary applications, 79% (11/14) had visible privacy policies.
• Of the diary apps with privacy policies, all (11/11) stated whether or not the app collects and stores information remotely.
• A total of 55% (6/11) stated that some user data were used to serve targeted advertisements.
• A total of 11/15 (73%) of the relaxation apps had privacy policies.

Minen MT, Stieglitz EJ, Sciortino R, Torous J. Privacy issues in smartphone applications: An analysis of headache/migraine applications. [Published online ahead of print July 4, 2018]. Headache. doi:10.1111/head.13341.

Headache smartphone applications (apps) shared information with third parties, posing privacy risks partly because there are few legal protections against the sale or disclosure of data from medical apps to third parties. This is according to a recent study that sought to assess whether there are privacy issues surrounding apps and the potential privacy implications of how the app companies (and other third parties) might use that information. Researchers conducted a systematic search of the most popular “headache” and “migraine” apps and developed a database of the types of data the apps requested for input by the user, and whether the apps had clear privacy policies. They also examined the content of the privacy policies and found:

• Twenty-nine apps were examined (14 diary apps, 15 relaxation apps).
• Of the diary applications, 79% (11/14) had visible privacy policies.
• Of the diary apps with privacy policies, all (11/11) stated whether or not the app collects and stores information remotely.
• A total of 55% (6/11) stated that some user data were used to serve targeted advertisements.
• A total of 11/15 (73%) of the relaxation apps had privacy policies.

Minen MT, Stieglitz EJ, Sciortino R, Torous J. Privacy issues in smartphone applications: An analysis of headache/migraine applications. [Published online ahead of print July 4, 2018]. Headache. doi:10.1111/head.13341.

Headache smartphone applications (apps) shared information with third parties, posing privacy risks partly because there are few legal protections against the sale or disclosure of data from medical apps to third parties. This is according to a recent study that sought to assess whether there are privacy issues surrounding apps and the potential privacy implications of how the app companies (and other third parties) might use that information. Researchers conducted a systematic search of the most popular “headache” and “migraine” apps and developed a database of the types of data the apps requested for input by the user, and whether the apps had clear privacy policies. They also examined the content of the privacy policies and found:

• Twenty-nine apps were examined (14 diary apps, 15 relaxation apps).
• Of the diary applications, 79% (11/14) had visible privacy policies.
• Of the diary apps with privacy policies, all (11/11) stated whether or not the app collects and stores information remotely.
• A total of 55% (6/11) stated that some user data were used to serve targeted advertisements.
• A total of 11/15 (73%) of the relaxation apps had privacy policies.

Minen MT, Stieglitz EJ, Sciortino R, Torous J. Privacy issues in smartphone applications: An analysis of headache/migraine applications. [Published online ahead of print July 4, 2018]. Headache. doi:10.1111/head.13341.

Patients with migraine undergoing surgery are at increased risk of 30-day hospital readmission due to pain, a recent study found. This hospital registry study examined 150,710 patients, aged 18 years or older, who underwent surgery with general anesthesia and mechanical ventilation between 2007 and 2015 at a tertiary care center and 2 affiliated community hospitals in Massachusetts. Researchers found:

• Migraine was associated with an increased risk of 30-day pain-related readmission after surgery (adjusted odds ratio [OR] 1.42).
• The association was stronger for migraine with aura (compared to migraine without aura: adjusted OR 1.69; compared to no migraine: adjusted OR 2.20).
• The predicted adjusted risk of pain-related 30-day readmissions was 9.1 in 1000 surgical patients with migraine with aura and 5.4 in 1,000 patients with migraine without aura, compared to 4.2 in 1000 patients with no migraine.
• Furthermore, migraine was associated with an increased risk of postsurgical 30-day readmission due to a priori defined migraine-related pain (headache or abdominal pain) (adjusted OR 1.55).

Platzbecker K, Zhang MB, Kurth T, et al. The association between migraine and hospital readmission due to pain after surgery: A hospital registry study. [Published online ahead of print July 8, 2018]. Cephalalgia. doi:10.1177/0333102418786457.

Patients with migraine undergoing surgery are at increased risk of 30-day hospital readmission due to pain, a recent study found. This hospital registry study examined 150,710 patients, aged 18 years or older, who underwent surgery with general anesthesia and mechanical ventilation between 2007 and 2015 at a tertiary care center and 2 affiliated community hospitals in Massachusetts. Researchers found:

• Migraine was associated with an increased risk of 30-day pain-related readmission after surgery (adjusted odds ratio [OR] 1.42).
• The association was stronger for migraine with aura (compared to migraine without aura: adjusted OR 1.69; compared to no migraine: adjusted OR 2.20).
• The predicted adjusted risk of pain-related 30-day readmissions was 9.1 in 1000 surgical patients with migraine with aura and 5.4 in 1,000 patients with migraine without aura, compared to 4.2 in 1000 patients with no migraine.
• Furthermore, migraine was associated with an increased risk of postsurgical 30-day readmission due to a priori defined migraine-related pain (headache or abdominal pain) (adjusted OR 1.55).

Platzbecker K, Zhang MB, Kurth T, et al. The association between migraine and hospital readmission due to pain after surgery: A hospital registry study. [Published online ahead of print July 8, 2018]. Cephalalgia. doi:10.1177/0333102418786457.

Patients with migraine undergoing surgery are at increased risk of 30-day hospital readmission due to pain, a recent study found. This hospital registry study examined 150,710 patients, aged 18 years or older, who underwent surgery with general anesthesia and mechanical ventilation between 2007 and 2015 at a tertiary care center and 2 affiliated community hospitals in Massachusetts. Researchers found:

• Migraine was associated with an increased risk of 30-day pain-related readmission after surgery (adjusted odds ratio [OR] 1.42).
• The association was stronger for migraine with aura (compared to migraine without aura: adjusted OR 1.69; compared to no migraine: adjusted OR 2.20).
• The predicted adjusted risk of pain-related 30-day readmissions was 9.1 in 1000 surgical patients with migraine with aura and 5.4 in 1,000 patients with migraine without aura, compared to 4.2 in 1000 patients with no migraine.
• Furthermore, migraine was associated with an increased risk of postsurgical 30-day readmission due to a priori defined migraine-related pain (headache or abdominal pain) (adjusted OR 1.55).

Platzbecker K, Zhang MB, Kurth T, et al. The association between migraine and hospital readmission due to pain after surgery: A hospital registry study. [Published online ahead of print July 8, 2018]. Cephalalgia. doi:10.1177/0333102418786457.

R. Allan Purdy, MD, FRCPC

Dr. Purdy is Professor of Medicine (Neurology) at Dalhousie University, Halifax, Nova Scotia.

Although migraine has been with humans since antiquity, it is truly amazing that over the past 25 years and a bit longer there have been remarkable advances in our clinical understanding of migraine and its variations, along with sophisticated epidemiologic evidence and basic research into the neurobiological basis of migraine. These advances have brought this disorder/disease to the forefront as a serious neurologic condition deserving of attention. Migraine is a major cause of neurologic disability in the world. This fact has only been fully recognized in recent years.

From the 1980s through the 1990s, a series of events led to a seminal study of a medication that would truly alter the vector for migraine in the future. Studies coming out of Glaxo in the United Kingdom, under the direction of Pat Humphrey, OBE, DSc, PhD, led to the discovery of sumatriptan, the first truly designer medication for the treatment of acute migraine. The story of how this medication biologically affects the brain serotonin receptors on blood vessels and brain tissue to abort a migraine attack is well known today. Early observations on patients receiving subcutaneous sumatriptan clearly showed how powerful this agent was in shutting down the migraine attack. Patients having migraine in extremis, with severe throbbing headache, pallor, nausea and vomiting, appearing markedly distressed and ill, within minutes to an hour would return to a normal state. Nothing that preceded sumatriptan demonstrated such a remarkable clinical response in patients with headache.

In the past century, sumatriptan came to be one of the most important therapeutic advances in neurology. After its discovery, six other triptans entered the market over time. All of them had minor tweaks on the original molecule’s pharmacology and pharmacokinetics, including various modes of delivery with different results in subgroups of patients. Nevertheless, on balance, the triptans acted in a similar manner to produce similar outcomes. Today, many patients take triptans regularly for help with acute migraine attacks; however, other patients with migraine remain undiagnosed and undertreated and do not receive optimal care.

In the past 20 years, sophisticated laboratory and neuroimaging research allowed in-depth analysis of the migraine attack and spectrum of the migraine disorder. The brain areas that subserve the migraine attack have been mapped neuroanatomically throughout the nervous system, with input from the brainstem, hypothalamus, thalamus, and cortical structures. Cortical-initiated electrical events possibly trigger the trigeminal vascular system, and/or peripheral or central activation mechanisms produce the symptoms of migraine. The migraine story is not complete, but evidence clearly shows migraine to be a valid neurobiological disorder and disease. For some people with migraine, it is occasional aggravation, but for others it can be life-altering and, rarely, life-threatening.

In the past few years, new targets for migraine therapy have been pursued. A CGRP receptor antagonist (or “gepant”) showed benefit in early trials; however, because of potential hepatic side effects, other gepants and CGRP monoclonal antibodies have been studied in clinical trials.

Results of recent trials—one in episodic migraine and the other in chronic migraine—show that anti-CGRP monoclonal antibodies appear to be quite efficacious, have few side effects, and are well tolerated. Time will determine whether there are long-term consequences of their use, and what is the effectiveness of using these large molecules to treat migraine, but current results appear promising. Another triptan-like agent, a ditan, which activates receptors of serotonin without vasoconstrictor properties, has shown promise in acute migraine. Neuromodulation devices are also showing promise in migraine therapy and appear to be safe and well tolerated. Nonpharmacological therapies are more often utilized with benefits and help to avoid problems with medications and their side effects.

Increasing knowledge of migraine epidemiology has shown that there is a transition from acute to more frequent, and from high frequency to subsequent chronic migraine attacks. This transformation, or chronification, appears unique in patients with migraine. This process appears to be bidirectional and reversible in migraine. Whether migraine becomes chronic as a process over time or whether migraine is a chronic disease with episodic fluctuations is something to be further explored in research and clinical practice. Nevertheless, these concepts can only lead to better understanding and, hopefully, new therapeutic interventions that will reduce the frequency and severity of this unique neurologic disease.

As migraine progresses or evolves it can be associated with multiple comorbid disorders, including stroke, depression, seizures, and medication overuse. New preventive therapies in development can be modifications of medications for other neurologic conditions, such as the antiepileptic medications, for example. There are many other potential targets that will be explored for the management of migraine in this century. The future looks promising in that regard.

For decades, and now centuries, neurologists have been interested in migraine and related disorders. Sumatriptan jump-started the modern revolution and evolution of therapeutic options to manage migraine pharmacologically. Since its discovery and use in clinical medicine, the world of migraine has changed dramatically. As headache clinicians are being trained in the latest advances in migraine and other headache disorders, they are showing increasing interest and knowledge,which is provided by some of the most unique and relevant research involving the brain in the world. A cure for migraine may not be possible, but a better understanding and control of all of migraine’s myriad of symptoms is probably within reach in this century.

Suggested Reading

Bigal ME, Lipton RB. Clinical course in migraine: conceptualizing migraine transformation. Neurology. 2008;71(11):848-855.

Deen M, Correnti E, Kamm K, et al. Blocking CGRP in migraine patients – a review of pros and cons. J Headache Pain. 2017;18(1):96.

Dodick DW. Migraine. Lancet. 2018;391(10127):1315-1330.

Färkkilä M, Diener HC, Géraud G, et al. Efficacy and tolerability of lasmiditan, an oral 5-HT(1F) receptor agonist, for the acute treatment of migraine: a phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study. Lancet Neurology. 2012;11(5):405-413.

Goadsby PJ, Reuter U, Hallström Y, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377(22):2123-2132.

Humphrey PP. The discovery and development of the triptans, a major therapeutic breakthrough. Headache. 2008;48(5):685-687.

Puledda F, Goadsby PJ. An update on non-pharmacological neuromodulation for the acute and preventive treatment of migraine. Headache. 2017;57(4):685-691.

Silberstein SD, Dodick DW, Bigal ME, et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med. 2017;377(22):2113-2122.

Wietecha LA, Kuca B, Case MG, et al. Phase 3 study (SPARTAN) of lasmiditan compared to placebo for acute treatment of migraine. Cephalalgia. 2017;37 (suppl 1):367-68 (abstr).

R. Allan Purdy, MD, FRCPC

Dr. Purdy is Professor of Medicine (Neurology) at Dalhousie University, Halifax, Nova Scotia.

Although migraine has been with humans since antiquity, it is truly amazing that over the past 25 years and a bit longer there have been remarkable advances in our clinical understanding of migraine and its variations, along with sophisticated epidemiologic evidence and basic research into the neurobiological basis of migraine. These advances have brought this disorder/disease to the forefront as a serious neurologic condition deserving of attention. Migraine is a major cause of neurologic disability in the world. This fact has only been fully recognized in recent years.

From the 1980s through the 1990s, a series of events led to a seminal study of a medication that would truly alter the vector for migraine in the future. Studies coming out of Glaxo in the United Kingdom, under the direction of Pat Humphrey, OBE, DSc, PhD, led to the discovery of sumatriptan, the first truly designer medication for the treatment of acute migraine. The story of how this medication biologically affects the brain serotonin receptors on blood vessels and brain tissue to abort a migraine attack is well known today. Early observations on patients receiving subcutaneous sumatriptan clearly showed how powerful this agent was in shutting down the migraine attack. Patients having migraine in extremis, with severe throbbing headache, pallor, nausea and vomiting, appearing markedly distressed and ill, within minutes to an hour would return to a normal state. Nothing that preceded sumatriptan demonstrated such a remarkable clinical response in patients with headache.

In the past century, sumatriptan came to be one of the most important therapeutic advances in neurology. After its discovery, six other triptans entered the market over time. All of them had minor tweaks on the original molecule’s pharmacology and pharmacokinetics, including various modes of delivery with different results in subgroups of patients. Nevertheless, on balance, the triptans acted in a similar manner to produce similar outcomes. Today, many patients take triptans regularly for help with acute migraine attacks; however, other patients with migraine remain undiagnosed and undertreated and do not receive optimal care.

In the past 20 years, sophisticated laboratory and neuroimaging research allowed in-depth analysis of the migraine attack and spectrum of the migraine disorder. The brain areas that subserve the migraine attack have been mapped neuroanatomically throughout the nervous system, with input from the brainstem, hypothalamus, thalamus, and cortical structures. Cortical-initiated electrical events possibly trigger the trigeminal vascular system, and/or peripheral or central activation mechanisms produce the symptoms of migraine. The migraine story is not complete, but evidence clearly shows migraine to be a valid neurobiological disorder and disease. For some people with migraine, it is occasional aggravation, but for others it can be life-altering and, rarely, life-threatening.

In the past few years, new targets for migraine therapy have been pursued. A CGRP receptor antagonist (or “gepant”) showed benefit in early trials; however, because of potential hepatic side effects, other gepants and CGRP monoclonal antibodies have been studied in clinical trials.

Results of recent trials—one in episodic migraine and the other in chronic migraine—show that anti-CGRP monoclonal antibodies appear to be quite efficacious, have few side effects, and are well tolerated. Time will determine whether there are long-term consequences of their use, and what is the effectiveness of using these large molecules to treat migraine, but current results appear promising. Another triptan-like agent, a ditan, which activates receptors of serotonin without vasoconstrictor properties, has shown promise in acute migraine. Neuromodulation devices are also showing promise in migraine therapy and appear to be safe and well tolerated. Nonpharmacological therapies are more often utilized with benefits and help to avoid problems with medications and their side effects.

Increasing knowledge of migraine epidemiology has shown that there is a transition from acute to more frequent, and from high frequency to subsequent chronic migraine attacks. This transformation, or chronification, appears unique in patients with migraine. This process appears to be bidirectional and reversible in migraine. Whether migraine becomes chronic as a process over time or whether migraine is a chronic disease with episodic fluctuations is something to be further explored in research and clinical practice. Nevertheless, these concepts can only lead to better understanding and, hopefully, new therapeutic interventions that will reduce the frequency and severity of this unique neurologic disease.

As migraine progresses or evolves it can be associated with multiple comorbid disorders, including stroke, depression, seizures, and medication overuse. New preventive therapies in development can be modifications of medications for other neurologic conditions, such as the antiepileptic medications, for example. There are many other potential targets that will be explored for the management of migraine in this century. The future looks promising in that regard.

For decades, and now centuries, neurologists have been interested in migraine and related disorders. Sumatriptan jump-started the modern revolution and evolution of therapeutic options to manage migraine pharmacologically. Since its discovery and use in clinical medicine, the world of migraine has changed dramatically. As headache clinicians are being trained in the latest advances in migraine and other headache disorders, they are showing increasing interest and knowledge,which is provided by some of the most unique and relevant research involving the brain in the world. A cure for migraine may not be possible, but a better understanding and control of all of migraine’s myriad of symptoms is probably within reach in this century.

Suggested Reading

Bigal ME, Lipton RB. Clinical course in migraine: conceptualizing migraine transformation. Neurology. 2008;71(11):848-855.

Deen M, Correnti E, Kamm K, et al. Blocking CGRP in migraine patients – a review of pros and cons. J Headache Pain. 2017;18(1):96.

Dodick DW. Migraine. Lancet. 2018;391(10127):1315-1330.

Färkkilä M, Diener HC, Géraud G, et al. Efficacy and tolerability of lasmiditan, an oral 5-HT(1F) receptor agonist, for the acute treatment of migraine: a phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study. Lancet Neurology. 2012;11(5):405-413.

Goadsby PJ, Reuter U, Hallström Y, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377(22):2123-2132.

Humphrey PP. The discovery and development of the triptans, a major therapeutic breakthrough. Headache. 2008;48(5):685-687.

Puledda F, Goadsby PJ. An update on non-pharmacological neuromodulation for the acute and preventive treatment of migraine. Headache. 2017;57(4):685-691.

Silberstein SD, Dodick DW, Bigal ME, et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med. 2017;377(22):2113-2122.

Wietecha LA, Kuca B, Case MG, et al. Phase 3 study (SPARTAN) of lasmiditan compared to placebo for acute treatment of migraine. Cephalalgia. 2017;37 (suppl 1):367-68 (abstr).

R. Allan Purdy, MD, FRCPC

Dr. Purdy is Professor of Medicine (Neurology) at Dalhousie University, Halifax, Nova Scotia.

Although migraine has been with humans since antiquity, it is truly amazing that over the past 25 years and a bit longer there have been remarkable advances in our clinical understanding of migraine and its variations, along with sophisticated epidemiologic evidence and basic research into the neurobiological basis of migraine. These advances have brought this disorder/disease to the forefront as a serious neurologic condition deserving of attention. Migraine is a major cause of neurologic disability in the world. This fact has only been fully recognized in recent years.

From the 1980s through the 1990s, a series of events led to a seminal study of a medication that would truly alter the vector for migraine in the future. Studies coming out of Glaxo in the United Kingdom, under the direction of Pat Humphrey, OBE, DSc, PhD, led to the discovery of sumatriptan, the first truly designer medication for the treatment of acute migraine. The story of how this medication biologically affects the brain serotonin receptors on blood vessels and brain tissue to abort a migraine attack is well known today. Early observations on patients receiving subcutaneous sumatriptan clearly showed how powerful this agent was in shutting down the migraine attack. Patients having migraine in extremis, with severe throbbing headache, pallor, nausea and vomiting, appearing markedly distressed and ill, within minutes to an hour would return to a normal state. Nothing that preceded sumatriptan demonstrated such a remarkable clinical response in patients with headache.

In the past century, sumatriptan came to be one of the most important therapeutic advances in neurology. After its discovery, six other triptans entered the market over time. All of them had minor tweaks on the original molecule’s pharmacology and pharmacokinetics, including various modes of delivery with different results in subgroups of patients. Nevertheless, on balance, the triptans acted in a similar manner to produce similar outcomes. Today, many patients take triptans regularly for help with acute migraine attacks; however, other patients with migraine remain undiagnosed and undertreated and do not receive optimal care.

In the past 20 years, sophisticated laboratory and neuroimaging research allowed in-depth analysis of the migraine attack and spectrum of the migraine disorder. The brain areas that subserve the migraine attack have been mapped neuroanatomically throughout the nervous system, with input from the brainstem, hypothalamus, thalamus, and cortical structures. Cortical-initiated electrical events possibly trigger the trigeminal vascular system, and/or peripheral or central activation mechanisms produce the symptoms of migraine. The migraine story is not complete, but evidence clearly shows migraine to be a valid neurobiological disorder and disease. For some people with migraine, it is occasional aggravation, but for others it can be life-altering and, rarely, life-threatening.

In the past few years, new targets for migraine therapy have been pursued. A CGRP receptor antagonist (or “gepant”) showed benefit in early trials; however, because of potential hepatic side effects, other gepants and CGRP monoclonal antibodies have been studied in clinical trials.

Results of recent trials—one in episodic migraine and the other in chronic migraine—show that anti-CGRP monoclonal antibodies appear to be quite efficacious, have few side effects, and are well tolerated. Time will determine whether there are long-term consequences of their use, and what is the effectiveness of using these large molecules to treat migraine, but current results appear promising. Another triptan-like agent, a ditan, which activates receptors of serotonin without vasoconstrictor properties, has shown promise in acute migraine. Neuromodulation devices are also showing promise in migraine therapy and appear to be safe and well tolerated. Nonpharmacological therapies are more often utilized with benefits and help to avoid problems with medications and their side effects.

Increasing knowledge of migraine epidemiology has shown that there is a transition from acute to more frequent, and from high frequency to subsequent chronic migraine attacks. This transformation, or chronification, appears unique in patients with migraine. This process appears to be bidirectional and reversible in migraine. Whether migraine becomes chronic as a process over time or whether migraine is a chronic disease with episodic fluctuations is something to be further explored in research and clinical practice. Nevertheless, these concepts can only lead to better understanding and, hopefully, new therapeutic interventions that will reduce the frequency and severity of this unique neurologic disease.

As migraine progresses or evolves it can be associated with multiple comorbid disorders, including stroke, depression, seizures, and medication overuse. New preventive therapies in development can be modifications of medications for other neurologic conditions, such as the antiepileptic medications, for example. There are many other potential targets that will be explored for the management of migraine in this century. The future looks promising in that regard.

For decades, and now centuries, neurologists have been interested in migraine and related disorders. Sumatriptan jump-started the modern revolution and evolution of therapeutic options to manage migraine pharmacologically. Since its discovery and use in clinical medicine, the world of migraine has changed dramatically. As headache clinicians are being trained in the latest advances in migraine and other headache disorders, they are showing increasing interest and knowledge,which is provided by some of the most unique and relevant research involving the brain in the world. A cure for migraine may not be possible, but a better understanding and control of all of migraine’s myriad of symptoms is probably within reach in this century.

Suggested Reading

Bigal ME, Lipton RB. Clinical course in migraine: conceptualizing migraine transformation. Neurology. 2008;71(11):848-855.

Deen M, Correnti E, Kamm K, et al. Blocking CGRP in migraine patients – a review of pros and cons. J Headache Pain. 2017;18(1):96.

Dodick DW. Migraine. Lancet. 2018;391(10127):1315-1330.

Färkkilä M, Diener HC, Géraud G, et al. Efficacy and tolerability of lasmiditan, an oral 5-HT(1F) receptor agonist, for the acute treatment of migraine: a phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study. Lancet Neurology. 2012;11(5):405-413.

Goadsby PJ, Reuter U, Hallström Y, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377(22):2123-2132.

Humphrey PP. The discovery and development of the triptans, a major therapeutic breakthrough. Headache. 2008;48(5):685-687.

Puledda F, Goadsby PJ. An update on non-pharmacological neuromodulation for the acute and preventive treatment of migraine. Headache. 2017;57(4):685-691.

Silberstein SD, Dodick DW, Bigal ME, et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med. 2017;377(22):2113-2122.

Wietecha LA, Kuca B, Case MG, et al. Phase 3 study (SPARTAN) of lasmiditan compared to placebo for acute treatment of migraine. Cephalalgia. 2017;37 (suppl 1):367-68 (abstr).

LOS ANGELES—Fremanezumab, a fully humanized monoclonal antibody, is a safe and effective therapy for the preventive treatment of chronic migraine, according to phase III data presented at the 70th Annual Meeting of the American Academy of Neurology. The treatment also has a flexible dosing profile.

Monthly and Quarterly Dosing Regimens

Fremanezumab selectively targets the calcitonin gene-related peptide ligand and is administered through subcutaneous injections. Stephen Silberstein, MD, Director of the Headache Center at Thomas Jefferson University Hospital in Philadelphia, and colleagues conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate two subcutaneous dose regimens of fremanezumab for the prevention of chronic migraine. Eligible patients were between ages 18 and 70. Exclusion criteria included use of onabotulinumtoxinA in the four months before screening, use of opioids or barbiturates for more than four days during the pretreatment period, and failure of two or more prior preventive medicines.

The investigators assigned 1,130 participants to one of three treatment arms. The first (monthly dosing) arm received 675 mg of fremanuzemab during the first month, followed by 225 mg of fremanezumab at months two and three. The second (quarterly dosing) arm received 675 mg of fremanezumab at month one, followed by placebo injections at months two and three. The third arm received monthly administration of matching placebo. The study’s primary efficacy end point was the mean change in the monthly average number of headache days of at least moderate severity from baseline (ie, a 28-day pretreatment period) to the 12-week double-blind treatment period. Dr. Silberstein and colleagues evaluated this end point using an analysis of covariance method or the Wilcoxon rank sum test.

During the 28-day baseline period, participants’ mean number of headache days of at least moderate severity was 13.1. During the 12-week period after the first dose, the number of monthly headache days of at least moderate severity decreased by 2.5 in the placebo arm, 4.6 in the monthly dosing arm, and 4.3 in the quarterly arm. The differences between the fremanezumab and placebo arms were statistically significant.

Secondary End Points Favored Fremanezumab

In addition, the number of monthly migraine days decreased significantly during the 12-week period after the first dose in the monthly dosing arm (by 5.0 from 16.0) and the quarterly dosing arm (by 4.9 from 16.2), compared with the placebo arm (by 3.2 from 16.3). The number of monthly migraine days also decreased significantly for both dosing regimens during the four weeks after the first dose.

Furthermore, 37.6% of patients in the quarterly dosing arm and 40.8% of patients in the monthly dosing arm had at least a 50% reduction in headache days of at least moderate severity, compared with 18.1% of the placebo arm. Similarly, 7.5% of patients in the quarterly dosing arm and 9.1% of patients in the monthly dosing arm had at least a 75% reduction in headache days of at least moderate severity, compared with 2.7% of the placebo arm.

Fremanezumab was associated with reductions in work productivity loss, compared with placebo. The change from baseline on the Work Productivity and Activity Impairment Questionnaire was −16.6 days in the quarterly dosing arm, −15.9 in the monthly dosing arm, and −9.1 in the placebo arm. In addition, mean score on the Headache Impact Test-6 decreased by 6.4 in the quarterly dosing arm, 6.8 in the monthly dosing arm, and 4.5 in the placebo arm.

The most common adverse event in the study was injection-site reaction. Discontinuation for adverse events was infrequent. Similar proportions of patients in each treatment group had at least one adverse event, and the frequency of these events was lower among controls.

“These results are consistent with [those of] the prior phase II trials in chronic migraine, with similar efficacy and similar treatment effects,” said Dr. Silberstein. Fremanezumab’s safety, tolerability, early onset of efficacy, and flexible dosing “may increase adherence and improve clinical outcomes for patients with migraine,” he concluded.

LOS ANGELES—Fremanezumab, a fully humanized monoclonal antibody, is a safe and effective therapy for the preventive treatment of chronic migraine, according to phase III data presented at the 70th Annual Meeting of the American Academy of Neurology. The treatment also has a flexible dosing profile.

Monthly and Quarterly Dosing Regimens

Fremanezumab selectively targets the calcitonin gene-related peptide ligand and is administered through subcutaneous injections. Stephen Silberstein, MD, Director of the Headache Center at Thomas Jefferson University Hospital in Philadelphia, and colleagues conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate two subcutaneous dose regimens of fremanezumab for the prevention of chronic migraine. Eligible patients were between ages 18 and 70. Exclusion criteria included use of onabotulinumtoxinA in the four months before screening, use of opioids or barbiturates for more than four days during the pretreatment period, and failure of two or more prior preventive medicines.

The investigators assigned 1,130 participants to one of three treatment arms. The first (monthly dosing) arm received 675 mg of fremanuzemab during the first month, followed by 225 mg of fremanezumab at months two and three. The second (quarterly dosing) arm received 675 mg of fremanezumab at month one, followed by placebo injections at months two and three. The third arm received monthly administration of matching placebo. The study’s primary efficacy end point was the mean change in the monthly average number of headache days of at least moderate severity from baseline (ie, a 28-day pretreatment period) to the 12-week double-blind treatment period. Dr. Silberstein and colleagues evaluated this end point using an analysis of covariance method or the Wilcoxon rank sum test.

During the 28-day baseline period, participants’ mean number of headache days of at least moderate severity was 13.1. During the 12-week period after the first dose, the number of monthly headache days of at least moderate severity decreased by 2.5 in the placebo arm, 4.6 in the monthly dosing arm, and 4.3 in the quarterly arm. The differences between the fremanezumab and placebo arms were statistically significant.

Secondary End Points Favored Fremanezumab

In addition, the number of monthly migraine days decreased significantly during the 12-week period after the first dose in the monthly dosing arm (by 5.0 from 16.0) and the quarterly dosing arm (by 4.9 from 16.2), compared with the placebo arm (by 3.2 from 16.3). The number of monthly migraine days also decreased significantly for both dosing regimens during the four weeks after the first dose.

Furthermore, 37.6% of patients in the quarterly dosing arm and 40.8% of patients in the monthly dosing arm had at least a 50% reduction in headache days of at least moderate severity, compared with 18.1% of the placebo arm. Similarly, 7.5% of patients in the quarterly dosing arm and 9.1% of patients in the monthly dosing arm had at least a 75% reduction in headache days of at least moderate severity, compared with 2.7% of the placebo arm.

Fremanezumab was associated with reductions in work productivity loss, compared with placebo. The change from baseline on the Work Productivity and Activity Impairment Questionnaire was −16.6 days in the quarterly dosing arm, −15.9 in the monthly dosing arm, and −9.1 in the placebo arm. In addition, mean score on the Headache Impact Test-6 decreased by 6.4 in the quarterly dosing arm, 6.8 in the monthly dosing arm, and 4.5 in the placebo arm.

The most common adverse event in the study was injection-site reaction. Discontinuation for adverse events was infrequent. Similar proportions of patients in each treatment group had at least one adverse event, and the frequency of these events was lower among controls.

“These results are consistent with [those of] the prior phase II trials in chronic migraine, with similar efficacy and similar treatment effects,” said Dr. Silberstein. Fremanezumab’s safety, tolerability, early onset of efficacy, and flexible dosing “may increase adherence and improve clinical outcomes for patients with migraine,” he concluded.

LOS ANGELES—Fremanezumab, a fully humanized monoclonal antibody, is a safe and effective therapy for the preventive treatment of chronic migraine, according to phase III data presented at the 70th Annual Meeting of the American Academy of Neurology. The treatment also has a flexible dosing profile.

Monthly and Quarterly Dosing Regimens

Fremanezumab selectively targets the calcitonin gene-related peptide ligand and is administered through subcutaneous injections. Stephen Silberstein, MD, Director of the Headache Center at Thomas Jefferson University Hospital in Philadelphia, and colleagues conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate two subcutaneous dose regimens of fremanezumab for the prevention of chronic migraine. Eligible patients were between ages 18 and 70. Exclusion criteria included use of onabotulinumtoxinA in the four months before screening, use of opioids or barbiturates for more than four days during the pretreatment period, and failure of two or more prior preventive medicines.

The investigators assigned 1,130 participants to one of three treatment arms. The first (monthly dosing) arm received 675 mg of fremanuzemab during the first month, followed by 225 mg of fremanezumab at months two and three. The second (quarterly dosing) arm received 675 mg of fremanezumab at month one, followed by placebo injections at months two and three. The third arm received monthly administration of matching placebo. The study’s primary efficacy end point was the mean change in the monthly average number of headache days of at least moderate severity from baseline (ie, a 28-day pretreatment period) to the 12-week double-blind treatment period. Dr. Silberstein and colleagues evaluated this end point using an analysis of covariance method or the Wilcoxon rank sum test.

During the 28-day baseline period, participants’ mean number of headache days of at least moderate severity was 13.1. During the 12-week period after the first dose, the number of monthly headache days of at least moderate severity decreased by 2.5 in the placebo arm, 4.6 in the monthly dosing arm, and 4.3 in the quarterly arm. The differences between the fremanezumab and placebo arms were statistically significant.

Secondary End Points Favored Fremanezumab

In addition, the number of monthly migraine days decreased significantly during the 12-week period after the first dose in the monthly dosing arm (by 5.0 from 16.0) and the quarterly dosing arm (by 4.9 from 16.2), compared with the placebo arm (by 3.2 from 16.3). The number of monthly migraine days also decreased significantly for both dosing regimens during the four weeks after the first dose.

Furthermore, 37.6% of patients in the quarterly dosing arm and 40.8% of patients in the monthly dosing arm had at least a 50% reduction in headache days of at least moderate severity, compared with 18.1% of the placebo arm. Similarly, 7.5% of patients in the quarterly dosing arm and 9.1% of patients in the monthly dosing arm had at least a 75% reduction in headache days of at least moderate severity, compared with 2.7% of the placebo arm.

Fremanezumab was associated with reductions in work productivity loss, compared with placebo. The change from baseline on the Work Productivity and Activity Impairment Questionnaire was −16.6 days in the quarterly dosing arm, −15.9 in the monthly dosing arm, and −9.1 in the placebo arm. In addition, mean score on the Headache Impact Test-6 decreased by 6.4 in the quarterly dosing arm, 6.8 in the monthly dosing arm, and 4.5 in the placebo arm.

The most common adverse event in the study was injection-site reaction. Discontinuation for adverse events was infrequent. Similar proportions of patients in each treatment group had at least one adverse event, and the frequency of these events was lower among controls.

“These results are consistent with [those of] the prior phase II trials in chronic migraine, with similar efficacy and similar treatment effects,” said Dr. Silberstein. Fremanezumab’s safety, tolerability, early onset of efficacy, and flexible dosing “may increase adherence and improve clinical outcomes for patients with migraine,” he concluded.

LOS ANGELES—Among patients with chronic migraine, IV infusion of eptinezumab significantly reduces the average number of migraine days per month, compared with placebo, according to phase III trial data presented at the 70th Annual Meeting of the American Academy of Neurology. In addition, one-year data from a trial of eptinezumab in patients with episodic migraine suggest that treatment response may improve with subsequent infusions, researchers said.

Eptinezumab (formerly known as ALD403) is a humanized monoclonal antibody that inhibits calcitonin gene-related peptide (CGRP). It is designed to be administered quarterly via IV infusion. Eptinezumab previously was found to be effective and well tolerated in phase II studies in episodic and chronic migraine and in a phase III trial in episodic migraine. Alder BioPharmaceuticals, based in Bothell, Washington, is developing the therapy.

Treatment-emergent adverse events in phase III studies were similar for eptinezumab and placebo, and the safety profile was consistent with that in prior studies, researchers said.

The PROMISE Clinical Trial Program

The Prevention of Migraine via Intravenous ALD403 Safety and Efficacy (PROMISE) clinical trial program includes phase III, randomized, double-blind, placebo-controlled trials of eptinezumab for chronic migraine prevention (PROMISE-2) and episodic migraine prevention (PROMISE-1).

In the PROMISE-2 trial, 1,072 patients were randomized to receive eptinezumab (300 mg), eptinezumab (100 mg), or placebo administered by IV infusion once every 12 weeks. Eligible patients had at least 15 headache days per month, of which at least eight met criteria for migraine. The primary end point was the mean change from baseline in monthly migraine days over the 12-week treatment period. Secondary end points included reduction in migraine prevalence on Day 1 and the proportion of patients with reductions of at least 50% and 75%.

In the PROMISE-1 trial, 888 patients were randomized to receive eptinezumab (300 mg), eptinezumab (100 mg), eptinezumab (30 mg), or placebo administered by IV infusion once every 12 weeks. Eligible patients had 14 or fewer headache days per month, of which at least four met the criteria for migraine. The primary end point was the mean change from baseline in monthly migraine days over the 12-week treatment period.

PROMISE-2

Patients in PROMISE-2 had an average of about 20 headache days per month, including 16 migraine days, at baseline, said Richard B. Lipton, MD, Edwin S. Lowe Chair in Neurology at Albert Einstein College of Medicine in New York. Patients’ mean age was about 40, mean BMI was 26, and about 88% were female.

Patients had had migraine for about 18 years on average, and mean duration of chronic migraine was about 12 years.

During the 12 weeks after treatment, the mean change from baseline in monthly migraine days was –7.7 for patients who received the 100-mg dose of eptinezumab and –8.2 for patients who received the 300-mg dose of eptinezumab, compared with –5.6 for patients who received placebo. The difference was statistically significant for both active treatment groups versus placebo.

Secondary end points significantly favored eptinezumab. The percentage of patients with at least a 75% reduction in migraine days was 15.0% for placebo, 26.7% for the 100-mg dose of eptinezumab, and 33.1% for the 300-mg dose of eptinezumab. The percentage of patients with at least a 50% reduction in migraine days was 39.3% for placebo, 57.6% for the 100-mg dose of eptinezumab, and 61.4% for the 300-mg dose of eptinezumab.

On Day 1 post infusion, the percentage of patients with migraine decreased by 51% and 52% in the 100-mg and 300-mg treatment arms, respectively, compared with a decrease of 27% in the placebo arm.

Adverse event rates among eptinezumab-treated subjects were similar to those in placebo-treated subjects. The most commonly reported adverse events for eptinezumab were nasopharyngitis (6.3%), upper respiratory infection (4.0%), and nausea (3.4%).

Treatment-emergent adverse events occurred in approximately 40% of all treatment arms (39% in the placebo group, 38% in the 100-mg group, and 44% in the 300-mg group). Serious adverse events were rare, occurred in approximately equal rates in all treatment arms, and were considered unrelated to study drug.

PROMISE-1

Patients in PROMISE-1 had a mean age of about 40, and about 85% were female. They had about 8.5 migraine days per month on average, said Stephen D. Silberstein, MD, Professor of Neurology and Director of the Jefferson Headache Center at Thomas Jefferson University in Philadelphia.

During Weeks 1–12, mean change in monthly migraine days was significantly greater among patients who received eptinezumab (–4.0 with the 30-mg dose, –3.9 with the 100-mg dose, and –4.3 with the 300-mg dose), compared with patients who received placebo (–3.2).

One-year data indicated that the percentage of participants in the trial with 75% and 50% reductions in migraine increased over time. “With each subsequent infusion, there seems to be a cumulative increase in response,” Dr. Silberstein said. At the end of the trial, the proportion of patients in the 300-mg dose group with at least a 75% reduction in migraine days was 52%, whereas the proportion at Month 3 was 37%. The long-term results are encouraging, said Dr. Silberstein.

In PROMISE-1, the most commonly reported adverse events among treated patients were upper respiratory infection (10.3%), nasopharyngitis (6.6%), and sinusitis (3.6%).

—Jake Remaly

LOS ANGELES—Among patients with chronic migraine, IV infusion of eptinezumab significantly reduces the average number of migraine days per month, compared with placebo, according to phase III trial data presented at the 70th Annual Meeting of the American Academy of Neurology. In addition, one-year data from a trial of eptinezumab in patients with episodic migraine suggest that treatment response may improve with subsequent infusions, researchers said.

Eptinezumab (formerly known as ALD403) is a humanized monoclonal antibody that inhibits calcitonin gene-related peptide (CGRP). It is designed to be administered quarterly via IV infusion. Eptinezumab previously was found to be effective and well tolerated in phase II studies in episodic and chronic migraine and in a phase III trial in episodic migraine. Alder BioPharmaceuticals, based in Bothell, Washington, is developing the therapy.

Treatment-emergent adverse events in phase III studies were similar for eptinezumab and placebo, and the safety profile was consistent with that in prior studies, researchers said.

The PROMISE Clinical Trial Program

The Prevention of Migraine via Intravenous ALD403 Safety and Efficacy (PROMISE) clinical trial program includes phase III, randomized, double-blind, placebo-controlled trials of eptinezumab for chronic migraine prevention (PROMISE-2) and episodic migraine prevention (PROMISE-1).

In the PROMISE-2 trial, 1,072 patients were randomized to receive eptinezumab (300 mg), eptinezumab (100 mg), or placebo administered by IV infusion once every 12 weeks. Eligible patients had at least 15 headache days per month, of which at least eight met criteria for migraine. The primary end point was the mean change from baseline in monthly migraine days over the 12-week treatment period. Secondary end points included reduction in migraine prevalence on Day 1 and the proportion of patients with reductions of at least 50% and 75%.

In the PROMISE-1 trial, 888 patients were randomized to receive eptinezumab (300 mg), eptinezumab (100 mg), eptinezumab (30 mg), or placebo administered by IV infusion once every 12 weeks. Eligible patients had 14 or fewer headache days per month, of which at least four met the criteria for migraine. The primary end point was the mean change from baseline in monthly migraine days over the 12-week treatment period.

PROMISE-2

Patients in PROMISE-2 had an average of about 20 headache days per month, including 16 migraine days, at baseline, said Richard B. Lipton, MD, Edwin S. Lowe Chair in Neurology at Albert Einstein College of Medicine in New York. Patients’ mean age was about 40, mean BMI was 26, and about 88% were female.

Patients had had migraine for about 18 years on average, and mean duration of chronic migraine was about 12 years.

During the 12 weeks after treatment, the mean change from baseline in monthly migraine days was –7.7 for patients who received the 100-mg dose of eptinezumab and –8.2 for patients who received the 300-mg dose of eptinezumab, compared with –5.6 for patients who received placebo. The difference was statistically significant for both active treatment groups versus placebo.

Secondary end points significantly favored eptinezumab. The percentage of patients with at least a 75% reduction in migraine days was 15.0% for placebo, 26.7% for the 100-mg dose of eptinezumab, and 33.1% for the 300-mg dose of eptinezumab. The percentage of patients with at least a 50% reduction in migraine days was 39.3% for placebo, 57.6% for the 100-mg dose of eptinezumab, and 61.4% for the 300-mg dose of eptinezumab.

On Day 1 post infusion, the percentage of patients with migraine decreased by 51% and 52% in the 100-mg and 300-mg treatment arms, respectively, compared with a decrease of 27% in the placebo arm.

Adverse event rates among eptinezumab-treated subjects were similar to those in placebo-treated subjects. The most commonly reported adverse events for eptinezumab were nasopharyngitis (6.3%), upper respiratory infection (4.0%), and nausea (3.4%).

Treatment-emergent adverse events occurred in approximately 40% of all treatment arms (39% in the placebo group, 38% in the 100-mg group, and 44% in the 300-mg group). Serious adverse events were rare, occurred in approximately equal rates in all treatment arms, and were considered unrelated to study drug.

PROMISE-1

Patients in PROMISE-1 had a mean age of about 40, and about 85% were female. They had about 8.5 migraine days per month on average, said Stephen D. Silberstein, MD, Professor of Neurology and Director of the Jefferson Headache Center at Thomas Jefferson University in Philadelphia.

During Weeks 1–12, mean change in monthly migraine days was significantly greater among patients who received eptinezumab (–4.0 with the 30-mg dose, –3.9 with the 100-mg dose, and –4.3 with the 300-mg dose), compared with patients who received placebo (–3.2).

One-year data indicated that the percentage of participants in the trial with 75% and 50% reductions in migraine increased over time. “With each subsequent infusion, there seems to be a cumulative increase in response,” Dr. Silberstein said. At the end of the trial, the proportion of patients in the 300-mg dose group with at least a 75% reduction in migraine days was 52%, whereas the proportion at Month 3 was 37%. The long-term results are encouraging, said Dr. Silberstein.

In PROMISE-1, the most commonly reported adverse events among treated patients were upper respiratory infection (10.3%), nasopharyngitis (6.6%), and sinusitis (3.6%).

—Jake Remaly

LOS ANGELES—Among patients with chronic migraine, IV infusion of eptinezumab significantly reduces the average number of migraine days per month, compared with placebo, according to phase III trial data presented at the 70th Annual Meeting of the American Academy of Neurology. In addition, one-year data from a trial of eptinezumab in patients with episodic migraine suggest that treatment response may improve with subsequent infusions, researchers said.

Eptinezumab (formerly known as ALD403) is a humanized monoclonal antibody that inhibits calcitonin gene-related peptide (CGRP). It is designed to be administered quarterly via IV infusion. Eptinezumab previously was found to be effective and well tolerated in phase II studies in episodic and chronic migraine and in a phase III trial in episodic migraine. Alder BioPharmaceuticals, based in Bothell, Washington, is developing the therapy.

Treatment-emergent adverse events in phase III studies were similar for eptinezumab and placebo, and the safety profile was consistent with that in prior studies, researchers said.

The PROMISE Clinical Trial Program

The Prevention of Migraine via Intravenous ALD403 Safety and Efficacy (PROMISE) clinical trial program includes phase III, randomized, double-blind, placebo-controlled trials of eptinezumab for chronic migraine prevention (PROMISE-2) and episodic migraine prevention (PROMISE-1).

In the PROMISE-2 trial, 1,072 patients were randomized to receive eptinezumab (300 mg), eptinezumab (100 mg), or placebo administered by IV infusion once every 12 weeks. Eligible patients had at least 15 headache days per month, of which at least eight met criteria for migraine. The primary end point was the mean change from baseline in monthly migraine days over the 12-week treatment period. Secondary end points included reduction in migraine prevalence on Day 1 and the proportion of patients with reductions of at least 50% and 75%.

In the PROMISE-1 trial, 888 patients were randomized to receive eptinezumab (300 mg), eptinezumab (100 mg), eptinezumab (30 mg), or placebo administered by IV infusion once every 12 weeks. Eligible patients had 14 or fewer headache days per month, of which at least four met the criteria for migraine. The primary end point was the mean change from baseline in monthly migraine days over the 12-week treatment period.

PROMISE-2

Patients in PROMISE-2 had an average of about 20 headache days per month, including 16 migraine days, at baseline, said Richard B. Lipton, MD, Edwin S. Lowe Chair in Neurology at Albert Einstein College of Medicine in New York. Patients’ mean age was about 40, mean BMI was 26, and about 88% were female.

Patients had had migraine for about 18 years on average, and mean duration of chronic migraine was about 12 years.

During the 12 weeks after treatment, the mean change from baseline in monthly migraine days was –7.7 for patients who received the 100-mg dose of eptinezumab and –8.2 for patients who received the 300-mg dose of eptinezumab, compared with –5.6 for patients who received placebo. The difference was statistically significant for both active treatment groups versus placebo.

Secondary end points significantly favored eptinezumab. The percentage of patients with at least a 75% reduction in migraine days was 15.0% for placebo, 26.7% for the 100-mg dose of eptinezumab, and 33.1% for the 300-mg dose of eptinezumab. The percentage of patients with at least a 50% reduction in migraine days was 39.3% for placebo, 57.6% for the 100-mg dose of eptinezumab, and 61.4% for the 300-mg dose of eptinezumab.

On Day 1 post infusion, the percentage of patients with migraine decreased by 51% and 52% in the 100-mg and 300-mg treatment arms, respectively, compared with a decrease of 27% in the placebo arm.

Adverse event rates among eptinezumab-treated subjects were similar to those in placebo-treated subjects. The most commonly reported adverse events for eptinezumab were nasopharyngitis (6.3%), upper respiratory infection (4.0%), and nausea (3.4%).

Treatment-emergent adverse events occurred in approximately 40% of all treatment arms (39% in the placebo group, 38% in the 100-mg group, and 44% in the 300-mg group). Serious adverse events were rare, occurred in approximately equal rates in all treatment arms, and were considered unrelated to study drug.

PROMISE-1

Patients in PROMISE-1 had a mean age of about 40, and about 85% were female. They had about 8.5 migraine days per month on average, said Stephen D. Silberstein, MD, Professor of Neurology and Director of the Jefferson Headache Center at Thomas Jefferson University in Philadelphia.

During Weeks 1–12, mean change in monthly migraine days was significantly greater among patients who received eptinezumab (–4.0 with the 30-mg dose, –3.9 with the 100-mg dose, and –4.3 with the 300-mg dose), compared with patients who received placebo (–3.2).

One-year data indicated that the percentage of participants in the trial with 75% and 50% reductions in migraine increased over time. “With each subsequent infusion, there seems to be a cumulative increase in response,” Dr. Silberstein said. At the end of the trial, the proportion of patients in the 300-mg dose group with at least a 75% reduction in migraine days was 52%, whereas the proportion at Month 3 was 37%. The long-term results are encouraging, said Dr. Silberstein.

In PROMISE-1, the most commonly reported adverse events among treated patients were upper respiratory infection (10.3%), nasopharyngitis (6.6%), and sinusitis (3.6%).

—Jake Remaly

Mind and body cognitive behavioral therapy (CBT‐HA) relaxation skills emerged as popular and effective for pediatric migraine sufferers, based on patient and parent reports in a recent study. Qualitative interviews were conducted with 10 patients and 9 of their parents who had undergone CBT‐HA. Interviews were analyzed using an inductive thematic analysis approach based upon modified grounded theory. Patients were ranged in age from 13 to 17.5 years (median=15.4, standard deviation=1.63) and had undergone CBT‐HA about 1 to 2 years prior to participating in the study. Researchers found:

• Overall, patients and their parents reported that CBT‐HA was helpful in reducing headache frequency and related disability.
• Although patients provided mixed reports on the effectiveness of different CBT‐HA skills, the majority of patients indicated that the mind and body relaxation skills of CBT‐HA (deep breathing, progressive muscle relaxation, and activity pacing in particular) were the most helpful and most frequently used skills.
• Patients and parents also generally reported that treatment was easy to learn, and noted at least some aspect of treatment was enjoyable.

CBT for pediatric migraine: A qualitative study of patient and parent experience. Headache. 2018;58(5):661-675. doi:10.1111/head.13285.

Mind and body cognitive behavioral therapy (CBT‐HA) relaxation skills emerged as popular and effective for pediatric migraine sufferers, based on patient and parent reports in a recent study. Qualitative interviews were conducted with 10 patients and 9 of their parents who had undergone CBT‐HA. Interviews were analyzed using an inductive thematic analysis approach based upon modified grounded theory. Patients were ranged in age from 13 to 17.5 years (median=15.4, standard deviation=1.63) and had undergone CBT‐HA about 1 to 2 years prior to participating in the study. Researchers found:

• Overall, patients and their parents reported that CBT‐HA was helpful in reducing headache frequency and related disability.
• Although patients provided mixed reports on the effectiveness of different CBT‐HA skills, the majority of patients indicated that the mind and body relaxation skills of CBT‐HA (deep breathing, progressive muscle relaxation, and activity pacing in particular) were the most helpful and most frequently used skills.
• Patients and parents also generally reported that treatment was easy to learn, and noted at least some aspect of treatment was enjoyable.

CBT for pediatric migraine: A qualitative study of patient and parent experience. Headache. 2018;58(5):661-675. doi:10.1111/head.13285.

Mind and body cognitive behavioral therapy (CBT‐HA) relaxation skills emerged as popular and effective for pediatric migraine sufferers, based on patient and parent reports in a recent study. Qualitative interviews were conducted with 10 patients and 9 of their parents who had undergone CBT‐HA. Interviews were analyzed using an inductive thematic analysis approach based upon modified grounded theory. Patients were ranged in age from 13 to 17.5 years (median=15.4, standard deviation=1.63) and had undergone CBT‐HA about 1 to 2 years prior to participating in the study. Researchers found:

• Overall, patients and their parents reported that CBT‐HA was helpful in reducing headache frequency and related disability.
• Although patients provided mixed reports on the effectiveness of different CBT‐HA skills, the majority of patients indicated that the mind and body relaxation skills of CBT‐HA (deep breathing, progressive muscle relaxation, and activity pacing in particular) were the most helpful and most frequently used skills.
• Patients and parents also generally reported that treatment was easy to learn, and noted at least some aspect of treatment was enjoyable.

CBT for pediatric migraine: A qualitative study of patient and parent experience. Headache. 2018;58(5):661-675. doi:10.1111/head.13285.

Visual quality of life (QOL) is significantly adversely affected in migraine sufferers, according to a recent study. In fact, patients with chronic migraine may have visual QOL impacts that are as significant as those associated with other common neuro‐ophthalmic disorders. In this cross‐sectional quantitative survey, visual QOL in individuals with chronic and episodic migraine was assessed using the National Eye Institute Visual Function Questionnaire‐25, and the 10‐item National Eye Institute Visual Function Questionnaire‐25 Neuro‐Ophthalmic Supplement. Overall headache severity and impact was assessed using the Migraine‐specific Quality of Life Questionnaire and the Headache Impact Test‐6. Researchers found:

• Among 29 participants with chronic migraine, vision‐specific QOL scores were all statistically significantly decreased compared to disease‐free controls.
• Among 37 participants with episodic migraine, vision‐specific QOL scores were also decreased compared to disease‐free controls.
• Chronic migraineurs had decreased visual QOL scores compared to those with episodic migraines.
• Participants with chronic migraine had visual QOL scores that were as poor as those previously published for patients with other neuro‐ophthalmic disorders, such as multiple sclerosis, myasthenia gravis, and ischemic optic neuropathy.
   

Patients with migraine have substantial reductions in measures of visual quality of life. [Published online ahead of print June 7, 2018]. Headache. doi:10.1111/head.13330.

Visual quality of life (QOL) is significantly adversely affected in migraine sufferers, according to a recent study. In fact, patients with chronic migraine may have visual QOL impacts that are as significant as those associated with other common neuro‐ophthalmic disorders. In this cross‐sectional quantitative survey, visual QOL in individuals with chronic and episodic migraine was assessed using the National Eye Institute Visual Function Questionnaire‐25, and the 10‐item National Eye Institute Visual Function Questionnaire‐25 Neuro‐Ophthalmic Supplement. Overall headache severity and impact was assessed using the Migraine‐specific Quality of Life Questionnaire and the Headache Impact Test‐6. Researchers found:

• Among 29 participants with chronic migraine, vision‐specific QOL scores were all statistically significantly decreased compared to disease‐free controls.
• Among 37 participants with episodic migraine, vision‐specific QOL scores were also decreased compared to disease‐free controls.
• Chronic migraineurs had decreased visual QOL scores compared to those with episodic migraines.
• Participants with chronic migraine had visual QOL scores that were as poor as those previously published for patients with other neuro‐ophthalmic disorders, such as multiple sclerosis, myasthenia gravis, and ischemic optic neuropathy.
   

Patients with migraine have substantial reductions in measures of visual quality of life. [Published online ahead of print June 7, 2018]. Headache. doi:10.1111/head.13330.

Visual quality of life (QOL) is significantly adversely affected in migraine sufferers, according to a recent study. In fact, patients with chronic migraine may have visual QOL impacts that are as significant as those associated with other common neuro‐ophthalmic disorders. In this cross‐sectional quantitative survey, visual QOL in individuals with chronic and episodic migraine was assessed using the National Eye Institute Visual Function Questionnaire‐25, and the 10‐item National Eye Institute Visual Function Questionnaire‐25 Neuro‐Ophthalmic Supplement. Overall headache severity and impact was assessed using the Migraine‐specific Quality of Life Questionnaire and the Headache Impact Test‐6. Researchers found:

• Among 29 participants with chronic migraine, vision‐specific QOL scores were all statistically significantly decreased compared to disease‐free controls.
• Among 37 participants with episodic migraine, vision‐specific QOL scores were also decreased compared to disease‐free controls.
• Chronic migraineurs had decreased visual QOL scores compared to those with episodic migraines.
• Participants with chronic migraine had visual QOL scores that were as poor as those previously published for patients with other neuro‐ophthalmic disorders, such as multiple sclerosis, myasthenia gravis, and ischemic optic neuropathy.
   

Patients with migraine have substantial reductions in measures of visual quality of life. [Published online ahead of print June 7, 2018]. Headache. doi:10.1111/head.13330.

Less than one-third of eligible migraineurs were referred for behavioral treatment and only about half initiated behavioral migraine treatment in a recent prospective cohort study. Researchers compared patients who initiated behavioral migraine treatment following a provider recommendation with those who did not (demographics, migraine characteristics, and locus of control) with analysis of variance and chi-square tests. They found:

• Of the 234 eligible patients, 69 (29.5%) were referred for behavioral treatment.
• 53 (76.8%) patients referred for behavioral treatment were reached by phone.
• The mean duration from time of referral to follow-up was 76 (median 76, SD=45) days.
• 30 (56.6%) patients initiated behavioral migraine treatment.
• There was no difference in initiation of behavioral migraine treatment with regard to sex, age, age of diagnosis, years suffered with headaches, health care utilization visits, Migraine Disability Assessment Screen, and locus of control.
• Patients who had previously seen a psychologist for migraine were more likely to initiate behavioral migraine treatment than patients who had not.
• Time constraints were the most common barrier cited for not initiating behavioral migraine treatment.

Factors related to migraine patients’ decisions to initiate behavioral migraine treatment following a headache specialist’s recommendation: A prospective observational study. [Published online ahead of print June 5, 2018]. Pain Medicine. doi:10.1093/pm/pny028.

Less than one-third of eligible migraineurs were referred for behavioral treatment and only about half initiated behavioral migraine treatment in a recent prospective cohort study. Researchers compared patients who initiated behavioral migraine treatment following a provider recommendation with those who did not (demographics, migraine characteristics, and locus of control) with analysis of variance and chi-square tests. They found:

• Of the 234 eligible patients, 69 (29.5%) were referred for behavioral treatment.
• 53 (76.8%) patients referred for behavioral treatment were reached by phone.
• The mean duration from time of referral to follow-up was 76 (median 76, SD=45) days.
• 30 (56.6%) patients initiated behavioral migraine treatment.
• There was no difference in initiation of behavioral migraine treatment with regard to sex, age, age of diagnosis, years suffered with headaches, health care utilization visits, Migraine Disability Assessment Screen, and locus of control.
• Patients who had previously seen a psychologist for migraine were more likely to initiate behavioral migraine treatment than patients who had not.
• Time constraints were the most common barrier cited for not initiating behavioral migraine treatment.

Factors related to migraine patients’ decisions to initiate behavioral migraine treatment following a headache specialist’s recommendation: A prospective observational study. [Published online ahead of print June 5, 2018]. Pain Medicine. doi:10.1093/pm/pny028.

Less than one-third of eligible migraineurs were referred for behavioral treatment and only about half initiated behavioral migraine treatment in a recent prospective cohort study. Researchers compared patients who initiated behavioral migraine treatment following a provider recommendation with those who did not (demographics, migraine characteristics, and locus of control) with analysis of variance and chi-square tests. They found:

• Of the 234 eligible patients, 69 (29.5%) were referred for behavioral treatment.
• 53 (76.8%) patients referred for behavioral treatment were reached by phone.
• The mean duration from time of referral to follow-up was 76 (median 76, SD=45) days.
• 30 (56.6%) patients initiated behavioral migraine treatment.
• There was no difference in initiation of behavioral migraine treatment with regard to sex, age, age of diagnosis, years suffered with headaches, health care utilization visits, Migraine Disability Assessment Screen, and locus of control.
• Patients who had previously seen a psychologist for migraine were more likely to initiate behavioral migraine treatment than patients who had not.
• Time constraints were the most common barrier cited for not initiating behavioral migraine treatment.

Factors related to migraine patients’ decisions to initiate behavioral migraine treatment following a headache specialist’s recommendation: A prospective observational study. [Published online ahead of print June 5, 2018]. Pain Medicine. doi:10.1093/pm/pny028.