Headache & Migraine

High levels of disability and low quality of life (QOL) were reported among children and adolescents with migraine utilizing infusion treatment, a new study found. Patients aged 6-19 years treated in an outpatient headache infusion center were included. A subset of these patients completed a behavioral health evaluation (treatment group) and were compared with a control group of similar age and gender to patients not seeking infusion treatment. Among the findings:

• 284 patients were included in the study (n=227 treatment group; n=57 controls).
• There was a promising difference in the Pediatric Pain Coping Inventory (PPCI) Distraction subscale, with a mean rank score of 61.90 for the treatment group vs 50.21 for the control group.
• There was a statistically significant difference on the Social Support subscale, with a mean rank score of 65.92 for the treatment group vs 46.26 for the control group.
• Patient-reported data also revealed a significantly higher level of disability among those seeking infusion treatment compared to the non-infusion group.

Woods K, et al. Psychosocial and demographic characteristics of children and adolescents with headache presenting for treatment in a headache infusion center. Headache. 2019;59(6):858-868. doi: 10.1111/head.13537.

High levels of disability and low quality of life (QOL) were reported among children and adolescents with migraine utilizing infusion treatment, a new study found. Patients aged 6-19 years treated in an outpatient headache infusion center were included. A subset of these patients completed a behavioral health evaluation (treatment group) and were compared with a control group of similar age and gender to patients not seeking infusion treatment. Among the findings:

• 284 patients were included in the study (n=227 treatment group; n=57 controls).
• There was a promising difference in the Pediatric Pain Coping Inventory (PPCI) Distraction subscale, with a mean rank score of 61.90 for the treatment group vs 50.21 for the control group.
• There was a statistically significant difference on the Social Support subscale, with a mean rank score of 65.92 for the treatment group vs 46.26 for the control group.
• Patient-reported data also revealed a significantly higher level of disability among those seeking infusion treatment compared to the non-infusion group.

Woods K, et al. Psychosocial and demographic characteristics of children and adolescents with headache presenting for treatment in a headache infusion center. Headache. 2019;59(6):858-868. doi: 10.1111/head.13537.

High levels of disability and low quality of life (QOL) were reported among children and adolescents with migraine utilizing infusion treatment, a new study found. Patients aged 6-19 years treated in an outpatient headache infusion center were included. A subset of these patients completed a behavioral health evaluation (treatment group) and were compared with a control group of similar age and gender to patients not seeking infusion treatment. Among the findings:

• 284 patients were included in the study (n=227 treatment group; n=57 controls).
• There was a promising difference in the Pediatric Pain Coping Inventory (PPCI) Distraction subscale, with a mean rank score of 61.90 for the treatment group vs 50.21 for the control group.
• There was a statistically significant difference on the Social Support subscale, with a mean rank score of 65.92 for the treatment group vs 46.26 for the control group.
• Patient-reported data also revealed a significantly higher level of disability among those seeking infusion treatment compared to the non-infusion group.

Woods K, et al. Psychosocial and demographic characteristics of children and adolescents with headache presenting for treatment in a headache infusion center. Headache. 2019;59(6):858-868. doi: 10.1111/head.13537.

Urinary melatonin metabolites do not predict migraine attacks in children and adolescents, however, they may be predictive in those who experience premonitory phase symptoms as part of their migraine attacks. This according to a study that examined whether evening urinary melatonin metabolite levels could predict migraine the next day in children and adolescents with migraine. Among the details:

• Twenty-one children and adolescents with migraine were recruited to provide urine samples for 10 days and maintain a prospective headache diary during the same period.
• Mean aMT6s levels the night prior to a migraine attack were 56.2 ±39.0 vs 55.4 ±46.6 ng/mL.
• Mean melatonin metabolite levels the night following migraine were 55.5 ±46.9 vs 57.0 ±37.7 ng/mL.
• However, in post hoc exploratory analyses, aMT6s levels were lower the night before a migraine in those who experienced aura or premonitory symptoms.

Berger A, et al. Preliminary evidence that melatonin is not a biomarker in children and adolescents with episodic migraine. [Published online ahead of print May 3, 2019]. Headache. doi: 10.1111/head.13547.

Urinary melatonin metabolites do not predict migraine attacks in children and adolescents, however, they may be predictive in those who experience premonitory phase symptoms as part of their migraine attacks. This according to a study that examined whether evening urinary melatonin metabolite levels could predict migraine the next day in children and adolescents with migraine. Among the details:

• Twenty-one children and adolescents with migraine were recruited to provide urine samples for 10 days and maintain a prospective headache diary during the same period.
• Mean aMT6s levels the night prior to a migraine attack were 56.2 ±39.0 vs 55.4 ±46.6 ng/mL.
• Mean melatonin metabolite levels the night following migraine were 55.5 ±46.9 vs 57.0 ±37.7 ng/mL.
• However, in post hoc exploratory analyses, aMT6s levels were lower the night before a migraine in those who experienced aura or premonitory symptoms.

Berger A, et al. Preliminary evidence that melatonin is not a biomarker in children and adolescents with episodic migraine. [Published online ahead of print May 3, 2019]. Headache. doi: 10.1111/head.13547.

Urinary melatonin metabolites do not predict migraine attacks in children and adolescents, however, they may be predictive in those who experience premonitory phase symptoms as part of their migraine attacks. This according to a study that examined whether evening urinary melatonin metabolite levels could predict migraine the next day in children and adolescents with migraine. Among the details:

• Twenty-one children and adolescents with migraine were recruited to provide urine samples for 10 days and maintain a prospective headache diary during the same period.
• Mean aMT6s levels the night prior to a migraine attack were 56.2 ±39.0 vs 55.4 ±46.6 ng/mL.
• Mean melatonin metabolite levels the night following migraine were 55.5 ±46.9 vs 57.0 ±37.7 ng/mL.
• However, in post hoc exploratory analyses, aMT6s levels were lower the night before a migraine in those who experienced aura or premonitory symptoms.

Berger A, et al. Preliminary evidence that melatonin is not a biomarker in children and adolescents with episodic migraine. [Published online ahead of print May 3, 2019]. Headache. doi: 10.1111/head.13547.

Food insecurity was significantly associated with migraine prevalence in young adults, according to Jason M. Nagata, MD, of the University of California, San Francisco, and associates.

Data were collected from a cross-sectional, nationally representative set of 14,786 young adults in the United States aged 24-32 years who participated in the 2008 National Longitudinal Study of Adolescent to Adult Health, the investigators wrote in a research letter published in JAMA Neurology.

Food insecurity was assessed by self-report through the interview question, “In the past 12 months, was there a time when (you/your household were/was) worried whether food would run out before you would get money to buy more?” Migraine was assessed by a positive answer to the interview question, “Has a doctor, nurse, or other health care professional ever told you that you have or had migraine headaches?”

In all, 1,647 study participants (11%) reported food insecurity; the prevalence of migraine in this group was 23.9%, compared with a prevalence of 13.6% in participants who did not report food insecurity. The association between food insecurity and migraine was significant both before (odds ratio, 2.00; 95% confidence interval, 1.68-2.38; P less than .001) and after adjustment (adjusted OR, .58; 95% CI, 1.30-1.95; P less than .001).

“Health care clinicians caring for persons who experience migraine should consider screening for food insecurity as a potential contributor to migraine exacerbations and provide referrals to programs such as the Supplemental Nutrition Assistance Program [formerly the Food Stamp Program] when appropriate,” the investigators concluded (JAMA Neurol. 2019 Jun 24. doi: 10.1001/jamaneurol.2019.1663).

No conflicts of interest were reported. The study was supported by grants from the University of California Global Food Initiative Fellowship, the American Academy of Pediatrics, the American Pediatric Society, and the Norman Schlossberger Research Fund from the University of California.

[email protected]

Food insecurity was significantly associated with migraine prevalence in young adults, according to Jason M. Nagata, MD, of the University of California, San Francisco, and associates.

Data were collected from a cross-sectional, nationally representative set of 14,786 young adults in the United States aged 24-32 years who participated in the 2008 National Longitudinal Study of Adolescent to Adult Health, the investigators wrote in a research letter published in JAMA Neurology.

Food insecurity was assessed by self-report through the interview question, “In the past 12 months, was there a time when (you/your household were/was) worried whether food would run out before you would get money to buy more?” Migraine was assessed by a positive answer to the interview question, “Has a doctor, nurse, or other health care professional ever told you that you have or had migraine headaches?”

In all, 1,647 study participants (11%) reported food insecurity; the prevalence of migraine in this group was 23.9%, compared with a prevalence of 13.6% in participants who did not report food insecurity. The association between food insecurity and migraine was significant both before (odds ratio, 2.00; 95% confidence interval, 1.68-2.38; P less than .001) and after adjustment (adjusted OR, .58; 95% CI, 1.30-1.95; P less than .001).

“Health care clinicians caring for persons who experience migraine should consider screening for food insecurity as a potential contributor to migraine exacerbations and provide referrals to programs such as the Supplemental Nutrition Assistance Program [formerly the Food Stamp Program] when appropriate,” the investigators concluded (JAMA Neurol. 2019 Jun 24. doi: 10.1001/jamaneurol.2019.1663).

No conflicts of interest were reported. The study was supported by grants from the University of California Global Food Initiative Fellowship, the American Academy of Pediatrics, the American Pediatric Society, and the Norman Schlossberger Research Fund from the University of California.

[email protected]

Food insecurity was significantly associated with migraine prevalence in young adults, according to Jason M. Nagata, MD, of the University of California, San Francisco, and associates.

Data were collected from a cross-sectional, nationally representative set of 14,786 young adults in the United States aged 24-32 years who participated in the 2008 National Longitudinal Study of Adolescent to Adult Health, the investigators wrote in a research letter published in JAMA Neurology.

Food insecurity was assessed by self-report through the interview question, “In the past 12 months, was there a time when (you/your household were/was) worried whether food would run out before you would get money to buy more?” Migraine was assessed by a positive answer to the interview question, “Has a doctor, nurse, or other health care professional ever told you that you have or had migraine headaches?”

In all, 1,647 study participants (11%) reported food insecurity; the prevalence of migraine in this group was 23.9%, compared with a prevalence of 13.6% in participants who did not report food insecurity. The association between food insecurity and migraine was significant both before (odds ratio, 2.00; 95% confidence interval, 1.68-2.38; P less than .001) and after adjustment (adjusted OR, .58; 95% CI, 1.30-1.95; P less than .001).

“Health care clinicians caring for persons who experience migraine should consider screening for food insecurity as a potential contributor to migraine exacerbations and provide referrals to programs such as the Supplemental Nutrition Assistance Program [formerly the Food Stamp Program] when appropriate,” the investigators concluded (JAMA Neurol. 2019 Jun 24. doi: 10.1001/jamaneurol.2019.1663).

No conflicts of interest were reported. The study was supported by grants from the University of California Global Food Initiative Fellowship, the American Academy of Pediatrics, the American Pediatric Society, and the Norman Schlossberger Research Fund from the University of California.

[email protected]

SAN ANTONIO – Episodic migraine patients benefit from mindfulness-based stress reduction training, according to new research. The intervention reduced headache frequency, slightly increased whole-brain gray matter volume, and reduced symptoms of anxiety, depression, and stress.

stockdevil/Thinkstock

The gray matter findings may indicate opportunities for therapeutic targets, while the psychosocial findings are important in understanding migraine burden, treatment response, and personalized medicine opportunities, Shana Burrowes, PhD, a postdoctoral associate at Boston University, said at the annual meeting of the College on Problems of Drug Dependence.

In a session focused on exploring alternatives to opioids for pain treatment, Dr. Burrowes described interim results of a randomized, controlled trial testing the effectiveness of mindfulness-based stress reduction (MBSR) training for managing migraine.

In discussing the rationale for study endpoints, she explained a three-pronged model for understanding migraine. Those elements include the symptoms themselves – unilateral throbbing pain, nausea, and photophobia – and the psychosocial symptoms and comorbidities, including anxiety, depression, stress, and catastrophizing. Up to 30%* of migraine patients have comorbid depression.

Those two prongs have a bidirectional relationship, since each increases the risk of the other. For example, frequent migraine can leave people feeling anxious about when their next migraine will occur, and that anxiety can increase the risk of it occurring.

Both elements lead to the third prong, which is change in gray matter volume. “If you’re a patient with migraine, an MRI on your brain is going to look different from somebody who does not have migraine,” Dr. Burrowes said. “With all these things going on in a patient, a migraine patient is actually pretty difficult to treat.”

Therefore, the researchers focused on outcomes from each of these three domains: gray matter volume in MRI; headache frequency as a clinical outcome; and the psychosocial comorbidities of anxiety, stress, and depression.

Study participants included 98 patients with episodic migraine, defined as fewer than 15 headache days a month, and 27 controls* matched by demographics to the patients and without any chronic pain conditions. The groups were 92% female and had similar ratios of whites (75% and 77%) and college graduates (95% and 96%).

Only the patients were randomized to the two interventions, one a training on MBSR and the other focusing on stress management for headache (SMH).

The MBSR training involved group sessions, eight 2.5-hour meditation sessions, at-home practice, a half-day retreat, and then an additional four biweekly sessions. The mindfulness training specifically focused on intentionally paying attention in the moment without judgment. The SMH arm focused on education for managing headache symptoms, stress, sleep hygiene, and diet, but it did not involve any specific skills training, such as relaxation training.

All participants, including healthy controls, underwent clinical assessment and baseline MRI and psychosocial questionnaires, followed by MRI and psychosocial questionnaire follow-ups at 3 and 6 months. MRI imaging focused on the whole brain and on the bilateral insula, dorsolateral prefrontal cortex, anterior cingulate cortex, and superior frontal gyrus. Patients also kept headache diaries throughout the trial.

Both intervention groups showed an increase in gray matter volume over 6 months, compared with healthy controls: 1.3% in the whole brain for SMH participants and 1.01% in the MBSR patients, compared with –1.37% in healthy participants. In the right superior frontal gyrus, gray matter volume also increased 2.62% in SMH participants and 1.25% in MBSR patients but decreased 0.19% in healthy participants.

Dr. Burrowes said she could not share specific findings on headache frequency and psychosocial outcomes because her team’s research is currently under review. Overall, however, headache frequency declined more than 50% post intervention, and 39% of migraine patients responded to the therapy.

In addition, anxiety, stress, and depression symptoms all saw improvements from MBSR and slightly but significantly mediated the effect of MBSR on migraine reduction.

Dr. Burrowes reported having no disclosures.

*The story was updated 6/20/2019.

SAN ANTONIO – Episodic migraine patients benefit from mindfulness-based stress reduction training, according to new research. The intervention reduced headache frequency, slightly increased whole-brain gray matter volume, and reduced symptoms of anxiety, depression, and stress.

stockdevil/Thinkstock

The gray matter findings may indicate opportunities for therapeutic targets, while the psychosocial findings are important in understanding migraine burden, treatment response, and personalized medicine opportunities, Shana Burrowes, PhD, a postdoctoral associate at Boston University, said at the annual meeting of the College on Problems of Drug Dependence.

In a session focused on exploring alternatives to opioids for pain treatment, Dr. Burrowes described interim results of a randomized, controlled trial testing the effectiveness of mindfulness-based stress reduction (MBSR) training for managing migraine.

In discussing the rationale for study endpoints, she explained a three-pronged model for understanding migraine. Those elements include the symptoms themselves – unilateral throbbing pain, nausea, and photophobia – and the psychosocial symptoms and comorbidities, including anxiety, depression, stress, and catastrophizing. Up to 30%* of migraine patients have comorbid depression.

Those two prongs have a bidirectional relationship, since each increases the risk of the other. For example, frequent migraine can leave people feeling anxious about when their next migraine will occur, and that anxiety can increase the risk of it occurring.

Both elements lead to the third prong, which is change in gray matter volume. “If you’re a patient with migraine, an MRI on your brain is going to look different from somebody who does not have migraine,” Dr. Burrowes said. “With all these things going on in a patient, a migraine patient is actually pretty difficult to treat.”

Therefore, the researchers focused on outcomes from each of these three domains: gray matter volume in MRI; headache frequency as a clinical outcome; and the psychosocial comorbidities of anxiety, stress, and depression.

Study participants included 98 patients with episodic migraine, defined as fewer than 15 headache days a month, and 27 controls* matched by demographics to the patients and without any chronic pain conditions. The groups were 92% female and had similar ratios of whites (75% and 77%) and college graduates (95% and 96%).

Only the patients were randomized to the two interventions, one a training on MBSR and the other focusing on stress management for headache (SMH).

The MBSR training involved group sessions, eight 2.5-hour meditation sessions, at-home practice, a half-day retreat, and then an additional four biweekly sessions. The mindfulness training specifically focused on intentionally paying attention in the moment without judgment. The SMH arm focused on education for managing headache symptoms, stress, sleep hygiene, and diet, but it did not involve any specific skills training, such as relaxation training.

All participants, including healthy controls, underwent clinical assessment and baseline MRI and psychosocial questionnaires, followed by MRI and psychosocial questionnaire follow-ups at 3 and 6 months. MRI imaging focused on the whole brain and on the bilateral insula, dorsolateral prefrontal cortex, anterior cingulate cortex, and superior frontal gyrus. Patients also kept headache diaries throughout the trial.

Both intervention groups showed an increase in gray matter volume over 6 months, compared with healthy controls: 1.3% in the whole brain for SMH participants and 1.01% in the MBSR patients, compared with –1.37% in healthy participants. In the right superior frontal gyrus, gray matter volume also increased 2.62% in SMH participants and 1.25% in MBSR patients but decreased 0.19% in healthy participants.

Dr. Burrowes said she could not share specific findings on headache frequency and psychosocial outcomes because her team’s research is currently under review. Overall, however, headache frequency declined more than 50% post intervention, and 39% of migraine patients responded to the therapy.

In addition, anxiety, stress, and depression symptoms all saw improvements from MBSR and slightly but significantly mediated the effect of MBSR on migraine reduction.

Dr. Burrowes reported having no disclosures.

*The story was updated 6/20/2019.

SAN ANTONIO – Episodic migraine patients benefit from mindfulness-based stress reduction training, according to new research. The intervention reduced headache frequency, slightly increased whole-brain gray matter volume, and reduced symptoms of anxiety, depression, and stress.

stockdevil/Thinkstock

The gray matter findings may indicate opportunities for therapeutic targets, while the psychosocial findings are important in understanding migraine burden, treatment response, and personalized medicine opportunities, Shana Burrowes, PhD, a postdoctoral associate at Boston University, said at the annual meeting of the College on Problems of Drug Dependence.

In a session focused on exploring alternatives to opioids for pain treatment, Dr. Burrowes described interim results of a randomized, controlled trial testing the effectiveness of mindfulness-based stress reduction (MBSR) training for managing migraine.

In discussing the rationale for study endpoints, she explained a three-pronged model for understanding migraine. Those elements include the symptoms themselves – unilateral throbbing pain, nausea, and photophobia – and the psychosocial symptoms and comorbidities, including anxiety, depression, stress, and catastrophizing. Up to 30%* of migraine patients have comorbid depression.

Those two prongs have a bidirectional relationship, since each increases the risk of the other. For example, frequent migraine can leave people feeling anxious about when their next migraine will occur, and that anxiety can increase the risk of it occurring.

Both elements lead to the third prong, which is change in gray matter volume. “If you’re a patient with migraine, an MRI on your brain is going to look different from somebody who does not have migraine,” Dr. Burrowes said. “With all these things going on in a patient, a migraine patient is actually pretty difficult to treat.”

Therefore, the researchers focused on outcomes from each of these three domains: gray matter volume in MRI; headache frequency as a clinical outcome; and the psychosocial comorbidities of anxiety, stress, and depression.

Study participants included 98 patients with episodic migraine, defined as fewer than 15 headache days a month, and 27 controls* matched by demographics to the patients and without any chronic pain conditions. The groups were 92% female and had similar ratios of whites (75% and 77%) and college graduates (95% and 96%).

Only the patients were randomized to the two interventions, one a training on MBSR and the other focusing on stress management for headache (SMH).

The MBSR training involved group sessions, eight 2.5-hour meditation sessions, at-home practice, a half-day retreat, and then an additional four biweekly sessions. The mindfulness training specifically focused on intentionally paying attention in the moment without judgment. The SMH arm focused on education for managing headache symptoms, stress, sleep hygiene, and diet, but it did not involve any specific skills training, such as relaxation training.

All participants, including healthy controls, underwent clinical assessment and baseline MRI and psychosocial questionnaires, followed by MRI and psychosocial questionnaire follow-ups at 3 and 6 months. MRI imaging focused on the whole brain and on the bilateral insula, dorsolateral prefrontal cortex, anterior cingulate cortex, and superior frontal gyrus. Patients also kept headache diaries throughout the trial.

Both intervention groups showed an increase in gray matter volume over 6 months, compared with healthy controls: 1.3% in the whole brain for SMH participants and 1.01% in the MBSR patients, compared with –1.37% in healthy participants. In the right superior frontal gyrus, gray matter volume also increased 2.62% in SMH participants and 1.25% in MBSR patients but decreased 0.19% in healthy participants.

Dr. Burrowes said she could not share specific findings on headache frequency and psychosocial outcomes because her team’s research is currently under review. Overall, however, headache frequency declined more than 50% post intervention, and 39% of migraine patients responded to the therapy.

In addition, anxiety, stress, and depression symptoms all saw improvements from MBSR and slightly but significantly mediated the effect of MBSR on migraine reduction.

Dr. Burrowes reported having no disclosures.

*The story was updated 6/20/2019.

The gepants and monoclonal antibodies (mAbs) against calcitonin gene-related peptide (CGRP) and its receptor appear to be effective, tolerable and safe, according to several posters recently presented at the 2019 American Academy of Neurology (AAN) Annual Meeting in Philadelphia. Information was presented on the 3 gepants being studied for US Food and Drug Administration (FDA) approval: 1 for acute care of migraine, 1 for prevention and 1 for both (though the presented data for rimegepant only covers acute care).

All drugs cause a small degree of adverse events (AEs), somewhat more than placebo. Based on the presented data, it seems that those associated with 3 times higher than normal elevation of liver enzymes, were usually not found to be the cause of that elevation. At no time was bilirubin elevated. This shows that all of these gepants appear to be effective and safe, despite the fact that some were found to have cause liver toxicity many years ago.

The first gepant study to be published was on olcegepant in 2004, in the New England Journal of Medicine. Professor Jes Olesen, MD, was the lead author of the study, which detailed the efficacy and safety of this small molecule CGRP receptor antagonist. Olcegepant was in an intravenous formulation and the plan was to convert it to a tablet, which never happened. Another company then produced telcagepant as a tablet and it was shown to be safe and effective in 2 large, multicenter, double-blind trials. Before receiving FDA approval for the acute care of migraine, it was studied on a daily basis for migraine prevention. It was found to cause some liver toxicity, so development was stopped. At that time several other gepants in development were placed on the shelf, partially for the fear of liver toxicity. The FDA is unlikely to approve a drug with significant liver toxicity, which can cause a range of symptoms including jaundice, itching, abdominal pain, fatigue, loss of appetite, nausea, vomiting, rash, and weight loss.

In the next few years we will have 4 mAbs for the prevention of migraine, and 3 gepants if all studies are positive. Below are the key takeaways from the presented posters on ubrogepant and atogepant, as information that is currently available on rimegepant.
 

Key Takeaways:

• Ubrogepant – Ailani J, Hutchinson S, Lipton R, et al.
  • Intermittent use of ubrogepant for the acute treatment of migraine over 1 year was well-tolerated with no identified safety concerns. Throughout the 1-year, Phase III study of 1254 participants, 22,454 migraine attacks were treated with 31,968 doses of ubrogepant.
  • Twenty cases of ALT/AST ≥3x ULN were reported and adjudicated by an independent panel of liver experts blinded to treatment.
  • Of the 20 cases, 17 (4 usual care, 3 ubrogepant 50-mg, and 10 ubrogepant 100-mg) were determined to be unlikely related based on plausible alternative etiology/confounding factors.
  • Just 2 cases (both ubrogepant 50-mg) were described as possibly related to study medication and 1 case (ubrogepant 100-mg) was adjudicated as probably related; however, confounding factors were noted.
  • All cases were asymptomatic with no concurrent bilirubin elevation. ALT/AST elevations resolved in those who continued dosing.
     
• Atogepant – Goadsby PJ, Dodick DW, Trugman JM, et al.
  • In a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial of adults with a history of migraine, with or without aura, atogepant was well tolerated with no treatment-related serious AEs.
  • Of the 834 randomized subjects, 825 were evaluated in the safety population. Treatment-emergent AEs were reported by 480 subjects (58.2%), and for 170 (20.6%), the AEs were considered treatment-related. Seven subjects (0.8%) reported serious AEs, but none were determined as treatment related.
  • There were 10 cases of treatment-emergent ALT/AST elevations >3x the upper limit of normal, and this was balanced across the treatment dosage groups (10 mg QD, 30 mg QD, 30 mg BID, 60 mg QD, and 60 mg BID).
     
• Rimegepant – See Biogen press release for more information
  • In December 2019, Biohaven announced initial positive results from an ongoing long-term, open-label safety study for rimegepant.
  • The interim results included hepatic safety and tolerability data of rimegepant 75 mg in study participants based on a review of adverse events and regularly scheduled liver function tests.
  • A panel of external independent liver experts provided a consensus based on the Drug-Induced Liver Injury Network (DILIN) causality assessment, determining that there were no liver cases probably related to the study drug and that there were no Hy’s Law cases identified.
  • The panel also concluded that there were no liver safety signals detected and that, compared to placebo arms of other migraine treatments, there was a very low incidence of overall elevations of liver abnormalities.

The gepants and monoclonal antibodies (mAbs) against calcitonin gene-related peptide (CGRP) and its receptor appear to be effective, tolerable and safe, according to several posters recently presented at the 2019 American Academy of Neurology (AAN) Annual Meeting in Philadelphia. Information was presented on the 3 gepants being studied for US Food and Drug Administration (FDA) approval: 1 for acute care of migraine, 1 for prevention and 1 for both (though the presented data for rimegepant only covers acute care).

All drugs cause a small degree of adverse events (AEs), somewhat more than placebo. Based on the presented data, it seems that those associated with 3 times higher than normal elevation of liver enzymes, were usually not found to be the cause of that elevation. At no time was bilirubin elevated. This shows that all of these gepants appear to be effective and safe, despite the fact that some were found to have cause liver toxicity many years ago.

The first gepant study to be published was on olcegepant in 2004, in the New England Journal of Medicine. Professor Jes Olesen, MD, was the lead author of the study, which detailed the efficacy and safety of this small molecule CGRP receptor antagonist. Olcegepant was in an intravenous formulation and the plan was to convert it to a tablet, which never happened. Another company then produced telcagepant as a tablet and it was shown to be safe and effective in 2 large, multicenter, double-blind trials. Before receiving FDA approval for the acute care of migraine, it was studied on a daily basis for migraine prevention. It was found to cause some liver toxicity, so development was stopped. At that time several other gepants in development were placed on the shelf, partially for the fear of liver toxicity. The FDA is unlikely to approve a drug with significant liver toxicity, which can cause a range of symptoms including jaundice, itching, abdominal pain, fatigue, loss of appetite, nausea, vomiting, rash, and weight loss.

In the next few years we will have 4 mAbs for the prevention of migraine, and 3 gepants if all studies are positive. Below are the key takeaways from the presented posters on ubrogepant and atogepant, as information that is currently available on rimegepant.
 

Key Takeaways:

• Ubrogepant – Ailani J, Hutchinson S, Lipton R, et al.
  • Intermittent use of ubrogepant for the acute treatment of migraine over 1 year was well-tolerated with no identified safety concerns. Throughout the 1-year, Phase III study of 1254 participants, 22,454 migraine attacks were treated with 31,968 doses of ubrogepant.
  • Twenty cases of ALT/AST ≥3x ULN were reported and adjudicated by an independent panel of liver experts blinded to treatment.
  • Of the 20 cases, 17 (4 usual care, 3 ubrogepant 50-mg, and 10 ubrogepant 100-mg) were determined to be unlikely related based on plausible alternative etiology/confounding factors.
  • Just 2 cases (both ubrogepant 50-mg) were described as possibly related to study medication and 1 case (ubrogepant 100-mg) was adjudicated as probably related; however, confounding factors were noted.
  • All cases were asymptomatic with no concurrent bilirubin elevation. ALT/AST elevations resolved in those who continued dosing.
     
• Atogepant – Goadsby PJ, Dodick DW, Trugman JM, et al.
  • In a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial of adults with a history of migraine, with or without aura, atogepant was well tolerated with no treatment-related serious AEs.
  • Of the 834 randomized subjects, 825 were evaluated in the safety population. Treatment-emergent AEs were reported by 480 subjects (58.2%), and for 170 (20.6%), the AEs were considered treatment-related. Seven subjects (0.8%) reported serious AEs, but none were determined as treatment related.
  • There were 10 cases of treatment-emergent ALT/AST elevations >3x the upper limit of normal, and this was balanced across the treatment dosage groups (10 mg QD, 30 mg QD, 30 mg BID, 60 mg QD, and 60 mg BID).
     
• Rimegepant – See Biogen press release for more information
  • In December 2019, Biohaven announced initial positive results from an ongoing long-term, open-label safety study for rimegepant.
  • The interim results included hepatic safety and tolerability data of rimegepant 75 mg in study participants based on a review of adverse events and regularly scheduled liver function tests.
  • A panel of external independent liver experts provided a consensus based on the Drug-Induced Liver Injury Network (DILIN) causality assessment, determining that there were no liver cases probably related to the study drug and that there were no Hy’s Law cases identified.
  • The panel also concluded that there were no liver safety signals detected and that, compared to placebo arms of other migraine treatments, there was a very low incidence of overall elevations of liver abnormalities.

The gepants and monoclonal antibodies (mAbs) against calcitonin gene-related peptide (CGRP) and its receptor appear to be effective, tolerable and safe, according to several posters recently presented at the 2019 American Academy of Neurology (AAN) Annual Meeting in Philadelphia. Information was presented on the 3 gepants being studied for US Food and Drug Administration (FDA) approval: 1 for acute care of migraine, 1 for prevention and 1 for both (though the presented data for rimegepant only covers acute care).

All drugs cause a small degree of adverse events (AEs), somewhat more than placebo. Based on the presented data, it seems that those associated with 3 times higher than normal elevation of liver enzymes, were usually not found to be the cause of that elevation. At no time was bilirubin elevated. This shows that all of these gepants appear to be effective and safe, despite the fact that some were found to have cause liver toxicity many years ago.

The first gepant study to be published was on olcegepant in 2004, in the New England Journal of Medicine. Professor Jes Olesen, MD, was the lead author of the study, which detailed the efficacy and safety of this small molecule CGRP receptor antagonist. Olcegepant was in an intravenous formulation and the plan was to convert it to a tablet, which never happened. Another company then produced telcagepant as a tablet and it was shown to be safe and effective in 2 large, multicenter, double-blind trials. Before receiving FDA approval for the acute care of migraine, it was studied on a daily basis for migraine prevention. It was found to cause some liver toxicity, so development was stopped. At that time several other gepants in development were placed on the shelf, partially for the fear of liver toxicity. The FDA is unlikely to approve a drug with significant liver toxicity, which can cause a range of symptoms including jaundice, itching, abdominal pain, fatigue, loss of appetite, nausea, vomiting, rash, and weight loss.

In the next few years we will have 4 mAbs for the prevention of migraine, and 3 gepants if all studies are positive. Below are the key takeaways from the presented posters on ubrogepant and atogepant, as information that is currently available on rimegepant.
 

Key Takeaways:

• Ubrogepant – Ailani J, Hutchinson S, Lipton R, et al.
  • Intermittent use of ubrogepant for the acute treatment of migraine over 1 year was well-tolerated with no identified safety concerns. Throughout the 1-year, Phase III study of 1254 participants, 22,454 migraine attacks were treated with 31,968 doses of ubrogepant.
  • Twenty cases of ALT/AST ≥3x ULN were reported and adjudicated by an independent panel of liver experts blinded to treatment.
  • Of the 20 cases, 17 (4 usual care, 3 ubrogepant 50-mg, and 10 ubrogepant 100-mg) were determined to be unlikely related based on plausible alternative etiology/confounding factors.
  • Just 2 cases (both ubrogepant 50-mg) were described as possibly related to study medication and 1 case (ubrogepant 100-mg) was adjudicated as probably related; however, confounding factors were noted.
  • All cases were asymptomatic with no concurrent bilirubin elevation. ALT/AST elevations resolved in those who continued dosing.
     
• Atogepant – Goadsby PJ, Dodick DW, Trugman JM, et al.
  • In a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial of adults with a history of migraine, with or without aura, atogepant was well tolerated with no treatment-related serious AEs.
  • Of the 834 randomized subjects, 825 were evaluated in the safety population. Treatment-emergent AEs were reported by 480 subjects (58.2%), and for 170 (20.6%), the AEs were considered treatment-related. Seven subjects (0.8%) reported serious AEs, but none were determined as treatment related.
  • There were 10 cases of treatment-emergent ALT/AST elevations >3x the upper limit of normal, and this was balanced across the treatment dosage groups (10 mg QD, 30 mg QD, 30 mg BID, 60 mg QD, and 60 mg BID).
     
• Rimegepant – See Biogen press release for more information
  • In December 2019, Biohaven announced initial positive results from an ongoing long-term, open-label safety study for rimegepant.
  • The interim results included hepatic safety and tolerability data of rimegepant 75 mg in study participants based on a review of adverse events and regularly scheduled liver function tests.
  • A panel of external independent liver experts provided a consensus based on the Drug-Induced Liver Injury Network (DILIN) causality assessment, determining that there were no liver cases probably related to the study drug and that there were no Hy’s Law cases identified.
  • The panel also concluded that there were no liver safety signals detected and that, compared to placebo arms of other migraine treatments, there was a very low incidence of overall elevations of liver abnormalities.

Cyclic Vomiting Syndrome and Primary Headache

Cyclic vomiting syndrome and benign paroxysmal torticollis are associated with a very high risk of developing headache, mostly migraine, later in life. This according to a longitudinal study that assessed the rate of headache in patients presenting with cyclic vomiting syndrome and benign paroxysmal torticollis during infancy and defined the main clinical features of the disorder. Researchers administered a questionnaire to the parents of pediatric patients with previous diagnosis of cyclic vomiting syndrome and/or benign paroxysmal torticollis. They found:

• 82 patients with cyclic vomiting syndrome and 33 with benign paroxysmal torticollis were included in the final analysis.
• 79% of patients with cyclic vomiting syndrome presented with headache during the follow-up with a mean age at onset of 6 years.
• 67% of patients with benign paroxysmal torticollis suffered from headache during the follow-up with a mean age at onset of 5 years.

Moavero R, et al. Cyclic vomiting syndrome and benign paroxysmal torticollis are associated with a high risk of developing primary headache: A longitudinal study. [Published online ahead of print April 13, 2019]. Cephalalgia. doi: 10.1177/0333102419844542.

Cyclic Vomiting Syndrome and Primary Headache

Cyclic vomiting syndrome and benign paroxysmal torticollis are associated with a very high risk of developing headache, mostly migraine, later in life. This according to a longitudinal study that assessed the rate of headache in patients presenting with cyclic vomiting syndrome and benign paroxysmal torticollis during infancy and defined the main clinical features of the disorder. Researchers administered a questionnaire to the parents of pediatric patients with previous diagnosis of cyclic vomiting syndrome and/or benign paroxysmal torticollis. They found:

• 82 patients with cyclic vomiting syndrome and 33 with benign paroxysmal torticollis were included in the final analysis.
• 79% of patients with cyclic vomiting syndrome presented with headache during the follow-up with a mean age at onset of 6 years.
• 67% of patients with benign paroxysmal torticollis suffered from headache during the follow-up with a mean age at onset of 5 years.

Moavero R, et al. Cyclic vomiting syndrome and benign paroxysmal torticollis are associated with a high risk of developing primary headache: A longitudinal study. [Published online ahead of print April 13, 2019]. Cephalalgia. doi: 10.1177/0333102419844542.

Cyclic Vomiting Syndrome and Primary Headache

Cyclic vomiting syndrome and benign paroxysmal torticollis are associated with a very high risk of developing headache, mostly migraine, later in life. This according to a longitudinal study that assessed the rate of headache in patients presenting with cyclic vomiting syndrome and benign paroxysmal torticollis during infancy and defined the main clinical features of the disorder. Researchers administered a questionnaire to the parents of pediatric patients with previous diagnosis of cyclic vomiting syndrome and/or benign paroxysmal torticollis. They found:

• 82 patients with cyclic vomiting syndrome and 33 with benign paroxysmal torticollis were included in the final analysis.
• 79% of patients with cyclic vomiting syndrome presented with headache during the follow-up with a mean age at onset of 6 years.
• 67% of patients with benign paroxysmal torticollis suffered from headache during the follow-up with a mean age at onset of 5 years.

Moavero R, et al. Cyclic vomiting syndrome and benign paroxysmal torticollis are associated with a high risk of developing primary headache: A longitudinal study. [Published online ahead of print April 13, 2019]. Cephalalgia. doi: 10.1177/0333102419844542.

The clinical characteristics of migraine attacks are sufficiently different in patients with and without neurocysticercosis, a new study found. Researchers investigated the characteristics of migraine attacks in patients with calcified neurocysticercosis (NCC) on brain imaging. Of 350 migraine patients, 166 had undergone brain imaging. Seventy-two patients with migraines had calcified NCC. The migraine attacks of the patients with calcification (MiC) were compared with those of 94 patients without calcification (MiNC). Among the findings:

• Side-locked headaches were seen in 48.6% of the MiC patients.
• Aura preceding the migraine attack was more common in the MiC group vs the MiNC group.
• The MiC group had fewer headache episodes per month with fewer common associated features and required fewer drugs for secondary prophylaxis.

Pradhan S, et al. Clinical characteristics of migraine in patients with calcified neurocysticercosis. [Published online ahead of print April 6, 2019]. Trans R Soc Trop Med Hyg. doi: 10.1093/trstmh/trz018.

The clinical characteristics of migraine attacks are sufficiently different in patients with and without neurocysticercosis, a new study found. Researchers investigated the characteristics of migraine attacks in patients with calcified neurocysticercosis (NCC) on brain imaging. Of 350 migraine patients, 166 had undergone brain imaging. Seventy-two patients with migraines had calcified NCC. The migraine attacks of the patients with calcification (MiC) were compared with those of 94 patients without calcification (MiNC). Among the findings:

• Side-locked headaches were seen in 48.6% of the MiC patients.
• Aura preceding the migraine attack was more common in the MiC group vs the MiNC group.
• The MiC group had fewer headache episodes per month with fewer common associated features and required fewer drugs for secondary prophylaxis.

Pradhan S, et al. Clinical characteristics of migraine in patients with calcified neurocysticercosis. [Published online ahead of print April 6, 2019]. Trans R Soc Trop Med Hyg. doi: 10.1093/trstmh/trz018.

The clinical characteristics of migraine attacks are sufficiently different in patients with and without neurocysticercosis, a new study found. Researchers investigated the characteristics of migraine attacks in patients with calcified neurocysticercosis (NCC) on brain imaging. Of 350 migraine patients, 166 had undergone brain imaging. Seventy-two patients with migraines had calcified NCC. The migraine attacks of the patients with calcification (MiC) were compared with those of 94 patients without calcification (MiNC). Among the findings:

• Side-locked headaches were seen in 48.6% of the MiC patients.
• Aura preceding the migraine attack was more common in the MiC group vs the MiNC group.
• The MiC group had fewer headache episodes per month with fewer common associated features and required fewer drugs for secondary prophylaxis.

Pradhan S, et al. Clinical characteristics of migraine in patients with calcified neurocysticercosis. [Published online ahead of print April 6, 2019]. Trans R Soc Trop Med Hyg. doi: 10.1093/trstmh/trz018.

Smartphone overuse in patients with migraine is related to poor sleep quality and daytime sleepiness, resulting in diminished quality of life, a new study found. The single-center, cross-sectional comparative study used the migraine disability assessment (MIDAS) questionnaire to evaluate the disability status, and Mobile Phone Problematic Use Scale (MPPUS) was used to evaluate smartphone use frequency. The Visual Analogue Scale (VAS), 24-h Migraine Quality of Life Questionnaire (24-h MQoLQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to evaluate the pain intensity, quality of life, sleep quality, and daytime sleepiness. Researchers found:

• The study included 123 patients.
• There was a significant difference between the groups in terms of pain intensity, frequency, and duration.
• There was a negative correlation between MPPUS and PQSI, a strong positive correlation between MPPUS and ESS, and a negative correlation between MPPUS and 24-h MQoLQ.

Demir YP, et al. Effects of smartphone overuse on headache, sleep and quality of life in migraine patients. Neurosciences (Riyadh). 2019;24(2):115-121. doi: 10.17712/nsj.2019.2.20180037.

Smartphone overuse in patients with migraine is related to poor sleep quality and daytime sleepiness, resulting in diminished quality of life, a new study found. The single-center, cross-sectional comparative study used the migraine disability assessment (MIDAS) questionnaire to evaluate the disability status, and Mobile Phone Problematic Use Scale (MPPUS) was used to evaluate smartphone use frequency. The Visual Analogue Scale (VAS), 24-h Migraine Quality of Life Questionnaire (24-h MQoLQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to evaluate the pain intensity, quality of life, sleep quality, and daytime sleepiness. Researchers found:

• The study included 123 patients.
• There was a significant difference between the groups in terms of pain intensity, frequency, and duration.
• There was a negative correlation between MPPUS and PQSI, a strong positive correlation between MPPUS and ESS, and a negative correlation between MPPUS and 24-h MQoLQ.

Demir YP, et al. Effects of smartphone overuse on headache, sleep and quality of life in migraine patients. Neurosciences (Riyadh). 2019;24(2):115-121. doi: 10.17712/nsj.2019.2.20180037.

Smartphone overuse in patients with migraine is related to poor sleep quality and daytime sleepiness, resulting in diminished quality of life, a new study found. The single-center, cross-sectional comparative study used the migraine disability assessment (MIDAS) questionnaire to evaluate the disability status, and Mobile Phone Problematic Use Scale (MPPUS) was used to evaluate smartphone use frequency. The Visual Analogue Scale (VAS), 24-h Migraine Quality of Life Questionnaire (24-h MQoLQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to evaluate the pain intensity, quality of life, sleep quality, and daytime sleepiness. Researchers found:

• The study included 123 patients.
• There was a significant difference between the groups in terms of pain intensity, frequency, and duration.
• There was a negative correlation between MPPUS and PQSI, a strong positive correlation between MPPUS and ESS, and a negative correlation between MPPUS and 24-h MQoLQ.

Demir YP, et al. Effects of smartphone overuse on headache, sleep and quality of life in migraine patients. Neurosciences (Riyadh). 2019;24(2):115-121. doi: 10.17712/nsj.2019.2.20180037.

The Food and Drug Administration has approved galcanezumab-gnlm (Emgality) for the preventive treatment of episodic cluster headache in adults. The drug, a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP), is administered by self-injection in 300-mg doses.

Galcanezumab is the first medication for episodic cluster headache that reduces the frequency of attacks, the agency said in an announcement.

Cluster headache can be more intense than migraine. The pain is unilateral and occurs in the orbital, supraorbital, or temporal regions. It reaches its peak intensity within 5-10 minutes and generally lasts for 30-90 minutes. Symptoms include a burning sensation, conjunctival injection, rhinorrhea, and photosensitivity. Patients often have one to three of these headaches per day, and the headaches appear to be linked to the circadian rhythm. An episodic cluster cycle can last for weeks to months of daily or near daily attacks.

A study presented at the recent meeting of the American Academy of Neurology provided evidence of the drug’s efficacy in cluster headache. In this trial, researchers randomized 106 patients with episodic cluster headache to galcanezumab or placebo. The baseline cluster headache frequency was 17.3 attacks per week, and galcanezumab reduced this frequency to 9.1 attacks per week, compared with 12.1 attacks per week with placebo. The most common side effect reported in this and other clinical trials was injection-site reactions.

Galcanezumab entails a risk of hypersensitivity reactions, according to the FDA. These reactions may occur several days after administration and may be prolonged. “If a serious hypersensitivity reaction occurs, treatment should be discontinued,” the agency said.

“It’s a very exciting day. There had never been a drug approved for prevention of cluster headache,” said Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth and director of the Dartmouth Headache Center, Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

Bruce Jancin/MDedge News

When asked for comment, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said “If this monoclonal antibody to the CGRP ligand works as well in real life as in the trial, it will be an important advance in the treatment of cluster headache.”

Prior to the approval of galcanezumab, noninvasive vagal nerve stimulation was approved in November 2018 for adjunctive use in the preventive treatment of cluster headache in adults.

The FDA granted the application for galcanezumab using a Priority Review and Breakthrough Therapy designation. The agency approved galcanezumab for the preventive treatment of migraine in adults in September 2018. The drug appears to have a similar safety profile in both patient populations. Eli Lilly, which is based in Indianapolis, Indiana, manufactures the drug.

[email protected]

This article was updated June 5, 2019.

The Food and Drug Administration has approved galcanezumab-gnlm (Emgality) for the preventive treatment of episodic cluster headache in adults. The drug, a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP), is administered by self-injection in 300-mg doses.

Galcanezumab is the first medication for episodic cluster headache that reduces the frequency of attacks, the agency said in an announcement.

Cluster headache can be more intense than migraine. The pain is unilateral and occurs in the orbital, supraorbital, or temporal regions. It reaches its peak intensity within 5-10 minutes and generally lasts for 30-90 minutes. Symptoms include a burning sensation, conjunctival injection, rhinorrhea, and photosensitivity. Patients often have one to three of these headaches per day, and the headaches appear to be linked to the circadian rhythm. An episodic cluster cycle can last for weeks to months of daily or near daily attacks.

A study presented at the recent meeting of the American Academy of Neurology provided evidence of the drug’s efficacy in cluster headache. In this trial, researchers randomized 106 patients with episodic cluster headache to galcanezumab or placebo. The baseline cluster headache frequency was 17.3 attacks per week, and galcanezumab reduced this frequency to 9.1 attacks per week, compared with 12.1 attacks per week with placebo. The most common side effect reported in this and other clinical trials was injection-site reactions.

Galcanezumab entails a risk of hypersensitivity reactions, according to the FDA. These reactions may occur several days after administration and may be prolonged. “If a serious hypersensitivity reaction occurs, treatment should be discontinued,” the agency said.

“It’s a very exciting day. There had never been a drug approved for prevention of cluster headache,” said Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth and director of the Dartmouth Headache Center, Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

Bruce Jancin/MDedge News

When asked for comment, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said “If this monoclonal antibody to the CGRP ligand works as well in real life as in the trial, it will be an important advance in the treatment of cluster headache.”

Prior to the approval of galcanezumab, noninvasive vagal nerve stimulation was approved in November 2018 for adjunctive use in the preventive treatment of cluster headache in adults.

The FDA granted the application for galcanezumab using a Priority Review and Breakthrough Therapy designation. The agency approved galcanezumab for the preventive treatment of migraine in adults in September 2018. The drug appears to have a similar safety profile in both patient populations. Eli Lilly, which is based in Indianapolis, Indiana, manufactures the drug.

[email protected]

This article was updated June 5, 2019.

The Food and Drug Administration has approved galcanezumab-gnlm (Emgality) for the preventive treatment of episodic cluster headache in adults. The drug, a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP), is administered by self-injection in 300-mg doses.

Galcanezumab is the first medication for episodic cluster headache that reduces the frequency of attacks, the agency said in an announcement.

Cluster headache can be more intense than migraine. The pain is unilateral and occurs in the orbital, supraorbital, or temporal regions. It reaches its peak intensity within 5-10 minutes and generally lasts for 30-90 minutes. Symptoms include a burning sensation, conjunctival injection, rhinorrhea, and photosensitivity. Patients often have one to three of these headaches per day, and the headaches appear to be linked to the circadian rhythm. An episodic cluster cycle can last for weeks to months of daily or near daily attacks.

A study presented at the recent meeting of the American Academy of Neurology provided evidence of the drug’s efficacy in cluster headache. In this trial, researchers randomized 106 patients with episodic cluster headache to galcanezumab or placebo. The baseline cluster headache frequency was 17.3 attacks per week, and galcanezumab reduced this frequency to 9.1 attacks per week, compared with 12.1 attacks per week with placebo. The most common side effect reported in this and other clinical trials was injection-site reactions.

Galcanezumab entails a risk of hypersensitivity reactions, according to the FDA. These reactions may occur several days after administration and may be prolonged. “If a serious hypersensitivity reaction occurs, treatment should be discontinued,” the agency said.

“It’s a very exciting day. There had never been a drug approved for prevention of cluster headache,” said Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth and director of the Dartmouth Headache Center, Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

Bruce Jancin/MDedge News

When asked for comment, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said “If this monoclonal antibody to the CGRP ligand works as well in real life as in the trial, it will be an important advance in the treatment of cluster headache.”

Prior to the approval of galcanezumab, noninvasive vagal nerve stimulation was approved in November 2018 for adjunctive use in the preventive treatment of cluster headache in adults.

The FDA granted the application for galcanezumab using a Priority Review and Breakthrough Therapy designation. The agency approved galcanezumab for the preventive treatment of migraine in adults in September 2018. The drug appears to have a similar safety profile in both patient populations. Eli Lilly, which is based in Indianapolis, Indiana, manufactures the drug.

[email protected]

This article was updated June 5, 2019.

Migraine with aura is associated with neuroimmune activation/neuroinflammation, a new study found. Thirteen migraineurs with aura and 16 healthy controls received integrated PET/MRI brain scans with [¹¹C]PBR28, a radioligand that binds to the 18 kDa translocator protein, a marker of glial activation. Standardized uptake value ratio (SUVR) was compared between groups. Researchers found:

• Compared to healthy controls, migraineurs demonstrated SUVR elevations in nociceptive processing areas, as well as in areas previously shown to be involved in cortical spreading depression.
• SUVR levels in frontoinsular cortex, primary/secondary somatosensory cortices, and basal ganglia were correlated with frequency of migraine attacks.

Albrecht DS, et al. Imaging of neuroinflammation in migraine with aura: A [¹¹C]PBR28 PET/MRI study. [Published online ahead of print March 27, 2019]. Neurology. doi:10.1212/WNL.0000000000007371.

Migraine with aura is associated with neuroimmune activation/neuroinflammation, a new study found. Thirteen migraineurs with aura and 16 healthy controls received integrated PET/MRI brain scans with [¹¹C]PBR28, a radioligand that binds to the 18 kDa translocator protein, a marker of glial activation. Standardized uptake value ratio (SUVR) was compared between groups. Researchers found:

• Compared to healthy controls, migraineurs demonstrated SUVR elevations in nociceptive processing areas, as well as in areas previously shown to be involved in cortical spreading depression.
• SUVR levels in frontoinsular cortex, primary/secondary somatosensory cortices, and basal ganglia were correlated with frequency of migraine attacks.

Albrecht DS, et al. Imaging of neuroinflammation in migraine with aura: A [¹¹C]PBR28 PET/MRI study. [Published online ahead of print March 27, 2019]. Neurology. doi:10.1212/WNL.0000000000007371.

Migraine with aura is associated with neuroimmune activation/neuroinflammation, a new study found. Thirteen migraineurs with aura and 16 healthy controls received integrated PET/MRI brain scans with [¹¹C]PBR28, a radioligand that binds to the 18 kDa translocator protein, a marker of glial activation. Standardized uptake value ratio (SUVR) was compared between groups. Researchers found:

• Compared to healthy controls, migraineurs demonstrated SUVR elevations in nociceptive processing areas, as well as in areas previously shown to be involved in cortical spreading depression.
• SUVR levels in frontoinsular cortex, primary/secondary somatosensory cortices, and basal ganglia were correlated with frequency of migraine attacks.

Albrecht DS, et al. Imaging of neuroinflammation in migraine with aura: A [¹¹C]PBR28 PET/MRI study. [Published online ahead of print March 27, 2019]. Neurology. doi:10.1212/WNL.0000000000007371.