Migraine ICYMI

Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) are an effective treatment option for vestibular migraine (VM), with a large proportion of patients showing simultaneous reduction in migraine days, vertigo days, and Migraine Disability Assessment (MIDAS) score.

Major finding: At 12 months after CGRP mAb treatment, the mean monthly dizziness/vestibular symptom days (mean difference [MD] 9.5 days), headache frequency (MD 13.8 days), and MIDAS score (MD 36.1) were significantly reduced in the overall cohort (P < .001) and 78% of patients showed ≥50% reduction in all 3 parameters.

Study details: Findings are from a prospective observational cohort study including 50 patients with chronic migraine who met the criteria for VM and were treated with fremanezumab (n = 25), galcanezumab (n = 18), or erenumab (n = 7).

Disclosures: This study did not receive any funding. CV Russo, F Sacca, and R De Simone declared receiving personal compensation, public speaking honoraria, or consulting fees from various sources.

Source: Russo CV et al. Anti-calcitonin gene-related peptide monoclonal antibodies for the treatment of vestibular migraine: A prospective observational cohort study. Cephalalgia. 2023;43(4):3331024231161809 (Mar 22). Doi: 10.1177/03331024231161809

Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) are an effective treatment option for vestibular migraine (VM), with a large proportion of patients showing simultaneous reduction in migraine days, vertigo days, and Migraine Disability Assessment (MIDAS) score.

Major finding: At 12 months after CGRP mAb treatment, the mean monthly dizziness/vestibular symptom days (mean difference [MD] 9.5 days), headache frequency (MD 13.8 days), and MIDAS score (MD 36.1) were significantly reduced in the overall cohort (P < .001) and 78% of patients showed ≥50% reduction in all 3 parameters.

Study details: Findings are from a prospective observational cohort study including 50 patients with chronic migraine who met the criteria for VM and were treated with fremanezumab (n = 25), galcanezumab (n = 18), or erenumab (n = 7).

Disclosures: This study did not receive any funding. CV Russo, F Sacca, and R De Simone declared receiving personal compensation, public speaking honoraria, or consulting fees from various sources.

Source: Russo CV et al. Anti-calcitonin gene-related peptide monoclonal antibodies for the treatment of vestibular migraine: A prospective observational cohort study. Cephalalgia. 2023;43(4):3331024231161809 (Mar 22). Doi: 10.1177/03331024231161809

Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) are an effective treatment option for vestibular migraine (VM), with a large proportion of patients showing simultaneous reduction in migraine days, vertigo days, and Migraine Disability Assessment (MIDAS) score.

Major finding: At 12 months after CGRP mAb treatment, the mean monthly dizziness/vestibular symptom days (mean difference [MD] 9.5 days), headache frequency (MD 13.8 days), and MIDAS score (MD 36.1) were significantly reduced in the overall cohort (P < .001) and 78% of patients showed ≥50% reduction in all 3 parameters.

Study details: Findings are from a prospective observational cohort study including 50 patients with chronic migraine who met the criteria for VM and were treated with fremanezumab (n = 25), galcanezumab (n = 18), or erenumab (n = 7).

Disclosures: This study did not receive any funding. CV Russo, F Sacca, and R De Simone declared receiving personal compensation, public speaking honoraria, or consulting fees from various sources.

Source: Russo CV et al. Anti-calcitonin gene-related peptide monoclonal antibodies for the treatment of vestibular migraine: A prospective observational cohort study. Cephalalgia. 2023;43(4):3331024231161809 (Mar 22). Doi: 10.1177/03331024231161809

Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) led to consistent reduction in migraine days throughout the menstrual cycle (perimenstrual and non-perimenstrual days), thereby supporting their prophylactic use in women with menstrual migraine.

Major finding: No significant association was observed between menstrual window and CGRP mAb treatment effect (P =  .726), indicating similar reductions in migraine days during the menstrual window and the remainder of the menstrual cycle (odds ratio 0.44; 95% CI 0.38-0.51).

Study details: This post hoc analysis of a single-arm study included 174 patients with migraine treated with either erenumab or fremanezumab for 6 months, and evaluated the effects of anti-CGRP mAb on perimenstrual and non-perimenstrual migraine days in 45 of 174 women with available data on migraine days during ≥3 menstrual cycles.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Verhagen IE et al. Both perimenstrual and non-perimenstrual migraine days respond to anti-calcitonin gene-related peptide (receptor) antibodies. Eur J Neurol. 2023 (Mar 20). Doi: 10.1111/ene.15794

Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) led to consistent reduction in migraine days throughout the menstrual cycle (perimenstrual and non-perimenstrual days), thereby supporting their prophylactic use in women with menstrual migraine.

Major finding: No significant association was observed between menstrual window and CGRP mAb treatment effect (P =  .726), indicating similar reductions in migraine days during the menstrual window and the remainder of the menstrual cycle (odds ratio 0.44; 95% CI 0.38-0.51).

Study details: This post hoc analysis of a single-arm study included 174 patients with migraine treated with either erenumab or fremanezumab for 6 months, and evaluated the effects of anti-CGRP mAb on perimenstrual and non-perimenstrual migraine days in 45 of 174 women with available data on migraine days during ≥3 menstrual cycles.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Verhagen IE et al. Both perimenstrual and non-perimenstrual migraine days respond to anti-calcitonin gene-related peptide (receptor) antibodies. Eur J Neurol. 2023 (Mar 20). Doi: 10.1111/ene.15794

Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) led to consistent reduction in migraine days throughout the menstrual cycle (perimenstrual and non-perimenstrual days), thereby supporting their prophylactic use in women with menstrual migraine.

Major finding: No significant association was observed between menstrual window and CGRP mAb treatment effect (P =  .726), indicating similar reductions in migraine days during the menstrual window and the remainder of the menstrual cycle (odds ratio 0.44; 95% CI 0.38-0.51).

Study details: This post hoc analysis of a single-arm study included 174 patients with migraine treated with either erenumab or fremanezumab for 6 months, and evaluated the effects of anti-CGRP mAb on perimenstrual and non-perimenstrual migraine days in 45 of 174 women with available data on migraine days during ≥3 menstrual cycles.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Verhagen IE et al. Both perimenstrual and non-perimenstrual migraine days respond to anti-calcitonin gene-related peptide (receptor) antibodies. Eur J Neurol. 2023 (Mar 20). Doi: 10.1111/ene.15794

Key clinical point: The risk for hypertensive disorders of pregnancy (HDOP) was significantly higher in women who experienced migraine before 20 weeks of pregnancy, with the risk being most prominent among women with migraine during the first trimester and those who used migraine medications.

Major finding: The risk for HDOP was significantly higher in women with vs without pre-pregnancy migraine (adjusted risk ratio [aRR] 1.17; 95% CI 1.09-1.26), with the risk being the highest in those with migraine that persisted during the first trimester (aRR 1.84; 95% CI 1.35-2.50) and in those who received migraine-specific medication (aRR 1.50; 95% CI 1.15-1.97).

Study details: Findings are from a population-based prospective cohort study including 1,049,839 women without a history of cardiovascular diseases or hypertension who had liveborn or stillborn singleton deliveries, of which 127,295 women had pre-pregnancy migraine.

Disclosures: This study was supported by the National Institute of Child Health and Human Development, US National Institutes of Health. The authors declared no conflicts of interest.

Source: Crowe HM et al. Migraine and risk of hypertensive disorders of pregnancy: A population-based cohort study. Cephalalgia. 2023;43(4):3331024231161746 (Mar 19). Doi: 10.1177/03331024231161746

Key clinical point: The risk for hypertensive disorders of pregnancy (HDOP) was significantly higher in women who experienced migraine before 20 weeks of pregnancy, with the risk being most prominent among women with migraine during the first trimester and those who used migraine medications.

Major finding: The risk for HDOP was significantly higher in women with vs without pre-pregnancy migraine (adjusted risk ratio [aRR] 1.17; 95% CI 1.09-1.26), with the risk being the highest in those with migraine that persisted during the first trimester (aRR 1.84; 95% CI 1.35-2.50) and in those who received migraine-specific medication (aRR 1.50; 95% CI 1.15-1.97).

Study details: Findings are from a population-based prospective cohort study including 1,049,839 women without a history of cardiovascular diseases or hypertension who had liveborn or stillborn singleton deliveries, of which 127,295 women had pre-pregnancy migraine.

Disclosures: This study was supported by the National Institute of Child Health and Human Development, US National Institutes of Health. The authors declared no conflicts of interest.

Source: Crowe HM et al. Migraine and risk of hypertensive disorders of pregnancy: A population-based cohort study. Cephalalgia. 2023;43(4):3331024231161746 (Mar 19). Doi: 10.1177/03331024231161746

Key clinical point: The risk for hypertensive disorders of pregnancy (HDOP) was significantly higher in women who experienced migraine before 20 weeks of pregnancy, with the risk being most prominent among women with migraine during the first trimester and those who used migraine medications.

Major finding: The risk for HDOP was significantly higher in women with vs without pre-pregnancy migraine (adjusted risk ratio [aRR] 1.17; 95% CI 1.09-1.26), with the risk being the highest in those with migraine that persisted during the first trimester (aRR 1.84; 95% CI 1.35-2.50) and in those who received migraine-specific medication (aRR 1.50; 95% CI 1.15-1.97).

Study details: Findings are from a population-based prospective cohort study including 1,049,839 women without a history of cardiovascular diseases or hypertension who had liveborn or stillborn singleton deliveries, of which 127,295 women had pre-pregnancy migraine.

Disclosures: This study was supported by the National Institute of Child Health and Human Development, US National Institutes of Health. The authors declared no conflicts of interest.

Source: Crowe HM et al. Migraine and risk of hypertensive disorders of pregnancy: A population-based cohort study. Cephalalgia. 2023;43(4):3331024231161746 (Mar 19). Doi: 10.1177/03331024231161746

Key clinical point: The efficacy of calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) galcanezumab “wore off” before the next injection but only in a small sub-population of patients with chronic migraine (CM).

Major finding: The efficacy of galcanezumab vs placebo wore off at a significantly higher rate in patients with CM (risk ratio [RR] 1.91; 95% CI 1.11-3.28); however, the wearing-off effects of galcanezumab and placebo were not significantly different in the overall cohort (RR 1.29; 95% CI 0.73-2.28).

Study details: The data come from a meta-analysis of four randomized controlled trials including 2409 patients with migraine.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Asawavichienjinda T et al. "Wearing-off" efficacy of CGRP monoclonal antibodies for migraine prevention: A meta-analysis of randomized controlled trials. Cephalalgia. 2023;43(4):3331024231161261 (Mar 16). Doi: 10.1177/03331024231161261

Key clinical point: The efficacy of calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) galcanezumab “wore off” before the next injection but only in a small sub-population of patients with chronic migraine (CM).

Major finding: The efficacy of galcanezumab vs placebo wore off at a significantly higher rate in patients with CM (risk ratio [RR] 1.91; 95% CI 1.11-3.28); however, the wearing-off effects of galcanezumab and placebo were not significantly different in the overall cohort (RR 1.29; 95% CI 0.73-2.28).

Study details: The data come from a meta-analysis of four randomized controlled trials including 2409 patients with migraine.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Asawavichienjinda T et al. "Wearing-off" efficacy of CGRP monoclonal antibodies for migraine prevention: A meta-analysis of randomized controlled trials. Cephalalgia. 2023;43(4):3331024231161261 (Mar 16). Doi: 10.1177/03331024231161261

Key clinical point: The efficacy of calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) galcanezumab “wore off” before the next injection but only in a small sub-population of patients with chronic migraine (CM).

Major finding: The efficacy of galcanezumab vs placebo wore off at a significantly higher rate in patients with CM (risk ratio [RR] 1.91; 95% CI 1.11-3.28); however, the wearing-off effects of galcanezumab and placebo were not significantly different in the overall cohort (RR 1.29; 95% CI 0.73-2.28).

Study details: The data come from a meta-analysis of four randomized controlled trials including 2409 patients with migraine.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Asawavichienjinda T et al. "Wearing-off" efficacy of CGRP monoclonal antibodies for migraine prevention: A meta-analysis of randomized controlled trials. Cephalalgia. 2023;43(4):3331024231161261 (Mar 16). Doi: 10.1177/03331024231161261

Since 2018, the field of headache medicine has changed significantly. The development of calcitonin gene-related peptide (CGRP)-targeting preventive medications has led to the ability to treat migraine in a much more specific manner. The development of CGRP acute oral medications over the past 2 years has allowed people with migraine the ability to use well-tolerated, migraine-specific, abortive treatments. Triptan medications were the first migraine-specific acute treatments developed, some of which were nonoral, such as injectable sumatriptan and intranasal sumatriptan and zolmitriptan. The study by Lipton and colleagues assesses the safety and tolerability of a novel acute CGRP antagonist nonoral treatment, zavegepant.

In this double-blind, randomized, multicentered trial, nearly 2000 participants were enrolled with a diagnosis of episodic migraine with or without aura; they were excluded if they had previously used another CGRP antagonist, either an injectable or oral medication, before enrolling in this study. In addition to assessing migraine pain, participants were asked to identify their otherwise most bothersome symptom, specifically photophobia, phonophobia, or nausea. They were given a nasal spray to self-administer and were assessed at 15 minutes after treatment and at multiple additional intervals, up to 48 hours after the initial dosing. The primary endpoints were freedom from pain and freedom from the most bothersome symptom at 2 hours after treatment onset. There were 17 secondary endpoints.

At 2 hours after treatment onset, a statistically significant group had achieved freedom from pain. The percentage, however, did remain somewhat low: 24%. Freedom from the most bothersome symptom was also statistically significant but was up to 40%. For 13 of the 17 endpoints, the results were also statistically significant, including pain relief at 2 hours, sustained pain relief at 2-24 hours and 48 hours, functional improvement, and freedom from photophobia and phonophobia. The most common adverse effects were poor taste, nasal discomfort, and throat irritation. No serious adverse events were noted.

Zavegepant has been FDA approved for the acute treatment of migraine on the basis of these data. This is a novel, well-tolerated, nonoral acute treatment for migraine. We can now treat patients with very severe nausea or more sudden-onset pain with a CGRP option that can potentially treat their attacks more quickly.

One early finding in many of the CGRP studies was that a certain subpopulation of migraine patients have a robust and rapid preventive response to monoclonal antibody treatment. Raffaelli and colleagues sought to evaluate potential characteristics that would better predict the efficacy of CGRP antagonist monoclonal antibodies for the prevention of migraine.

In this study, the definition of a superresponse to CGRP antagonist treatment was a >75% reduction in monthly headache days after 3 months of treatment. Nonresponse was defined as <25% reduction over this same period. This was a retrospective cohort study at one headache center in Berlin, Germany. A total of 260 patients were enrolled, all with a diagnosis of migraine and all given a preventive CGRP monoclonal antibody.

There was no significant difference between nonresponders and superresponders when compared for sex, age, or time since migraine diagnosis. Erenumab was the most commonly prescribed CGRP antagonist medication, but all CGRP antagonists were included. There was no significant difference when CGRP receptor or ligand targeting antibodies were compared. Nonresponders were seen as more likely to have chronic migraine and higher monthly headache day and monthly migraine day frequencies. Superresponders were seen to have more "typical" migraine characteristics, such as unilateral or localized migraines or migraines with pulsating/throbbing characteristics, as well as the presence of photophobia and nausea; however, this was not statistically significant. Of note, superresponders were also significantly more likely to report improvement of their acute migraine attacks with triptan medications as compared with nonresponders.

Patients with less frequent migraine attacks and more classic migraine attacks appear to be much more likely to respond quickly and effectively to many preventive options; this appears to be most robust with the CGRP antibody class. Although the reason for this robust response is not entirely clear, it would certainly be best for providers to consider the initiation of CGRP antagonist preventive treatment in patients with these characteristics.

The newest generation of migraine-specific medications targets either the inflammatory neurotransmitter CGRP or the CGRP receptor. Erenumab is a CGRP receptor blocker, whereas both fremanezumab and galcanezumab block the CGRP ligand. Erenumab has been associated with constipation and high blood pressure, whereas the other CGRP antagonist medications are not associated with these side effects. Whether this is due to the difference in mechanism of action, and specifically whether the antibodies block the CGRP receptor or are an antagonist, is under consideration. Schiano di Cola and colleagues specifically sought to investigate the subtle differences between these two subclasses of treatment.

Patients with high-frequency episodic and chronic migraine were enrolled in this retrospective study; 6 months of data were included. The researchers here specifically looked at efficacy after 1, 3, and 6 months of treatment. They examined, as a primary outcome, monthly headache and migraine days, and migraine disability as based on the Migraine Disability Assessment Scale (MIDAS) and Headache Impact Test (HIT-6) score. Concomitant analgesic medication consumption and response rate relative to baseline were also compared.

A total of 152 patients were enrolled, 68 with CGRP ligand-targeting therapy and 84 with CGRP receptor-blocking therapy. Medication overuse was present in 73% of patients. Although a significant improvement from baseline was noted in monthly headache days, monthly migraine days, severity, analgesic consumption, and disability, MIDAS scores were significantly lower in the CGRP ligand-blocking group compared with the CGRP receptor group at 1 and 3 months. Number of monthly migraine days was also lower in the CGRP ligand-blocking group, but only after 3 months. The other variables, including monthly headache days per month, analgesic consumption, severity, and disability, were not statistically different.

Adverse events were not compared between the two groups, even though this was a prior noted difference between these two classes of medications. Although there are some slight differences in efficacy, the majority of outcome metrics did not appear to be significantly different in either group. One would be hard-pressed to choose a specific CGRP medication on the basis of these data.

Since 2018, the field of headache medicine has changed significantly. The development of calcitonin gene-related peptide (CGRP)-targeting preventive medications has led to the ability to treat migraine in a much more specific manner. The development of CGRP acute oral medications over the past 2 years has allowed people with migraine the ability to use well-tolerated, migraine-specific, abortive treatments. Triptan medications were the first migraine-specific acute treatments developed, some of which were nonoral, such as injectable sumatriptan and intranasal sumatriptan and zolmitriptan. The study by Lipton and colleagues assesses the safety and tolerability of a novel acute CGRP antagonist nonoral treatment, zavegepant.

In this double-blind, randomized, multicentered trial, nearly 2000 participants were enrolled with a diagnosis of episodic migraine with or without aura; they were excluded if they had previously used another CGRP antagonist, either an injectable or oral medication, before enrolling in this study. In addition to assessing migraine pain, participants were asked to identify their otherwise most bothersome symptom, specifically photophobia, phonophobia, or nausea. They were given a nasal spray to self-administer and were assessed at 15 minutes after treatment and at multiple additional intervals, up to 48 hours after the initial dosing. The primary endpoints were freedom from pain and freedom from the most bothersome symptom at 2 hours after treatment onset. There were 17 secondary endpoints.

At 2 hours after treatment onset, a statistically significant group had achieved freedom from pain. The percentage, however, did remain somewhat low: 24%. Freedom from the most bothersome symptom was also statistically significant but was up to 40%. For 13 of the 17 endpoints, the results were also statistically significant, including pain relief at 2 hours, sustained pain relief at 2-24 hours and 48 hours, functional improvement, and freedom from photophobia and phonophobia. The most common adverse effects were poor taste, nasal discomfort, and throat irritation. No serious adverse events were noted.

Zavegepant has been FDA approved for the acute treatment of migraine on the basis of these data. This is a novel, well-tolerated, nonoral acute treatment for migraine. We can now treat patients with very severe nausea or more sudden-onset pain with a CGRP option that can potentially treat their attacks more quickly.

One early finding in many of the CGRP studies was that a certain subpopulation of migraine patients have a robust and rapid preventive response to monoclonal antibody treatment. Raffaelli and colleagues sought to evaluate potential characteristics that would better predict the efficacy of CGRP antagonist monoclonal antibodies for the prevention of migraine.

In this study, the definition of a superresponse to CGRP antagonist treatment was a >75% reduction in monthly headache days after 3 months of treatment. Nonresponse was defined as <25% reduction over this same period. This was a retrospective cohort study at one headache center in Berlin, Germany. A total of 260 patients were enrolled, all with a diagnosis of migraine and all given a preventive CGRP monoclonal antibody.

There was no significant difference between nonresponders and superresponders when compared for sex, age, or time since migraine diagnosis. Erenumab was the most commonly prescribed CGRP antagonist medication, but all CGRP antagonists were included. There was no significant difference when CGRP receptor or ligand targeting antibodies were compared. Nonresponders were seen as more likely to have chronic migraine and higher monthly headache day and monthly migraine day frequencies. Superresponders were seen to have more "typical" migraine characteristics, such as unilateral or localized migraines or migraines with pulsating/throbbing characteristics, as well as the presence of photophobia and nausea; however, this was not statistically significant. Of note, superresponders were also significantly more likely to report improvement of their acute migraine attacks with triptan medications as compared with nonresponders.

Patients with less frequent migraine attacks and more classic migraine attacks appear to be much more likely to respond quickly and effectively to many preventive options; this appears to be most robust with the CGRP antibody class. Although the reason for this robust response is not entirely clear, it would certainly be best for providers to consider the initiation of CGRP antagonist preventive treatment in patients with these characteristics.

The newest generation of migraine-specific medications targets either the inflammatory neurotransmitter CGRP or the CGRP receptor. Erenumab is a CGRP receptor blocker, whereas both fremanezumab and galcanezumab block the CGRP ligand. Erenumab has been associated with constipation and high blood pressure, whereas the other CGRP antagonist medications are not associated with these side effects. Whether this is due to the difference in mechanism of action, and specifically whether the antibodies block the CGRP receptor or are an antagonist, is under consideration. Schiano di Cola and colleagues specifically sought to investigate the subtle differences between these two subclasses of treatment.

Patients with high-frequency episodic and chronic migraine were enrolled in this retrospective study; 6 months of data were included. The researchers here specifically looked at efficacy after 1, 3, and 6 months of treatment. They examined, as a primary outcome, monthly headache and migraine days, and migraine disability as based on the Migraine Disability Assessment Scale (MIDAS) and Headache Impact Test (HIT-6) score. Concomitant analgesic medication consumption and response rate relative to baseline were also compared.

A total of 152 patients were enrolled, 68 with CGRP ligand-targeting therapy and 84 with CGRP receptor-blocking therapy. Medication overuse was present in 73% of patients. Although a significant improvement from baseline was noted in monthly headache days, monthly migraine days, severity, analgesic consumption, and disability, MIDAS scores were significantly lower in the CGRP ligand-blocking group compared with the CGRP receptor group at 1 and 3 months. Number of monthly migraine days was also lower in the CGRP ligand-blocking group, but only after 3 months. The other variables, including monthly headache days per month, analgesic consumption, severity, and disability, were not statistically different.

Adverse events were not compared between the two groups, even though this was a prior noted difference between these two classes of medications. Although there are some slight differences in efficacy, the majority of outcome metrics did not appear to be significantly different in either group. One would be hard-pressed to choose a specific CGRP medication on the basis of these data.

Since 2018, the field of headache medicine has changed significantly. The development of calcitonin gene-related peptide (CGRP)-targeting preventive medications has led to the ability to treat migraine in a much more specific manner. The development of CGRP acute oral medications over the past 2 years has allowed people with migraine the ability to use well-tolerated, migraine-specific, abortive treatments. Triptan medications were the first migraine-specific acute treatments developed, some of which were nonoral, such as injectable sumatriptan and intranasal sumatriptan and zolmitriptan. The study by Lipton and colleagues assesses the safety and tolerability of a novel acute CGRP antagonist nonoral treatment, zavegepant.

In this double-blind, randomized, multicentered trial, nearly 2000 participants were enrolled with a diagnosis of episodic migraine with or without aura; they were excluded if they had previously used another CGRP antagonist, either an injectable or oral medication, before enrolling in this study. In addition to assessing migraine pain, participants were asked to identify their otherwise most bothersome symptom, specifically photophobia, phonophobia, or nausea. They were given a nasal spray to self-administer and were assessed at 15 minutes after treatment and at multiple additional intervals, up to 48 hours after the initial dosing. The primary endpoints were freedom from pain and freedom from the most bothersome symptom at 2 hours after treatment onset. There were 17 secondary endpoints.

At 2 hours after treatment onset, a statistically significant group had achieved freedom from pain. The percentage, however, did remain somewhat low: 24%. Freedom from the most bothersome symptom was also statistically significant but was up to 40%. For 13 of the 17 endpoints, the results were also statistically significant, including pain relief at 2 hours, sustained pain relief at 2-24 hours and 48 hours, functional improvement, and freedom from photophobia and phonophobia. The most common adverse effects were poor taste, nasal discomfort, and throat irritation. No serious adverse events were noted.

Zavegepant has been FDA approved for the acute treatment of migraine on the basis of these data. This is a novel, well-tolerated, nonoral acute treatment for migraine. We can now treat patients with very severe nausea or more sudden-onset pain with a CGRP option that can potentially treat their attacks more quickly.

One early finding in many of the CGRP studies was that a certain subpopulation of migraine patients have a robust and rapid preventive response to monoclonal antibody treatment. Raffaelli and colleagues sought to evaluate potential characteristics that would better predict the efficacy of CGRP antagonist monoclonal antibodies for the prevention of migraine.

In this study, the definition of a superresponse to CGRP antagonist treatment was a >75% reduction in monthly headache days after 3 months of treatment. Nonresponse was defined as <25% reduction over this same period. This was a retrospective cohort study at one headache center in Berlin, Germany. A total of 260 patients were enrolled, all with a diagnosis of migraine and all given a preventive CGRP monoclonal antibody.

There was no significant difference between nonresponders and superresponders when compared for sex, age, or time since migraine diagnosis. Erenumab was the most commonly prescribed CGRP antagonist medication, but all CGRP antagonists were included. There was no significant difference when CGRP receptor or ligand targeting antibodies were compared. Nonresponders were seen as more likely to have chronic migraine and higher monthly headache day and monthly migraine day frequencies. Superresponders were seen to have more "typical" migraine characteristics, such as unilateral or localized migraines or migraines with pulsating/throbbing characteristics, as well as the presence of photophobia and nausea; however, this was not statistically significant. Of note, superresponders were also significantly more likely to report improvement of their acute migraine attacks with triptan medications as compared with nonresponders.

Patients with less frequent migraine attacks and more classic migraine attacks appear to be much more likely to respond quickly and effectively to many preventive options; this appears to be most robust with the CGRP antibody class. Although the reason for this robust response is not entirely clear, it would certainly be best for providers to consider the initiation of CGRP antagonist preventive treatment in patients with these characteristics.

The newest generation of migraine-specific medications targets either the inflammatory neurotransmitter CGRP or the CGRP receptor. Erenumab is a CGRP receptor blocker, whereas both fremanezumab and galcanezumab block the CGRP ligand. Erenumab has been associated with constipation and high blood pressure, whereas the other CGRP antagonist medications are not associated with these side effects. Whether this is due to the difference in mechanism of action, and specifically whether the antibodies block the CGRP receptor or are an antagonist, is under consideration. Schiano di Cola and colleagues specifically sought to investigate the subtle differences between these two subclasses of treatment.

Patients with high-frequency episodic and chronic migraine were enrolled in this retrospective study; 6 months of data were included. The researchers here specifically looked at efficacy after 1, 3, and 6 months of treatment. They examined, as a primary outcome, monthly headache and migraine days, and migraine disability as based on the Migraine Disability Assessment Scale (MIDAS) and Headache Impact Test (HIT-6) score. Concomitant analgesic medication consumption and response rate relative to baseline were also compared.

A total of 152 patients were enrolled, 68 with CGRP ligand-targeting therapy and 84 with CGRP receptor-blocking therapy. Medication overuse was present in 73% of patients. Although a significant improvement from baseline was noted in monthly headache days, monthly migraine days, severity, analgesic consumption, and disability, MIDAS scores were significantly lower in the CGRP ligand-blocking group compared with the CGRP receptor group at 1 and 3 months. Number of monthly migraine days was also lower in the CGRP ligand-blocking group, but only after 3 months. The other variables, including monthly headache days per month, analgesic consumption, severity, and disability, were not statistically different.

Adverse events were not compared between the two groups, even though this was a prior noted difference between these two classes of medications. Although there are some slight differences in efficacy, the majority of outcome metrics did not appear to be significantly different in either group. One would be hard-pressed to choose a specific CGRP medication on the basis of these data.

Key clinical point: Lasmiditan, rimegepant, and ubrogepant demonstrated superior efficacy over placebo for the acute treatment of migraine attacks, with lasmiditan being the most effective at high doses but with higher odds of adverse events.

Major finding: Compared with placebo, 200 mg lasmiditan (odds ratio [OR] 2.88; 95% CI 2.22-3.73), followed by 100 mg lasmiditan (OR 2.28; 95% CI 1.75-2.96), rimegepant (OR 2.0; 95% CI 1.45-2.75), and 100 mg ubrogepant (OR 1.97; 95% CI 1.27-3.07) were more efficacious for achieving pain freedom at 2 hours post-dose before the use of any rescue medication. However, the odds of dizziness, nausea, and somnolence were greater with all doses of lasmiditan.

Study details: This network meta-analysis of seven phase 3 randomized controlled trials included 12,859 patients with migraine

Disclosures: This study did not report the funding source. PJ Goadsby and C Tassorelli declared receiving grants or personal fees or participating in advisory boards or lecturing at symposia for various sources.

Source: Puledda F et al. Efficacy, safety and indirect comparisons of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine: A systematic review and network meta-analysis of the literature. Cephalalgia. 2023;43(3): 03331024231151419 (Feb 14). Doi: 10.1177/03331024231151419

Key clinical point: Lasmiditan, rimegepant, and ubrogepant demonstrated superior efficacy over placebo for the acute treatment of migraine attacks, with lasmiditan being the most effective at high doses but with higher odds of adverse events.

Major finding: Compared with placebo, 200 mg lasmiditan (odds ratio [OR] 2.88; 95% CI 2.22-3.73), followed by 100 mg lasmiditan (OR 2.28; 95% CI 1.75-2.96), rimegepant (OR 2.0; 95% CI 1.45-2.75), and 100 mg ubrogepant (OR 1.97; 95% CI 1.27-3.07) were more efficacious for achieving pain freedom at 2 hours post-dose before the use of any rescue medication. However, the odds of dizziness, nausea, and somnolence were greater with all doses of lasmiditan.

Study details: This network meta-analysis of seven phase 3 randomized controlled trials included 12,859 patients with migraine

Disclosures: This study did not report the funding source. PJ Goadsby and C Tassorelli declared receiving grants or personal fees or participating in advisory boards or lecturing at symposia for various sources.

Source: Puledda F et al. Efficacy, safety and indirect comparisons of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine: A systematic review and network meta-analysis of the literature. Cephalalgia. 2023;43(3): 03331024231151419 (Feb 14). Doi: 10.1177/03331024231151419

Key clinical point: Lasmiditan, rimegepant, and ubrogepant demonstrated superior efficacy over placebo for the acute treatment of migraine attacks, with lasmiditan being the most effective at high doses but with higher odds of adverse events.

Major finding: Compared with placebo, 200 mg lasmiditan (odds ratio [OR] 2.88; 95% CI 2.22-3.73), followed by 100 mg lasmiditan (OR 2.28; 95% CI 1.75-2.96), rimegepant (OR 2.0; 95% CI 1.45-2.75), and 100 mg ubrogepant (OR 1.97; 95% CI 1.27-3.07) were more efficacious for achieving pain freedom at 2 hours post-dose before the use of any rescue medication. However, the odds of dizziness, nausea, and somnolence were greater with all doses of lasmiditan.

Study details: This network meta-analysis of seven phase 3 randomized controlled trials included 12,859 patients with migraine

Disclosures: This study did not report the funding source. PJ Goadsby and C Tassorelli declared receiving grants or personal fees or participating in advisory boards or lecturing at symposia for various sources.

Source: Puledda F et al. Efficacy, safety and indirect comparisons of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine: A systematic review and network meta-analysis of the literature. Cephalalgia. 2023;43(3): 03331024231151419 (Feb 14). Doi: 10.1177/03331024231151419

Key clinical point: Both types of anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb), those against CGRP ligand (anti-CGRP) and those against CGRP receptor (anti-CGRP-R), showed benefits as preventive treatments for migraine; however, the proportion of anti-CGRP super responders was higher.

Major finding: Patients receiving anti-CGRP vs anti-CGRP-R had a significantly lower Migraine Disability Assessment scale score at 1 (P = .040) and 3 (P = .048) months and mean migraine days at 3 months (P = .01). The proportion of super responders were significantly higher in the anti-CGRP vs anti-CGRP-R group at 3-month (P = .041) and 6-month (P = .047) follow-ups.

Study details: This retrospective observational study included 152 patients with high-frequency episodic migraine or chronic migraine, of whom 68 were treated with anti-CGRP mAbs and 84 were treated with anti-CGRP-R mAbs.

Disclosures: This study did not receive any specific funding. Three authors declared serving as consultants and on scientific advisory boards or receiving speaker honoraria from various sources.

Source: Schiano di Cola F et al. An observational study on monoclonal antibodies against CGRP and its receptor. Eur J Neurol. 2023 (Mar 1). Doi: 10.1111/ene.15761

Key clinical point: Both types of anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb), those against CGRP ligand (anti-CGRP) and those against CGRP receptor (anti-CGRP-R), showed benefits as preventive treatments for migraine; however, the proportion of anti-CGRP super responders was higher.

Major finding: Patients receiving anti-CGRP vs anti-CGRP-R had a significantly lower Migraine Disability Assessment scale score at 1 (P = .040) and 3 (P = .048) months and mean migraine days at 3 months (P = .01). The proportion of super responders were significantly higher in the anti-CGRP vs anti-CGRP-R group at 3-month (P = .041) and 6-month (P = .047) follow-ups.

Study details: This retrospective observational study included 152 patients with high-frequency episodic migraine or chronic migraine, of whom 68 were treated with anti-CGRP mAbs and 84 were treated with anti-CGRP-R mAbs.

Disclosures: This study did not receive any specific funding. Three authors declared serving as consultants and on scientific advisory boards or receiving speaker honoraria from various sources.

Source: Schiano di Cola F et al. An observational study on monoclonal antibodies against CGRP and its receptor. Eur J Neurol. 2023 (Mar 1). Doi: 10.1111/ene.15761

Key clinical point: Both types of anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb), those against CGRP ligand (anti-CGRP) and those against CGRP receptor (anti-CGRP-R), showed benefits as preventive treatments for migraine; however, the proportion of anti-CGRP super responders was higher.

Major finding: Patients receiving anti-CGRP vs anti-CGRP-R had a significantly lower Migraine Disability Assessment scale score at 1 (P = .040) and 3 (P = .048) months and mean migraine days at 3 months (P = .01). The proportion of super responders were significantly higher in the anti-CGRP vs anti-CGRP-R group at 3-month (P = .041) and 6-month (P = .047) follow-ups.

Study details: This retrospective observational study included 152 patients with high-frequency episodic migraine or chronic migraine, of whom 68 were treated with anti-CGRP mAbs and 84 were treated with anti-CGRP-R mAbs.

Disclosures: This study did not receive any specific funding. Three authors declared serving as consultants and on scientific advisory boards or receiving speaker honoraria from various sources.

Source: Schiano di Cola F et al. An observational study on monoclonal antibodies against CGRP and its receptor. Eur J Neurol. 2023 (Mar 1). Doi: 10.1111/ene.15761

Key clinical point: Real-world data support fremanezumab as an effective, safe, and well-tolerated treatment option in patients with difficult-to-treat migraine and multiple preventive treatment failures.

Major finding: Overall, 83.5% and 62.6% of patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM) receiving fremanezumab achieved ≥50% reduction in monthly headache days (MHD), respectively, along with a significant improvement in mean MHD, MHD with peak headache intensity of ≤5, intake of any abortive medications, migraine-related disability, and quality of life (all P < .001). Only 36 cases of mild adverse events were reported.

Study details: This open-label, single-arm, prospective, multicenter, clinical study included 204 patients with HFEM (n = 97) or CM (n = 107) who received ≥3 monthly courses of fremanezumab.

Disclosures: This study did not receive any funding. Some authors declared receiving investigator fees or travel grants from, or serving as consultants or advisory board members for various sources.

Source: Argyriou AA et al. Efficacy and safety of fremanezumab for migraine prophylaxis in patients with at least three previous preventive failures: Prospective, multicenter, real-world data from a Greek registry. Eur J Neurol. 2023 (Feb 11). Doi: 10.1111/ene.15740

Key clinical point: Real-world data support fremanezumab as an effective, safe, and well-tolerated treatment option in patients with difficult-to-treat migraine and multiple preventive treatment failures.

Major finding: Overall, 83.5% and 62.6% of patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM) receiving fremanezumab achieved ≥50% reduction in monthly headache days (MHD), respectively, along with a significant improvement in mean MHD, MHD with peak headache intensity of ≤5, intake of any abortive medications, migraine-related disability, and quality of life (all P < .001). Only 36 cases of mild adverse events were reported.

Study details: This open-label, single-arm, prospective, multicenter, clinical study included 204 patients with HFEM (n = 97) or CM (n = 107) who received ≥3 monthly courses of fremanezumab.

Disclosures: This study did not receive any funding. Some authors declared receiving investigator fees or travel grants from, or serving as consultants or advisory board members for various sources.

Source: Argyriou AA et al. Efficacy and safety of fremanezumab for migraine prophylaxis in patients with at least three previous preventive failures: Prospective, multicenter, real-world data from a Greek registry. Eur J Neurol. 2023 (Feb 11). Doi: 10.1111/ene.15740

Key clinical point: Real-world data support fremanezumab as an effective, safe, and well-tolerated treatment option in patients with difficult-to-treat migraine and multiple preventive treatment failures.

Major finding: Overall, 83.5% and 62.6% of patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM) receiving fremanezumab achieved ≥50% reduction in monthly headache days (MHD), respectively, along with a significant improvement in mean MHD, MHD with peak headache intensity of ≤5, intake of any abortive medications, migraine-related disability, and quality of life (all P < .001). Only 36 cases of mild adverse events were reported.

Study details: This open-label, single-arm, prospective, multicenter, clinical study included 204 patients with HFEM (n = 97) or CM (n = 107) who received ≥3 monthly courses of fremanezumab.

Disclosures: This study did not receive any funding. Some authors declared receiving investigator fees or travel grants from, or serving as consultants or advisory board members for various sources.

Source: Argyriou AA et al. Efficacy and safety of fremanezumab for migraine prophylaxis in patients with at least three previous preventive failures: Prospective, multicenter, real-world data from a Greek registry. Eur J Neurol. 2023 (Feb 11). Doi: 10.1111/ene.15740

Key clinical point: Clinical characteristics differed significantly among patients with migraine who experienced ≥75% (super-responders [SR]) vs ≤25% (non-responders [NR]) reduction in monthly headache days in the third month after initiating prophylactic treatment with calcitonin gene-related peptide receptor (CGRP-R) monoclonal antibodies (mAb).

Major finding: SR vs NR were more likely to report vomiting (P = .031) and a significant improvement in acute migraine headache with triptan treatment (P = .010). However, NR vs SR experienced chronic migraine (P = .001), medication overuse headache (P = .024), and concomitant depression (P = .005) more frequently.

Study details: This was a retrospective real-world study including 260 patients with migraine who received ≥1 treatment with CGRP-R mAbs for migraine prevention, of which 29 and 26 were SR and NR, respectively.

Disclosures: This study did not report the source of funding. Four authors declared receiving research grants, personal fees, or honoraria for consulting and lectures from various sources.

Source: Raffaelli B et al. Clinical evaluation of super-responders vs non-responders to CGRP(-receptor) monoclonal antibodies: A real-world experience. J Headache Pain. 2023;24(1):16 (Feb 27). Doi: 10.1186/s10194-023-01552-x

Key clinical point: Clinical characteristics differed significantly among patients with migraine who experienced ≥75% (super-responders [SR]) vs ≤25% (non-responders [NR]) reduction in monthly headache days in the third month after initiating prophylactic treatment with calcitonin gene-related peptide receptor (CGRP-R) monoclonal antibodies (mAb).

Major finding: SR vs NR were more likely to report vomiting (P = .031) and a significant improvement in acute migraine headache with triptan treatment (P = .010). However, NR vs SR experienced chronic migraine (P = .001), medication overuse headache (P = .024), and concomitant depression (P = .005) more frequently.

Study details: This was a retrospective real-world study including 260 patients with migraine who received ≥1 treatment with CGRP-R mAbs for migraine prevention, of which 29 and 26 were SR and NR, respectively.

Disclosures: This study did not report the source of funding. Four authors declared receiving research grants, personal fees, or honoraria for consulting and lectures from various sources.

Source: Raffaelli B et al. Clinical evaluation of super-responders vs non-responders to CGRP(-receptor) monoclonal antibodies: A real-world experience. J Headache Pain. 2023;24(1):16 (Feb 27). Doi: 10.1186/s10194-023-01552-x

Key clinical point: Clinical characteristics differed significantly among patients with migraine who experienced ≥75% (super-responders [SR]) vs ≤25% (non-responders [NR]) reduction in monthly headache days in the third month after initiating prophylactic treatment with calcitonin gene-related peptide receptor (CGRP-R) monoclonal antibodies (mAb).

Major finding: SR vs NR were more likely to report vomiting (P = .031) and a significant improvement in acute migraine headache with triptan treatment (P = .010). However, NR vs SR experienced chronic migraine (P = .001), medication overuse headache (P = .024), and concomitant depression (P = .005) more frequently.

Study details: This was a retrospective real-world study including 260 patients with migraine who received ≥1 treatment with CGRP-R mAbs for migraine prevention, of which 29 and 26 were SR and NR, respectively.

Disclosures: This study did not report the source of funding. Four authors declared receiving research grants, personal fees, or honoraria for consulting and lectures from various sources.

Source: Raffaelli B et al. Clinical evaluation of super-responders vs non-responders to CGRP(-receptor) monoclonal antibodies: A real-world experience. J Headache Pain. 2023;24(1):16 (Feb 27). Doi: 10.1186/s10194-023-01552-x

Key clinical point: Patients with traumatic brain injury (TBI) were at a significantly higher risk for subsequent migraine, with the risk being even higher among patients with TBI who were hospitalized and those who had a major trauma.

Major finding: The risk for migraine was significantly higher among patients with vs without TBI (adjusted hazard ratio [aHR] 1.484), with migraine incidence being higher after major vs minor trauma (aHR 1.670) and among hospitalized patients vs patients visiting the outpatient department (aHR 1.557; all P < .001).

Study details: This retrospective cohort study included 151,098 patients with newly diagnosed TBI and 604,394 propensity score-matched patients without TBI.

Disclosures: This study was supported by the National Science and Technology Council of the Republic of China, Cardinal Tien Hospital, and Tri-Service General Hospital Research Foundation. The authors declared no conflicts of interest.

Source: Chen MH et al. Risk of migraine after traumatic brain injury and effects of injury management levels and treatment modalities: A nationwide population-based cohort study in Taiwan. J Clin Med. 2023;12(4):1530 (Feb 15). Doi: 10.3390/jcm12041530

Key clinical point: Patients with traumatic brain injury (TBI) were at a significantly higher risk for subsequent migraine, with the risk being even higher among patients with TBI who were hospitalized and those who had a major trauma.

Major finding: The risk for migraine was significantly higher among patients with vs without TBI (adjusted hazard ratio [aHR] 1.484), with migraine incidence being higher after major vs minor trauma (aHR 1.670) and among hospitalized patients vs patients visiting the outpatient department (aHR 1.557; all P < .001).

Study details: This retrospective cohort study included 151,098 patients with newly diagnosed TBI and 604,394 propensity score-matched patients without TBI.

Disclosures: This study was supported by the National Science and Technology Council of the Republic of China, Cardinal Tien Hospital, and Tri-Service General Hospital Research Foundation. The authors declared no conflicts of interest.

Source: Chen MH et al. Risk of migraine after traumatic brain injury and effects of injury management levels and treatment modalities: A nationwide population-based cohort study in Taiwan. J Clin Med. 2023;12(4):1530 (Feb 15). Doi: 10.3390/jcm12041530

Key clinical point: Patients with traumatic brain injury (TBI) were at a significantly higher risk for subsequent migraine, with the risk being even higher among patients with TBI who were hospitalized and those who had a major trauma.

Major finding: The risk for migraine was significantly higher among patients with vs without TBI (adjusted hazard ratio [aHR] 1.484), with migraine incidence being higher after major vs minor trauma (aHR 1.670) and among hospitalized patients vs patients visiting the outpatient department (aHR 1.557; all P < .001).

Study details: This retrospective cohort study included 151,098 patients with newly diagnosed TBI and 604,394 propensity score-matched patients without TBI.

Disclosures: This study was supported by the National Science and Technology Council of the Republic of China, Cardinal Tien Hospital, and Tri-Service General Hospital Research Foundation. The authors declared no conflicts of interest.

Source: Chen MH et al. Risk of migraine after traumatic brain injury and effects of injury management levels and treatment modalities: A nationwide population-based cohort study in Taiwan. J Clin Med. 2023;12(4):1530 (Feb 15). Doi: 10.3390/jcm12041530