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Migraine device expands treatment possibilities
AUSTIN, TEX – Migraine treatment and prevention is challenging in any population, but some present even more difficulties. Pregnant women and pediatric patients are two such groups where physicians and patients may be hesitant to use drugs.
Neuromodulation devices are proven alternatives to medical interventions, and the remote electrical neuromodulation device Nerivio (Theranica) was cleared by the Food and Drug Administration for acute treatment of migraine patients aged 12 and over in 2021. In March 2023, the agency expanded the clearance to include prevention of migration in adolescents aged 12 and over as well as adults.
Two studies presented at the annual meeting of the American Headache Society showed The latter study yielded similar findings to adults and was used by FDA in its decision to expand the device’s indication in adolescents in 2023, according to Teshamae Monteith, MD, who presented the study at a poster session.
The device, worn on the arm, allows the user to modulate the intensity of the stimulation so that it activates nociceptive pain receptors, but not in a painful way. “Each [patient] raises the intensity until it feels strong, yet comfortable, and when that happens, they activate the nociceptive receptors and the arm sends a signal all the way back up to the brainstem, where the pain control area is. Activating it causes the release of neurotransmitters that inhibit pain. That inhibition is a global pain inhibition mechanism, which causes inhibition of the migraine pain, and also the symptoms associated with migraine like photophobia and vomiting,” said Alit Stark-Inbar, PhD, who presented the study of treatment of pregnant women during a poster session.
Declining treatment days over time in adolescents
Dr. Monteith’s team studied high-frequency remote electrical neuromodulation device use in adolescents who had migraine on 10 days or more per month. They also required at least three treatment days in months 2 and 3 to control for the possibility that patients might stop using the device because they couldn’t afford it or for some reason other than efficacy or because their migraines went away.
The study included 83 adolescents aged 12-17 (mean, 15.9 years, 89% female). In the first month of use, the mean number of migraine treatment days was 12.6, which dropped to 9.0 in month 2 (P < .001), and 7.4 in month 3 (P < .001 from month 2). At 2 hours after treatment, 61.9% had pain relief, 24.5% had freedom from pain, 67.4% had functional disability relief, and 41.3% had functional disability freedom.
“It parallels the findings of the randomized, sham-controlled study in adults. The safety profile was excellent with just one person complaining of minor discomfort of the arm that resolved after treatment. The combination of the exceedingly safe profile and the likelihood of efficacy based on using monthly migraine treatment days as a proxy, the FDA decided to clear this for an adolescent indication,” said Dr. Monteith, associate professor of clinical neurology and chief of the headache division at the University of Miami.
The device design is convenient, according to Dr. Monteith. “The arm is just an easy place to stimulate. It’s a wearable device, and it’s 45 minutes [of treatment] and it’s app controlled. You know adolescents like their technology. They can track their symptoms here, and there’s some biobehavioral power to this because they can do biobehavioral exercises in addition to receiving the simulation,” she said.
The fact that the device is discrete is also an advantage for adolescents in school. “You have to go to the nurse to get your medication versus a device, you can just put it on, it’s easy, no one sees it, and no one’s making fun of you,” said Dr. Monteith.
Advantages for adolescents
The device offers a useful alternative to medication, according to Alan M. Rapoport, MD, who was asked for comment on the adolescent study. “I’d rather not give medication and certainly not preventive medication to an adolescent,” he said. He noted that over-the-counter acute care migraine medications such as aspirin or acetaminophen and combination medications with caffeine, as well as prescription medications such as triptans, “all have possible side effects, and when used to an increased extent can even cause medication overuse headache, increasing the severity and frequency of headache and migraine days per month,” Dr. Rapoport said. Using an effective device with almost no side effects is preferable to any of these acute care medications, especially if there are several headaches a month,” he said. Some newer medications that block calcitonin gene-related peptide might be quite effective when they are approved for adolescents, and should have few adverse events, he added.
In the past, Dr. Rapoport has favored biofeedback training for acute and especially preventive treatment of migraine in adolescents. “[Remote electrical neuromodulation] seems to do just as well, children enjoy it, and it’s easier for a patient to do at home,” said Dr. Rapoport.
Biofeedback training is usually taught to patients by a PhD psychologist. Once the patients have been on the biofeedback equipment and learn the techniques, they can practice on their own at home without equipment. “This new device treatment using Nerivio for acute care and prevention of migraine in adults and children 12 and older, where they can easily apply the device in almost any situation, whether they are at home or possibly even in school or out and about, looks very promising,” said Dr. Rapoport. It is quite effective and has almost no adverse events, which is what you really want, especially for adolescents,” he said.
Also asked to comment on the study of remote electrical neuromodulation use in adolescents, Abraham Avi Ashkenazi, MD, director of the Headache Clinic at Shaare Zedek Medical Center in Jerusalem, who attended the session, was enthusiastic, and said he has begun using it in his own practice. “It shows that remote electrical neuromodulation can not only be effective for the acute migraine attack, but also has a potential preventive effect on future migraine attacks. [This] actually makes sense, because we know that the more migraine attacks a person has, the more likely they are to progress to a more chronic form of the disease,” he said in an interview.
Asked what distinguishes REN from other neuromodulation therapies such as vagus nerve stimulation or transcranial magnetic stimulation (TMS), Dr. Ashkenazi said: “It’s just a different way of modulating the brain system via a different mechanism. In both ways, though, the advantage is that there are literally no adverse effects, as opposed to drug treatment.”
An alternative during pregnancy
Adolescents aren’t the only population where there is reluctance to use medication. Physicians have been prescribing the device for pregnant women, who are reluctant to take medication due to concerns effects on the fetus. However, pregnant women were not included in the pivotal studies. “They expect it to be safe. This study was done in order to validate that assumption. We reached out to women who either used the device during pregnancy or women from the same database who started it using afterwards, but did not use it during the pregnancy,” said Dr. Stark-Inbar, vice president of medical information at Theranica.
The study included 140 women, 59 in the remote electrical neuromodulation device group and 81 controls. The primary endpoint was gestational age, which was 38 weeks and 5 days in the remote electrical neuromodulation device group and 39 weeks among controls (P = .150). There were no significant between-group differences with respect to newborn birth weight, miscarriage rate, preterm birth rate, birth defect rate, developmental milestone rate, or emergency department visit rate.
Dr. Monteith and Dr. Ashkenazi have no relevant financial disclosures. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. Dr. Rapoport is the editor-in-chief of Neurology Reviews and on the editorial board of CNS Drugs.
AUSTIN, TEX – Migraine treatment and prevention is challenging in any population, but some present even more difficulties. Pregnant women and pediatric patients are two such groups where physicians and patients may be hesitant to use drugs.
Neuromodulation devices are proven alternatives to medical interventions, and the remote electrical neuromodulation device Nerivio (Theranica) was cleared by the Food and Drug Administration for acute treatment of migraine patients aged 12 and over in 2021. In March 2023, the agency expanded the clearance to include prevention of migration in adolescents aged 12 and over as well as adults.
Two studies presented at the annual meeting of the American Headache Society showed The latter study yielded similar findings to adults and was used by FDA in its decision to expand the device’s indication in adolescents in 2023, according to Teshamae Monteith, MD, who presented the study at a poster session.
The device, worn on the arm, allows the user to modulate the intensity of the stimulation so that it activates nociceptive pain receptors, but not in a painful way. “Each [patient] raises the intensity until it feels strong, yet comfortable, and when that happens, they activate the nociceptive receptors and the arm sends a signal all the way back up to the brainstem, where the pain control area is. Activating it causes the release of neurotransmitters that inhibit pain. That inhibition is a global pain inhibition mechanism, which causes inhibition of the migraine pain, and also the symptoms associated with migraine like photophobia and vomiting,” said Alit Stark-Inbar, PhD, who presented the study of treatment of pregnant women during a poster session.
Declining treatment days over time in adolescents
Dr. Monteith’s team studied high-frequency remote electrical neuromodulation device use in adolescents who had migraine on 10 days or more per month. They also required at least three treatment days in months 2 and 3 to control for the possibility that patients might stop using the device because they couldn’t afford it or for some reason other than efficacy or because their migraines went away.
The study included 83 adolescents aged 12-17 (mean, 15.9 years, 89% female). In the first month of use, the mean number of migraine treatment days was 12.6, which dropped to 9.0 in month 2 (P < .001), and 7.4 in month 3 (P < .001 from month 2). At 2 hours after treatment, 61.9% had pain relief, 24.5% had freedom from pain, 67.4% had functional disability relief, and 41.3% had functional disability freedom.
“It parallels the findings of the randomized, sham-controlled study in adults. The safety profile was excellent with just one person complaining of minor discomfort of the arm that resolved after treatment. The combination of the exceedingly safe profile and the likelihood of efficacy based on using monthly migraine treatment days as a proxy, the FDA decided to clear this for an adolescent indication,” said Dr. Monteith, associate professor of clinical neurology and chief of the headache division at the University of Miami.
The device design is convenient, according to Dr. Monteith. “The arm is just an easy place to stimulate. It’s a wearable device, and it’s 45 minutes [of treatment] and it’s app controlled. You know adolescents like their technology. They can track their symptoms here, and there’s some biobehavioral power to this because they can do biobehavioral exercises in addition to receiving the simulation,” she said.
The fact that the device is discrete is also an advantage for adolescents in school. “You have to go to the nurse to get your medication versus a device, you can just put it on, it’s easy, no one sees it, and no one’s making fun of you,” said Dr. Monteith.
Advantages for adolescents
The device offers a useful alternative to medication, according to Alan M. Rapoport, MD, who was asked for comment on the adolescent study. “I’d rather not give medication and certainly not preventive medication to an adolescent,” he said. He noted that over-the-counter acute care migraine medications such as aspirin or acetaminophen and combination medications with caffeine, as well as prescription medications such as triptans, “all have possible side effects, and when used to an increased extent can even cause medication overuse headache, increasing the severity and frequency of headache and migraine days per month,” Dr. Rapoport said. Using an effective device with almost no side effects is preferable to any of these acute care medications, especially if there are several headaches a month,” he said. Some newer medications that block calcitonin gene-related peptide might be quite effective when they are approved for adolescents, and should have few adverse events, he added.
In the past, Dr. Rapoport has favored biofeedback training for acute and especially preventive treatment of migraine in adolescents. “[Remote electrical neuromodulation] seems to do just as well, children enjoy it, and it’s easier for a patient to do at home,” said Dr. Rapoport.
Biofeedback training is usually taught to patients by a PhD psychologist. Once the patients have been on the biofeedback equipment and learn the techniques, they can practice on their own at home without equipment. “This new device treatment using Nerivio for acute care and prevention of migraine in adults and children 12 and older, where they can easily apply the device in almost any situation, whether they are at home or possibly even in school or out and about, looks very promising,” said Dr. Rapoport. It is quite effective and has almost no adverse events, which is what you really want, especially for adolescents,” he said.
Also asked to comment on the study of remote electrical neuromodulation use in adolescents, Abraham Avi Ashkenazi, MD, director of the Headache Clinic at Shaare Zedek Medical Center in Jerusalem, who attended the session, was enthusiastic, and said he has begun using it in his own practice. “It shows that remote electrical neuromodulation can not only be effective for the acute migraine attack, but also has a potential preventive effect on future migraine attacks. [This] actually makes sense, because we know that the more migraine attacks a person has, the more likely they are to progress to a more chronic form of the disease,” he said in an interview.
Asked what distinguishes REN from other neuromodulation therapies such as vagus nerve stimulation or transcranial magnetic stimulation (TMS), Dr. Ashkenazi said: “It’s just a different way of modulating the brain system via a different mechanism. In both ways, though, the advantage is that there are literally no adverse effects, as opposed to drug treatment.”
An alternative during pregnancy
Adolescents aren’t the only population where there is reluctance to use medication. Physicians have been prescribing the device for pregnant women, who are reluctant to take medication due to concerns effects on the fetus. However, pregnant women were not included in the pivotal studies. “They expect it to be safe. This study was done in order to validate that assumption. We reached out to women who either used the device during pregnancy or women from the same database who started it using afterwards, but did not use it during the pregnancy,” said Dr. Stark-Inbar, vice president of medical information at Theranica.
The study included 140 women, 59 in the remote electrical neuromodulation device group and 81 controls. The primary endpoint was gestational age, which was 38 weeks and 5 days in the remote electrical neuromodulation device group and 39 weeks among controls (P = .150). There were no significant between-group differences with respect to newborn birth weight, miscarriage rate, preterm birth rate, birth defect rate, developmental milestone rate, or emergency department visit rate.
Dr. Monteith and Dr. Ashkenazi have no relevant financial disclosures. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. Dr. Rapoport is the editor-in-chief of Neurology Reviews and on the editorial board of CNS Drugs.
AUSTIN, TEX – Migraine treatment and prevention is challenging in any population, but some present even more difficulties. Pregnant women and pediatric patients are two such groups where physicians and patients may be hesitant to use drugs.
Neuromodulation devices are proven alternatives to medical interventions, and the remote electrical neuromodulation device Nerivio (Theranica) was cleared by the Food and Drug Administration for acute treatment of migraine patients aged 12 and over in 2021. In March 2023, the agency expanded the clearance to include prevention of migration in adolescents aged 12 and over as well as adults.
Two studies presented at the annual meeting of the American Headache Society showed The latter study yielded similar findings to adults and was used by FDA in its decision to expand the device’s indication in adolescents in 2023, according to Teshamae Monteith, MD, who presented the study at a poster session.
The device, worn on the arm, allows the user to modulate the intensity of the stimulation so that it activates nociceptive pain receptors, but not in a painful way. “Each [patient] raises the intensity until it feels strong, yet comfortable, and when that happens, they activate the nociceptive receptors and the arm sends a signal all the way back up to the brainstem, where the pain control area is. Activating it causes the release of neurotransmitters that inhibit pain. That inhibition is a global pain inhibition mechanism, which causes inhibition of the migraine pain, and also the symptoms associated with migraine like photophobia and vomiting,” said Alit Stark-Inbar, PhD, who presented the study of treatment of pregnant women during a poster session.
Declining treatment days over time in adolescents
Dr. Monteith’s team studied high-frequency remote electrical neuromodulation device use in adolescents who had migraine on 10 days or more per month. They also required at least three treatment days in months 2 and 3 to control for the possibility that patients might stop using the device because they couldn’t afford it or for some reason other than efficacy or because their migraines went away.
The study included 83 adolescents aged 12-17 (mean, 15.9 years, 89% female). In the first month of use, the mean number of migraine treatment days was 12.6, which dropped to 9.0 in month 2 (P < .001), and 7.4 in month 3 (P < .001 from month 2). At 2 hours after treatment, 61.9% had pain relief, 24.5% had freedom from pain, 67.4% had functional disability relief, and 41.3% had functional disability freedom.
“It parallels the findings of the randomized, sham-controlled study in adults. The safety profile was excellent with just one person complaining of minor discomfort of the arm that resolved after treatment. The combination of the exceedingly safe profile and the likelihood of efficacy based on using monthly migraine treatment days as a proxy, the FDA decided to clear this for an adolescent indication,” said Dr. Monteith, associate professor of clinical neurology and chief of the headache division at the University of Miami.
The device design is convenient, according to Dr. Monteith. “The arm is just an easy place to stimulate. It’s a wearable device, and it’s 45 minutes [of treatment] and it’s app controlled. You know adolescents like their technology. They can track their symptoms here, and there’s some biobehavioral power to this because they can do biobehavioral exercises in addition to receiving the simulation,” she said.
The fact that the device is discrete is also an advantage for adolescents in school. “You have to go to the nurse to get your medication versus a device, you can just put it on, it’s easy, no one sees it, and no one’s making fun of you,” said Dr. Monteith.
Advantages for adolescents
The device offers a useful alternative to medication, according to Alan M. Rapoport, MD, who was asked for comment on the adolescent study. “I’d rather not give medication and certainly not preventive medication to an adolescent,” he said. He noted that over-the-counter acute care migraine medications such as aspirin or acetaminophen and combination medications with caffeine, as well as prescription medications such as triptans, “all have possible side effects, and when used to an increased extent can even cause medication overuse headache, increasing the severity and frequency of headache and migraine days per month,” Dr. Rapoport said. Using an effective device with almost no side effects is preferable to any of these acute care medications, especially if there are several headaches a month,” he said. Some newer medications that block calcitonin gene-related peptide might be quite effective when they are approved for adolescents, and should have few adverse events, he added.
In the past, Dr. Rapoport has favored biofeedback training for acute and especially preventive treatment of migraine in adolescents. “[Remote electrical neuromodulation] seems to do just as well, children enjoy it, and it’s easier for a patient to do at home,” said Dr. Rapoport.
Biofeedback training is usually taught to patients by a PhD psychologist. Once the patients have been on the biofeedback equipment and learn the techniques, they can practice on their own at home without equipment. “This new device treatment using Nerivio for acute care and prevention of migraine in adults and children 12 and older, where they can easily apply the device in almost any situation, whether they are at home or possibly even in school or out and about, looks very promising,” said Dr. Rapoport. It is quite effective and has almost no adverse events, which is what you really want, especially for adolescents,” he said.
Also asked to comment on the study of remote electrical neuromodulation use in adolescents, Abraham Avi Ashkenazi, MD, director of the Headache Clinic at Shaare Zedek Medical Center in Jerusalem, who attended the session, was enthusiastic, and said he has begun using it in his own practice. “It shows that remote electrical neuromodulation can not only be effective for the acute migraine attack, but also has a potential preventive effect on future migraine attacks. [This] actually makes sense, because we know that the more migraine attacks a person has, the more likely they are to progress to a more chronic form of the disease,” he said in an interview.
Asked what distinguishes REN from other neuromodulation therapies such as vagus nerve stimulation or transcranial magnetic stimulation (TMS), Dr. Ashkenazi said: “It’s just a different way of modulating the brain system via a different mechanism. In both ways, though, the advantage is that there are literally no adverse effects, as opposed to drug treatment.”
An alternative during pregnancy
Adolescents aren’t the only population where there is reluctance to use medication. Physicians have been prescribing the device for pregnant women, who are reluctant to take medication due to concerns effects on the fetus. However, pregnant women were not included in the pivotal studies. “They expect it to be safe. This study was done in order to validate that assumption. We reached out to women who either used the device during pregnancy or women from the same database who started it using afterwards, but did not use it during the pregnancy,” said Dr. Stark-Inbar, vice president of medical information at Theranica.
The study included 140 women, 59 in the remote electrical neuromodulation device group and 81 controls. The primary endpoint was gestational age, which was 38 weeks and 5 days in the remote electrical neuromodulation device group and 39 weeks among controls (P = .150). There were no significant between-group differences with respect to newborn birth weight, miscarriage rate, preterm birth rate, birth defect rate, developmental milestone rate, or emergency department visit rate.
Dr. Monteith and Dr. Ashkenazi have no relevant financial disclosures. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. Dr. Rapoport is the editor-in-chief of Neurology Reviews and on the editorial board of CNS Drugs.
AT AHS 2023
Migraine clusters emerge from machine-learning analysis
AUSTIN, TEX. – The findings could point to new therapeutic strategies, according to study author Ali Ezzati, MD.
“A lot of diagnostic criteria that we have in the migraine world come from consensus groups of experts, and based on their experience and available data. They classify different types of headache and then on top of that different types of migraine. Unfortunately, this type of classification does not necessarily lead to having very homogeneous groups,” said Dr. Ezzati, who presented the study at the annual meeting of the American Headache Society.
Migraines are generally categorized as episodic (0-14 headache days per month) or chronic (15 or more per month), or as with or without aura. But these broad categories fail to capture the true diversity of migraine, according to Dr. Ezzati, and this may contribute to the fact that response to migraine therapy hovers around 60%. “We feel that the key to improving therapeutic efficacy is to identify individuals who are more homogeneous, more similar to each other, so that when we give a treatment, it is specifically targeting the underlying pathophysiology that those people have,” said Dr. Ezzati, who is an associate professor of neurology and director of the neuroinformatics program at University of California, Irvine.
The analysis revealed some clinically interesting results, said Dr. Ezzati. “For example, allodynia is a symptom that is not particularly used for classification of different types of migraine. There was a specific group that was very high in allodynia, and they were not very responsive to treatments, so that might be a [group] that people have to focus on. Also, we talk a lot about comorbidities in migraine, but we don’t talk about how these comorbidities affect the therapeutic strategies and treatment response to specific medications. We showed that people who have depression are actually less responsive than other groups to treatments, especially prescription medications,” he said.
Machine learning reveals clusters
The researchers analyzed data from 4,423 patients drawn from the American Migraine Prevalence and Prevention Study, which was conducted every year between 2005 and 2009. They included adult patients who filled out surveys in both 2006 and 2007. The study population was 83.7% female and had a mean age of 46.8 years, and 6.4% had chronic migraine. The researchers then used a machine-learning based self-organizing map to group patients into similar clusters.
The algorithm produced five such groups: Cluster 1 had the lowest symptom severity, and 0.6% had chronic migraine. Cluster 2 had mild symptom severity with no chronic migraine. Cluster 3 had moderate symptom severity and a high prevalence of allodynia (88.5%, vs. 63.4% overall, P < .001) and no chronic migraine. Cluster 4 had a high frequency of depressive symptoms (63.1% vs. 19.8% overall, P < .001) and 5.2% had chronic migraine. Cluster 5 had frequent and severe migraines, and most (83.0%) had chronic migraine (P < .001).
There were some other broader trends. Triptans were more commonly used in clusters 2 (25.6%), 3 (27.9%), and 5 (28.0%), but less so in cluster 4 (17.1%; P < .001). Pain freedom at 2 hours was most common in cluster 1 (53.1%), followed by cluster 2 (46.4%), but was significantly less frequent in clusters 3 (32.2%), 4 (32.2%), and 5 (34.7%; P < .001).
Therapeutic implications
Dr. Ezzati believes that machine learning and data analysis could point the way to a future of more tailored migraine therapies. “I think we have to in general go down the path of using more evidence and more data to inform us about individualized planning for patients. For that we need larger clinical studies and larger epidemiological studies to help us identify more homogeneous subtypes of patients that we can eventually target in clinical trials,” he said.
Catherine Chong, MD, who chaired the session where the research was presented, praised the study in an interview. “Episodic migraine and chronic migraine have been developed [as categories] by headache frequency per month, and it was basically based on consensus in committee. They made basically a determination that 15 and under migraine days would be episodic migraine and over would be chronic migraine. So they dichotomized migraine, in a way, based on what people thought in the field. Looking at the data freely, and letting the algorithm determine the different subtypes, and putting everybody with migraine in it, and having these groups naturally appear from the data, I think is fascinating,” Dr. Chong said.
She echoed Dr. Ezzati’s call for further research that could create even more subgroups. “Is it really truly the case that somebody with less than 15 migraine days [per month], that 14 migraines days would be so different than somebody with 15 or over, or 8? I think we need to look at it further to see whether there are additional subgroups within that data. I think there are probably more [groups identifiable] from different data that we have out there,” said Dr. Chong.
Dr. Ezzati has consulted for or been a reviewer or advisory board member for Corium, Eisai, GlaxoSmithKline, Mint Research, and Health Care Horizon Scanning System. He has received research funding from Amgen. Dr. Chong has no relevant financial disclosures.
AUSTIN, TEX. – The findings could point to new therapeutic strategies, according to study author Ali Ezzati, MD.
“A lot of diagnostic criteria that we have in the migraine world come from consensus groups of experts, and based on their experience and available data. They classify different types of headache and then on top of that different types of migraine. Unfortunately, this type of classification does not necessarily lead to having very homogeneous groups,” said Dr. Ezzati, who presented the study at the annual meeting of the American Headache Society.
Migraines are generally categorized as episodic (0-14 headache days per month) or chronic (15 or more per month), or as with or without aura. But these broad categories fail to capture the true diversity of migraine, according to Dr. Ezzati, and this may contribute to the fact that response to migraine therapy hovers around 60%. “We feel that the key to improving therapeutic efficacy is to identify individuals who are more homogeneous, more similar to each other, so that when we give a treatment, it is specifically targeting the underlying pathophysiology that those people have,” said Dr. Ezzati, who is an associate professor of neurology and director of the neuroinformatics program at University of California, Irvine.
The analysis revealed some clinically interesting results, said Dr. Ezzati. “For example, allodynia is a symptom that is not particularly used for classification of different types of migraine. There was a specific group that was very high in allodynia, and they were not very responsive to treatments, so that might be a [group] that people have to focus on. Also, we talk a lot about comorbidities in migraine, but we don’t talk about how these comorbidities affect the therapeutic strategies and treatment response to specific medications. We showed that people who have depression are actually less responsive than other groups to treatments, especially prescription medications,” he said.
Machine learning reveals clusters
The researchers analyzed data from 4,423 patients drawn from the American Migraine Prevalence and Prevention Study, which was conducted every year between 2005 and 2009. They included adult patients who filled out surveys in both 2006 and 2007. The study population was 83.7% female and had a mean age of 46.8 years, and 6.4% had chronic migraine. The researchers then used a machine-learning based self-organizing map to group patients into similar clusters.
The algorithm produced five such groups: Cluster 1 had the lowest symptom severity, and 0.6% had chronic migraine. Cluster 2 had mild symptom severity with no chronic migraine. Cluster 3 had moderate symptom severity and a high prevalence of allodynia (88.5%, vs. 63.4% overall, P < .001) and no chronic migraine. Cluster 4 had a high frequency of depressive symptoms (63.1% vs. 19.8% overall, P < .001) and 5.2% had chronic migraine. Cluster 5 had frequent and severe migraines, and most (83.0%) had chronic migraine (P < .001).
There were some other broader trends. Triptans were more commonly used in clusters 2 (25.6%), 3 (27.9%), and 5 (28.0%), but less so in cluster 4 (17.1%; P < .001). Pain freedom at 2 hours was most common in cluster 1 (53.1%), followed by cluster 2 (46.4%), but was significantly less frequent in clusters 3 (32.2%), 4 (32.2%), and 5 (34.7%; P < .001).
Therapeutic implications
Dr. Ezzati believes that machine learning and data analysis could point the way to a future of more tailored migraine therapies. “I think we have to in general go down the path of using more evidence and more data to inform us about individualized planning for patients. For that we need larger clinical studies and larger epidemiological studies to help us identify more homogeneous subtypes of patients that we can eventually target in clinical trials,” he said.
Catherine Chong, MD, who chaired the session where the research was presented, praised the study in an interview. “Episodic migraine and chronic migraine have been developed [as categories] by headache frequency per month, and it was basically based on consensus in committee. They made basically a determination that 15 and under migraine days would be episodic migraine and over would be chronic migraine. So they dichotomized migraine, in a way, based on what people thought in the field. Looking at the data freely, and letting the algorithm determine the different subtypes, and putting everybody with migraine in it, and having these groups naturally appear from the data, I think is fascinating,” Dr. Chong said.
She echoed Dr. Ezzati’s call for further research that could create even more subgroups. “Is it really truly the case that somebody with less than 15 migraine days [per month], that 14 migraines days would be so different than somebody with 15 or over, or 8? I think we need to look at it further to see whether there are additional subgroups within that data. I think there are probably more [groups identifiable] from different data that we have out there,” said Dr. Chong.
Dr. Ezzati has consulted for or been a reviewer or advisory board member for Corium, Eisai, GlaxoSmithKline, Mint Research, and Health Care Horizon Scanning System. He has received research funding from Amgen. Dr. Chong has no relevant financial disclosures.
AUSTIN, TEX. – The findings could point to new therapeutic strategies, according to study author Ali Ezzati, MD.
“A lot of diagnostic criteria that we have in the migraine world come from consensus groups of experts, and based on their experience and available data. They classify different types of headache and then on top of that different types of migraine. Unfortunately, this type of classification does not necessarily lead to having very homogeneous groups,” said Dr. Ezzati, who presented the study at the annual meeting of the American Headache Society.
Migraines are generally categorized as episodic (0-14 headache days per month) or chronic (15 or more per month), or as with or without aura. But these broad categories fail to capture the true diversity of migraine, according to Dr. Ezzati, and this may contribute to the fact that response to migraine therapy hovers around 60%. “We feel that the key to improving therapeutic efficacy is to identify individuals who are more homogeneous, more similar to each other, so that when we give a treatment, it is specifically targeting the underlying pathophysiology that those people have,” said Dr. Ezzati, who is an associate professor of neurology and director of the neuroinformatics program at University of California, Irvine.
The analysis revealed some clinically interesting results, said Dr. Ezzati. “For example, allodynia is a symptom that is not particularly used for classification of different types of migraine. There was a specific group that was very high in allodynia, and they were not very responsive to treatments, so that might be a [group] that people have to focus on. Also, we talk a lot about comorbidities in migraine, but we don’t talk about how these comorbidities affect the therapeutic strategies and treatment response to specific medications. We showed that people who have depression are actually less responsive than other groups to treatments, especially prescription medications,” he said.
Machine learning reveals clusters
The researchers analyzed data from 4,423 patients drawn from the American Migraine Prevalence and Prevention Study, which was conducted every year between 2005 and 2009. They included adult patients who filled out surveys in both 2006 and 2007. The study population was 83.7% female and had a mean age of 46.8 years, and 6.4% had chronic migraine. The researchers then used a machine-learning based self-organizing map to group patients into similar clusters.
The algorithm produced five such groups: Cluster 1 had the lowest symptom severity, and 0.6% had chronic migraine. Cluster 2 had mild symptom severity with no chronic migraine. Cluster 3 had moderate symptom severity and a high prevalence of allodynia (88.5%, vs. 63.4% overall, P < .001) and no chronic migraine. Cluster 4 had a high frequency of depressive symptoms (63.1% vs. 19.8% overall, P < .001) and 5.2% had chronic migraine. Cluster 5 had frequent and severe migraines, and most (83.0%) had chronic migraine (P < .001).
There were some other broader trends. Triptans were more commonly used in clusters 2 (25.6%), 3 (27.9%), and 5 (28.0%), but less so in cluster 4 (17.1%; P < .001). Pain freedom at 2 hours was most common in cluster 1 (53.1%), followed by cluster 2 (46.4%), but was significantly less frequent in clusters 3 (32.2%), 4 (32.2%), and 5 (34.7%; P < .001).
Therapeutic implications
Dr. Ezzati believes that machine learning and data analysis could point the way to a future of more tailored migraine therapies. “I think we have to in general go down the path of using more evidence and more data to inform us about individualized planning for patients. For that we need larger clinical studies and larger epidemiological studies to help us identify more homogeneous subtypes of patients that we can eventually target in clinical trials,” he said.
Catherine Chong, MD, who chaired the session where the research was presented, praised the study in an interview. “Episodic migraine and chronic migraine have been developed [as categories] by headache frequency per month, and it was basically based on consensus in committee. They made basically a determination that 15 and under migraine days would be episodic migraine and over would be chronic migraine. So they dichotomized migraine, in a way, based on what people thought in the field. Looking at the data freely, and letting the algorithm determine the different subtypes, and putting everybody with migraine in it, and having these groups naturally appear from the data, I think is fascinating,” Dr. Chong said.
She echoed Dr. Ezzati’s call for further research that could create even more subgroups. “Is it really truly the case that somebody with less than 15 migraine days [per month], that 14 migraines days would be so different than somebody with 15 or over, or 8? I think we need to look at it further to see whether there are additional subgroups within that data. I think there are probably more [groups identifiable] from different data that we have out there,” said Dr. Chong.
Dr. Ezzati has consulted for or been a reviewer or advisory board member for Corium, Eisai, GlaxoSmithKline, Mint Research, and Health Care Horizon Scanning System. He has received research funding from Amgen. Dr. Chong has no relevant financial disclosures.
FROM AHS 2023