Migraine ICYMI

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.

During posttreament periods, galcanezumab treatment effects in patients with migraine were reduced, but did not return to baseline, a new study found. Adults with episodic migraine were enrolled into EVOLVE-1 and EVOLVE-, which randomized 858 and 915 patients, respectively, to galcanezumab 120 mg, galcanezumab 240 mg, or placebo, administered subcutaneously once monthly for 6 months. After treatment completion or discontinuation, patients entered a 4-month posttreatment period. Researchers found:

• There were 740 patients (EVOLVE-1) and 830 (EVOLVE-2) patients entered into the posttreatment periods.
• About 95% (EVOLVE-1) and 96% (EVOLVE-2) of patients completed their respective trial.
• In both trials, change from pre-randomization baseline in monthly migraine headache days decreased over the posttreatment period.
• During posttreatment periods, 1.6% (EVOLVE-1) and 2.3% (EVOLVE-2) of patients initiated migraine preventive treatments.
• There were no unexpected adverse events after galcanezumab cessation.

Stauffer VL, et al. Effect of galcanezumab following treatment cessation in patients with migraine: Results from 2 randomized phase 3 trials. [Published online ahead of print April 3, 2019]. Headache. doi: 10.1111/head.13508.

During posttreament periods, galcanezumab treatment effects in patients with migraine were reduced, but did not return to baseline, a new study found. Adults with episodic migraine were enrolled into EVOLVE-1 and EVOLVE-, which randomized 858 and 915 patients, respectively, to galcanezumab 120 mg, galcanezumab 240 mg, or placebo, administered subcutaneously once monthly for 6 months. After treatment completion or discontinuation, patients entered a 4-month posttreatment period. Researchers found:

• There were 740 patients (EVOLVE-1) and 830 (EVOLVE-2) patients entered into the posttreatment periods.
• About 95% (EVOLVE-1) and 96% (EVOLVE-2) of patients completed their respective trial.
• In both trials, change from pre-randomization baseline in monthly migraine headache days decreased over the posttreatment period.
• During posttreatment periods, 1.6% (EVOLVE-1) and 2.3% (EVOLVE-2) of patients initiated migraine preventive treatments.
• There were no unexpected adverse events after galcanezumab cessation.

Stauffer VL, et al. Effect of galcanezumab following treatment cessation in patients with migraine: Results from 2 randomized phase 3 trials. [Published online ahead of print April 3, 2019]. Headache. doi: 10.1111/head.13508.

During posttreament periods, galcanezumab treatment effects in patients with migraine were reduced, but did not return to baseline, a new study found. Adults with episodic migraine were enrolled into EVOLVE-1 and EVOLVE-, which randomized 858 and 915 patients, respectively, to galcanezumab 120 mg, galcanezumab 240 mg, or placebo, administered subcutaneously once monthly for 6 months. After treatment completion or discontinuation, patients entered a 4-month posttreatment period. Researchers found:

• There were 740 patients (EVOLVE-1) and 830 (EVOLVE-2) patients entered into the posttreatment periods.
• About 95% (EVOLVE-1) and 96% (EVOLVE-2) of patients completed their respective trial.
• In both trials, change from pre-randomization baseline in monthly migraine headache days decreased over the posttreatment period.
• During posttreatment periods, 1.6% (EVOLVE-1) and 2.3% (EVOLVE-2) of patients initiated migraine preventive treatments.
• There were no unexpected adverse events after galcanezumab cessation.

Stauffer VL, et al. Effect of galcanezumab following treatment cessation in patients with migraine: Results from 2 randomized phase 3 trials. [Published online ahead of print April 3, 2019]. Headache. doi: 10.1111/head.13508.

Health state utilities associated with migraine treatment estimated from a general population sample may be used to represent route of administration and adverse events (AEs) in cost-utility models, a new study found. In time trade-off interviews, patients with migraine and general population participants in the United Kingdom valued health state vignettes based on literature, medication labels, and clinician interviews. All respondents valued migraine health states varying in route of administration. Researchers found:

• A total of 400 participants completed interviews (200 general population, 200 migraine patients).
• In the general population sample, mean utilities of health states without aura were 0.79 with daily oral medication, 0.78 with 1 injection per month, and 0.72 with between 31 and 39 injections once every 3 months.
• The greatest disutilities were for AEs associated with oral medications.

Matza LS, et al. Health state utilities associated with attributes of migraine preventive treatments based on patient and general population preferences. [Published online ahead of print March 28, 2019]. Qual Life Res. doi: 10.1007/s11136-019-02163-3.

Health state utilities associated with migraine treatment estimated from a general population sample may be used to represent route of administration and adverse events (AEs) in cost-utility models, a new study found. In time trade-off interviews, patients with migraine and general population participants in the United Kingdom valued health state vignettes based on literature, medication labels, and clinician interviews. All respondents valued migraine health states varying in route of administration. Researchers found:

• A total of 400 participants completed interviews (200 general population, 200 migraine patients).
• In the general population sample, mean utilities of health states without aura were 0.79 with daily oral medication, 0.78 with 1 injection per month, and 0.72 with between 31 and 39 injections once every 3 months.
• The greatest disutilities were for AEs associated with oral medications.

Matza LS, et al. Health state utilities associated with attributes of migraine preventive treatments based on patient and general population preferences. [Published online ahead of print March 28, 2019]. Qual Life Res. doi: 10.1007/s11136-019-02163-3.

Health state utilities associated with migraine treatment estimated from a general population sample may be used to represent route of administration and adverse events (AEs) in cost-utility models, a new study found. In time trade-off interviews, patients with migraine and general population participants in the United Kingdom valued health state vignettes based on literature, medication labels, and clinician interviews. All respondents valued migraine health states varying in route of administration. Researchers found:

• A total of 400 participants completed interviews (200 general population, 200 migraine patients).
• In the general population sample, mean utilities of health states without aura were 0.79 with daily oral medication, 0.78 with 1 injection per month, and 0.72 with between 31 and 39 injections once every 3 months.
• The greatest disutilities were for AEs associated with oral medications.

Matza LS, et al. Health state utilities associated with attributes of migraine preventive treatments based on patient and general population preferences. [Published online ahead of print March 28, 2019]. Qual Life Res. doi: 10.1007/s11136-019-02163-3.

Persons with migraine had a much higher prevalence of ever attempting suicide than those without migraine, a recent study found. The study, a nationally representative analysis of the 2012 Canadian Community Health Survey – Mental Health, identified the gender-specific prevalence of suicide attempts among those with migraine and examined the factors associated with suicide attempts among migraineurs. Among the details:

• Of 21,744 respondents, 2223 had migraine.
• Those with migraine had a much higher prevalence of ever attempting suicide vs those without migraine (men: 7.5% vs 1.9%; women: 9.3% vs 2.7%).
• Among migraineurs, the odds of suicide attempts were higher among poorer respondents, those in chronic pain and those with a history of childhood adversities, substance dependence and/or mental illness.

Fuller-Thomson E, Hodgins GA. Suicide attempts among those with migraine: Finding from a nationally representative Canadian study. [Published online ahead of print April 4, 2019]. Arch Suicide Res. doi: 10.1080/13811118.2019.1578710.

Persons with migraine had a much higher prevalence of ever attempting suicide than those without migraine, a recent study found. The study, a nationally representative analysis of the 2012 Canadian Community Health Survey – Mental Health, identified the gender-specific prevalence of suicide attempts among those with migraine and examined the factors associated with suicide attempts among migraineurs. Among the details:

• Of 21,744 respondents, 2223 had migraine.
• Those with migraine had a much higher prevalence of ever attempting suicide vs those without migraine (men: 7.5% vs 1.9%; women: 9.3% vs 2.7%).
• Among migraineurs, the odds of suicide attempts were higher among poorer respondents, those in chronic pain and those with a history of childhood adversities, substance dependence and/or mental illness.

Fuller-Thomson E, Hodgins GA. Suicide attempts among those with migraine: Finding from a nationally representative Canadian study. [Published online ahead of print April 4, 2019]. Arch Suicide Res. doi: 10.1080/13811118.2019.1578710.

Persons with migraine had a much higher prevalence of ever attempting suicide than those without migraine, a recent study found. The study, a nationally representative analysis of the 2012 Canadian Community Health Survey – Mental Health, identified the gender-specific prevalence of suicide attempts among those with migraine and examined the factors associated with suicide attempts among migraineurs. Among the details:

• Of 21,744 respondents, 2223 had migraine.
• Those with migraine had a much higher prevalence of ever attempting suicide vs those without migraine (men: 7.5% vs 1.9%; women: 9.3% vs 2.7%).
• Among migraineurs, the odds of suicide attempts were higher among poorer respondents, those in chronic pain and those with a history of childhood adversities, substance dependence and/or mental illness.

Fuller-Thomson E, Hodgins GA. Suicide attempts among those with migraine: Finding from a nationally representative Canadian study. [Published online ahead of print April 4, 2019]. Arch Suicide Res. doi: 10.1080/13811118.2019.1578710.

Pharmacy databases are a valid source for identification of treatment response in migraine, a recent study found. In a clinical cohort, 1913 migraineurs were interviewed using a semi-structured interview to retrieve treatment response data for acute and prophylactic migraine drugs. Researchers assessed whether number or purchases at different thresholds could predict the specificity and sensitivity of treatment response. The found:

• Purchase of drugs was significantly associated with treatment response.
• Specifically, for migraine drugs, it was concluded that 10 purchases of triptans, or 4 purchases of prophylactic drugs, are sufficient to predict a positive treatment response.
• In the Danish pharmacy database, 73% of migraine patients had purchased 10 or more triptans, while 55% to 63% had purchased 1 or more of the 4 prophylactic drugs.

Hansen TF, Chalmer MA, Haspang TM, Kogelman L, Olesen J. Predicting treatment response using pharmacy register in migraine. J Headache Pain. 2019;20(1):31. doi:10.1186/s10194-019-0987-y.

Pharmacy databases are a valid source for identification of treatment response in migraine, a recent study found. In a clinical cohort, 1913 migraineurs were interviewed using a semi-structured interview to retrieve treatment response data for acute and prophylactic migraine drugs. Researchers assessed whether number or purchases at different thresholds could predict the specificity and sensitivity of treatment response. The found:

• Purchase of drugs was significantly associated with treatment response.
• Specifically, for migraine drugs, it was concluded that 10 purchases of triptans, or 4 purchases of prophylactic drugs, are sufficient to predict a positive treatment response.
• In the Danish pharmacy database, 73% of migraine patients had purchased 10 or more triptans, while 55% to 63% had purchased 1 or more of the 4 prophylactic drugs.

Hansen TF, Chalmer MA, Haspang TM, Kogelman L, Olesen J. Predicting treatment response using pharmacy register in migraine. J Headache Pain. 2019;20(1):31. doi:10.1186/s10194-019-0987-y.

Pharmacy databases are a valid source for identification of treatment response in migraine, a recent study found. In a clinical cohort, 1913 migraineurs were interviewed using a semi-structured interview to retrieve treatment response data for acute and prophylactic migraine drugs. Researchers assessed whether number or purchases at different thresholds could predict the specificity and sensitivity of treatment response. The found:

• Purchase of drugs was significantly associated with treatment response.
• Specifically, for migraine drugs, it was concluded that 10 purchases of triptans, or 4 purchases of prophylactic drugs, are sufficient to predict a positive treatment response.
• In the Danish pharmacy database, 73% of migraine patients had purchased 10 or more triptans, while 55% to 63% had purchased 1 or more of the 4 prophylactic drugs.

Hansen TF, Chalmer MA, Haspang TM, Kogelman L, Olesen J. Predicting treatment response using pharmacy register in migraine. J Headache Pain. 2019;20(1):31. doi:10.1186/s10194-019-0987-y.

Adolescents with migraine headaches have shorter sleep duration and wake up earlier compared to those without migraine, a new study found. The study sample included 10,123 adolescents in the National Comorbidity Survey – Adolescent Supplement, a face-to-face survey of adolescents aged 13 to 18 years in the continental United States. The cross-sectional study examined the associations of sleep patterns, symptoms, and disorders with specific headache subtypes in this population. Researchers found:

• No significant difference in bedtime between youth with and without headache was reported.
• Those with any headache, particularly migraine, had significantly more sleep disturbances than those without headache.
• Youth with migraine and aura were more likely to report difficultly maintaining sleep, early morning awakening, daytime fatigue, and persistent insomnia symptoms vs those with migraine without aura.

Lateef T, Witonsky K, He J, Merikangas KR. Headaches and sleep duration problems in US adolescents: Findings from the National Comorbidity Survey – Adolescent Supplement (NCS-A). [Published online ahead of print April 13, 2019]. Cephalalgia. doi:10.1177/0333102419835466.

Adolescents with migraine headaches have shorter sleep duration and wake up earlier compared to those without migraine, a new study found. The study sample included 10,123 adolescents in the National Comorbidity Survey – Adolescent Supplement, a face-to-face survey of adolescents aged 13 to 18 years in the continental United States. The cross-sectional study examined the associations of sleep patterns, symptoms, and disorders with specific headache subtypes in this population. Researchers found:

• No significant difference in bedtime between youth with and without headache was reported.
• Those with any headache, particularly migraine, had significantly more sleep disturbances than those without headache.
• Youth with migraine and aura were more likely to report difficultly maintaining sleep, early morning awakening, daytime fatigue, and persistent insomnia symptoms vs those with migraine without aura.

Lateef T, Witonsky K, He J, Merikangas KR. Headaches and sleep duration problems in US adolescents: Findings from the National Comorbidity Survey – Adolescent Supplement (NCS-A). [Published online ahead of print April 13, 2019]. Cephalalgia. doi:10.1177/0333102419835466.

Adolescents with migraine headaches have shorter sleep duration and wake up earlier compared to those without migraine, a new study found. The study sample included 10,123 adolescents in the National Comorbidity Survey – Adolescent Supplement, a face-to-face survey of adolescents aged 13 to 18 years in the continental United States. The cross-sectional study examined the associations of sleep patterns, symptoms, and disorders with specific headache subtypes in this population. Researchers found:

• No significant difference in bedtime between youth with and without headache was reported.
• Those with any headache, particularly migraine, had significantly more sleep disturbances than those without headache.
• Youth with migraine and aura were more likely to report difficultly maintaining sleep, early morning awakening, daytime fatigue, and persistent insomnia symptoms vs those with migraine without aura.

Lateef T, Witonsky K, He J, Merikangas KR. Headaches and sleep duration problems in US adolescents: Findings from the National Comorbidity Survey – Adolescent Supplement (NCS-A). [Published online ahead of print April 13, 2019]. Cephalalgia. doi:10.1177/0333102419835466.

PHILADELPHIA – An orally dissolving tablet formulation of rimegepant has significant effects on pain relief and functional ability at 60 minutes post dose, according to phase 3 trial results presented at the annual meeting of the American Academy of Neurology. The treatment’s efficacy is sustained for 2-48 hours, researchers reported.

Rimegepant is a small molecule calcitonin gene–related peptide receptor antagonist. A 75-mg oral tablet formulation was effective in phase 3 trials. The present study evaluated a novel, orally dissolving tablet formulation that is intended to speed the drug’s onset. The tablet’s time to peak concentration is 1.50 hours, compared with 1.99 hours for the oral tablet.

Formulation preferences

“People with migraine prefer orally dissolving tablets to oral tablets, mainly for their convenience, onset of action, and ability to be taken without drinking liquids,” said first author Richard B. Lipton, MD, of Albert Einstein College of Medicine, New York, and colleagues.

To assess the formulation’s efficacy and safety, the investigators conducted a double-blind, randomized, placebo-controlled, multicenter trial. Participants were aged at least 18 years and had migraine for at least 1 year. They had 2-8 moderate or severe migraine attacks and fewer than 15 headache days per month during the 3 months before the trial. Their preventive migraine medication doses, if any, had been stable for at least 3 months.

Coprimary efficacy endpoints were pain freedom 2 hours post dose and freedom from the most bothersome symptom at 2 hours post dose. The efficacy analyses included randomized subjects who had a qualifying migraine attack, took the study medication, and provided at least one postbaseline efficacy data point.

The investigators included 1,351 patients in their efficacy analysis – 669 who received rimegepant and 682 who received placebo. About 85% were female, and patients’ mean age was 40.2 years. They averaged 4.6 migraine attacks per month, and their most bothersome symptoms included photophobia (57%), nausea (23.5%), and phonophobia (19.3%). About 14% used preventive treatment.

Within 45 days of randomization, patients treated a migraine attack of moderate to severe intensity and completed an electronic diary predose to 48 hours post dose.

Less use of rescue medication

At 2 hours post dose, patients who received 75 mg rimegepant were more likely than patients who received placebo to achieve pain freedom (21.2% vs. 10.9%) and freedom from the most bothersome symptom (35.1% vs. 26.8%).

Numerical differences in the likelihood of pain relief between group began 15 minutes post dose, and the difference was statistically significant at 60 minutes (36.8% vs. 31.2%).

Various secondary endpoints, including ability to function normally at 2 hours post dose (38.1% vs. 25.8%), sustained pain relief from 2-48 hours (42.2% vs. 25.2%), and use of rescue medications within 24 hours (14.2% vs. 29.2%), also were statistically significant.

In the safety analysis, the most common adverse events were nausea (1.6% in the rimegepant group and 0.4% in the placebo group) and urinary tract infection (1.5% in the rimegepant group and 0.6% in the placebo group). There were no serious adverse events. “Safety and tolerability were similar to placebo,” Dr. Lipton and colleagues said.

Biohaven Pharmaceuticals, the developer of the drug, sponsored the study. Dr. Lipton has received honoraria and research support from Biohaven and holds stock in the company. Coauthors are employees of Biohaven.

[email protected]

PHILADELPHIA – An orally dissolving tablet formulation of rimegepant has significant effects on pain relief and functional ability at 60 minutes post dose, according to phase 3 trial results presented at the annual meeting of the American Academy of Neurology. The treatment’s efficacy is sustained for 2-48 hours, researchers reported.

Rimegepant is a small molecule calcitonin gene–related peptide receptor antagonist. A 75-mg oral tablet formulation was effective in phase 3 trials. The present study evaluated a novel, orally dissolving tablet formulation that is intended to speed the drug’s onset. The tablet’s time to peak concentration is 1.50 hours, compared with 1.99 hours for the oral tablet.

Formulation preferences

“People with migraine prefer orally dissolving tablets to oral tablets, mainly for their convenience, onset of action, and ability to be taken without drinking liquids,” said first author Richard B. Lipton, MD, of Albert Einstein College of Medicine, New York, and colleagues.

To assess the formulation’s efficacy and safety, the investigators conducted a double-blind, randomized, placebo-controlled, multicenter trial. Participants were aged at least 18 years and had migraine for at least 1 year. They had 2-8 moderate or severe migraine attacks and fewer than 15 headache days per month during the 3 months before the trial. Their preventive migraine medication doses, if any, had been stable for at least 3 months.

Coprimary efficacy endpoints were pain freedom 2 hours post dose and freedom from the most bothersome symptom at 2 hours post dose. The efficacy analyses included randomized subjects who had a qualifying migraine attack, took the study medication, and provided at least one postbaseline efficacy data point.

The investigators included 1,351 patients in their efficacy analysis – 669 who received rimegepant and 682 who received placebo. About 85% were female, and patients’ mean age was 40.2 years. They averaged 4.6 migraine attacks per month, and their most bothersome symptoms included photophobia (57%), nausea (23.5%), and phonophobia (19.3%). About 14% used preventive treatment.

Within 45 days of randomization, patients treated a migraine attack of moderate to severe intensity and completed an electronic diary predose to 48 hours post dose.

Less use of rescue medication

At 2 hours post dose, patients who received 75 mg rimegepant were more likely than patients who received placebo to achieve pain freedom (21.2% vs. 10.9%) and freedom from the most bothersome symptom (35.1% vs. 26.8%).

Numerical differences in the likelihood of pain relief between group began 15 minutes post dose, and the difference was statistically significant at 60 minutes (36.8% vs. 31.2%).

Various secondary endpoints, including ability to function normally at 2 hours post dose (38.1% vs. 25.8%), sustained pain relief from 2-48 hours (42.2% vs. 25.2%), and use of rescue medications within 24 hours (14.2% vs. 29.2%), also were statistically significant.

In the safety analysis, the most common adverse events were nausea (1.6% in the rimegepant group and 0.4% in the placebo group) and urinary tract infection (1.5% in the rimegepant group and 0.6% in the placebo group). There were no serious adverse events. “Safety and tolerability were similar to placebo,” Dr. Lipton and colleagues said.

Biohaven Pharmaceuticals, the developer of the drug, sponsored the study. Dr. Lipton has received honoraria and research support from Biohaven and holds stock in the company. Coauthors are employees of Biohaven.

[email protected]

PHILADELPHIA – An orally dissolving tablet formulation of rimegepant has significant effects on pain relief and functional ability at 60 minutes post dose, according to phase 3 trial results presented at the annual meeting of the American Academy of Neurology. The treatment’s efficacy is sustained for 2-48 hours, researchers reported.

Rimegepant is a small molecule calcitonin gene–related peptide receptor antagonist. A 75-mg oral tablet formulation was effective in phase 3 trials. The present study evaluated a novel, orally dissolving tablet formulation that is intended to speed the drug’s onset. The tablet’s time to peak concentration is 1.50 hours, compared with 1.99 hours for the oral tablet.

Formulation preferences

“People with migraine prefer orally dissolving tablets to oral tablets, mainly for their convenience, onset of action, and ability to be taken without drinking liquids,” said first author Richard B. Lipton, MD, of Albert Einstein College of Medicine, New York, and colleagues.

To assess the formulation’s efficacy and safety, the investigators conducted a double-blind, randomized, placebo-controlled, multicenter trial. Participants were aged at least 18 years and had migraine for at least 1 year. They had 2-8 moderate or severe migraine attacks and fewer than 15 headache days per month during the 3 months before the trial. Their preventive migraine medication doses, if any, had been stable for at least 3 months.

Coprimary efficacy endpoints were pain freedom 2 hours post dose and freedom from the most bothersome symptom at 2 hours post dose. The efficacy analyses included randomized subjects who had a qualifying migraine attack, took the study medication, and provided at least one postbaseline efficacy data point.

The investigators included 1,351 patients in their efficacy analysis – 669 who received rimegepant and 682 who received placebo. About 85% were female, and patients’ mean age was 40.2 years. They averaged 4.6 migraine attacks per month, and their most bothersome symptoms included photophobia (57%), nausea (23.5%), and phonophobia (19.3%). About 14% used preventive treatment.

Within 45 days of randomization, patients treated a migraine attack of moderate to severe intensity and completed an electronic diary predose to 48 hours post dose.

Less use of rescue medication

At 2 hours post dose, patients who received 75 mg rimegepant were more likely than patients who received placebo to achieve pain freedom (21.2% vs. 10.9%) and freedom from the most bothersome symptom (35.1% vs. 26.8%).

Numerical differences in the likelihood of pain relief between group began 15 minutes post dose, and the difference was statistically significant at 60 minutes (36.8% vs. 31.2%).

Various secondary endpoints, including ability to function normally at 2 hours post dose (38.1% vs. 25.8%), sustained pain relief from 2-48 hours (42.2% vs. 25.2%), and use of rescue medications within 24 hours (14.2% vs. 29.2%), also were statistically significant.

In the safety analysis, the most common adverse events were nausea (1.6% in the rimegepant group and 0.4% in the placebo group) and urinary tract infection (1.5% in the rimegepant group and 0.6% in the placebo group). There were no serious adverse events. “Safety and tolerability were similar to placebo,” Dr. Lipton and colleagues said.

Biohaven Pharmaceuticals, the developer of the drug, sponsored the study. Dr. Lipton has received honoraria and research support from Biohaven and holds stock in the company. Coauthors are employees of Biohaven.

[email protected]

PHILADELPHIA – At the annual meeting of the American Academy of Neurology, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, sat down with Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H., to discuss in a video some of the new data presented at the meeting regarding the CGRP monoclonal antibodies, the small molecule receptor antagonists (gepants), and what Dr. Tepper described as “a real shift in paradigm and a watershed moment in migraine.”

The three gepants that are farthest along in clinical trials are ubrogepant, rimegepant, and atogepant. “Reassuring data” was presented, Dr. Tepper said, regarding liver toxicity, which has been a concern with earlier generations of the gepants. The Food and Drug Administration had mandated a close look at liver function with the use of these drugs, which are metabolized in the liver, and, to date, no safety signals have emerged.

The three CGRP monoclonal antibodies that are currently on the market are erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality). Data from numerous open-label extension studies were presented. In general, it seems that “the monoclonal antibodies accumulate greater efficacy over time,” Dr. Tepper said. No safety concerns have emerged from 5 years of clinical trial data. With 250,000 patients on these drugs worldwide, that is “very reassuring,” Dr. Tepper said.

New data also show that the majority of patients with chronic migraine who are taking monoclonal antibodies convert from chronic migraine to episodic migraine. Additionally, new data show that use of monoclonal antibodies “dramatically reduce all migraine medication use,” Dr. Tepper said.

[email protected]

PHILADELPHIA – At the annual meeting of the American Academy of Neurology, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, sat down with Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H., to discuss in a video some of the new data presented at the meeting regarding the CGRP monoclonal antibodies, the small molecule receptor antagonists (gepants), and what Dr. Tepper described as “a real shift in paradigm and a watershed moment in migraine.”

The three gepants that are farthest along in clinical trials are ubrogepant, rimegepant, and atogepant. “Reassuring data” was presented, Dr. Tepper said, regarding liver toxicity, which has been a concern with earlier generations of the gepants. The Food and Drug Administration had mandated a close look at liver function with the use of these drugs, which are metabolized in the liver, and, to date, no safety signals have emerged.

The three CGRP monoclonal antibodies that are currently on the market are erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality). Data from numerous open-label extension studies were presented. In general, it seems that “the monoclonal antibodies accumulate greater efficacy over time,” Dr. Tepper said. No safety concerns have emerged from 5 years of clinical trial data. With 250,000 patients on these drugs worldwide, that is “very reassuring,” Dr. Tepper said.

New data also show that the majority of patients with chronic migraine who are taking monoclonal antibodies convert from chronic migraine to episodic migraine. Additionally, new data show that use of monoclonal antibodies “dramatically reduce all migraine medication use,” Dr. Tepper said.

[email protected]

PHILADELPHIA – At the annual meeting of the American Academy of Neurology, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, sat down with Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H., to discuss in a video some of the new data presented at the meeting regarding the CGRP monoclonal antibodies, the small molecule receptor antagonists (gepants), and what Dr. Tepper described as “a real shift in paradigm and a watershed moment in migraine.”

The three gepants that are farthest along in clinical trials are ubrogepant, rimegepant, and atogepant. “Reassuring data” was presented, Dr. Tepper said, regarding liver toxicity, which has been a concern with earlier generations of the gepants. The Food and Drug Administration had mandated a close look at liver function with the use of these drugs, which are metabolized in the liver, and, to date, no safety signals have emerged.

The three CGRP monoclonal antibodies that are currently on the market are erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality). Data from numerous open-label extension studies were presented. In general, it seems that “the monoclonal antibodies accumulate greater efficacy over time,” Dr. Tepper said. No safety concerns have emerged from 5 years of clinical trial data. With 250,000 patients on these drugs worldwide, that is “very reassuring,” Dr. Tepper said.

New data also show that the majority of patients with chronic migraine who are taking monoclonal antibodies convert from chronic migraine to episodic migraine. Additionally, new data show that use of monoclonal antibodies “dramatically reduce all migraine medication use,” Dr. Tepper said.

[email protected]

PHILADELPHIA – Galcanezumab reduces weekly attack frequency in patients with episodic cluster headache, according to study results presented at the annual meeting of the American Academy of Neurology. The treatment has a similar safety profile in this patient population as it has among people with episodic or chronic migraine, said the researchers.

Calcitonin gene-related peptide (CGRP) has an important role in the pathogenesis of cluster headache. Galcanezumab (Emgality)is a humanized monoclonal antibody that binds to CGRP. Eli Lilly & Co. developed the molecule as a treatment for migraine. Cluster headache is characterized by recurrent unilateral headache attacks accompanied by autonomic symptoms. The most common acute treatments for cluster headache are sumatriptan (Imitrex) and high-flow oxygen, but some patients do not respond to these therapies.

David W. Dodick, MD, director of the headache, sports neurology, and concussion programs at Mayo Clinic in Phoenix, and colleagues conducted a trial to evaluate the efficacy and safety of galcanezumab in patients with episodic cluster headache.

After screening, participants underwent a prospective baseline diary phase for 7 consecutive days. The investigators subsequently randomized patients in equal groups to galcanezumab (300 mg subcutaneously) or placebo. Treatment was administered subcutaneously once monthly. The double-blind treatment period lasted for 8 weeks, and a washout period followed. The trial’s primary endpoint was the overall mean change from baseline in weekly cluster headache attack frequency during weeks 1-3, as recorded in patient diaries. The main secondary endpoint was the proportion of patients who had a reduction in weekly cluster headache attack frequency of 50% or more at week 3.

In all, 49 patients were randomized to galcanezumab, and 57 were randomized to placebo. Mean age was 45-47 years. Between 82% and 84% of patients were male. The mean number of weekly cluster headache attacks at baseline was approximately 17.5 in both groups.

During weeks 1-3, the mean change in weekly attack frequency was −8.7 in the galcanezumab group and −5.2 for controls. The difference between groups was statistically significant. The percentage of participants with a reduction in weekly attack frequency of at least 50% at week 3 was 76% for galcanezumab versus 57% for placebo. The between-group differences in these endpoints were statistically significant.

The discontinuation rate was 8% (4 participants) in the galcanezumab group and 21% (12 participants) in the placebo group. Eight participants (14%) in the placebo group discontinued treatment because of lack of efficacy, compared with one participant (2%) in the galcanezumab group. The researchers observed no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a greater incidence of injection-site pain with galcanezumab versus placebo (8.2% vs. 0%).

Eli Lilly and Co. sponsored the study. Dr. Dodick has a consulting relationship with the company.

[email protected]

SOURCE: Bardos JN et al. AAN 2019, Abstract 02.004.

PHILADELPHIA – Galcanezumab reduces weekly attack frequency in patients with episodic cluster headache, according to study results presented at the annual meeting of the American Academy of Neurology. The treatment has a similar safety profile in this patient population as it has among people with episodic or chronic migraine, said the researchers.

Calcitonin gene-related peptide (CGRP) has an important role in the pathogenesis of cluster headache. Galcanezumab (Emgality)is a humanized monoclonal antibody that binds to CGRP. Eli Lilly & Co. developed the molecule as a treatment for migraine. Cluster headache is characterized by recurrent unilateral headache attacks accompanied by autonomic symptoms. The most common acute treatments for cluster headache are sumatriptan (Imitrex) and high-flow oxygen, but some patients do not respond to these therapies.

David W. Dodick, MD, director of the headache, sports neurology, and concussion programs at Mayo Clinic in Phoenix, and colleagues conducted a trial to evaluate the efficacy and safety of galcanezumab in patients with episodic cluster headache.

After screening, participants underwent a prospective baseline diary phase for 7 consecutive days. The investigators subsequently randomized patients in equal groups to galcanezumab (300 mg subcutaneously) or placebo. Treatment was administered subcutaneously once monthly. The double-blind treatment period lasted for 8 weeks, and a washout period followed. The trial’s primary endpoint was the overall mean change from baseline in weekly cluster headache attack frequency during weeks 1-3, as recorded in patient diaries. The main secondary endpoint was the proportion of patients who had a reduction in weekly cluster headache attack frequency of 50% or more at week 3.

In all, 49 patients were randomized to galcanezumab, and 57 were randomized to placebo. Mean age was 45-47 years. Between 82% and 84% of patients were male. The mean number of weekly cluster headache attacks at baseline was approximately 17.5 in both groups.

During weeks 1-3, the mean change in weekly attack frequency was −8.7 in the galcanezumab group and −5.2 for controls. The difference between groups was statistically significant. The percentage of participants with a reduction in weekly attack frequency of at least 50% at week 3 was 76% for galcanezumab versus 57% for placebo. The between-group differences in these endpoints were statistically significant.

The discontinuation rate was 8% (4 participants) in the galcanezumab group and 21% (12 participants) in the placebo group. Eight participants (14%) in the placebo group discontinued treatment because of lack of efficacy, compared with one participant (2%) in the galcanezumab group. The researchers observed no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a greater incidence of injection-site pain with galcanezumab versus placebo (8.2% vs. 0%).

Eli Lilly and Co. sponsored the study. Dr. Dodick has a consulting relationship with the company.

[email protected]

SOURCE: Bardos JN et al. AAN 2019, Abstract 02.004.

PHILADELPHIA – Galcanezumab reduces weekly attack frequency in patients with episodic cluster headache, according to study results presented at the annual meeting of the American Academy of Neurology. The treatment has a similar safety profile in this patient population as it has among people with episodic or chronic migraine, said the researchers.

Calcitonin gene-related peptide (CGRP) has an important role in the pathogenesis of cluster headache. Galcanezumab (Emgality)is a humanized monoclonal antibody that binds to CGRP. Eli Lilly & Co. developed the molecule as a treatment for migraine. Cluster headache is characterized by recurrent unilateral headache attacks accompanied by autonomic symptoms. The most common acute treatments for cluster headache are sumatriptan (Imitrex) and high-flow oxygen, but some patients do not respond to these therapies.

David W. Dodick, MD, director of the headache, sports neurology, and concussion programs at Mayo Clinic in Phoenix, and colleagues conducted a trial to evaluate the efficacy and safety of galcanezumab in patients with episodic cluster headache.

After screening, participants underwent a prospective baseline diary phase for 7 consecutive days. The investigators subsequently randomized patients in equal groups to galcanezumab (300 mg subcutaneously) or placebo. Treatment was administered subcutaneously once monthly. The double-blind treatment period lasted for 8 weeks, and a washout period followed. The trial’s primary endpoint was the overall mean change from baseline in weekly cluster headache attack frequency during weeks 1-3, as recorded in patient diaries. The main secondary endpoint was the proportion of patients who had a reduction in weekly cluster headache attack frequency of 50% or more at week 3.

In all, 49 patients were randomized to galcanezumab, and 57 were randomized to placebo. Mean age was 45-47 years. Between 82% and 84% of patients were male. The mean number of weekly cluster headache attacks at baseline was approximately 17.5 in both groups.

During weeks 1-3, the mean change in weekly attack frequency was −8.7 in the galcanezumab group and −5.2 for controls. The difference between groups was statistically significant. The percentage of participants with a reduction in weekly attack frequency of at least 50% at week 3 was 76% for galcanezumab versus 57% for placebo. The between-group differences in these endpoints were statistically significant.

The discontinuation rate was 8% (4 participants) in the galcanezumab group and 21% (12 participants) in the placebo group. Eight participants (14%) in the placebo group discontinued treatment because of lack of efficacy, compared with one participant (2%) in the galcanezumab group. The researchers observed no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a greater incidence of injection-site pain with galcanezumab versus placebo (8.2% vs. 0%).

Eli Lilly and Co. sponsored the study. Dr. Dodick has a consulting relationship with the company.

[email protected]

SOURCE: Bardos JN et al. AAN 2019, Abstract 02.004.

PHILADELPHIA – Fremanezumab was efficacious in migraine patients who had not benefited from taking other migraine preventive medication, according to a poster presented at the annual meeting of the American Academy of Neurology.

To assess the efficacy of fremanezumab in patients with migraine who had not received relief from trying at least one prior preventive migraine medication, Peter McAllister, MD and colleagues analyzed data from 2 phase 3 trials (HALO EM and HALO CM). Trial participants had either episodic or chronic migraine, confirmed during a 28-day pretreatment baseline period, then received subcutaneous fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), monthly (for chronic migraine: 675 mg at baseline and 225 mg at weeks 4 and 8; for episodic migraine: 225 mg at baseline and weeks 4 and 8), or placebo (at baseline and weeks 4 and 8).

The present analysis included data from 186 patients with episodic migraine and 407 patients with chronic migraine, which represents the subgroup of study participants in the larger HALO trials who had failed at least one prior preventive migraine medication. Dr. McAllister, who is cofounder and chief medical officer at the New England Institute for Clinical Research in Stamford, Connecticut, and his colleagues, assessed mean changes from baseline in the monthly average number of headache days of at least moderate severity or the monthly average number of migraine days during the 12-week treatment period.

In patients with chronic migraine, fremanezumab yielded greater reductions in the number of headache days of at least moderate severity (quarterly [least-squares mean change]: –4.0, P less than 0.0001; monthly: –4.5, P less than 0.0001) compared with placebo (–1.8). There were similar reductions in the number of migraine days (quarterly: –4.1, P = 0.0027; monthly: –4.8, P less than 0.0001) compared with placebo (–2.3).

In patients with episodic migraine, fremanezumab yielded greater reductions in the number of headache days of at least moderate severity (quarterly: –3.1, P less than 0.0001; monthly: –3.2, P less than 0.0001) compared with placebo (–0.8). There were similar reductions in the number of migraine days (quarterly: –3.3, P = 0.0015; monthly: –3.7, P less than 0.0001) compared with placebo (–1.3).

“The phase 3 HALO CM and HALO EM trials showed that fremanezumab is efficacious in patients who failed one or more prior preventive medication, a potentially difficult-to-treat population,” Dr. McAllister and colleagues said in their poster.

“Effect sizes in this subgroup were greater than those in the overall trial population,” they said. In addition, “both quarterly and monthly fremanezumab were well-tolerated in this subgroup.”

This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.

[email protected]

SOURCE: McAllister P et al. AAN 2019. P1.10-011.

PHILADELPHIA – Fremanezumab was efficacious in migraine patients who had not benefited from taking other migraine preventive medication, according to a poster presented at the annual meeting of the American Academy of Neurology.

To assess the efficacy of fremanezumab in patients with migraine who had not received relief from trying at least one prior preventive migraine medication, Peter McAllister, MD and colleagues analyzed data from 2 phase 3 trials (HALO EM and HALO CM). Trial participants had either episodic or chronic migraine, confirmed during a 28-day pretreatment baseline period, then received subcutaneous fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), monthly (for chronic migraine: 675 mg at baseline and 225 mg at weeks 4 and 8; for episodic migraine: 225 mg at baseline and weeks 4 and 8), or placebo (at baseline and weeks 4 and 8).

The present analysis included data from 186 patients with episodic migraine and 407 patients with chronic migraine, which represents the subgroup of study participants in the larger HALO trials who had failed at least one prior preventive migraine medication. Dr. McAllister, who is cofounder and chief medical officer at the New England Institute for Clinical Research in Stamford, Connecticut, and his colleagues, assessed mean changes from baseline in the monthly average number of headache days of at least moderate severity or the monthly average number of migraine days during the 12-week treatment period.

In patients with chronic migraine, fremanezumab yielded greater reductions in the number of headache days of at least moderate severity (quarterly [least-squares mean change]: –4.0, P less than 0.0001; monthly: –4.5, P less than 0.0001) compared with placebo (–1.8). There were similar reductions in the number of migraine days (quarterly: –4.1, P = 0.0027; monthly: –4.8, P less than 0.0001) compared with placebo (–2.3).

In patients with episodic migraine, fremanezumab yielded greater reductions in the number of headache days of at least moderate severity (quarterly: –3.1, P less than 0.0001; monthly: –3.2, P less than 0.0001) compared with placebo (–0.8). There were similar reductions in the number of migraine days (quarterly: –3.3, P = 0.0015; monthly: –3.7, P less than 0.0001) compared with placebo (–1.3).

“The phase 3 HALO CM and HALO EM trials showed that fremanezumab is efficacious in patients who failed one or more prior preventive medication, a potentially difficult-to-treat population,” Dr. McAllister and colleagues said in their poster.

“Effect sizes in this subgroup were greater than those in the overall trial population,” they said. In addition, “both quarterly and monthly fremanezumab were well-tolerated in this subgroup.”

This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.

[email protected]

SOURCE: McAllister P et al. AAN 2019. P1.10-011.

PHILADELPHIA – Fremanezumab was efficacious in migraine patients who had not benefited from taking other migraine preventive medication, according to a poster presented at the annual meeting of the American Academy of Neurology.

To assess the efficacy of fremanezumab in patients with migraine who had not received relief from trying at least one prior preventive migraine medication, Peter McAllister, MD and colleagues analyzed data from 2 phase 3 trials (HALO EM and HALO CM). Trial participants had either episodic or chronic migraine, confirmed during a 28-day pretreatment baseline period, then received subcutaneous fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), monthly (for chronic migraine: 675 mg at baseline and 225 mg at weeks 4 and 8; for episodic migraine: 225 mg at baseline and weeks 4 and 8), or placebo (at baseline and weeks 4 and 8).

The present analysis included data from 186 patients with episodic migraine and 407 patients with chronic migraine, which represents the subgroup of study participants in the larger HALO trials who had failed at least one prior preventive migraine medication. Dr. McAllister, who is cofounder and chief medical officer at the New England Institute for Clinical Research in Stamford, Connecticut, and his colleagues, assessed mean changes from baseline in the monthly average number of headache days of at least moderate severity or the monthly average number of migraine days during the 12-week treatment period.

In patients with chronic migraine, fremanezumab yielded greater reductions in the number of headache days of at least moderate severity (quarterly [least-squares mean change]: –4.0, P less than 0.0001; monthly: –4.5, P less than 0.0001) compared with placebo (–1.8). There were similar reductions in the number of migraine days (quarterly: –4.1, P = 0.0027; monthly: –4.8, P less than 0.0001) compared with placebo (–2.3).

In patients with episodic migraine, fremanezumab yielded greater reductions in the number of headache days of at least moderate severity (quarterly: –3.1, P less than 0.0001; monthly: –3.2, P less than 0.0001) compared with placebo (–0.8). There were similar reductions in the number of migraine days (quarterly: –3.3, P = 0.0015; monthly: –3.7, P less than 0.0001) compared with placebo (–1.3).

“The phase 3 HALO CM and HALO EM trials showed that fremanezumab is efficacious in patients who failed one or more prior preventive medication, a potentially difficult-to-treat population,” Dr. McAllister and colleagues said in their poster.

“Effect sizes in this subgroup were greater than those in the overall trial population,” they said. In addition, “both quarterly and monthly fremanezumab were well-tolerated in this subgroup.”

This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.

[email protected]

SOURCE: McAllister P et al. AAN 2019. P1.10-011.