Migraine ICYMI

Key clinical point: Monthly fremanezumab appeared to be effective and well-tolerated for ≤ 12 months in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) and multiple failures to previous preventive treatments.

Major finding: At 12 months of fremanezumab treatment, the monthly headache days (MHD) were reduced significantly (median reduction −9.0; P < .001), with 76.5% of patients achieving ≥ 50% response rate. Acute medication use, disability scores, and the percentage of patients with medication overuse reduced significantly from baseline (all P < .001). No severe treatment-related adverse events were reported.

Study details: Findings are from a prospective multicenter long-term study including 83 patients with HFEM (n = 16) or CM (n = 67) and multiple preventive treatment failures who received monthly fremanezumab.

Disclosures: This study was funded by Università degli Studi di Firenze, Italy, within the CRUI-CARE Agreement. Several authors declared receiving travel or research grants, personal fees as speakers or advisors, or honoraria for scientific presentations from various sources.

Source: Caponnetto V et al for The Italian Headache Registry (RICe) Study Group. Long-term treatment over 52 weeks with monthly fremanezumab in drug-resistant migraine: A prospective multicenter cohort study. CNS Drugs. 2023;37:1069-1080 (Nov 24). doi: 10.1007/s40263-023-01050-3

Key clinical point: Monthly fremanezumab appeared to be effective and well-tolerated for ≤ 12 months in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) and multiple failures to previous preventive treatments.

Major finding: At 12 months of fremanezumab treatment, the monthly headache days (MHD) were reduced significantly (median reduction −9.0; P < .001), with 76.5% of patients achieving ≥ 50% response rate. Acute medication use, disability scores, and the percentage of patients with medication overuse reduced significantly from baseline (all P < .001). No severe treatment-related adverse events were reported.

Study details: Findings are from a prospective multicenter long-term study including 83 patients with HFEM (n = 16) or CM (n = 67) and multiple preventive treatment failures who received monthly fremanezumab.

Disclosures: This study was funded by Università degli Studi di Firenze, Italy, within the CRUI-CARE Agreement. Several authors declared receiving travel or research grants, personal fees as speakers or advisors, or honoraria for scientific presentations from various sources.

Source: Caponnetto V et al for The Italian Headache Registry (RICe) Study Group. Long-term treatment over 52 weeks with monthly fremanezumab in drug-resistant migraine: A prospective multicenter cohort study. CNS Drugs. 2023;37:1069-1080 (Nov 24). doi: 10.1007/s40263-023-01050-3

Key clinical point: Monthly fremanezumab appeared to be effective and well-tolerated for ≤ 12 months in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) and multiple failures to previous preventive treatments.

Major finding: At 12 months of fremanezumab treatment, the monthly headache days (MHD) were reduced significantly (median reduction −9.0; P < .001), with 76.5% of patients achieving ≥ 50% response rate. Acute medication use, disability scores, and the percentage of patients with medication overuse reduced significantly from baseline (all P < .001). No severe treatment-related adverse events were reported.

Study details: Findings are from a prospective multicenter long-term study including 83 patients with HFEM (n = 16) or CM (n = 67) and multiple preventive treatment failures who received monthly fremanezumab.

Disclosures: This study was funded by Università degli Studi di Firenze, Italy, within the CRUI-CARE Agreement. Several authors declared receiving travel or research grants, personal fees as speakers or advisors, or honoraria for scientific presentations from various sources.

Source: Caponnetto V et al for The Italian Headache Registry (RICe) Study Group. Long-term treatment over 52 weeks with monthly fremanezumab in drug-resistant migraine: A prospective multicenter cohort study. CNS Drugs. 2023;37:1069-1080 (Nov 24). doi: 10.1007/s40263-023-01050-3

Key clinical point: The interim analysis of this real-world study confirmed the effectiveness and safety of fremanezumab for the prevention of both chronic migraine (CM) and episodic migraine (EM) attacks.

Major finding: The majority of patients (55.9%) with migraine achieved ≥50% reduction in monthly migraine days (MMD) during 6 months after fremanezumab initiation, with 69.4% and 51.9% of participants with EM and CM, respectively, achieving ≥50% MMD reduction. Very few patients (2.2%) discontinued treatment due to adverse events.

Study details: This interim analysis of the pan-European Real Life study, an ongoing phase 4 study, included 574 patients with EM (25.8%) or CM (74.2%) who initiated fremanezumab on a monthly or quarterly basis.

Disclosures: This study was funded by Teva Pharmaceuticals. Four authors declared being current or former employees or shareholders of Teva Pharmaceuticals. Other authors declared receiving personal fees, research grants, travel grants, honoraria, or research support from or having other ties with various sources, including Teva.

Source: Ashina M et al. Real-world effectiveness of fremanezumab for the preventive treatment of migraine: Interim analysis of the pan-European, prospective, observational, phase 4 PEARL study. Cephalalgia. 2023;43(11):3331024231214987 (Nov 21). doi: 10.1177/03331024231214987

Key clinical point: The interim analysis of this real-world study confirmed the effectiveness and safety of fremanezumab for the prevention of both chronic migraine (CM) and episodic migraine (EM) attacks.

Major finding: The majority of patients (55.9%) with migraine achieved ≥50% reduction in monthly migraine days (MMD) during 6 months after fremanezumab initiation, with 69.4% and 51.9% of participants with EM and CM, respectively, achieving ≥50% MMD reduction. Very few patients (2.2%) discontinued treatment due to adverse events.

Study details: This interim analysis of the pan-European Real Life study, an ongoing phase 4 study, included 574 patients with EM (25.8%) or CM (74.2%) who initiated fremanezumab on a monthly or quarterly basis.

Disclosures: This study was funded by Teva Pharmaceuticals. Four authors declared being current or former employees or shareholders of Teva Pharmaceuticals. Other authors declared receiving personal fees, research grants, travel grants, honoraria, or research support from or having other ties with various sources, including Teva.

Source: Ashina M et al. Real-world effectiveness of fremanezumab for the preventive treatment of migraine: Interim analysis of the pan-European, prospective, observational, phase 4 PEARL study. Cephalalgia. 2023;43(11):3331024231214987 (Nov 21). doi: 10.1177/03331024231214987

Key clinical point: The interim analysis of this real-world study confirmed the effectiveness and safety of fremanezumab for the prevention of both chronic migraine (CM) and episodic migraine (EM) attacks.

Major finding: The majority of patients (55.9%) with migraine achieved ≥50% reduction in monthly migraine days (MMD) during 6 months after fremanezumab initiation, with 69.4% and 51.9% of participants with EM and CM, respectively, achieving ≥50% MMD reduction. Very few patients (2.2%) discontinued treatment due to adverse events.

Study details: This interim analysis of the pan-European Real Life study, an ongoing phase 4 study, included 574 patients with EM (25.8%) or CM (74.2%) who initiated fremanezumab on a monthly or quarterly basis.

Disclosures: This study was funded by Teva Pharmaceuticals. Four authors declared being current or former employees or shareholders of Teva Pharmaceuticals. Other authors declared receiving personal fees, research grants, travel grants, honoraria, or research support from or having other ties with various sources, including Teva.

Source: Ashina M et al. Real-world effectiveness of fremanezumab for the preventive treatment of migraine: Interim analysis of the pan-European, prospective, observational, phase 4 PEARL study. Cephalalgia. 2023;43(11):3331024231214987 (Nov 21). doi: 10.1177/03331024231214987

Key clinical point: Eptinezumab vs placebo reduced the monthly migraine days by ≥30% in a significantly higher proportion of patients with migraine during the first infusion (weeks 1-12), with further improvements in migraine response following the second infusion (weeks 13-24).

Major finding: A significantly higher proportion of patients receiving 100 mg and 300 mg eptinezumab vs placebo achieved ≥30% reduction in monthly migraine days during weeks 1-12 (65.9% and 71.0% vs 36.9%, respectively; P < .0001) and weeks 13-24 (70.4% and 74.5% vs 43.1%, respectively; P < .0001).

Study details: This post hoc analysis of the DELIVER trial included 890 patients with migraine who had experienced 2-4 prior preventive treatment failures and were randomly assigned to receive 100 mg or 300 mg eptinezumab or placebo every 12 weeks.

Disclosures: This study was funded by H. Lundbeck A/S. Three authors declared being full-time employees of H. Lundbeck A/S or one of its subsidiary companies. Other authors declared having ties with various sources including H. Lundbeck A/S.

Source: Ashina M et al. Responder rates with eptinezumab over 24 weeks in patients with prior preventive migraine treatment failures: Post hoc analysis of the DELIVER randomized clinical trial. Eur J Neurol. 2023 (Nov 13). doi: 10.1111/ene.16131

Key clinical point: Eptinezumab vs placebo reduced the monthly migraine days by ≥30% in a significantly higher proportion of patients with migraine during the first infusion (weeks 1-12), with further improvements in migraine response following the second infusion (weeks 13-24).

Major finding: A significantly higher proportion of patients receiving 100 mg and 300 mg eptinezumab vs placebo achieved ≥30% reduction in monthly migraine days during weeks 1-12 (65.9% and 71.0% vs 36.9%, respectively; P < .0001) and weeks 13-24 (70.4% and 74.5% vs 43.1%, respectively; P < .0001).

Study details: This post hoc analysis of the DELIVER trial included 890 patients with migraine who had experienced 2-4 prior preventive treatment failures and were randomly assigned to receive 100 mg or 300 mg eptinezumab or placebo every 12 weeks.

Disclosures: This study was funded by H. Lundbeck A/S. Three authors declared being full-time employees of H. Lundbeck A/S or one of its subsidiary companies. Other authors declared having ties with various sources including H. Lundbeck A/S.

Source: Ashina M et al. Responder rates with eptinezumab over 24 weeks in patients with prior preventive migraine treatment failures: Post hoc analysis of the DELIVER randomized clinical trial. Eur J Neurol. 2023 (Nov 13). doi: 10.1111/ene.16131

Key clinical point: Eptinezumab vs placebo reduced the monthly migraine days by ≥30% in a significantly higher proportion of patients with migraine during the first infusion (weeks 1-12), with further improvements in migraine response following the second infusion (weeks 13-24).

Major finding: A significantly higher proportion of patients receiving 100 mg and 300 mg eptinezumab vs placebo achieved ≥30% reduction in monthly migraine days during weeks 1-12 (65.9% and 71.0% vs 36.9%, respectively; P < .0001) and weeks 13-24 (70.4% and 74.5% vs 43.1%, respectively; P < .0001).

Study details: This post hoc analysis of the DELIVER trial included 890 patients with migraine who had experienced 2-4 prior preventive treatment failures and were randomly assigned to receive 100 mg or 300 mg eptinezumab or placebo every 12 weeks.

Disclosures: This study was funded by H. Lundbeck A/S. Three authors declared being full-time employees of H. Lundbeck A/S or one of its subsidiary companies. Other authors declared having ties with various sources including H. Lundbeck A/S.

Source: Ashina M et al. Responder rates with eptinezumab over 24 weeks in patients with prior preventive migraine treatment failures: Post hoc analysis of the DELIVER randomized clinical trial. Eur J Neurol. 2023 (Nov 13). doi: 10.1111/ene.16131

Key clinical point: When taken during the prodrome, ubrogepant was more effective than placebo in reducing headaches in patients with a ≥1-year history of migraine and had a tolerable safety profile.

Major finding: A significantly higher proportion of patients reported the absence of moderate or severe headaches within 24 hours of receiving ubrogepant vs placebo (46% vs 29%; odds ratio 2.09; P < .0001). Nausea, fatigue, dizziness, and somnolence were reported by ≤5% of patients receiving ubrogepant.

Study details: The PRODROME trial included 518 patients with migraine who were randomly assigned to receive placebo followed by 100 mg ubrogepant to treat the first and second qualifying prodrome events, respectively, or 100 mg ubrogepant followed by placebo to treat the first and second qualifying prodrome events, respectively.

Disclosures: This study was funded by AbbVie. Six authors declared being current or former employees of or holding stocks in AbbVie. Other authors declared having ties with various sources including AbbVie.

Source: Dodick DW et al. Ubrogepant for the treatment of migraine attacks during the prodrome: A phase 3, multicentre, randomised, double-blind, placebo-controlled, crossover trial in the USA. Lancet. 2023 (Nov 15). doi: 10.1016/S0140-6736(23)01683-5

Key clinical point: When taken during the prodrome, ubrogepant was more effective than placebo in reducing headaches in patients with a ≥1-year history of migraine and had a tolerable safety profile.

Major finding: A significantly higher proportion of patients reported the absence of moderate or severe headaches within 24 hours of receiving ubrogepant vs placebo (46% vs 29%; odds ratio 2.09; P < .0001). Nausea, fatigue, dizziness, and somnolence were reported by ≤5% of patients receiving ubrogepant.

Study details: The PRODROME trial included 518 patients with migraine who were randomly assigned to receive placebo followed by 100 mg ubrogepant to treat the first and second qualifying prodrome events, respectively, or 100 mg ubrogepant followed by placebo to treat the first and second qualifying prodrome events, respectively.

Disclosures: This study was funded by AbbVie. Six authors declared being current or former employees of or holding stocks in AbbVie. Other authors declared having ties with various sources including AbbVie.

Source: Dodick DW et al. Ubrogepant for the treatment of migraine attacks during the prodrome: A phase 3, multicentre, randomised, double-blind, placebo-controlled, crossover trial in the USA. Lancet. 2023 (Nov 15). doi: 10.1016/S0140-6736(23)01683-5

Key clinical point: When taken during the prodrome, ubrogepant was more effective than placebo in reducing headaches in patients with a ≥1-year history of migraine and had a tolerable safety profile.

Major finding: A significantly higher proportion of patients reported the absence of moderate or severe headaches within 24 hours of receiving ubrogepant vs placebo (46% vs 29%; odds ratio 2.09; P < .0001). Nausea, fatigue, dizziness, and somnolence were reported by ≤5% of patients receiving ubrogepant.

Study details: The PRODROME trial included 518 patients with migraine who were randomly assigned to receive placebo followed by 100 mg ubrogepant to treat the first and second qualifying prodrome events, respectively, or 100 mg ubrogepant followed by placebo to treat the first and second qualifying prodrome events, respectively.

Disclosures: This study was funded by AbbVie. Six authors declared being current or former employees of or holding stocks in AbbVie. Other authors declared having ties with various sources including AbbVie.

Source: Dodick DW et al. Ubrogepant for the treatment of migraine attacks during the prodrome: A phase 3, multicentre, randomised, double-blind, placebo-controlled, crossover trial in the USA. Lancet. 2023 (Nov 15). doi: 10.1016/S0140-6736(23)01683-5

Depression is one of the most common comorbidities associated with migraine. Major depressive disorder is both a risk factor for chronic migraine and a condition that one is more likely to develop after being diagnosed with chronic migraine. The study by de Vries Lentsch and colleagues investigated the use of two of the calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) treatments — erenumab and fremanezumab — compared with a control group of patients with chronic migraine, with an eye on outcomes to measure depression. Of note, reduction in headache frequency (defined as reduction in monthly migraine days) was also investigated as an independent variable.

This was a single-center study performed at the University of Leiden Headache Center. It was not a randomized trial, but all patients were followed with an e-diary and Day 0 vs Day 90 questionnaires that tracked their headache frequency and severity as well as a number of metrics related to depression. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Center for Epidemiological Studies Depression Scale (CES-D). The Headache Impact Test (HIT-6) was used to follow headache-related impact and disability, and the Perceived Stress Scale (PSS) was used to measure the degree of stressful situations the patient was experiencing.

The baseline depression scales between the three groups were 70%, 60%, and 66%, respectively; there were similar baseline levels of migraine frequency and disability as well. Both intervention groups showed a significant decrease in the symptoms of depression, and having a greater level of depression was negatively associated with reduction in monthly migraine days after 3 months. Of note, logistic-regression analysis determined that the reduction in depressive symptoms was independent of the reduction in migraine frequency.

Nearly all headache care providers are faced with challenging situations on a daily basis; often this is due to the comorbidity of mood disorders and high-frequency migraine. A traditional approach has been to provide the patient with a migraine preventive medication in the antidepressant family, such as a tricyclic antidepressant or serotonin and norepinephrine reuptake inhibitor (SNRI). Although these can be helpful, they are less specific for migraine prevention. Many patients are also already taking antidepressant medications, and the addition of a migraine-preventive antidepressant would be contraindicated. This study broadens the possibilities for prevention in these complicated patients and shows that there is benefit in both migraine-related outcomes and markers for depression when using CGRP-based therapy.

The way headache medicine is practiced changed dramatically in 2018 with the advent of CGRP monoclonal antibody (mAb) treatments for migraine. These medications have allowed us to target migraine specifically, whereas all of the preventive medications for migraine prior to 2018 were developed for other conditions and only secondarily helped migraine. These include the antidepressant, antihypertensive, and antiepileptic classes of medications, as well as onabotulinum toxin A, which, although approved for migraine, is not targeting a migraine-specific factor. Moskatel and colleagues sought to better understand the changing patterns of prescribing the nonspecific, or "traditional," migraine preventive medications in light of the advent of CGRP treatment.

This was a retrospective cohort study using aggregated data from the Stanford headache center. The percentage of patients with chronic migraine who had been prescribed one of the 10 most prescribed oral preventive medications or onabotulinum toxin A, or any of the four CGRP mAb, were calculated relative to the total number of patients with chronic migraine who received a prescription for any medication from the clinic during the pre-CGRP mAb years of 2015-2017 and post-approval years of 2019-2021.

The Stanford (STARR) database was filtered, searching for patients living in a California ZIP code with a diagnosis of chronic migraine who were followed from 2015 to 2021. The 10 most common non-CGRP preventive medications were amitriptyline/nortriptyline, valproate, duloxetine, gabapentin, memantine, propranolol, venlafaxine, verapamil, and onabotulinumtoxinA.

Erenumab was noted to initially be the most prescribed CGRP monoclonal antibody medication, but this was overtaken by galcanezumab after the second quarter of 2020 and throughout 2021. There is a statistically significant decrease in the percentage of patients receiving any of the non-CGRP preventive medications since 2018. The most significant decreases were in the tricyclic antidepressant class, as well as valproate, duloxetine, memantine, and onabotulinum toxin A. There was no statistically significant change in venlafaxine or gabapentin prescriptions.

This study highlights the changing face of headache medicine, and having a new class of migraine-specific treatment has significantly affected prescribing patterns. Although there is a statistically significant decrease in the prescribing of these non–migraine-specific preventive medications, they are still often recommended due to step-therapy regulations from insurance formularies, or as part of a polypharmacy regimen that may be more beneficial for a patient. These medications do improve patient outcomes and will remain a mainstay in migraine treatment.

Nearly all patients with migraine are recommended an acute medication to treat migraine attacks abortively; some patients are also recommended preventive therapies if migraine frequency significantly affects their quality of life. The American Headache Society/American Academy of Neurology guidelines for prevention recommend the initiation of a preventive medication at a frequency of 4-5 headache days per month or approximately 1 per week. Lipton and colleagues sought to determine whether there were any efficacy concerns in combining a CGRP mAb for prevention with ubrogepant, an oral CGRP antagonist, for acute treatment.

This was a prospective, open-level observational study assessing pain relief, return to normal function, and treatment satisfaction with patients given 50 or 100 mg of ubrogepant while concomitantly being given a seizure or mAb medication. Patients were allowed to be taking onabotulinumtoxinA as well as a CGRP mAb. The patients in this study were asked to track their headache symptoms using the Migraine Buddy e-diary. Meaningful pain relief was defined as a rating of migraine-related pain with one of the following choices 4 hours after taking the medication: no pain, mild pain, moderate pain, or severe pain. Return to normal function was defined as whether the patient determined they were able to function normally relative to their baseline at specific times post intervention. This was based on a functional disability scale. Treatment satisfaction was determined on the basis of a seven-point rating scale for how satisfied the patient felt with the medication at the end of the trial period.

A total of 245 participants provided at least 30 days of data, with 44.5% of the patients taking erenumab, 35.1% taking galcanezumab, 18.0% taking fremanezumab, and 2.9% taking eptinezumab. Meaningful pain relief was achieved by 61.6% of patients at 2 hours and 80.4% of patients at 4 hours post dose for both the 50-mg and 100-mg dose of ubrogepant. Return to normal function was achieved by 34.7% of patients at 2 hours and 50.5% at 4 hours post dose as well. Patients reported a 72.7% satisfaction level with the medication.

When CGRP acute medications were first approved, there was concern about the use of a mAb together with an oral antagonist. It was thought that CGRP medications would be associated with fewer benefits than when these medications were used alone, due to the belief that only a specific amount of CGRP could be blocked at any specific time. This trial shows that the efficacy of CGRP acute medications is not affected by concomitant use of mAb. Many patients who respond well to CGRP mAb will benefit significantly from the additional abortive use of oral antagonists.

Depression is one of the most common comorbidities associated with migraine. Major depressive disorder is both a risk factor for chronic migraine and a condition that one is more likely to develop after being diagnosed with chronic migraine. The study by de Vries Lentsch and colleagues investigated the use of two of the calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) treatments — erenumab and fremanezumab — compared with a control group of patients with chronic migraine, with an eye on outcomes to measure depression. Of note, reduction in headache frequency (defined as reduction in monthly migraine days) was also investigated as an independent variable.

This was a single-center study performed at the University of Leiden Headache Center. It was not a randomized trial, but all patients were followed with an e-diary and Day 0 vs Day 90 questionnaires that tracked their headache frequency and severity as well as a number of metrics related to depression. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Center for Epidemiological Studies Depression Scale (CES-D). The Headache Impact Test (HIT-6) was used to follow headache-related impact and disability, and the Perceived Stress Scale (PSS) was used to measure the degree of stressful situations the patient was experiencing.

The baseline depression scales between the three groups were 70%, 60%, and 66%, respectively; there were similar baseline levels of migraine frequency and disability as well. Both intervention groups showed a significant decrease in the symptoms of depression, and having a greater level of depression was negatively associated with reduction in monthly migraine days after 3 months. Of note, logistic-regression analysis determined that the reduction in depressive symptoms was independent of the reduction in migraine frequency.

Nearly all headache care providers are faced with challenging situations on a daily basis; often this is due to the comorbidity of mood disorders and high-frequency migraine. A traditional approach has been to provide the patient with a migraine preventive medication in the antidepressant family, such as a tricyclic antidepressant or serotonin and norepinephrine reuptake inhibitor (SNRI). Although these can be helpful, they are less specific for migraine prevention. Many patients are also already taking antidepressant medications, and the addition of a migraine-preventive antidepressant would be contraindicated. This study broadens the possibilities for prevention in these complicated patients and shows that there is benefit in both migraine-related outcomes and markers for depression when using CGRP-based therapy.

The way headache medicine is practiced changed dramatically in 2018 with the advent of CGRP monoclonal antibody (mAb) treatments for migraine. These medications have allowed us to target migraine specifically, whereas all of the preventive medications for migraine prior to 2018 were developed for other conditions and only secondarily helped migraine. These include the antidepressant, antihypertensive, and antiepileptic classes of medications, as well as onabotulinum toxin A, which, although approved for migraine, is not targeting a migraine-specific factor. Moskatel and colleagues sought to better understand the changing patterns of prescribing the nonspecific, or "traditional," migraine preventive medications in light of the advent of CGRP treatment.

This was a retrospective cohort study using aggregated data from the Stanford headache center. The percentage of patients with chronic migraine who had been prescribed one of the 10 most prescribed oral preventive medications or onabotulinum toxin A, or any of the four CGRP mAb, were calculated relative to the total number of patients with chronic migraine who received a prescription for any medication from the clinic during the pre-CGRP mAb years of 2015-2017 and post-approval years of 2019-2021.

The Stanford (STARR) database was filtered, searching for patients living in a California ZIP code with a diagnosis of chronic migraine who were followed from 2015 to 2021. The 10 most common non-CGRP preventive medications were amitriptyline/nortriptyline, valproate, duloxetine, gabapentin, memantine, propranolol, venlafaxine, verapamil, and onabotulinumtoxinA.

Erenumab was noted to initially be the most prescribed CGRP monoclonal antibody medication, but this was overtaken by galcanezumab after the second quarter of 2020 and throughout 2021. There is a statistically significant decrease in the percentage of patients receiving any of the non-CGRP preventive medications since 2018. The most significant decreases were in the tricyclic antidepressant class, as well as valproate, duloxetine, memantine, and onabotulinum toxin A. There was no statistically significant change in venlafaxine or gabapentin prescriptions.

This study highlights the changing face of headache medicine, and having a new class of migraine-specific treatment has significantly affected prescribing patterns. Although there is a statistically significant decrease in the prescribing of these non–migraine-specific preventive medications, they are still often recommended due to step-therapy regulations from insurance formularies, or as part of a polypharmacy regimen that may be more beneficial for a patient. These medications do improve patient outcomes and will remain a mainstay in migraine treatment.

Nearly all patients with migraine are recommended an acute medication to treat migraine attacks abortively; some patients are also recommended preventive therapies if migraine frequency significantly affects their quality of life. The American Headache Society/American Academy of Neurology guidelines for prevention recommend the initiation of a preventive medication at a frequency of 4-5 headache days per month or approximately 1 per week. Lipton and colleagues sought to determine whether there were any efficacy concerns in combining a CGRP mAb for prevention with ubrogepant, an oral CGRP antagonist, for acute treatment.

This was a prospective, open-level observational study assessing pain relief, return to normal function, and treatment satisfaction with patients given 50 or 100 mg of ubrogepant while concomitantly being given a seizure or mAb medication. Patients were allowed to be taking onabotulinumtoxinA as well as a CGRP mAb. The patients in this study were asked to track their headache symptoms using the Migraine Buddy e-diary. Meaningful pain relief was defined as a rating of migraine-related pain with one of the following choices 4 hours after taking the medication: no pain, mild pain, moderate pain, or severe pain. Return to normal function was defined as whether the patient determined they were able to function normally relative to their baseline at specific times post intervention. This was based on a functional disability scale. Treatment satisfaction was determined on the basis of a seven-point rating scale for how satisfied the patient felt with the medication at the end of the trial period.

A total of 245 participants provided at least 30 days of data, with 44.5% of the patients taking erenumab, 35.1% taking galcanezumab, 18.0% taking fremanezumab, and 2.9% taking eptinezumab. Meaningful pain relief was achieved by 61.6% of patients at 2 hours and 80.4% of patients at 4 hours post dose for both the 50-mg and 100-mg dose of ubrogepant. Return to normal function was achieved by 34.7% of patients at 2 hours and 50.5% at 4 hours post dose as well. Patients reported a 72.7% satisfaction level with the medication.

When CGRP acute medications were first approved, there was concern about the use of a mAb together with an oral antagonist. It was thought that CGRP medications would be associated with fewer benefits than when these medications were used alone, due to the belief that only a specific amount of CGRP could be blocked at any specific time. This trial shows that the efficacy of CGRP acute medications is not affected by concomitant use of mAb. Many patients who respond well to CGRP mAb will benefit significantly from the additional abortive use of oral antagonists.

Depression is one of the most common comorbidities associated with migraine. Major depressive disorder is both a risk factor for chronic migraine and a condition that one is more likely to develop after being diagnosed with chronic migraine. The study by de Vries Lentsch and colleagues investigated the use of two of the calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) treatments — erenumab and fremanezumab — compared with a control group of patients with chronic migraine, with an eye on outcomes to measure depression. Of note, reduction in headache frequency (defined as reduction in monthly migraine days) was also investigated as an independent variable.

This was a single-center study performed at the University of Leiden Headache Center. It was not a randomized trial, but all patients were followed with an e-diary and Day 0 vs Day 90 questionnaires that tracked their headache frequency and severity as well as a number of metrics related to depression. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Center for Epidemiological Studies Depression Scale (CES-D). The Headache Impact Test (HIT-6) was used to follow headache-related impact and disability, and the Perceived Stress Scale (PSS) was used to measure the degree of stressful situations the patient was experiencing.

The baseline depression scales between the three groups were 70%, 60%, and 66%, respectively; there were similar baseline levels of migraine frequency and disability as well. Both intervention groups showed a significant decrease in the symptoms of depression, and having a greater level of depression was negatively associated with reduction in monthly migraine days after 3 months. Of note, logistic-regression analysis determined that the reduction in depressive symptoms was independent of the reduction in migraine frequency.

Nearly all headache care providers are faced with challenging situations on a daily basis; often this is due to the comorbidity of mood disorders and high-frequency migraine. A traditional approach has been to provide the patient with a migraine preventive medication in the antidepressant family, such as a tricyclic antidepressant or serotonin and norepinephrine reuptake inhibitor (SNRI). Although these can be helpful, they are less specific for migraine prevention. Many patients are also already taking antidepressant medications, and the addition of a migraine-preventive antidepressant would be contraindicated. This study broadens the possibilities for prevention in these complicated patients and shows that there is benefit in both migraine-related outcomes and markers for depression when using CGRP-based therapy.

The way headache medicine is practiced changed dramatically in 2018 with the advent of CGRP monoclonal antibody (mAb) treatments for migraine. These medications have allowed us to target migraine specifically, whereas all of the preventive medications for migraine prior to 2018 were developed for other conditions and only secondarily helped migraine. These include the antidepressant, antihypertensive, and antiepileptic classes of medications, as well as onabotulinum toxin A, which, although approved for migraine, is not targeting a migraine-specific factor. Moskatel and colleagues sought to better understand the changing patterns of prescribing the nonspecific, or "traditional," migraine preventive medications in light of the advent of CGRP treatment.

This was a retrospective cohort study using aggregated data from the Stanford headache center. The percentage of patients with chronic migraine who had been prescribed one of the 10 most prescribed oral preventive medications or onabotulinum toxin A, or any of the four CGRP mAb, were calculated relative to the total number of patients with chronic migraine who received a prescription for any medication from the clinic during the pre-CGRP mAb years of 2015-2017 and post-approval years of 2019-2021.

The Stanford (STARR) database was filtered, searching for patients living in a California ZIP code with a diagnosis of chronic migraine who were followed from 2015 to 2021. The 10 most common non-CGRP preventive medications were amitriptyline/nortriptyline, valproate, duloxetine, gabapentin, memantine, propranolol, venlafaxine, verapamil, and onabotulinumtoxinA.

Erenumab was noted to initially be the most prescribed CGRP monoclonal antibody medication, but this was overtaken by galcanezumab after the second quarter of 2020 and throughout 2021. There is a statistically significant decrease in the percentage of patients receiving any of the non-CGRP preventive medications since 2018. The most significant decreases were in the tricyclic antidepressant class, as well as valproate, duloxetine, memantine, and onabotulinum toxin A. There was no statistically significant change in venlafaxine or gabapentin prescriptions.

This study highlights the changing face of headache medicine, and having a new class of migraine-specific treatment has significantly affected prescribing patterns. Although there is a statistically significant decrease in the prescribing of these non–migraine-specific preventive medications, they are still often recommended due to step-therapy regulations from insurance formularies, or as part of a polypharmacy regimen that may be more beneficial for a patient. These medications do improve patient outcomes and will remain a mainstay in migraine treatment.

Nearly all patients with migraine are recommended an acute medication to treat migraine attacks abortively; some patients are also recommended preventive therapies if migraine frequency significantly affects their quality of life. The American Headache Society/American Academy of Neurology guidelines for prevention recommend the initiation of a preventive medication at a frequency of 4-5 headache days per month or approximately 1 per week. Lipton and colleagues sought to determine whether there were any efficacy concerns in combining a CGRP mAb for prevention with ubrogepant, an oral CGRP antagonist, for acute treatment.

This was a prospective, open-level observational study assessing pain relief, return to normal function, and treatment satisfaction with patients given 50 or 100 mg of ubrogepant while concomitantly being given a seizure or mAb medication. Patients were allowed to be taking onabotulinumtoxinA as well as a CGRP mAb. The patients in this study were asked to track their headache symptoms using the Migraine Buddy e-diary. Meaningful pain relief was defined as a rating of migraine-related pain with one of the following choices 4 hours after taking the medication: no pain, mild pain, moderate pain, or severe pain. Return to normal function was defined as whether the patient determined they were able to function normally relative to their baseline at specific times post intervention. This was based on a functional disability scale. Treatment satisfaction was determined on the basis of a seven-point rating scale for how satisfied the patient felt with the medication at the end of the trial period.

A total of 245 participants provided at least 30 days of data, with 44.5% of the patients taking erenumab, 35.1% taking galcanezumab, 18.0% taking fremanezumab, and 2.9% taking eptinezumab. Meaningful pain relief was achieved by 61.6% of patients at 2 hours and 80.4% of patients at 4 hours post dose for both the 50-mg and 100-mg dose of ubrogepant. Return to normal function was achieved by 34.7% of patients at 2 hours and 50.5% at 4 hours post dose as well. Patients reported a 72.7% satisfaction level with the medication.

When CGRP acute medications were first approved, there was concern about the use of a mAb together with an oral antagonist. It was thought that CGRP medications would be associated with fewer benefits than when these medications were used alone, due to the belief that only a specific amount of CGRP could be blocked at any specific time. This trial shows that the efficacy of CGRP acute medications is not affected by concomitant use of mAb. Many patients who respond well to CGRP mAb will benefit significantly from the additional abortive use of oral antagonists.

TOPLINE:

For relief of acute migraine, triptans, ergots, and antiemetics are two to five times more effective than ibuprofen, and acetaminophen is the least effective medication, new results from large, real-world analysis of self-reported patient data show. 

METHODOLOGY: 

• Researchers analyzed nearly 11 million migraine attack records extracted from Migraine Buddy, an e-diary smartphone app, over a 6-year period. 
• They evaluated self-reported treatment effectiveness for 25 acute migraine medications among seven classes: acetaminophen, NSAIDs, triptans, combination analgesics, ergots, antiemetics, and opioids. 
• A two-level nested multivariate logistic regression model adjusted for within-subject dependency and for concomitant medications taken within each analyzed migraine attack. 
• The final analysis included nearly 5 million medication-outcome pairs from 3.1 million migraine attacks in 278,000 medication users. 

TAKEAWAY:

• Using ibuprofen as the reference, triptans, ergots, and antiemetics were the top three medication classes with the highest effectiveness (mean odds ratios [OR] 4.80, 3.02, and 2.67, respectively). 
• The next most effective medication classes were opioids (OR, 2.49), NSAIDs other than ibuprofen (OR, 1.94), combination analgesics acetaminophen/acetylsalicylic acid/caffeine (OR, 1.69), and others (OR, 1.49).
• Acetaminophen (OR, 0.83) was considered to be the least effective.
• The most effective individual medications were eletriptan (Relpax) (OR, 6.1); zolmitriptan (Zomig) (OR, 5.7); and sumatriptan (Imitrex) (OR, 5.2).

IN PRACTICE:

“Our findings that triptans, ergots, and antiemetics are the most effective classes of medications align with the guideline recommendations and offer generalizable insights to complement clinical practice,” the authors wrote. 

laflor/gettyimages

SOURCE:

The study, with first author Chia-Chun Chiang, MD, Department of Neurology, Mayo Clinic, Rochester, Minnesota, was published online November 29 in Neurology.

LIMITATIONS:

The findings are based on subjective user-reported ratings of effectiveness and information on side effects, dosages, and formulations were not available. The newer migraine medication classes, gepants and ditans, were not included due to the relatively lower number of treated attacks. The regression model did not include age, gender, pain intensity, and other migraine-associated symptoms, which could potentially affect treatment effectiveness. 

DISCLOSURES: 

Funding for the study was provided by the Kanagawa University of Human Service research fund. A full list of author disclosures can be found with the original article.

A version of this article first appeared on Medscape.com.

TOPLINE:

For relief of acute migraine, triptans, ergots, and antiemetics are two to five times more effective than ibuprofen, and acetaminophen is the least effective medication, new results from large, real-world analysis of self-reported patient data show. 

METHODOLOGY: 

• Researchers analyzed nearly 11 million migraine attack records extracted from Migraine Buddy, an e-diary smartphone app, over a 6-year period. 
• They evaluated self-reported treatment effectiveness for 25 acute migraine medications among seven classes: acetaminophen, NSAIDs, triptans, combination analgesics, ergots, antiemetics, and opioids. 
• A two-level nested multivariate logistic regression model adjusted for within-subject dependency and for concomitant medications taken within each analyzed migraine attack. 
• The final analysis included nearly 5 million medication-outcome pairs from 3.1 million migraine attacks in 278,000 medication users. 

TAKEAWAY:

• Using ibuprofen as the reference, triptans, ergots, and antiemetics were the top three medication classes with the highest effectiveness (mean odds ratios [OR] 4.80, 3.02, and 2.67, respectively). 
• The next most effective medication classes were opioids (OR, 2.49), NSAIDs other than ibuprofen (OR, 1.94), combination analgesics acetaminophen/acetylsalicylic acid/caffeine (OR, 1.69), and others (OR, 1.49).
• Acetaminophen (OR, 0.83) was considered to be the least effective.
• The most effective individual medications were eletriptan (Relpax) (OR, 6.1); zolmitriptan (Zomig) (OR, 5.7); and sumatriptan (Imitrex) (OR, 5.2).

IN PRACTICE:

“Our findings that triptans, ergots, and antiemetics are the most effective classes of medications align with the guideline recommendations and offer generalizable insights to complement clinical practice,” the authors wrote. 

laflor/gettyimages

SOURCE:

The study, with first author Chia-Chun Chiang, MD, Department of Neurology, Mayo Clinic, Rochester, Minnesota, was published online November 29 in Neurology.

LIMITATIONS:

The findings are based on subjective user-reported ratings of effectiveness and information on side effects, dosages, and formulations were not available. The newer migraine medication classes, gepants and ditans, were not included due to the relatively lower number of treated attacks. The regression model did not include age, gender, pain intensity, and other migraine-associated symptoms, which could potentially affect treatment effectiveness. 

DISCLOSURES: 

Funding for the study was provided by the Kanagawa University of Human Service research fund. A full list of author disclosures can be found with the original article.

A version of this article first appeared on Medscape.com.

TOPLINE:

For relief of acute migraine, triptans, ergots, and antiemetics are two to five times more effective than ibuprofen, and acetaminophen is the least effective medication, new results from large, real-world analysis of self-reported patient data show. 

METHODOLOGY: 

• Researchers analyzed nearly 11 million migraine attack records extracted from Migraine Buddy, an e-diary smartphone app, over a 6-year period. 
• They evaluated self-reported treatment effectiveness for 25 acute migraine medications among seven classes: acetaminophen, NSAIDs, triptans, combination analgesics, ergots, antiemetics, and opioids. 
• A two-level nested multivariate logistic regression model adjusted for within-subject dependency and for concomitant medications taken within each analyzed migraine attack. 
• The final analysis included nearly 5 million medication-outcome pairs from 3.1 million migraine attacks in 278,000 medication users. 

TAKEAWAY:

• Using ibuprofen as the reference, triptans, ergots, and antiemetics were the top three medication classes with the highest effectiveness (mean odds ratios [OR] 4.80, 3.02, and 2.67, respectively). 
• The next most effective medication classes were opioids (OR, 2.49), NSAIDs other than ibuprofen (OR, 1.94), combination analgesics acetaminophen/acetylsalicylic acid/caffeine (OR, 1.69), and others (OR, 1.49).
• Acetaminophen (OR, 0.83) was considered to be the least effective.
• The most effective individual medications were eletriptan (Relpax) (OR, 6.1); zolmitriptan (Zomig) (OR, 5.7); and sumatriptan (Imitrex) (OR, 5.2).

IN PRACTICE:

“Our findings that triptans, ergots, and antiemetics are the most effective classes of medications align with the guideline recommendations and offer generalizable insights to complement clinical practice,” the authors wrote. 

laflor/gettyimages

SOURCE:

The study, with first author Chia-Chun Chiang, MD, Department of Neurology, Mayo Clinic, Rochester, Minnesota, was published online November 29 in Neurology.

LIMITATIONS:

The findings are based on subjective user-reported ratings of effectiveness and information on side effects, dosages, and formulations were not available. The newer migraine medication classes, gepants and ditans, were not included due to the relatively lower number of treated attacks. The regression model did not include age, gender, pain intensity, and other migraine-associated symptoms, which could potentially affect treatment effectiveness. 

DISCLOSURES: 

Funding for the study was provided by the Kanagawa University of Human Service research fund. A full list of author disclosures can be found with the original article.

A version of this article first appeared on Medscape.com.

Repairing patent foramen ovale (PFO) and other right-to-left shunt disorders for the prevention of migraine has generated mixed results, but the potential for these repairs also includes reducing the risk of stroke, according to a discussion at the 2023 Scottsdale Headache Symposium.

In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.

UCLA

One Intervention, Two Potential Benefits

Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.

Use of oral contraceptives, which produce a hypercoagulable state, is an example.

“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.

The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
 

Primary Endpoint Missed in Clinical Trials

The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.

In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).

A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.

There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.

Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.

“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
 

Migraine Days Might Be a Better Endpoint

For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.

“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.

He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.

One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.

Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.

Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.

“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.

Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”

In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).

The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”

As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.

“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.

Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.

Repairing patent foramen ovale (PFO) and other right-to-left shunt disorders for the prevention of migraine has generated mixed results, but the potential for these repairs also includes reducing the risk of stroke, according to a discussion at the 2023 Scottsdale Headache Symposium.

In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.

UCLA

One Intervention, Two Potential Benefits

Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.

Use of oral contraceptives, which produce a hypercoagulable state, is an example.

“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.

The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
 

Primary Endpoint Missed in Clinical Trials

The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.

In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).

A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.

There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.

Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.

“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
 

Migraine Days Might Be a Better Endpoint

For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.

“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.

He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.

One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.

Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.

Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.

“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.

Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”

In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).

The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”

As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.

“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.

Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.

Repairing patent foramen ovale (PFO) and other right-to-left shunt disorders for the prevention of migraine has generated mixed results, but the potential for these repairs also includes reducing the risk of stroke, according to a discussion at the 2023 Scottsdale Headache Symposium.

In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.

UCLA

One Intervention, Two Potential Benefits

Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.

Use of oral contraceptives, which produce a hypercoagulable state, is an example.

“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.

The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
 

Primary Endpoint Missed in Clinical Trials

The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.

In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).

A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.

There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.

Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.

“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
 

Migraine Days Might Be a Better Endpoint

For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.

“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.

He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.

One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.

Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.

Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.

“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.

Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”

In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).

The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”

As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.

“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.

Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.

Drugs offered to treat the headache phase of migraine are not necessarily the best to abort the premonitory or prodromal phases, according to experts attempting to put these puzzle pieces together at the 2023 Scottsdale Headache Symposium.

As the details of the complex chain of molecular events become better understood, there is reason to believe that the targets for aborting events early in the process are not necessarily therapeutic at later stages or vice versa, according to Peter Goadsby, MBBS, MD, PhD, director of the National Institute for Health Research and professor of neurology, King’s College, London.

“I think this explains some of the frustration at trigger modulation. I think we are often trying to modulate a process that has already got started,” he said. The analogy might be closing the barn door after the animals have escaped.
 

Migraine phases might explain pathology

Given the progress in understanding each step that leads from one phase to the next in migraine onset, this premise is not surprising. Increased blood flow, trigeminal activation, and release of calcitonin gene–related peptide (CGRP) are early events in this process, according to Dr. Goadsby, but there is still uncertainty about the triggers of brainstem stimulation and cranial blood flow that precedes these events.

In his talk about the advances that led to the development of CGRP-targeted therapy, Dr. Goadsby explained how and why CGRP inhibition, along with triptans, pituitary adenylate cyclase–activating polypeptide (PACAP) inhibitors, and ditans, have been developed as treatment targets in migraine, while other once-promising targets, such as substance P inhibition and inducible nitric oxide synthase (INOS) inhibition, have not.

Much of this progress has been by trial and error through clinical studies in which efficacy has or has not been seen. Despite the progress in mapping the release of CGRP and its activity, Dr. Goadsby acknowledged that there is still much about its participation in migraine pathophysiology that remains poorly defined.

“Anyone who tells you that they know how CGRP works I think is blowing smoke, frankly,” Dr. Goadsby said. “Clearly these things are complex.”
 

CGRP is active in the CSF

This includes the site of action. Dr. Goadsby said that it is widely believed that CGRP inhibitors are active in the dura and not in the cerebrospinal fluid (CSF). However, Dr. Goadsby said that a study undertaken with monoclonal antibodies targeting CGRP have produced compelling evidence that CGRP is reduced in the CSF.

“They clearly get into the CSF,” said Dr. Goadsby, noting that the barrier between peripheral blood and the CSF “is different from the blood-brain barrier.”

Widely regarded as playing a pivotal role in the development of CGRP as a therapeutic target in migraine, Dr. Goadsby spent some time speculating about its potential for preventing the earliest steps in the process that leads from the premonitory state to allodynia, prodromal symptoms, migraine, and postdromal recovery.

Of triggers, “light is my favorite example,” he said. He noted that many patients are convinced that light initiates the subsequent steps that end in a migraine. This is fair assumption for those who have seen a sequence of events in which light in the absence of any other symptom always precedes prodromal symptoms and migraine.

“Why would you not think that?” he asked. “Unless you point out that the attack had already started and the reason that you are noticing the light is because of photophobia that started during the premonitory phase.”

It is increasingly clear that CGRP inhibition does have clinical benefit when started at early signs of a coming migraine, according to Dr. Goadsby. He cited a phase 3 study published just days before he spoke at the Scottsdale Headache Symposium. Called PRODROME, the study associated the CGRP receptor antagonist ubrogepant, which is already approved for treatment of migraine, with a significant reduction in the risk of moderate to severe headache relative to placebo when measured 24 hours after randomization (46% vs. 29%; P < .0001).


 

Brain activity monitoring supports phases

Citing imaging studies in his own laboratory, Todd J. Schwedt, MD, chair of neurology research, Mayo Clinic, Phoenix, substantiated several of the points made by Dr. Goadsby in a separate talk he made on migraine phases. By monitoring brain activity during each phase of migraine, he suggested his data support the role of CGRP in producing an inflammatory response as well as sensitizing the trigeminal cervical system in steps that appear to be important to the pain process.

Mitchel L. Zoler/MDedge News

Dr. Schwedt showed several pieces of evidence suggesting that CGRP is an early mediator even if it is not necessarily the first step in a process for every patient. However, like Dr. Goadsby, Dr. Schwedt also acknowledged that the interplay between events is complex and might differ between patients.

Yet, he says that brain activity on imaging is not the only evidence of the role of CGRP activation early in the process leading toward migraine.

“I am a little biased towards imaging, but it’s not just about imaging,” Dr. Schwedt said.

“If we look at preictal salivary CGRP levels and then follow them into the headache phase, we see the levels increase, but they go back to normal a couple of hours into the attack and then stay normal, presumably, until the patient gets closer to the next attack,” Dr. Schwedt said.

Despite progress there is more to be done to determine why CGRP is released and whether it can be inhibited early to abort migraine before the headache phase, but both Dr. Goadsby and Dr. Schwedt pointed to this as a very early event. This is not to say that others, such as cortical spreading depression, do not have an equally important role in the evolution of migraine, but each expert considers migraine phases to be useful divisions for tracing the sequence of pathogenic events.

The phase of a migraine attack and their corresponding symptoms “can be mapped to altered brain function and release of neuropeptides and neurotransmitters,” Dr. Schwedt said. The implication is that better targets for blocking migraine before it reaches the headache phase might be discovered in these early phases.

Dr. Goadsby and Dr. Schwedt listed more than 10 pharmaceutical companies to which they have financial relationships, but both claimed that none of these relationships posed a potential conflict of interest.

Drugs offered to treat the headache phase of migraine are not necessarily the best to abort the premonitory or prodromal phases, according to experts attempting to put these puzzle pieces together at the 2023 Scottsdale Headache Symposium.

As the details of the complex chain of molecular events become better understood, there is reason to believe that the targets for aborting events early in the process are not necessarily therapeutic at later stages or vice versa, according to Peter Goadsby, MBBS, MD, PhD, director of the National Institute for Health Research and professor of neurology, King’s College, London.

“I think this explains some of the frustration at trigger modulation. I think we are often trying to modulate a process that has already got started,” he said. The analogy might be closing the barn door after the animals have escaped.
 

Migraine phases might explain pathology

Given the progress in understanding each step that leads from one phase to the next in migraine onset, this premise is not surprising. Increased blood flow, trigeminal activation, and release of calcitonin gene–related peptide (CGRP) are early events in this process, according to Dr. Goadsby, but there is still uncertainty about the triggers of brainstem stimulation and cranial blood flow that precedes these events.

In his talk about the advances that led to the development of CGRP-targeted therapy, Dr. Goadsby explained how and why CGRP inhibition, along with triptans, pituitary adenylate cyclase–activating polypeptide (PACAP) inhibitors, and ditans, have been developed as treatment targets in migraine, while other once-promising targets, such as substance P inhibition and inducible nitric oxide synthase (INOS) inhibition, have not.

Much of this progress has been by trial and error through clinical studies in which efficacy has or has not been seen. Despite the progress in mapping the release of CGRP and its activity, Dr. Goadsby acknowledged that there is still much about its participation in migraine pathophysiology that remains poorly defined.

“Anyone who tells you that they know how CGRP works I think is blowing smoke, frankly,” Dr. Goadsby said. “Clearly these things are complex.”
 

CGRP is active in the CSF

This includes the site of action. Dr. Goadsby said that it is widely believed that CGRP inhibitors are active in the dura and not in the cerebrospinal fluid (CSF). However, Dr. Goadsby said that a study undertaken with monoclonal antibodies targeting CGRP have produced compelling evidence that CGRP is reduced in the CSF.

“They clearly get into the CSF,” said Dr. Goadsby, noting that the barrier between peripheral blood and the CSF “is different from the blood-brain barrier.”

Widely regarded as playing a pivotal role in the development of CGRP as a therapeutic target in migraine, Dr. Goadsby spent some time speculating about its potential for preventing the earliest steps in the process that leads from the premonitory state to allodynia, prodromal symptoms, migraine, and postdromal recovery.

Of triggers, “light is my favorite example,” he said. He noted that many patients are convinced that light initiates the subsequent steps that end in a migraine. This is fair assumption for those who have seen a sequence of events in which light in the absence of any other symptom always precedes prodromal symptoms and migraine.

“Why would you not think that?” he asked. “Unless you point out that the attack had already started and the reason that you are noticing the light is because of photophobia that started during the premonitory phase.”

It is increasingly clear that CGRP inhibition does have clinical benefit when started at early signs of a coming migraine, according to Dr. Goadsby. He cited a phase 3 study published just days before he spoke at the Scottsdale Headache Symposium. Called PRODROME, the study associated the CGRP receptor antagonist ubrogepant, which is already approved for treatment of migraine, with a significant reduction in the risk of moderate to severe headache relative to placebo when measured 24 hours after randomization (46% vs. 29%; P < .0001).


 

Brain activity monitoring supports phases

Citing imaging studies in his own laboratory, Todd J. Schwedt, MD, chair of neurology research, Mayo Clinic, Phoenix, substantiated several of the points made by Dr. Goadsby in a separate talk he made on migraine phases. By monitoring brain activity during each phase of migraine, he suggested his data support the role of CGRP in producing an inflammatory response as well as sensitizing the trigeminal cervical system in steps that appear to be important to the pain process.

Mitchel L. Zoler/MDedge News

Dr. Schwedt showed several pieces of evidence suggesting that CGRP is an early mediator even if it is not necessarily the first step in a process for every patient. However, like Dr. Goadsby, Dr. Schwedt also acknowledged that the interplay between events is complex and might differ between patients.

Yet, he says that brain activity on imaging is not the only evidence of the role of CGRP activation early in the process leading toward migraine.

“I am a little biased towards imaging, but it’s not just about imaging,” Dr. Schwedt said.

“If we look at preictal salivary CGRP levels and then follow them into the headache phase, we see the levels increase, but they go back to normal a couple of hours into the attack and then stay normal, presumably, until the patient gets closer to the next attack,” Dr. Schwedt said.

Despite progress there is more to be done to determine why CGRP is released and whether it can be inhibited early to abort migraine before the headache phase, but both Dr. Goadsby and Dr. Schwedt pointed to this as a very early event. This is not to say that others, such as cortical spreading depression, do not have an equally important role in the evolution of migraine, but each expert considers migraine phases to be useful divisions for tracing the sequence of pathogenic events.

The phase of a migraine attack and their corresponding symptoms “can be mapped to altered brain function and release of neuropeptides and neurotransmitters,” Dr. Schwedt said. The implication is that better targets for blocking migraine before it reaches the headache phase might be discovered in these early phases.

Dr. Goadsby and Dr. Schwedt listed more than 10 pharmaceutical companies to which they have financial relationships, but both claimed that none of these relationships posed a potential conflict of interest.

Drugs offered to treat the headache phase of migraine are not necessarily the best to abort the premonitory or prodromal phases, according to experts attempting to put these puzzle pieces together at the 2023 Scottsdale Headache Symposium.

As the details of the complex chain of molecular events become better understood, there is reason to believe that the targets for aborting events early in the process are not necessarily therapeutic at later stages or vice versa, according to Peter Goadsby, MBBS, MD, PhD, director of the National Institute for Health Research and professor of neurology, King’s College, London.

“I think this explains some of the frustration at trigger modulation. I think we are often trying to modulate a process that has already got started,” he said. The analogy might be closing the barn door after the animals have escaped.
 

Migraine phases might explain pathology

Given the progress in understanding each step that leads from one phase to the next in migraine onset, this premise is not surprising. Increased blood flow, trigeminal activation, and release of calcitonin gene–related peptide (CGRP) are early events in this process, according to Dr. Goadsby, but there is still uncertainty about the triggers of brainstem stimulation and cranial blood flow that precedes these events.

In his talk about the advances that led to the development of CGRP-targeted therapy, Dr. Goadsby explained how and why CGRP inhibition, along with triptans, pituitary adenylate cyclase–activating polypeptide (PACAP) inhibitors, and ditans, have been developed as treatment targets in migraine, while other once-promising targets, such as substance P inhibition and inducible nitric oxide synthase (INOS) inhibition, have not.

Much of this progress has been by trial and error through clinical studies in which efficacy has or has not been seen. Despite the progress in mapping the release of CGRP and its activity, Dr. Goadsby acknowledged that there is still much about its participation in migraine pathophysiology that remains poorly defined.

“Anyone who tells you that they know how CGRP works I think is blowing smoke, frankly,” Dr. Goadsby said. “Clearly these things are complex.”
 

CGRP is active in the CSF

This includes the site of action. Dr. Goadsby said that it is widely believed that CGRP inhibitors are active in the dura and not in the cerebrospinal fluid (CSF). However, Dr. Goadsby said that a study undertaken with monoclonal antibodies targeting CGRP have produced compelling evidence that CGRP is reduced in the CSF.

“They clearly get into the CSF,” said Dr. Goadsby, noting that the barrier between peripheral blood and the CSF “is different from the blood-brain barrier.”

Widely regarded as playing a pivotal role in the development of CGRP as a therapeutic target in migraine, Dr. Goadsby spent some time speculating about its potential for preventing the earliest steps in the process that leads from the premonitory state to allodynia, prodromal symptoms, migraine, and postdromal recovery.

Of triggers, “light is my favorite example,” he said. He noted that many patients are convinced that light initiates the subsequent steps that end in a migraine. This is fair assumption for those who have seen a sequence of events in which light in the absence of any other symptom always precedes prodromal symptoms and migraine.

“Why would you not think that?” he asked. “Unless you point out that the attack had already started and the reason that you are noticing the light is because of photophobia that started during the premonitory phase.”

It is increasingly clear that CGRP inhibition does have clinical benefit when started at early signs of a coming migraine, according to Dr. Goadsby. He cited a phase 3 study published just days before he spoke at the Scottsdale Headache Symposium. Called PRODROME, the study associated the CGRP receptor antagonist ubrogepant, which is already approved for treatment of migraine, with a significant reduction in the risk of moderate to severe headache relative to placebo when measured 24 hours after randomization (46% vs. 29%; P < .0001).


 

Brain activity monitoring supports phases

Citing imaging studies in his own laboratory, Todd J. Schwedt, MD, chair of neurology research, Mayo Clinic, Phoenix, substantiated several of the points made by Dr. Goadsby in a separate talk he made on migraine phases. By monitoring brain activity during each phase of migraine, he suggested his data support the role of CGRP in producing an inflammatory response as well as sensitizing the trigeminal cervical system in steps that appear to be important to the pain process.

Mitchel L. Zoler/MDedge News

Dr. Schwedt showed several pieces of evidence suggesting that CGRP is an early mediator even if it is not necessarily the first step in a process for every patient. However, like Dr. Goadsby, Dr. Schwedt also acknowledged that the interplay between events is complex and might differ between patients.

Yet, he says that brain activity on imaging is not the only evidence of the role of CGRP activation early in the process leading toward migraine.

“I am a little biased towards imaging, but it’s not just about imaging,” Dr. Schwedt said.

“If we look at preictal salivary CGRP levels and then follow them into the headache phase, we see the levels increase, but they go back to normal a couple of hours into the attack and then stay normal, presumably, until the patient gets closer to the next attack,” Dr. Schwedt said.

Despite progress there is more to be done to determine why CGRP is released and whether it can be inhibited early to abort migraine before the headache phase, but both Dr. Goadsby and Dr. Schwedt pointed to this as a very early event. This is not to say that others, such as cortical spreading depression, do not have an equally important role in the evolution of migraine, but each expert considers migraine phases to be useful divisions for tracing the sequence of pathogenic events.

The phase of a migraine attack and their corresponding symptoms “can be mapped to altered brain function and release of neuropeptides and neurotransmitters,” Dr. Schwedt said. The implication is that better targets for blocking migraine before it reaches the headache phase might be discovered in these early phases.

Dr. Goadsby and Dr. Schwedt listed more than 10 pharmaceutical companies to which they have financial relationships, but both claimed that none of these relationships posed a potential conflict of interest.

Key clinical point: This real-world study confirms the efficacy and safety of erenumab in patients with migraine associated with extreme unmet needs.

Major finding: Overall, 52.9%, 58.5%, 57.0%, and 58.8% of patients receiving erenumab achieved ≥50% reduction in monthly migraine days at 3, 6, 9, and 12 months, respectively, with significant reductions in the proportion of patients with chronic migraine at all time points compared with baseline (P < .001). At month 3, 57.3% of patients changed from chronic migraine to episodic migraine. No treatment-related serious adverse events were reported.

Study details: Findings are from a 1-year prospective, real-word study including 140 patients with migraine and previous migraine preventive treatment failures who received ≥1 dose of erenumab.

Disclosures: This study did not receive funding from any source. Several authors declared receiving personal fees for consultancy activities or research support from various sources, and some authors declared no conflicts of interest.

Source: Lanteri-Minet M et al. One-year prospective real-world assessment of effectiveness and safety of erenumab in migraine prevention: Results of the French FHU INOVPAIN registry study. J Headache Pain. 2023;24:152 (Nov 8). doi: 10.1186/s10194-023-01680-4

Key clinical point: This real-world study confirms the efficacy and safety of erenumab in patients with migraine associated with extreme unmet needs.

Major finding: Overall, 52.9%, 58.5%, 57.0%, and 58.8% of patients receiving erenumab achieved ≥50% reduction in monthly migraine days at 3, 6, 9, and 12 months, respectively, with significant reductions in the proportion of patients with chronic migraine at all time points compared with baseline (P < .001). At month 3, 57.3% of patients changed from chronic migraine to episodic migraine. No treatment-related serious adverse events were reported.

Study details: Findings are from a 1-year prospective, real-word study including 140 patients with migraine and previous migraine preventive treatment failures who received ≥1 dose of erenumab.

Disclosures: This study did not receive funding from any source. Several authors declared receiving personal fees for consultancy activities or research support from various sources, and some authors declared no conflicts of interest.

Source: Lanteri-Minet M et al. One-year prospective real-world assessment of effectiveness and safety of erenumab in migraine prevention: Results of the French FHU INOVPAIN registry study. J Headache Pain. 2023;24:152 (Nov 8). doi: 10.1186/s10194-023-01680-4

Key clinical point: This real-world study confirms the efficacy and safety of erenumab in patients with migraine associated with extreme unmet needs.

Major finding: Overall, 52.9%, 58.5%, 57.0%, and 58.8% of patients receiving erenumab achieved ≥50% reduction in monthly migraine days at 3, 6, 9, and 12 months, respectively, with significant reductions in the proportion of patients with chronic migraine at all time points compared with baseline (P < .001). At month 3, 57.3% of patients changed from chronic migraine to episodic migraine. No treatment-related serious adverse events were reported.

Study details: Findings are from a 1-year prospective, real-word study including 140 patients with migraine and previous migraine preventive treatment failures who received ≥1 dose of erenumab.

Disclosures: This study did not receive funding from any source. Several authors declared receiving personal fees for consultancy activities or research support from various sources, and some authors declared no conflicts of interest.

Source: Lanteri-Minet M et al. One-year prospective real-world assessment of effectiveness and safety of erenumab in migraine prevention: Results of the French FHU INOVPAIN registry study. J Headache Pain. 2023;24:152 (Nov 8). doi: 10.1186/s10194-023-01680-4

Key clinical point: Heavy secondhand smoke (SHS) exposure was positively associated with a higher risk for severe headaches or migraine in adults who never smoked.

Major finding: Heavy SHS exposure (serum cotinine level 1-10 ng/mL) was positively associated with severe headaches or migraine (adjusted odds ratio 2.02; P = .011). No significant association was observed between low SHS exposure (serum cotinine level 0.05-0.99 ng/mL) and headaches or migraine (P = .226).

Study details: This nationwide cross-sectional study included 4560 adults who had never smoked, of which 20% had severe headaches or migraine.

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

Source: Wu J, Yang P, et al. Association between secondhand smoke exposure and severe headaches or migraine in never-smoking adults. Headache. 2023 (Nov 8). doi: 10.1111/head.14640

Key clinical point: Heavy secondhand smoke (SHS) exposure was positively associated with a higher risk for severe headaches or migraine in adults who never smoked.

Major finding: Heavy SHS exposure (serum cotinine level 1-10 ng/mL) was positively associated with severe headaches or migraine (adjusted odds ratio 2.02; P = .011). No significant association was observed between low SHS exposure (serum cotinine level 0.05-0.99 ng/mL) and headaches or migraine (P = .226).

Study details: This nationwide cross-sectional study included 4560 adults who had never smoked, of which 20% had severe headaches or migraine.

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

Source: Wu J, Yang P, et al. Association between secondhand smoke exposure and severe headaches or migraine in never-smoking adults. Headache. 2023 (Nov 8). doi: 10.1111/head.14640

Key clinical point: Heavy secondhand smoke (SHS) exposure was positively associated with a higher risk for severe headaches or migraine in adults who never smoked.

Major finding: Heavy SHS exposure (serum cotinine level 1-10 ng/mL) was positively associated with severe headaches or migraine (adjusted odds ratio 2.02; P = .011). No significant association was observed between low SHS exposure (serum cotinine level 0.05-0.99 ng/mL) and headaches or migraine (P = .226).

Study details: This nationwide cross-sectional study included 4560 adults who had never smoked, of which 20% had severe headaches or migraine.

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

Source: Wu J, Yang P, et al. Association between secondhand smoke exposure and severe headaches or migraine in never-smoking adults. Headache. 2023 (Nov 8). doi: 10.1111/head.14640