Headache & Migraine

Key clinical point: A higher proportion of patients with episodic migraine (EM), chronic migraine (CM), or treatment-resistant migraine receiving galcanezumab vs placebo achieved a ≥50% response within the first 3 months of treatment, which was sustained for 4-6 months.

Major finding: Galcanezumab vs placebo was associated with higher odds of clinical response in patients with EM (120 mg galcanezumab: odds ratio [OR] 2.7) and CM (120 mg galcanezumab: OR 19.4; all P < .001), with a higher proportion of galcanezumab- vs placebo-treated patients maintaining ≥50% response for 3-6 months of the double-blind treatment period (P < .001).

Study details: This post hoc analysis included 3348 patients with EM (EVOLVE-1 and EVOLVE-2 trials), CM (REGAIN trial), or EM or CM with 2-4 prior treatment failures (CONQUER trial) who received galcanezumab or placebo.

Disclosures: This study was funded by Eli Lilly and Company or one of its subsidiaries, Indianapolis, IN, USA. Three authors declared being employees of Eli Lilly. SJ Tepper declared ties with various sources, including Eli Lilly.

Source: Tepper SJ et al. Sustained response of galcanezumab in migraine prevention: Patient-level data from a post hoc analysis in patients with episodic or chronic migraine. Headache. 2023 (May 3). doi: 10.1111/head.14494

Key clinical point: A higher proportion of patients with episodic migraine (EM), chronic migraine (CM), or treatment-resistant migraine receiving galcanezumab vs placebo achieved a ≥50% response within the first 3 months of treatment, which was sustained for 4-6 months.

Major finding: Galcanezumab vs placebo was associated with higher odds of clinical response in patients with EM (120 mg galcanezumab: odds ratio [OR] 2.7) and CM (120 mg galcanezumab: OR 19.4; all P < .001), with a higher proportion of galcanezumab- vs placebo-treated patients maintaining ≥50% response for 3-6 months of the double-blind treatment period (P < .001).

Study details: This post hoc analysis included 3348 patients with EM (EVOLVE-1 and EVOLVE-2 trials), CM (REGAIN trial), or EM or CM with 2-4 prior treatment failures (CONQUER trial) who received galcanezumab or placebo.

Disclosures: This study was funded by Eli Lilly and Company or one of its subsidiaries, Indianapolis, IN, USA. Three authors declared being employees of Eli Lilly. SJ Tepper declared ties with various sources, including Eli Lilly.

Source: Tepper SJ et al. Sustained response of galcanezumab in migraine prevention: Patient-level data from a post hoc analysis in patients with episodic or chronic migraine. Headache. 2023 (May 3). doi: 10.1111/head.14494

Key clinical point: A higher proportion of patients with episodic migraine (EM), chronic migraine (CM), or treatment-resistant migraine receiving galcanezumab vs placebo achieved a ≥50% response within the first 3 months of treatment, which was sustained for 4-6 months.

Major finding: Galcanezumab vs placebo was associated with higher odds of clinical response in patients with EM (120 mg galcanezumab: odds ratio [OR] 2.7) and CM (120 mg galcanezumab: OR 19.4; all P < .001), with a higher proportion of galcanezumab- vs placebo-treated patients maintaining ≥50% response for 3-6 months of the double-blind treatment period (P < .001).

Study details: This post hoc analysis included 3348 patients with EM (EVOLVE-1 and EVOLVE-2 trials), CM (REGAIN trial), or EM or CM with 2-4 prior treatment failures (CONQUER trial) who received galcanezumab or placebo.

Disclosures: This study was funded by Eli Lilly and Company or one of its subsidiaries, Indianapolis, IN, USA. Three authors declared being employees of Eli Lilly. SJ Tepper declared ties with various sources, including Eli Lilly.

Source: Tepper SJ et al. Sustained response of galcanezumab in migraine prevention: Patient-level data from a post hoc analysis in patients with episodic or chronic migraine. Headache. 2023 (May 3). doi: 10.1111/head.14494

Key clinical point: Eptinezumab led to significantly greater reductions in monthly migraine days (MMD) in patients with migraine who previously failed multiple migraine preventive treatments.

Major finding: Reduction in monthly migraine days over 1-12 weeks was significantly higher with 100 mg eptinezumab (−4.8 days) and 300 mg eptinezumab (−5.3 days) vs placebo (−2.1 days; both P < .0001), with reductions sustained or improved over 13-24 weeks and the odds of achieving ≥50% and ≥75% reduction in MMD favoring eptinezumab over placebo (P < .05).

Study details: This subgroup analysis of the DELIVER trial included 299, 293, and 298 patients with migraine and multiple unsuccessful treatments who were randomly assigned to receive 100 mg eptinezumab, 300 mg eptinezumab, and placebo, respectively.

Disclosures: This study was funded by H. Lundbeck A/S. Some authors declared receiving personal fees or honoraria or serving as consultants or on advisory board for various sources. The other authors declared being full-time employees of H. Lundbeck A/S or one of its subsidiary companies.

Source: Ashina M et al. Efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures: Subgroup analysis of the randomized, placebo-controlled DELIVER study. Cephalalgia. 2023 (Apr 26). doi: 10.1177/03331024231170807

Key clinical point: Eptinezumab led to significantly greater reductions in monthly migraine days (MMD) in patients with migraine who previously failed multiple migraine preventive treatments.

Major finding: Reduction in monthly migraine days over 1-12 weeks was significantly higher with 100 mg eptinezumab (−4.8 days) and 300 mg eptinezumab (−5.3 days) vs placebo (−2.1 days; both P < .0001), with reductions sustained or improved over 13-24 weeks and the odds of achieving ≥50% and ≥75% reduction in MMD favoring eptinezumab over placebo (P < .05).

Study details: This subgroup analysis of the DELIVER trial included 299, 293, and 298 patients with migraine and multiple unsuccessful treatments who were randomly assigned to receive 100 mg eptinezumab, 300 mg eptinezumab, and placebo, respectively.

Disclosures: This study was funded by H. Lundbeck A/S. Some authors declared receiving personal fees or honoraria or serving as consultants or on advisory board for various sources. The other authors declared being full-time employees of H. Lundbeck A/S or one of its subsidiary companies.

Source: Ashina M et al. Efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures: Subgroup analysis of the randomized, placebo-controlled DELIVER study. Cephalalgia. 2023 (Apr 26). doi: 10.1177/03331024231170807

Key clinical point: Eptinezumab led to significantly greater reductions in monthly migraine days (MMD) in patients with migraine who previously failed multiple migraine preventive treatments.

Major finding: Reduction in monthly migraine days over 1-12 weeks was significantly higher with 100 mg eptinezumab (−4.8 days) and 300 mg eptinezumab (−5.3 days) vs placebo (−2.1 days; both P < .0001), with reductions sustained or improved over 13-24 weeks and the odds of achieving ≥50% and ≥75% reduction in MMD favoring eptinezumab over placebo (P < .05).

Study details: This subgroup analysis of the DELIVER trial included 299, 293, and 298 patients with migraine and multiple unsuccessful treatments who were randomly assigned to receive 100 mg eptinezumab, 300 mg eptinezumab, and placebo, respectively.

Disclosures: This study was funded by H. Lundbeck A/S. Some authors declared receiving personal fees or honoraria or serving as consultants or on advisory board for various sources. The other authors declared being full-time employees of H. Lundbeck A/S or one of its subsidiary companies.

Source: Ashina M et al. Efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures: Subgroup analysis of the randomized, placebo-controlled DELIVER study. Cephalalgia. 2023 (Apr 26). doi: 10.1177/03331024231170807

Key clinical point: Half of the patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) who did not respond to anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) at 12 weeks were indeed late responders, suggesting the need for extension of treatment duration beyond 12 months.

Major finding: At 12 weeks, 34.4% were nonresponders, of which 55.1% showed response between 13 and 24 weeks and were classified as late responders. Compared with responders, late responders had a higher body mass index (P = .024), more frequent prior treatment failures (P = .017), and psychiatric comorbidities (P = .041).

Study details: This was a prospective, real-life study including 771 patients with HFEM or CM who received anti-CGRP mAb for ≥24 weeks.

Disclosures: This study was partially supported by the Italian Ministry of Health, IRCCS San Raffaele Roma, and Fondazione Italiana Cefalee. Some authors declared receiving travel grants or honoraria for advisory board participations or serving on speaker panels or clinical investigation studies for various sources.

Source: Barbanti P et al for the Italian Migraine Registry study group. Late response to anti-CGRP monoclonal antibodies in migraine: A multicenter, prospective, observational study. Neurology. 2023 (Apr 18). doi: 10.1212/WNL.0000000000207292

Key clinical point: Half of the patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) who did not respond to anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) at 12 weeks were indeed late responders, suggesting the need for extension of treatment duration beyond 12 months.

Major finding: At 12 weeks, 34.4% were nonresponders, of which 55.1% showed response between 13 and 24 weeks and were classified as late responders. Compared with responders, late responders had a higher body mass index (P = .024), more frequent prior treatment failures (P = .017), and psychiatric comorbidities (P = .041).

Study details: This was a prospective, real-life study including 771 patients with HFEM or CM who received anti-CGRP mAb for ≥24 weeks.

Disclosures: This study was partially supported by the Italian Ministry of Health, IRCCS San Raffaele Roma, and Fondazione Italiana Cefalee. Some authors declared receiving travel grants or honoraria for advisory board participations or serving on speaker panels or clinical investigation studies for various sources.

Source: Barbanti P et al for the Italian Migraine Registry study group. Late response to anti-CGRP monoclonal antibodies in migraine: A multicenter, prospective, observational study. Neurology. 2023 (Apr 18). doi: 10.1212/WNL.0000000000207292

Key clinical point: Half of the patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) who did not respond to anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) at 12 weeks were indeed late responders, suggesting the need for extension of treatment duration beyond 12 months.

Major finding: At 12 weeks, 34.4% were nonresponders, of which 55.1% showed response between 13 and 24 weeks and were classified as late responders. Compared with responders, late responders had a higher body mass index (P = .024), more frequent prior treatment failures (P = .017), and psychiatric comorbidities (P = .041).

Study details: This was a prospective, real-life study including 771 patients with HFEM or CM who received anti-CGRP mAb for ≥24 weeks.

Disclosures: This study was partially supported by the Italian Ministry of Health, IRCCS San Raffaele Roma, and Fondazione Italiana Cefalee. Some authors declared receiving travel grants or honoraria for advisory board participations or serving on speaker panels or clinical investigation studies for various sources.

Source: Barbanti P et al for the Italian Migraine Registry study group. Late response to anti-CGRP monoclonal antibodies in migraine: A multicenter, prospective, observational study. Neurology. 2023 (Apr 18). doi: 10.1212/WNL.0000000000207292

The theme of this month's round-up is women's health, specifically as it relates to migraine. Three recent studies have highlighted the connection between estrogen and migraine, in terms of the potential increase in risk for certain conditions, such as gestational hypertension and endometriosis, and the use of potential therapies, such as calcitonin gene-related peptide (CGRP) antagonist medications to treat menstrual migraine.

Although most practitioners know that there is a deep connection between vascular risk and migraine, most are unfamiliar with the specific interplay between these two conditions. Antihypertensive medications are common preventive treatments for migraine, and migraine itself has been associated with an increased risk for specific vascular issues in pregnancy, most notably venous sinus thrombosis. Crowe and colleagues specifically looked at whether women with migraine experience a higher risk for hypertensive disorders of pregnancy.

This was a UK-based prospective cohort study using a large longitudinal database called the Clinical Practice Research Datalink. Over 1 million live-born or stillborn deliveries were analyzed from 1993 through 2020. The data were linked to diagnosis and prescription codes for migraine that were filled or documented before 20 weeks of gestation and compared with diagnosis codes for hypertensive disorders that occurred from week 20 through the pregnancy and delivery. Regression models were then used to estimate risk ratios and CI. Only single pregnancies were counted because multiple pregnancies already are associated with a higher risk for most other vascular conditions.

Any history of migraine prior to pregnancy was associated with an increased risk for gestational hypertension, eclampsia, and preeclampsia (relative risk 1.17). The greatest risk was higher frequency. Migraine that persisted into the first trimester led to a relative risk of 1.84. The use of migraine medications, especially vasoconstrictive-type medications, was also associated with a higher risk compared with women without migraine.

Women with migraine frequently present before family planning to discuss the potential risks and options of migraine treatment during pregnancy. In addition to discussing the most appropriate preventive and acute medications, it would be appropriate also to discuss any potential red flag symptoms that may occur during pregnancy. This discussion should include hypertensive disorders of pregnancy as per this study.

Since the advent of CGRP antagonist treatments for migraine, many practitioners and patients have been curious to know whether specific features of migraine are better treated with this class of medication. There are now both acute and preventive CGRP antagonists, both as small molecule agents and monoclonal antibodies (mAb). Menstrual migraines specifically can be a more difficult-to-treat subtype, and often when other triggers are negated, hormonal fluctuation can still be a significant problem for many patients. Verhagen and colleagues set out to determine whether CGRP mAb are more or less effective for menstrually associated migraine.

This analysis was post hoc, using data from a single-arm study investigating the efficacy of two of the CGRP mAb medications: erenumab and fremanezumab. Patients were included if they had a history of migraine with > 8 monthly migraine days and at least one antihypertensive or antiepileptic preventive treatment for migraine had previously failed. Any other prophylactic medications were tapered before starting this trial; patients were given a validated electronic diary, and adherence to this diary had to be > 80%. Women were also excluded if they did not have regular menses (for instance, if they were on continuous hormonal contraception) or they were postmenopausal. Logistic regression was used to compare the preventive effect of these medications on perimenstrual and non-perimenstrual migraine attacks.

A total of 45 women were included in this observation. The relative reduction in total monthly migraine days was 31.4%; 28% were noted during and around menses, 32% were during other times of the menstrual cycle. Sensitivity analysis showed no significant difference between these two periods of time, and the ratio remained statistically similar as well.

It appears that the relative reduction in monthly migraine days did not fluctuate when the patient was treated with a CGRP antagonist mAb. Although other classes of preventive medication, specifically onabotulinumtoxinA (Botox), may affect menstrually associated migraine less potently, it appears that the CGRP antagonist class may be just as effective regardless of the underlying migraine trigger. It would definitely be worth considering a CGRP antagonist trial, or the addition of a CGRP mAb, if menstrual migraine remains significant despite otherwise effective preventive treatment.

Migraine is strongly affected by fluctuations in estrogen, and women with endometriosis often experience headaches associated with their severe attacks. Pasquini and colleagues specifically looked to see if the headache associated with endometriosis could be better diagnosed. Specifically, were these women experiencing migraine or another headache disorder?

This was a consecutive case-control series of 131 women admitted to a specialty endometriosis clinic. They were given a validated headache questionnaire that was reviewed by a neurologist to determine a diagnosis of migraine vs a diagnosis of another headache disorder. The case group included women with a history of endometriosis who were previously diagnosed with migraine, while the control group consisted of women with endometriosis only who did not have a history of headache.

Diagnosis of migraine was made in 53.4% of all patients: 18.6% of those experienced pure menstrual migraine (defined as migraine only occurring perimenstrually), 46% had some menstrually associated migraine symptoms, and 36% had purely non-menstrual migraine. Painful periods and dysuria were more frequent in patients with endometriosis and migraine compared with those without migraine. Other menstrually related conditions, including the duration of endometriosis, the phenotype of endometriosis, the presence of other systemic comorbidities, or heavy menstrual bleeding did not seem to differ significantly between the migraine and non-migraine groups.

Women of reproductive age consistently are seen most often for migraine and other headache conditions. Much of this is related to menstrual migraine and the effect that hormonal fluctuation has on migraine frequency and severity. Most practitioners work closely with their patient's gynecologist to determine which hormonal treatments and migraine treatments are most appropriate and safe for each individual situation. This study in particular sheds light on the particular phenotypes of headache pain and the specific headache diagnosis that most women with endometriosis experience.

The theme of this month's round-up is women's health, specifically as it relates to migraine. Three recent studies have highlighted the connection between estrogen and migraine, in terms of the potential increase in risk for certain conditions, such as gestational hypertension and endometriosis, and the use of potential therapies, such as calcitonin gene-related peptide (CGRP) antagonist medications to treat menstrual migraine.

Although most practitioners know that there is a deep connection between vascular risk and migraine, most are unfamiliar with the specific interplay between these two conditions. Antihypertensive medications are common preventive treatments for migraine, and migraine itself has been associated with an increased risk for specific vascular issues in pregnancy, most notably venous sinus thrombosis. Crowe and colleagues specifically looked at whether women with migraine experience a higher risk for hypertensive disorders of pregnancy.

This was a UK-based prospective cohort study using a large longitudinal database called the Clinical Practice Research Datalink. Over 1 million live-born or stillborn deliveries were analyzed from 1993 through 2020. The data were linked to diagnosis and prescription codes for migraine that were filled or documented before 20 weeks of gestation and compared with diagnosis codes for hypertensive disorders that occurred from week 20 through the pregnancy and delivery. Regression models were then used to estimate risk ratios and CI. Only single pregnancies were counted because multiple pregnancies already are associated with a higher risk for most other vascular conditions.

Any history of migraine prior to pregnancy was associated with an increased risk for gestational hypertension, eclampsia, and preeclampsia (relative risk 1.17). The greatest risk was higher frequency. Migraine that persisted into the first trimester led to a relative risk of 1.84. The use of migraine medications, especially vasoconstrictive-type medications, was also associated with a higher risk compared with women without migraine.

Women with migraine frequently present before family planning to discuss the potential risks and options of migraine treatment during pregnancy. In addition to discussing the most appropriate preventive and acute medications, it would be appropriate also to discuss any potential red flag symptoms that may occur during pregnancy. This discussion should include hypertensive disorders of pregnancy as per this study.

Since the advent of CGRP antagonist treatments for migraine, many practitioners and patients have been curious to know whether specific features of migraine are better treated with this class of medication. There are now both acute and preventive CGRP antagonists, both as small molecule agents and monoclonal antibodies (mAb). Menstrual migraines specifically can be a more difficult-to-treat subtype, and often when other triggers are negated, hormonal fluctuation can still be a significant problem for many patients. Verhagen and colleagues set out to determine whether CGRP mAb are more or less effective for menstrually associated migraine.

This analysis was post hoc, using data from a single-arm study investigating the efficacy of two of the CGRP mAb medications: erenumab and fremanezumab. Patients were included if they had a history of migraine with > 8 monthly migraine days and at least one antihypertensive or antiepileptic preventive treatment for migraine had previously failed. Any other prophylactic medications were tapered before starting this trial; patients were given a validated electronic diary, and adherence to this diary had to be > 80%. Women were also excluded if they did not have regular menses (for instance, if they were on continuous hormonal contraception) or they were postmenopausal. Logistic regression was used to compare the preventive effect of these medications on perimenstrual and non-perimenstrual migraine attacks.

A total of 45 women were included in this observation. The relative reduction in total monthly migraine days was 31.4%; 28% were noted during and around menses, 32% were during other times of the menstrual cycle. Sensitivity analysis showed no significant difference between these two periods of time, and the ratio remained statistically similar as well.

It appears that the relative reduction in monthly migraine days did not fluctuate when the patient was treated with a CGRP antagonist mAb. Although other classes of preventive medication, specifically onabotulinumtoxinA (Botox), may affect menstrually associated migraine less potently, it appears that the CGRP antagonist class may be just as effective regardless of the underlying migraine trigger. It would definitely be worth considering a CGRP antagonist trial, or the addition of a CGRP mAb, if menstrual migraine remains significant despite otherwise effective preventive treatment.

Migraine is strongly affected by fluctuations in estrogen, and women with endometriosis often experience headaches associated with their severe attacks. Pasquini and colleagues specifically looked to see if the headache associated with endometriosis could be better diagnosed. Specifically, were these women experiencing migraine or another headache disorder?

This was a consecutive case-control series of 131 women admitted to a specialty endometriosis clinic. They were given a validated headache questionnaire that was reviewed by a neurologist to determine a diagnosis of migraine vs a diagnosis of another headache disorder. The case group included women with a history of endometriosis who were previously diagnosed with migraine, while the control group consisted of women with endometriosis only who did not have a history of headache.

Diagnosis of migraine was made in 53.4% of all patients: 18.6% of those experienced pure menstrual migraine (defined as migraine only occurring perimenstrually), 46% had some menstrually associated migraine symptoms, and 36% had purely non-menstrual migraine. Painful periods and dysuria were more frequent in patients with endometriosis and migraine compared with those without migraine. Other menstrually related conditions, including the duration of endometriosis, the phenotype of endometriosis, the presence of other systemic comorbidities, or heavy menstrual bleeding did not seem to differ significantly between the migraine and non-migraine groups.

Women of reproductive age consistently are seen most often for migraine and other headache conditions. Much of this is related to menstrual migraine and the effect that hormonal fluctuation has on migraine frequency and severity. Most practitioners work closely with their patient's gynecologist to determine which hormonal treatments and migraine treatments are most appropriate and safe for each individual situation. This study in particular sheds light on the particular phenotypes of headache pain and the specific headache diagnosis that most women with endometriosis experience.

The theme of this month's round-up is women's health, specifically as it relates to migraine. Three recent studies have highlighted the connection between estrogen and migraine, in terms of the potential increase in risk for certain conditions, such as gestational hypertension and endometriosis, and the use of potential therapies, such as calcitonin gene-related peptide (CGRP) antagonist medications to treat menstrual migraine.

Although most practitioners know that there is a deep connection between vascular risk and migraine, most are unfamiliar with the specific interplay between these two conditions. Antihypertensive medications are common preventive treatments for migraine, and migraine itself has been associated with an increased risk for specific vascular issues in pregnancy, most notably venous sinus thrombosis. Crowe and colleagues specifically looked at whether women with migraine experience a higher risk for hypertensive disorders of pregnancy.

This was a UK-based prospective cohort study using a large longitudinal database called the Clinical Practice Research Datalink. Over 1 million live-born or stillborn deliveries were analyzed from 1993 through 2020. The data were linked to diagnosis and prescription codes for migraine that were filled or documented before 20 weeks of gestation and compared with diagnosis codes for hypertensive disorders that occurred from week 20 through the pregnancy and delivery. Regression models were then used to estimate risk ratios and CI. Only single pregnancies were counted because multiple pregnancies already are associated with a higher risk for most other vascular conditions.

Any history of migraine prior to pregnancy was associated with an increased risk for gestational hypertension, eclampsia, and preeclampsia (relative risk 1.17). The greatest risk was higher frequency. Migraine that persisted into the first trimester led to a relative risk of 1.84. The use of migraine medications, especially vasoconstrictive-type medications, was also associated with a higher risk compared with women without migraine.

Women with migraine frequently present before family planning to discuss the potential risks and options of migraine treatment during pregnancy. In addition to discussing the most appropriate preventive and acute medications, it would be appropriate also to discuss any potential red flag symptoms that may occur during pregnancy. This discussion should include hypertensive disorders of pregnancy as per this study.

Since the advent of CGRP antagonist treatments for migraine, many practitioners and patients have been curious to know whether specific features of migraine are better treated with this class of medication. There are now both acute and preventive CGRP antagonists, both as small molecule agents and monoclonal antibodies (mAb). Menstrual migraines specifically can be a more difficult-to-treat subtype, and often when other triggers are negated, hormonal fluctuation can still be a significant problem for many patients. Verhagen and colleagues set out to determine whether CGRP mAb are more or less effective for menstrually associated migraine.

This analysis was post hoc, using data from a single-arm study investigating the efficacy of two of the CGRP mAb medications: erenumab and fremanezumab. Patients were included if they had a history of migraine with > 8 monthly migraine days and at least one antihypertensive or antiepileptic preventive treatment for migraine had previously failed. Any other prophylactic medications were tapered before starting this trial; patients were given a validated electronic diary, and adherence to this diary had to be > 80%. Women were also excluded if they did not have regular menses (for instance, if they were on continuous hormonal contraception) or they were postmenopausal. Logistic regression was used to compare the preventive effect of these medications on perimenstrual and non-perimenstrual migraine attacks.

A total of 45 women were included in this observation. The relative reduction in total monthly migraine days was 31.4%; 28% were noted during and around menses, 32% were during other times of the menstrual cycle. Sensitivity analysis showed no significant difference between these two periods of time, and the ratio remained statistically similar as well.

It appears that the relative reduction in monthly migraine days did not fluctuate when the patient was treated with a CGRP antagonist mAb. Although other classes of preventive medication, specifically onabotulinumtoxinA (Botox), may affect menstrually associated migraine less potently, it appears that the CGRP antagonist class may be just as effective regardless of the underlying migraine trigger. It would definitely be worth considering a CGRP antagonist trial, or the addition of a CGRP mAb, if menstrual migraine remains significant despite otherwise effective preventive treatment.

Migraine is strongly affected by fluctuations in estrogen, and women with endometriosis often experience headaches associated with their severe attacks. Pasquini and colleagues specifically looked to see if the headache associated with endometriosis could be better diagnosed. Specifically, were these women experiencing migraine or another headache disorder?

This was a consecutive case-control series of 131 women admitted to a specialty endometriosis clinic. They were given a validated headache questionnaire that was reviewed by a neurologist to determine a diagnosis of migraine vs a diagnosis of another headache disorder. The case group included women with a history of endometriosis who were previously diagnosed with migraine, while the control group consisted of women with endometriosis only who did not have a history of headache.

Diagnosis of migraine was made in 53.4% of all patients: 18.6% of those experienced pure menstrual migraine (defined as migraine only occurring perimenstrually), 46% had some menstrually associated migraine symptoms, and 36% had purely non-menstrual migraine. Painful periods and dysuria were more frequent in patients with endometriosis and migraine compared with those without migraine. Other menstrually related conditions, including the duration of endometriosis, the phenotype of endometriosis, the presence of other systemic comorbidities, or heavy menstrual bleeding did not seem to differ significantly between the migraine and non-migraine groups.

Women of reproductive age consistently are seen most often for migraine and other headache conditions. Much of this is related to menstrual migraine and the effect that hormonal fluctuation has on migraine frequency and severity. Most practitioners work closely with their patient's gynecologist to determine which hormonal treatments and migraine treatments are most appropriate and safe for each individual situation. This study in particular sheds light on the particular phenotypes of headache pain and the specific headache diagnosis that most women with endometriosis experience.

BOSTON – When it comes to relieving migraine, triptans, ergots, and antiemetics are the most effective classes of medications, a new real-world analysis of data on more than 3 million migraine attacks shows.

The findings “align with results of clinical trials and recommendations from clinical treatment guidelines” and provide insights to complement clinical practice, said study investigator Chia-Chun Chiang, MD, a neurologist with Mayo Clinic, Rochester, Minn.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
 

The power of big data

Despite a wide variety of acute migraine medications that are available, large-scale, head-to-head comparisons of treatment effectiveness from real-world patient experience reports are lacking, Dr. Chiang explained.

“To the best of our knowledge, this is the first study that simultaneously compared multiple acute migraine medications using a Big Data analysis approach based on real-world patient-provided data,” she said.

The researchers extracted more than 10 million self-reported migraine attack records from a migraine smartphone app called Migraine Buddy, where users can document whether a treatment was helpful, somewhat helpful, unsure, or unhelpful.

They analyzed 25 acute medications among seven classes: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, combination analgesics (acetaminophen/aspirin/caffeine), ergots, antiemetics, and opioids. The newer gepants and ditan medication classes of medications were not included because of the relatively lower numbers of usage when data was extracted (2014-2020).

The researchers employed a two-level nested logistic regression model to analyze the odds of treatment effectiveness of each medication by adjusting concurrent medications and the covariance within the same user.

The final analysis included more than 3.1 million migraine attacks among 278,000 users globally.

Using ibuprofen as the reference, triptans, ergots, and antiemetics had the highest efficacy with mean odds ratios of 4.8, 3.02, and 2.67, respectively, followed by opioids (OR, 2.49), NSAIDs (OR, 1.94), combination analgesics (OR, 1.69), others (OR, 1.49), and acetaminophen (OR, 0.83).

Individual medications with the highest patient-reported effectiveness were eletriptan (Relpax; OR, 6.1), zolmitriptan (Zomig; OR, 5.7) and sumatriptan (Zecuity; OR, 5.2).

This migraine medication comparative effectiveness analysis, based on patient-reported outcomes, “supports and complements the treatment recommendations from national headache societies based on randomized controlled trials and meta-analyses and strongly supports the use of triptans,” Dr. Chiang said.
 

End of trial-and-error?

Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said “This is a great study of Big Data in that it shows the power of the smartphone to collect real-world data and smart researchers like at Mayo Clinic to analyze them.”

“The study sheds light on how different therapeutics compare with each other. The next iteration of this line of research, I would hope, would be to determine if particular medications are effective for a particular migraine population, and even down to individuals with migraine,” said Dr. Lakhan, who wasn’t involved in the study.

“Once those models are appropriately built, long gone will be the era of trial-and-error medicine,” Dr. Lakhan added.

The study had no specific funding. Dr. Chiang has served as a consultant for Satsuma. Dr. Lakhan reports no relevant financial relationships.

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

BOSTON – When it comes to relieving migraine, triptans, ergots, and antiemetics are the most effective classes of medications, a new real-world analysis of data on more than 3 million migraine attacks shows.

The findings “align with results of clinical trials and recommendations from clinical treatment guidelines” and provide insights to complement clinical practice, said study investigator Chia-Chun Chiang, MD, a neurologist with Mayo Clinic, Rochester, Minn.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
 

The power of big data

Despite a wide variety of acute migraine medications that are available, large-scale, head-to-head comparisons of treatment effectiveness from real-world patient experience reports are lacking, Dr. Chiang explained.

“To the best of our knowledge, this is the first study that simultaneously compared multiple acute migraine medications using a Big Data analysis approach based on real-world patient-provided data,” she said.

The researchers extracted more than 10 million self-reported migraine attack records from a migraine smartphone app called Migraine Buddy, where users can document whether a treatment was helpful, somewhat helpful, unsure, or unhelpful.

They analyzed 25 acute medications among seven classes: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, combination analgesics (acetaminophen/aspirin/caffeine), ergots, antiemetics, and opioids. The newer gepants and ditan medication classes of medications were not included because of the relatively lower numbers of usage when data was extracted (2014-2020).

The researchers employed a two-level nested logistic regression model to analyze the odds of treatment effectiveness of each medication by adjusting concurrent medications and the covariance within the same user.

The final analysis included more than 3.1 million migraine attacks among 278,000 users globally.

Using ibuprofen as the reference, triptans, ergots, and antiemetics had the highest efficacy with mean odds ratios of 4.8, 3.02, and 2.67, respectively, followed by opioids (OR, 2.49), NSAIDs (OR, 1.94), combination analgesics (OR, 1.69), others (OR, 1.49), and acetaminophen (OR, 0.83).

Individual medications with the highest patient-reported effectiveness were eletriptan (Relpax; OR, 6.1), zolmitriptan (Zomig; OR, 5.7) and sumatriptan (Zecuity; OR, 5.2).

This migraine medication comparative effectiveness analysis, based on patient-reported outcomes, “supports and complements the treatment recommendations from national headache societies based on randomized controlled trials and meta-analyses and strongly supports the use of triptans,” Dr. Chiang said.
 

End of trial-and-error?

Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said “This is a great study of Big Data in that it shows the power of the smartphone to collect real-world data and smart researchers like at Mayo Clinic to analyze them.”

“The study sheds light on how different therapeutics compare with each other. The next iteration of this line of research, I would hope, would be to determine if particular medications are effective for a particular migraine population, and even down to individuals with migraine,” said Dr. Lakhan, who wasn’t involved in the study.

“Once those models are appropriately built, long gone will be the era of trial-and-error medicine,” Dr. Lakhan added.

The study had no specific funding. Dr. Chiang has served as a consultant for Satsuma. Dr. Lakhan reports no relevant financial relationships.

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

BOSTON – When it comes to relieving migraine, triptans, ergots, and antiemetics are the most effective classes of medications, a new real-world analysis of data on more than 3 million migraine attacks shows.

The findings “align with results of clinical trials and recommendations from clinical treatment guidelines” and provide insights to complement clinical practice, said study investigator Chia-Chun Chiang, MD, a neurologist with Mayo Clinic, Rochester, Minn.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
 

The power of big data

Despite a wide variety of acute migraine medications that are available, large-scale, head-to-head comparisons of treatment effectiveness from real-world patient experience reports are lacking, Dr. Chiang explained.

“To the best of our knowledge, this is the first study that simultaneously compared multiple acute migraine medications using a Big Data analysis approach based on real-world patient-provided data,” she said.

The researchers extracted more than 10 million self-reported migraine attack records from a migraine smartphone app called Migraine Buddy, where users can document whether a treatment was helpful, somewhat helpful, unsure, or unhelpful.

They analyzed 25 acute medications among seven classes: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, combination analgesics (acetaminophen/aspirin/caffeine), ergots, antiemetics, and opioids. The newer gepants and ditan medication classes of medications were not included because of the relatively lower numbers of usage when data was extracted (2014-2020).

The researchers employed a two-level nested logistic regression model to analyze the odds of treatment effectiveness of each medication by adjusting concurrent medications and the covariance within the same user.

The final analysis included more than 3.1 million migraine attacks among 278,000 users globally.

Using ibuprofen as the reference, triptans, ergots, and antiemetics had the highest efficacy with mean odds ratios of 4.8, 3.02, and 2.67, respectively, followed by opioids (OR, 2.49), NSAIDs (OR, 1.94), combination analgesics (OR, 1.69), others (OR, 1.49), and acetaminophen (OR, 0.83).

Individual medications with the highest patient-reported effectiveness were eletriptan (Relpax; OR, 6.1), zolmitriptan (Zomig; OR, 5.7) and sumatriptan (Zecuity; OR, 5.2).

This migraine medication comparative effectiveness analysis, based on patient-reported outcomes, “supports and complements the treatment recommendations from national headache societies based on randomized controlled trials and meta-analyses and strongly supports the use of triptans,” Dr. Chiang said.
 

End of trial-and-error?

Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said “This is a great study of Big Data in that it shows the power of the smartphone to collect real-world data and smart researchers like at Mayo Clinic to analyze them.”

“The study sheds light on how different therapeutics compare with each other. The next iteration of this line of research, I would hope, would be to determine if particular medications are effective for a particular migraine population, and even down to individuals with migraine,” said Dr. Lakhan, who wasn’t involved in the study.

“Once those models are appropriately built, long gone will be the era of trial-and-error medicine,” Dr. Lakhan added.

The study had no specific funding. Dr. Chiang has served as a consultant for Satsuma. Dr. Lakhan reports no relevant financial relationships.

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

The Food and Drug Administration has approved an expanded indication for atogepant (Qulipta, Abbvie) to include prevention of chronic migraine in adults. The approval makes atogepant the first, and only, oral calcitonin gene-related peptide receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic, the company said in a news release.

The FDA initially approved atogepant in 2021 for the prevention of episodic migraine in adults.

Once-daily atogepant is available in three doses – 10 mg, 30 mg, and 60 mg – for prevention of episodic migraine. However, only the 60-mg dose of medication is indicated for the preventive treatment of chronic migraine.

The expanded indication in chronic migraine is based on positive results of the phase 3 PROGRESS trial, which evaluated atogepant in more than 700 adults with chronic migraine.

The trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days with atogepant compared with placebo across the 12-week treatment period.

Treatment with atogepant also led to statistically significant improvements in all six secondary endpoints, including the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across 12 weeks and improvements in function and reduction in activity impairment caused by migraine.

The efficacy results are consistent with those in the ADVANCE episodic migraine trial.

The overall safety profile of atogepant is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.

“The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe, and effective treatment option in a convenient, once-daily pill,” Peter McAllister, MD, director of the New England Center for Neurology and Headache, Stamford, Conn., said in the news release.

The data demonstrate that atogepant “helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine,” Dr. McAllister added.

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

The Food and Drug Administration has approved an expanded indication for atogepant (Qulipta, Abbvie) to include prevention of chronic migraine in adults. The approval makes atogepant the first, and only, oral calcitonin gene-related peptide receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic, the company said in a news release.

The FDA initially approved atogepant in 2021 for the prevention of episodic migraine in adults.

Once-daily atogepant is available in three doses – 10 mg, 30 mg, and 60 mg – for prevention of episodic migraine. However, only the 60-mg dose of medication is indicated for the preventive treatment of chronic migraine.

The expanded indication in chronic migraine is based on positive results of the phase 3 PROGRESS trial, which evaluated atogepant in more than 700 adults with chronic migraine.

The trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days with atogepant compared with placebo across the 12-week treatment period.

Treatment with atogepant also led to statistically significant improvements in all six secondary endpoints, including the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across 12 weeks and improvements in function and reduction in activity impairment caused by migraine.

The efficacy results are consistent with those in the ADVANCE episodic migraine trial.

The overall safety profile of atogepant is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.

“The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe, and effective treatment option in a convenient, once-daily pill,” Peter McAllister, MD, director of the New England Center for Neurology and Headache, Stamford, Conn., said in the news release.

The data demonstrate that atogepant “helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine,” Dr. McAllister added.

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

The Food and Drug Administration has approved an expanded indication for atogepant (Qulipta, Abbvie) to include prevention of chronic migraine in adults. The approval makes atogepant the first, and only, oral calcitonin gene-related peptide receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic, the company said in a news release.

The FDA initially approved atogepant in 2021 for the prevention of episodic migraine in adults.

Once-daily atogepant is available in three doses – 10 mg, 30 mg, and 60 mg – for prevention of episodic migraine. However, only the 60-mg dose of medication is indicated for the preventive treatment of chronic migraine.

The expanded indication in chronic migraine is based on positive results of the phase 3 PROGRESS trial, which evaluated atogepant in more than 700 adults with chronic migraine.

The trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days with atogepant compared with placebo across the 12-week treatment period.

Treatment with atogepant also led to statistically significant improvements in all six secondary endpoints, including the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across 12 weeks and improvements in function and reduction in activity impairment caused by migraine.

The efficacy results are consistent with those in the ADVANCE episodic migraine trial.

The overall safety profile of atogepant is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.

“The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe, and effective treatment option in a convenient, once-daily pill,” Peter McAllister, MD, director of the New England Center for Neurology and Headache, Stamford, Conn., said in the news release.

The data demonstrate that atogepant “helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine,” Dr. McAllister added.

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

BOSTON – Atogepant helped reduce the number of mean migraine days among adults with episodic migraine who failed multiple other oral migraine medications, according to findings from a study presented at the 2023 annual meeting of the American Academy of Neurology.

Initial results from the double-blind ELEVATE trial showed the oral atogepant group had significantly fewer mean monthly migraine days (MMD) compared with a placebo group. There was also a significant difference in the number of participants who achieved 50% or greater reduction in the number of mean MMDs and a significant reduction in acute medication use days compared with the placebo group, according to Patricia Pozo-Rosich, MD, PhD, a headache specialist in the neurology department and director of the headache and craniofacial pain clinical unit and the Migraine Adaptive Brain Center at the Vall d’Hebron University Hospital in Barcelona, and colleagues.

Vall d’Hebron University Hospital

The oral calcitonin gene-related peptide (CGRP) receptor antagonist is currently approved in the United States by the Food and Drug Administration as a preventative for both episodic and chronic migraine.
 

Results from ELEVATE

Overall, ELEVATE’s initial efficacy analysis population consisted of 309 adults aged between 18 and 80 years from North America and Europe with episodic migraine who had 4-14 MMDs and had treatment failure with at least two classes of conventional oral medication. After a 28-day screening period, participants received either 60 mg of oral atogepant once per day (154 participants) or a placebo (155 participants). In the efficacy analysis population, 56.0% of participants had failed two oral migraine preventative medication classes, while 44.0% failed three or more classes of medication. Dr. Pozo-Rosich noted that participants were taking a number of different oral preventatives across different medication classes, including flunarizine, beta blockers, topiramate, and amitriptyline, but data are not yet available on which participants had received certain combinations of oral medications.

“[T]hese people have already taken some type of prevention, so they’re not naive patients,” she said. “They’re usually more or less well treated in the sense of having had a contact with specialists or a general neurologist, someone that actually tries to do some prevention.”

The researchers examined change from MMDs at baseline and at 12 weeks as a primary outcome, with 50% or greater MMD reduction, change in mean monthly headache days, and change in acute medication use days as secondary outcomes. Regarding the different acute medications used, Dr. Pozo-Rosich said the main three types were analgesics, nonsteroid anti-inflammatory drugs, and triptans, with participants excluded from the trial if they were taking opioids.

The results showed participants in the atogepant group had significantly fewer mean MMDs compared with the placebo group at 12 weeks compared with baseline (–4.20 vs. –1.85 days; P < .0001). Researchers also found statistically significant improvement in the atogepant group for 50% or greater reduction in MMD, change in mean monthly headache days, and change in acute medication use days across 12 weeks of treatment compared with the placebo group. While the specific data analyses for secondary outcomes were not conducted in the initial analysis, Dr. Pozo-Rosich said the numbers “correlate with the primary outcome” as seen in other migraine trials.

Compared with the placebo group, participants in the atogepant group had higher rates of constipation (10.3% vs. 2.5%), COVID-19 (9.6% vs. 8.3%), and nausea (7.1% vs. 3.2%), while the placebo group had a higher rate of nasopharyngitis (5.1% vs. 7.6%).*

Migraine is a prevalent and undertreated disease, and patients around the world with migraine are in need of treatment options that are both safe and effective, Dr. Pozo-Rosich said in an interview. “[E]ven in these hard-to-treat or difficult-to-treat migraine patients, you have a drug that works, and is safe, and well tolerated and effective,” she said.

That’s “kind of good news for all of us,” she said. Patients “need this type of good news and solution,” she explained, because they may not tolerate or have access to injectable medications. Atogepant would also give clinicians have another option to offer patients with difficult-to-treat migraine cases, she noted. “It makes life easier for many physicians and many patients for many different reasons,” she said.

Dr. Pozo-Rosich said the likely next step in the research is to conduct the main analysis as well as post hoc analyses with accumulated data from pathology trials “to understand patterns of response, understand the sustainability of the response, [and] adherence to the treatment in the long term.”
 

‘Exciting that it works well’ in difficult-to-treat patients

Commenting on the study, Alan M. Rapoport, MD, clinical professor of neurology at University of California, Los Angeles, and past president of the International Headache Society, agreed that better options in migraine treatment and prevention are needed.

“We needed something that was going to be better than what we had before,” he said.

Dr. Rapoport noted the study was well designed with strongly positive results. “It looks like it’s an effective drug, and it looks really good in that it’s effective for people that have failed all these preventives that have very little hope for the future,” he said.

He specifically praised the inclusion of older participants in the population. “You never see a study on 80-year-olds,” he said, “but I like that, because they felt it would be safe. There are 80-year-old patients – fewer of them than 40-year-old patients – but there are 80-year-old patients who still have migraine, so I’m really glad they put older patients in it,” he said.

For atogepant, he noted that “some patients won’t get the side effects, and some patients will tolerate the side effects because it’s working really well.” While the study was not a head-to-head comparison against other oral migraine preventatives, he pointed out the high rate of constipation among participants in the trial setting may be a warning sign of future issues, as seen with other CGRP receptor agonists.

“I can tell you that with erenumab, the monoclonal antibody that was injected in the double-blind studies, they didn’t find any significant increase in constipation,” he explained. However, some clinicians using erenumab in the real world have reported up to 20% of their patients are constipated. “It’s not good that they’re reporting 10% are constipated” in the study, he said.

Overall, “all you can really say is it does work well,” Dr. Rapoport said. “It’s exciting that it works well in such difficult-to-treat patients, and it does come with some side effects.”

Dr. Pozo-Rosich reports serving as a consultant and developing education materials for AbbVie, Eli Lilly, Novartis, Teva Pharmaceuticals, and Pfizer. Dr. Rapoport is the editor-in-chief of Neurology Reviews; he reports being a consultant for AbbVie, the developer of atogepant. The ELEVATE trial is supported by AbbVie.

*Correction, 5/4/23: An earlier version of this article misstated the percentage of COVID-positive patients in the study population. 

BOSTON – Atogepant helped reduce the number of mean migraine days among adults with episodic migraine who failed multiple other oral migraine medications, according to findings from a study presented at the 2023 annual meeting of the American Academy of Neurology.

Initial results from the double-blind ELEVATE trial showed the oral atogepant group had significantly fewer mean monthly migraine days (MMD) compared with a placebo group. There was also a significant difference in the number of participants who achieved 50% or greater reduction in the number of mean MMDs and a significant reduction in acute medication use days compared with the placebo group, according to Patricia Pozo-Rosich, MD, PhD, a headache specialist in the neurology department and director of the headache and craniofacial pain clinical unit and the Migraine Adaptive Brain Center at the Vall d’Hebron University Hospital in Barcelona, and colleagues.

Vall d’Hebron University Hospital

The oral calcitonin gene-related peptide (CGRP) receptor antagonist is currently approved in the United States by the Food and Drug Administration as a preventative for both episodic and chronic migraine.
 

Results from ELEVATE

Overall, ELEVATE’s initial efficacy analysis population consisted of 309 adults aged between 18 and 80 years from North America and Europe with episodic migraine who had 4-14 MMDs and had treatment failure with at least two classes of conventional oral medication. After a 28-day screening period, participants received either 60 mg of oral atogepant once per day (154 participants) or a placebo (155 participants). In the efficacy analysis population, 56.0% of participants had failed two oral migraine preventative medication classes, while 44.0% failed three or more classes of medication. Dr. Pozo-Rosich noted that participants were taking a number of different oral preventatives across different medication classes, including flunarizine, beta blockers, topiramate, and amitriptyline, but data are not yet available on which participants had received certain combinations of oral medications.

“[T]hese people have already taken some type of prevention, so they’re not naive patients,” she said. “They’re usually more or less well treated in the sense of having had a contact with specialists or a general neurologist, someone that actually tries to do some prevention.”

The researchers examined change from MMDs at baseline and at 12 weeks as a primary outcome, with 50% or greater MMD reduction, change in mean monthly headache days, and change in acute medication use days as secondary outcomes. Regarding the different acute medications used, Dr. Pozo-Rosich said the main three types were analgesics, nonsteroid anti-inflammatory drugs, and triptans, with participants excluded from the trial if they were taking opioids.

The results showed participants in the atogepant group had significantly fewer mean MMDs compared with the placebo group at 12 weeks compared with baseline (–4.20 vs. –1.85 days; P < .0001). Researchers also found statistically significant improvement in the atogepant group for 50% or greater reduction in MMD, change in mean monthly headache days, and change in acute medication use days across 12 weeks of treatment compared with the placebo group. While the specific data analyses for secondary outcomes were not conducted in the initial analysis, Dr. Pozo-Rosich said the numbers “correlate with the primary outcome” as seen in other migraine trials.

Compared with the placebo group, participants in the atogepant group had higher rates of constipation (10.3% vs. 2.5%), COVID-19 (9.6% vs. 8.3%), and nausea (7.1% vs. 3.2%), while the placebo group had a higher rate of nasopharyngitis (5.1% vs. 7.6%).*

Migraine is a prevalent and undertreated disease, and patients around the world with migraine are in need of treatment options that are both safe and effective, Dr. Pozo-Rosich said in an interview. “[E]ven in these hard-to-treat or difficult-to-treat migraine patients, you have a drug that works, and is safe, and well tolerated and effective,” she said.

That’s “kind of good news for all of us,” she said. Patients “need this type of good news and solution,” she explained, because they may not tolerate or have access to injectable medications. Atogepant would also give clinicians have another option to offer patients with difficult-to-treat migraine cases, she noted. “It makes life easier for many physicians and many patients for many different reasons,” she said.

Dr. Pozo-Rosich said the likely next step in the research is to conduct the main analysis as well as post hoc analyses with accumulated data from pathology trials “to understand patterns of response, understand the sustainability of the response, [and] adherence to the treatment in the long term.”
 

‘Exciting that it works well’ in difficult-to-treat patients

Commenting on the study, Alan M. Rapoport, MD, clinical professor of neurology at University of California, Los Angeles, and past president of the International Headache Society, agreed that better options in migraine treatment and prevention are needed.

“We needed something that was going to be better than what we had before,” he said.

Dr. Rapoport noted the study was well designed with strongly positive results. “It looks like it’s an effective drug, and it looks really good in that it’s effective for people that have failed all these preventives that have very little hope for the future,” he said.

He specifically praised the inclusion of older participants in the population. “You never see a study on 80-year-olds,” he said, “but I like that, because they felt it would be safe. There are 80-year-old patients – fewer of them than 40-year-old patients – but there are 80-year-old patients who still have migraine, so I’m really glad they put older patients in it,” he said.

For atogepant, he noted that “some patients won’t get the side effects, and some patients will tolerate the side effects because it’s working really well.” While the study was not a head-to-head comparison against other oral migraine preventatives, he pointed out the high rate of constipation among participants in the trial setting may be a warning sign of future issues, as seen with other CGRP receptor agonists.

“I can tell you that with erenumab, the monoclonal antibody that was injected in the double-blind studies, they didn’t find any significant increase in constipation,” he explained. However, some clinicians using erenumab in the real world have reported up to 20% of their patients are constipated. “It’s not good that they’re reporting 10% are constipated” in the study, he said.

Overall, “all you can really say is it does work well,” Dr. Rapoport said. “It’s exciting that it works well in such difficult-to-treat patients, and it does come with some side effects.”

Dr. Pozo-Rosich reports serving as a consultant and developing education materials for AbbVie, Eli Lilly, Novartis, Teva Pharmaceuticals, and Pfizer. Dr. Rapoport is the editor-in-chief of Neurology Reviews; he reports being a consultant for AbbVie, the developer of atogepant. The ELEVATE trial is supported by AbbVie.

*Correction, 5/4/23: An earlier version of this article misstated the percentage of COVID-positive patients in the study population. 

BOSTON – Atogepant helped reduce the number of mean migraine days among adults with episodic migraine who failed multiple other oral migraine medications, according to findings from a study presented at the 2023 annual meeting of the American Academy of Neurology.

Initial results from the double-blind ELEVATE trial showed the oral atogepant group had significantly fewer mean monthly migraine days (MMD) compared with a placebo group. There was also a significant difference in the number of participants who achieved 50% or greater reduction in the number of mean MMDs and a significant reduction in acute medication use days compared with the placebo group, according to Patricia Pozo-Rosich, MD, PhD, a headache specialist in the neurology department and director of the headache and craniofacial pain clinical unit and the Migraine Adaptive Brain Center at the Vall d’Hebron University Hospital in Barcelona, and colleagues.

Vall d’Hebron University Hospital

The oral calcitonin gene-related peptide (CGRP) receptor antagonist is currently approved in the United States by the Food and Drug Administration as a preventative for both episodic and chronic migraine.
 

Results from ELEVATE

Overall, ELEVATE’s initial efficacy analysis population consisted of 309 adults aged between 18 and 80 years from North America and Europe with episodic migraine who had 4-14 MMDs and had treatment failure with at least two classes of conventional oral medication. After a 28-day screening period, participants received either 60 mg of oral atogepant once per day (154 participants) or a placebo (155 participants). In the efficacy analysis population, 56.0% of participants had failed two oral migraine preventative medication classes, while 44.0% failed three or more classes of medication. Dr. Pozo-Rosich noted that participants were taking a number of different oral preventatives across different medication classes, including flunarizine, beta blockers, topiramate, and amitriptyline, but data are not yet available on which participants had received certain combinations of oral medications.

“[T]hese people have already taken some type of prevention, so they’re not naive patients,” she said. “They’re usually more or less well treated in the sense of having had a contact with specialists or a general neurologist, someone that actually tries to do some prevention.”

The researchers examined change from MMDs at baseline and at 12 weeks as a primary outcome, with 50% or greater MMD reduction, change in mean monthly headache days, and change in acute medication use days as secondary outcomes. Regarding the different acute medications used, Dr. Pozo-Rosich said the main three types were analgesics, nonsteroid anti-inflammatory drugs, and triptans, with participants excluded from the trial if they were taking opioids.

The results showed participants in the atogepant group had significantly fewer mean MMDs compared with the placebo group at 12 weeks compared with baseline (–4.20 vs. –1.85 days; P < .0001). Researchers also found statistically significant improvement in the atogepant group for 50% or greater reduction in MMD, change in mean monthly headache days, and change in acute medication use days across 12 weeks of treatment compared with the placebo group. While the specific data analyses for secondary outcomes were not conducted in the initial analysis, Dr. Pozo-Rosich said the numbers “correlate with the primary outcome” as seen in other migraine trials.

Compared with the placebo group, participants in the atogepant group had higher rates of constipation (10.3% vs. 2.5%), COVID-19 (9.6% vs. 8.3%), and nausea (7.1% vs. 3.2%), while the placebo group had a higher rate of nasopharyngitis (5.1% vs. 7.6%).*

Migraine is a prevalent and undertreated disease, and patients around the world with migraine are in need of treatment options that are both safe and effective, Dr. Pozo-Rosich said in an interview. “[E]ven in these hard-to-treat or difficult-to-treat migraine patients, you have a drug that works, and is safe, and well tolerated and effective,” she said.

That’s “kind of good news for all of us,” she said. Patients “need this type of good news and solution,” she explained, because they may not tolerate or have access to injectable medications. Atogepant would also give clinicians have another option to offer patients with difficult-to-treat migraine cases, she noted. “It makes life easier for many physicians and many patients for many different reasons,” she said.

Dr. Pozo-Rosich said the likely next step in the research is to conduct the main analysis as well as post hoc analyses with accumulated data from pathology trials “to understand patterns of response, understand the sustainability of the response, [and] adherence to the treatment in the long term.”
 

‘Exciting that it works well’ in difficult-to-treat patients

Commenting on the study, Alan M. Rapoport, MD, clinical professor of neurology at University of California, Los Angeles, and past president of the International Headache Society, agreed that better options in migraine treatment and prevention are needed.

“We needed something that was going to be better than what we had before,” he said.

Dr. Rapoport noted the study was well designed with strongly positive results. “It looks like it’s an effective drug, and it looks really good in that it’s effective for people that have failed all these preventives that have very little hope for the future,” he said.

He specifically praised the inclusion of older participants in the population. “You never see a study on 80-year-olds,” he said, “but I like that, because they felt it would be safe. There are 80-year-old patients – fewer of them than 40-year-old patients – but there are 80-year-old patients who still have migraine, so I’m really glad they put older patients in it,” he said.

For atogepant, he noted that “some patients won’t get the side effects, and some patients will tolerate the side effects because it’s working really well.” While the study was not a head-to-head comparison against other oral migraine preventatives, he pointed out the high rate of constipation among participants in the trial setting may be a warning sign of future issues, as seen with other CGRP receptor agonists.

“I can tell you that with erenumab, the monoclonal antibody that was injected in the double-blind studies, they didn’t find any significant increase in constipation,” he explained. However, some clinicians using erenumab in the real world have reported up to 20% of their patients are constipated. “It’s not good that they’re reporting 10% are constipated” in the study, he said.

Overall, “all you can really say is it does work well,” Dr. Rapoport said. “It’s exciting that it works well in such difficult-to-treat patients, and it does come with some side effects.”

Dr. Pozo-Rosich reports serving as a consultant and developing education materials for AbbVie, Eli Lilly, Novartis, Teva Pharmaceuticals, and Pfizer. Dr. Rapoport is the editor-in-chief of Neurology Reviews; he reports being a consultant for AbbVie, the developer of atogepant. The ELEVATE trial is supported by AbbVie.

*Correction, 5/4/23: An earlier version of this article misstated the percentage of COVID-positive patients in the study population. 

Key clinical point: Women with endometriosis seemed prone to migraine, with menstrual-related migraine being the most common type and dysmenorrhea and dysuria being more frequent when endometriosis and migraine coexisted.

Major finding: Overall, 53.4% of women had migraine, of which 64.3% had migraine related to menstruation and 35.7% had non-menstrual migraine. Typical endometriosis-related pain symptoms such as dysmenorrhea (94.3% vs 82.0%; P  =  .03) and dysuria (27.1% vs 9.8%; P < .01) occurred significantly more frequently in patients with vs without migraine.

Study details: This was a prospective, nested case-control study including 131 women with endometriosis with or without migraine.

Disclosures: This study was supported by a grant from Ministero della Salute, Italy. The authors declared no conflicts of interest.

Source: Pasquini B, Seravalli V, et al. Endometriosis and the diagnosis of different forms of migraine: an association with dysmenorrhea. Reprod Biomed Online. 2023 (Apr 6). Doi: 10.1016/j.rbmo.2023.03.020

Key clinical point: Women with endometriosis seemed prone to migraine, with menstrual-related migraine being the most common type and dysmenorrhea and dysuria being more frequent when endometriosis and migraine coexisted.

Major finding: Overall, 53.4% of women had migraine, of which 64.3% had migraine related to menstruation and 35.7% had non-menstrual migraine. Typical endometriosis-related pain symptoms such as dysmenorrhea (94.3% vs 82.0%; P  =  .03) and dysuria (27.1% vs 9.8%; P < .01) occurred significantly more frequently in patients with vs without migraine.

Study details: This was a prospective, nested case-control study including 131 women with endometriosis with or without migraine.

Disclosures: This study was supported by a grant from Ministero della Salute, Italy. The authors declared no conflicts of interest.

Source: Pasquini B, Seravalli V, et al. Endometriosis and the diagnosis of different forms of migraine: an association with dysmenorrhea. Reprod Biomed Online. 2023 (Apr 6). Doi: 10.1016/j.rbmo.2023.03.020

Key clinical point: Women with endometriosis seemed prone to migraine, with menstrual-related migraine being the most common type and dysmenorrhea and dysuria being more frequent when endometriosis and migraine coexisted.

Major finding: Overall, 53.4% of women had migraine, of which 64.3% had migraine related to menstruation and 35.7% had non-menstrual migraine. Typical endometriosis-related pain symptoms such as dysmenorrhea (94.3% vs 82.0%; P  =  .03) and dysuria (27.1% vs 9.8%; P < .01) occurred significantly more frequently in patients with vs without migraine.

Study details: This was a prospective, nested case-control study including 131 women with endometriosis with or without migraine.

Disclosures: This study was supported by a grant from Ministero della Salute, Italy. The authors declared no conflicts of interest.

Source: Pasquini B, Seravalli V, et al. Endometriosis and the diagnosis of different forms of migraine: an association with dysmenorrhea. Reprod Biomed Online. 2023 (Apr 6). Doi: 10.1016/j.rbmo.2023.03.020

Key clinical point: Women with endometriosis seemed prone to migraine, with menstrual-related migraine being the most common type and dysmenorrhea and dysuria being more frequent when endometriosis and migraine coexisted.

Major finding: Overall, 53.4% of women had migraine, of which 64.3% had migraine related to menstruation and 35.7% had non-menstrual migraine. Typical endometriosis-related pain symptoms such as dysmenorrhea (94.3% vs 82.0%; P  =  .03) and dysuria (27.1% vs 9.8%; P < .01) occurred significantly more frequently in patients with vs without migraine.

Study details: This was a prospective, nested case-control study including 131 women with endometriosis with or without migraine.

Disclosures: This study was supported by a grant from Ministero della Salute, Italy. The authors declared no conflicts of interest.

Source: Pasquini B, Seravalli V, et al. Endometriosis and the diagnosis of different forms of migraine: an association with dysmenorrhea. Reprod Biomed Online. 2023 (Apr 6). Doi: 10.1016/j.rbmo.2023.03.020

Key clinical point: Women with endometriosis seemed prone to migraine, with menstrual-related migraine being the most common type and dysmenorrhea and dysuria being more frequent when endometriosis and migraine coexisted.

Major finding: Overall, 53.4% of women had migraine, of which 64.3% had migraine related to menstruation and 35.7% had non-menstrual migraine. Typical endometriosis-related pain symptoms such as dysmenorrhea (94.3% vs 82.0%; P  =  .03) and dysuria (27.1% vs 9.8%; P < .01) occurred significantly more frequently in patients with vs without migraine.

Study details: This was a prospective, nested case-control study including 131 women with endometriosis with or without migraine.

Disclosures: This study was supported by a grant from Ministero della Salute, Italy. The authors declared no conflicts of interest.

Source: Pasquini B, Seravalli V, et al. Endometriosis and the diagnosis of different forms of migraine: an association with dysmenorrhea. Reprod Biomed Online. 2023 (Apr 6). Doi: 10.1016/j.rbmo.2023.03.020

Key clinical point: Women with endometriosis seemed prone to migraine, with menstrual-related migraine being the most common type and dysmenorrhea and dysuria being more frequent when endometriosis and migraine coexisted.

Major finding: Overall, 53.4% of women had migraine, of which 64.3% had migraine related to menstruation and 35.7% had non-menstrual migraine. Typical endometriosis-related pain symptoms such as dysmenorrhea (94.3% vs 82.0%; P  =  .03) and dysuria (27.1% vs 9.8%; P < .01) occurred significantly more frequently in patients with vs without migraine.

Study details: This was a prospective, nested case-control study including 131 women with endometriosis with or without migraine.

Disclosures: This study was supported by a grant from Ministero della Salute, Italy. The authors declared no conflicts of interest.

Source: Pasquini B, Seravalli V, et al. Endometriosis and the diagnosis of different forms of migraine: an association with dysmenorrhea. Reprod Biomed Online. 2023 (Apr 6). Doi: 10.1016/j.rbmo.2023.03.020

Key clinical point: Migraine diagnosis was not significantly correlated with a higher frequency of an absence of ischemic penumbra, its volume, or the prognosis of ischemic stroke.

Major finding: There was no significant association between migraine diagnosis and the absence of ischemic penumbra (P  =  .649), stroke volume (P  =  .995), or prognosis of ischemic stroke.

Study details: Findings are from a prospective cohort study including 221 patients with ischemic stroke who were hospitalized within 72 hours of the onset of symptoms, of which 59 had migraine.

Disclosures: The study was financed in part by the Coordenaçao de Aperfeiçoamento de Pessoal de Nível Superior-Brasil. The authors declared no conflicts of interest.

Source: Oliveira FAA et al. Assessing the influence of migraine on ischemic penumbra and on the prognosis of ischemic stroke: A prospective cohort study. Headache. 2023;63:549-558 (Mar 29). Doi: 10.1111/head.14492

Key clinical point: Migraine diagnosis was not significantly correlated with a higher frequency of an absence of ischemic penumbra, its volume, or the prognosis of ischemic stroke.

Major finding: There was no significant association between migraine diagnosis and the absence of ischemic penumbra (P  =  .649), stroke volume (P  =  .995), or prognosis of ischemic stroke.

Study details: Findings are from a prospective cohort study including 221 patients with ischemic stroke who were hospitalized within 72 hours of the onset of symptoms, of which 59 had migraine.

Disclosures: The study was financed in part by the Coordenaçao de Aperfeiçoamento de Pessoal de Nível Superior-Brasil. The authors declared no conflicts of interest.

Source: Oliveira FAA et al. Assessing the influence of migraine on ischemic penumbra and on the prognosis of ischemic stroke: A prospective cohort study. Headache. 2023;63:549-558 (Mar 29). Doi: 10.1111/head.14492

Key clinical point: Migraine diagnosis was not significantly correlated with a higher frequency of an absence of ischemic penumbra, its volume, or the prognosis of ischemic stroke.

Major finding: There was no significant association between migraine diagnosis and the absence of ischemic penumbra (P  =  .649), stroke volume (P  =  .995), or prognosis of ischemic stroke.

Study details: Findings are from a prospective cohort study including 221 patients with ischemic stroke who were hospitalized within 72 hours of the onset of symptoms, of which 59 had migraine.

Disclosures: The study was financed in part by the Coordenaçao de Aperfeiçoamento de Pessoal de Nível Superior-Brasil. The authors declared no conflicts of interest.

Source: Oliveira FAA et al. Assessing the influence of migraine on ischemic penumbra and on the prognosis of ischemic stroke: A prospective cohort study. Headache. 2023;63:549-558 (Mar 29). Doi: 10.1111/head.14492