Headache & Migraine

Key clinical point: Fremanezumab demonstrated early and sustained efficacy with an optimal safety profile in patients with high disability and high-frequency episodic migraine (HFEM) or chronic migraine (CM) with multiple preventive failures and diverse comorbidities.

Major finding: At 21-24 weeks, fremanezumab significantly reduced monthly migraine days in patients with HFEM (−6.9 ± 3.6; P < .001) and monthly headache days in patients with CM (−14.2 ± 7.6; P < .001) along with significant reductions in monthly analgesic medications and Numerical Rating Scale scores in both patients with HFEM and CM (P < .001), with benefits sustaining throughout treatment period and adverse events being rare.

Study details: This multicenter, prospective real-life study included 148 patients with migraine (HFEM, n = 52; CM, n = 96) who were treated with fremanezumab for ≥24 weeks.

Disclosures: The study was partially supported by the Italian Ministry of Health Institutional Funding Ricerca Corrente San Raffaele Roma, Italy. Some authors declared receiving research support, travel grants, or honoraria for advisory board participation, speaking, or clinical investigation studies from various sources.

Source: Barbanti P et al for the FRIEND-Study Group. Early and sustained efficacy of fremanezumab over 24-weeks in migraine patients with multiple preventive treatment failures: The multicenter, prospective, real-life FRIEND2 study. J Headache Pain. 2023;24:30 (Mar 23). Doi: 10.1186/s10194-023-01561-w

Key clinical point: Fremanezumab demonstrated early and sustained efficacy with an optimal safety profile in patients with high disability and high-frequency episodic migraine (HFEM) or chronic migraine (CM) with multiple preventive failures and diverse comorbidities.

Major finding: At 21-24 weeks, fremanezumab significantly reduced monthly migraine days in patients with HFEM (−6.9 ± 3.6; P < .001) and monthly headache days in patients with CM (−14.2 ± 7.6; P < .001) along with significant reductions in monthly analgesic medications and Numerical Rating Scale scores in both patients with HFEM and CM (P < .001), with benefits sustaining throughout treatment period and adverse events being rare.

Study details: This multicenter, prospective real-life study included 148 patients with migraine (HFEM, n = 52; CM, n = 96) who were treated with fremanezumab for ≥24 weeks.

Disclosures: The study was partially supported by the Italian Ministry of Health Institutional Funding Ricerca Corrente San Raffaele Roma, Italy. Some authors declared receiving research support, travel grants, or honoraria for advisory board participation, speaking, or clinical investigation studies from various sources.

Source: Barbanti P et al for the FRIEND-Study Group. Early and sustained efficacy of fremanezumab over 24-weeks in migraine patients with multiple preventive treatment failures: The multicenter, prospective, real-life FRIEND2 study. J Headache Pain. 2023;24:30 (Mar 23). Doi: 10.1186/s10194-023-01561-w

Key clinical point: Fremanezumab demonstrated early and sustained efficacy with an optimal safety profile in patients with high disability and high-frequency episodic migraine (HFEM) or chronic migraine (CM) with multiple preventive failures and diverse comorbidities.

Major finding: At 21-24 weeks, fremanezumab significantly reduced monthly migraine days in patients with HFEM (−6.9 ± 3.6; P < .001) and monthly headache days in patients with CM (−14.2 ± 7.6; P < .001) along with significant reductions in monthly analgesic medications and Numerical Rating Scale scores in both patients with HFEM and CM (P < .001), with benefits sustaining throughout treatment period and adverse events being rare.

Study details: This multicenter, prospective real-life study included 148 patients with migraine (HFEM, n = 52; CM, n = 96) who were treated with fremanezumab for ≥24 weeks.

Disclosures: The study was partially supported by the Italian Ministry of Health Institutional Funding Ricerca Corrente San Raffaele Roma, Italy. Some authors declared receiving research support, travel grants, or honoraria for advisory board participation, speaking, or clinical investigation studies from various sources.

Source: Barbanti P et al for the FRIEND-Study Group. Early and sustained efficacy of fremanezumab over 24-weeks in migraine patients with multiple preventive treatment failures: The multicenter, prospective, real-life FRIEND2 study. J Headache Pain. 2023;24:30 (Mar 23). Doi: 10.1186/s10194-023-01561-w

Key clinical point: The odds of having migraine with or without aura is higher among patients with migraine with vs without inflammatory bowel disease (IBD); however, patients with migraine and IBD are less likely to have chronic migraine or receive treatment for migraine.

Major finding: Patients with migraine with vs without IBD were more likely to have migraine with (odds ratio [OR] 2.20; P < .001) and without (OR 2.79; P < .001) aura, but were less likely to have chronic migraine (OR 0.23; P < .001) or receive treatment for migraine (OR 0.23-0.55; P ≤ .037).

Study details: Findings are from a retrospective cohort study including 675 patients with migraine, of which 280 patients had IBD.

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

Source: Sileno SM et al. Comparison of migraine characteristics in patients with and without inflammatory bowel disease: A retrospective cohort study. J Prim Care Community Health. 2023 (Mar 23). Doi: 10.1177/21501319231164307

Key clinical point: The odds of having migraine with or without aura is higher among patients with migraine with vs without inflammatory bowel disease (IBD); however, patients with migraine and IBD are less likely to have chronic migraine or receive treatment for migraine.

Major finding: Patients with migraine with vs without IBD were more likely to have migraine with (odds ratio [OR] 2.20; P < .001) and without (OR 2.79; P < .001) aura, but were less likely to have chronic migraine (OR 0.23; P < .001) or receive treatment for migraine (OR 0.23-0.55; P ≤ .037).

Study details: Findings are from a retrospective cohort study including 675 patients with migraine, of which 280 patients had IBD.

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

Source: Sileno SM et al. Comparison of migraine characteristics in patients with and without inflammatory bowel disease: A retrospective cohort study. J Prim Care Community Health. 2023 (Mar 23). Doi: 10.1177/21501319231164307

Key clinical point: The odds of having migraine with or without aura is higher among patients with migraine with vs without inflammatory bowel disease (IBD); however, patients with migraine and IBD are less likely to have chronic migraine or receive treatment for migraine.

Major finding: Patients with migraine with vs without IBD were more likely to have migraine with (odds ratio [OR] 2.20; P < .001) and without (OR 2.79; P < .001) aura, but were less likely to have chronic migraine (OR 0.23; P < .001) or receive treatment for migraine (OR 0.23-0.55; P ≤ .037).

Study details: Findings are from a retrospective cohort study including 675 patients with migraine, of which 280 patients had IBD.

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

Source: Sileno SM et al. Comparison of migraine characteristics in patients with and without inflammatory bowel disease: A retrospective cohort study. J Prim Care Community Health. 2023 (Mar 23). Doi: 10.1177/21501319231164307

Key clinical point: Patients with migraine are at a higher risk of developing subsequent primary open angle glaucoma (POAG), with the risk being even higher among patients with chronic and severe migraine.

Major finding: Over 9 years of follow-up, the incidence rates of POAG were 3.249 and 2.408 per 1000 person-years in patients with and without migraine, respectively. Compared with individuals without migraine, patients with migraine and severe migraine had 1.19 (adjusted HR [aHR] 1.188; 95% CI 1.140-1.239) and 1.29 (aHR 1.285; 95% CI 1.166-1.415) times higher risk for POAG, respectively.

Study details: Findings are from a retrospective cohort study including 2,716,562 individuals aged ≥40 years, of which 87,809 had migraine.

Disclosures: The study was funded by Catholic Medical Center Research Foundation, New Hampshire. The authors declared no competing interests.

Source: Ohn K et al. Presence and severity of migraine is associated with development of primary open angle glaucoma: A population-based longitudinal cohort study. PLoS One. 2023;18(3):e0283495 (Mar 24). Doi: 10.1371/journal.pone.0283495

Key clinical point: Patients with migraine are at a higher risk of developing subsequent primary open angle glaucoma (POAG), with the risk being even higher among patients with chronic and severe migraine.

Major finding: Over 9 years of follow-up, the incidence rates of POAG were 3.249 and 2.408 per 1000 person-years in patients with and without migraine, respectively. Compared with individuals without migraine, patients with migraine and severe migraine had 1.19 (adjusted HR [aHR] 1.188; 95% CI 1.140-1.239) and 1.29 (aHR 1.285; 95% CI 1.166-1.415) times higher risk for POAG, respectively.

Study details: Findings are from a retrospective cohort study including 2,716,562 individuals aged ≥40 years, of which 87,809 had migraine.

Disclosures: The study was funded by Catholic Medical Center Research Foundation, New Hampshire. The authors declared no competing interests.

Source: Ohn K et al. Presence and severity of migraine is associated with development of primary open angle glaucoma: A population-based longitudinal cohort study. PLoS One. 2023;18(3):e0283495 (Mar 24). Doi: 10.1371/journal.pone.0283495

Key clinical point: Patients with migraine are at a higher risk of developing subsequent primary open angle glaucoma (POAG), with the risk being even higher among patients with chronic and severe migraine.

Major finding: Over 9 years of follow-up, the incidence rates of POAG were 3.249 and 2.408 per 1000 person-years in patients with and without migraine, respectively. Compared with individuals without migraine, patients with migraine and severe migraine had 1.19 (adjusted HR [aHR] 1.188; 95% CI 1.140-1.239) and 1.29 (aHR 1.285; 95% CI 1.166-1.415) times higher risk for POAG, respectively.

Study details: Findings are from a retrospective cohort study including 2,716,562 individuals aged ≥40 years, of which 87,809 had migraine.

Disclosures: The study was funded by Catholic Medical Center Research Foundation, New Hampshire. The authors declared no competing interests.

Source: Ohn K et al. Presence and severity of migraine is associated with development of primary open angle glaucoma: A population-based longitudinal cohort study. PLoS One. 2023;18(3):e0283495 (Mar 24). Doi: 10.1371/journal.pone.0283495

Key clinical point: Ultrasound-guided stellate ganglion blockade (SGB) is a safe and effective treatment option for patients with chronic migraine (CM); however, comorbid anxiety, or depression negatively predict SGB efficacy.

Major finding: The effective rates of ultrasound-guided SGB treatment were 90.7%, 82.5%, and 71.1% at 1-, 2-, and 3-month follow-ups, respectively, with the number of SGB being significantly greater in patients who did vs did not respond to SGB at the 3-month follow-up (P  =  .02) and comorbid anxiety or depression being a negative predictor of poor response to SGB (B −0.25; P  =  .01). Overall, the SGB-associated adverse event rate was 9.3%, with all adverse events being transient.

Study details: The data come from a retrospective, single-center study including 97 patients with CM who received ≥1 ultrasound-guided SGB treatment with a time interval of 1-7 days.

Disclosures: The study funded by The Capital’s Funds for Health Improvement and Research, China. The authors declared no conflicts of interest.

Source: Yu B et al. Effectiveness, safety, and predictors of response to ultrasound-guided stellate ganglion blockades for the treatment of patients with chronic migraine: A retrospective and observational study. Pain Pract. 2023 (Mar 16). Doi: 10.1111/papr.13224

Key clinical point: Ultrasound-guided stellate ganglion blockade (SGB) is a safe and effective treatment option for patients with chronic migraine (CM); however, comorbid anxiety, or depression negatively predict SGB efficacy.

Major finding: The effective rates of ultrasound-guided SGB treatment were 90.7%, 82.5%, and 71.1% at 1-, 2-, and 3-month follow-ups, respectively, with the number of SGB being significantly greater in patients who did vs did not respond to SGB at the 3-month follow-up (P  =  .02) and comorbid anxiety or depression being a negative predictor of poor response to SGB (B −0.25; P  =  .01). Overall, the SGB-associated adverse event rate was 9.3%, with all adverse events being transient.

Study details: The data come from a retrospective, single-center study including 97 patients with CM who received ≥1 ultrasound-guided SGB treatment with a time interval of 1-7 days.

Disclosures: The study funded by The Capital’s Funds for Health Improvement and Research, China. The authors declared no conflicts of interest.

Source: Yu B et al. Effectiveness, safety, and predictors of response to ultrasound-guided stellate ganglion blockades for the treatment of patients with chronic migraine: A retrospective and observational study. Pain Pract. 2023 (Mar 16). Doi: 10.1111/papr.13224

Key clinical point: Ultrasound-guided stellate ganglion blockade (SGB) is a safe and effective treatment option for patients with chronic migraine (CM); however, comorbid anxiety, or depression negatively predict SGB efficacy.

Major finding: The effective rates of ultrasound-guided SGB treatment were 90.7%, 82.5%, and 71.1% at 1-, 2-, and 3-month follow-ups, respectively, with the number of SGB being significantly greater in patients who did vs did not respond to SGB at the 3-month follow-up (P  =  .02) and comorbid anxiety or depression being a negative predictor of poor response to SGB (B −0.25; P  =  .01). Overall, the SGB-associated adverse event rate was 9.3%, with all adverse events being transient.

Study details: The data come from a retrospective, single-center study including 97 patients with CM who received ≥1 ultrasound-guided SGB treatment with a time interval of 1-7 days.

Disclosures: The study funded by The Capital’s Funds for Health Improvement and Research, China. The authors declared no conflicts of interest.

Source: Yu B et al. Effectiveness, safety, and predictors of response to ultrasound-guided stellate ganglion blockades for the treatment of patients with chronic migraine: A retrospective and observational study. Pain Pract. 2023 (Mar 16). Doi: 10.1111/papr.13224

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Cluster headache and migraine have strong ties to the circadian system at multiple levels, say new findings that could have significant treatment implications.

A meta-analysis of 16 studies showed a circadian pattern in 71% of cluster headache attacks (3,490 of 4,953), with a clear circadian peak between 9:00 p.m. and 3:00 a.m.

Migraine was also associated with a circadian pattern in 50% of cases (2,698 of 5,385) across eight studies, with a clear circadian trough between 11:00 p.m. and 7:00 a.m.

Seasonal peaks were also evident for cluster headache (spring and autumn) and migraine (April to October).

“In the short term, these findings help us explain the timing to patients – for example, it is possible that a headache at 8 a.m. is due to their internal body clock instead of their pillow, or breakfast food, or morning medications,” lead investigator Mark Burish, MD, PhD, associate professor, department of neurosurgery, at University of Texas Health Houston, told this news organization.

“In the long term, these findings do suggest that medications that target the circadian system could be effective in migraine and headache patients,” Dr. Burish added.

The study was published online in Neurology.


 

Treatment implications?

Across studies, chronotype was “highly variable” for both cluster headache and migraine, the investigators report.

Cluster headache was associated with lower melatonin and higher cortisol levels, compared with non–cluster headache controls.

On a genetic level, cluster headache was associated with two core circadian genes (CLOCK and REV-ERB–alpha), and five of the nine genes that increase the likelihood of having cluster headache are genes with a circadian pattern of expression.

Migraine headache was associated with lower urinary melatonin levels and with the core circadian genes, CK1-delta and ROR-alpha, and 110 of the 168 genes associated with migraine were clock-controlled genes.

“The data suggest that both of these headache disorders are highly circadian at multiple levels, especially cluster headache,” Dr. Burish said in a release.

“This reinforces the importance of the hypothalamus – the area of the brain that houses the primary biological clock – and its role in cluster headache and migraine. It also raises the question of the genetics of triggers such as sleep changes that are known triggers for migraine and are cues for the body’s circadian rhythm,” Dr. Burish said.

“We hope that future research will look into circadian medications as a new treatment option for migraine and cluster headache patients,” Dr. Burish told this news organization.
 

Importance of sleep regulation

The authors of an accompanying editorial note that even though the study doesn’t have immediate clinical implications, it offers a better understanding of the way chronobiologic factors may influence treatment.

“At a minimum, interventions known to regulate and improve sleep (e.g., melatonin, cognitive behavioral therapy), and which are safe and straightforward to introduce, may be useful in some individuals susceptible to circadian misalignment or sleep disorders,” write Heidi Sutherland, PhD, and Lyn Griffiths, PhD, with Queensland University of Technology, Brisbane, Australia.

“Treatment of comorbidities (e.g., insomnia) that result in sleep disturbances may also help headache management. Furthermore, chronobiological aspects of any pharmacological interventions should be considered, as some frequently used headache and migraine drugs can modulate circadian cycles and influence the expression of circadian genes (e.g., verapamil), or have sleep-related side effects,” they add.

A limitation of the study was the lack of information on factors that could influence the circadian cycle, such as medications; other disorders, such as bipolar disorder; or circadian rhythm issues, such as night-shift work.

The study was supported by grants from the Japan Society for the Promotion of Science, the National Institutes of Health, The Welch Foundation, and The Will Erwin Headache Research Foundation. Dr. Burish is an unpaid member of the medical advisory board of Clusterbusters, and a site investigator for a cluster headache clinical trial funded by Lundbeck. Dr. Sutherland has received grant funding from the U.S. Migraine Research Foundation, and received institute support from Queensland University of Technology for genetics research. Dr. Griffiths has received grant funding from the Australian NHMRC, U.S. Department of Defense, and the U.S. Migraine Research Foundation, and consultancy funding from TEVA.

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

Cluster headache and migraine have strong ties to the circadian system at multiple levels, say new findings that could have significant treatment implications.

A meta-analysis of 16 studies showed a circadian pattern in 71% of cluster headache attacks (3,490 of 4,953), with a clear circadian peak between 9:00 p.m. and 3:00 a.m.

Migraine was also associated with a circadian pattern in 50% of cases (2,698 of 5,385) across eight studies, with a clear circadian trough between 11:00 p.m. and 7:00 a.m.

Seasonal peaks were also evident for cluster headache (spring and autumn) and migraine (April to October).

“In the short term, these findings help us explain the timing to patients – for example, it is possible that a headache at 8 a.m. is due to their internal body clock instead of their pillow, or breakfast food, or morning medications,” lead investigator Mark Burish, MD, PhD, associate professor, department of neurosurgery, at University of Texas Health Houston, told this news organization.

“In the long term, these findings do suggest that medications that target the circadian system could be effective in migraine and headache patients,” Dr. Burish added.

The study was published online in Neurology.


 

Treatment implications?

Across studies, chronotype was “highly variable” for both cluster headache and migraine, the investigators report.

Cluster headache was associated with lower melatonin and higher cortisol levels, compared with non–cluster headache controls.

On a genetic level, cluster headache was associated with two core circadian genes (CLOCK and REV-ERB–alpha), and five of the nine genes that increase the likelihood of having cluster headache are genes with a circadian pattern of expression.

Migraine headache was associated with lower urinary melatonin levels and with the core circadian genes, CK1-delta and ROR-alpha, and 110 of the 168 genes associated with migraine were clock-controlled genes.

“The data suggest that both of these headache disorders are highly circadian at multiple levels, especially cluster headache,” Dr. Burish said in a release.

“This reinforces the importance of the hypothalamus – the area of the brain that houses the primary biological clock – and its role in cluster headache and migraine. It also raises the question of the genetics of triggers such as sleep changes that are known triggers for migraine and are cues for the body’s circadian rhythm,” Dr. Burish said.

“We hope that future research will look into circadian medications as a new treatment option for migraine and cluster headache patients,” Dr. Burish told this news organization.
 

Importance of sleep regulation

The authors of an accompanying editorial note that even though the study doesn’t have immediate clinical implications, it offers a better understanding of the way chronobiologic factors may influence treatment.

“At a minimum, interventions known to regulate and improve sleep (e.g., melatonin, cognitive behavioral therapy), and which are safe and straightforward to introduce, may be useful in some individuals susceptible to circadian misalignment or sleep disorders,” write Heidi Sutherland, PhD, and Lyn Griffiths, PhD, with Queensland University of Technology, Brisbane, Australia.

“Treatment of comorbidities (e.g., insomnia) that result in sleep disturbances may also help headache management. Furthermore, chronobiological aspects of any pharmacological interventions should be considered, as some frequently used headache and migraine drugs can modulate circadian cycles and influence the expression of circadian genes (e.g., verapamil), or have sleep-related side effects,” they add.

A limitation of the study was the lack of information on factors that could influence the circadian cycle, such as medications; other disorders, such as bipolar disorder; or circadian rhythm issues, such as night-shift work.

The study was supported by grants from the Japan Society for the Promotion of Science, the National Institutes of Health, The Welch Foundation, and The Will Erwin Headache Research Foundation. Dr. Burish is an unpaid member of the medical advisory board of Clusterbusters, and a site investigator for a cluster headache clinical trial funded by Lundbeck. Dr. Sutherland has received grant funding from the U.S. Migraine Research Foundation, and received institute support from Queensland University of Technology for genetics research. Dr. Griffiths has received grant funding from the Australian NHMRC, U.S. Department of Defense, and the U.S. Migraine Research Foundation, and consultancy funding from TEVA.

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

Cluster headache and migraine have strong ties to the circadian system at multiple levels, say new findings that could have significant treatment implications.

A meta-analysis of 16 studies showed a circadian pattern in 71% of cluster headache attacks (3,490 of 4,953), with a clear circadian peak between 9:00 p.m. and 3:00 a.m.

Migraine was also associated with a circadian pattern in 50% of cases (2,698 of 5,385) across eight studies, with a clear circadian trough between 11:00 p.m. and 7:00 a.m.

Seasonal peaks were also evident for cluster headache (spring and autumn) and migraine (April to October).

“In the short term, these findings help us explain the timing to patients – for example, it is possible that a headache at 8 a.m. is due to their internal body clock instead of their pillow, or breakfast food, or morning medications,” lead investigator Mark Burish, MD, PhD, associate professor, department of neurosurgery, at University of Texas Health Houston, told this news organization.

“In the long term, these findings do suggest that medications that target the circadian system could be effective in migraine and headache patients,” Dr. Burish added.

The study was published online in Neurology.


 

Treatment implications?

Across studies, chronotype was “highly variable” for both cluster headache and migraine, the investigators report.

Cluster headache was associated with lower melatonin and higher cortisol levels, compared with non–cluster headache controls.

On a genetic level, cluster headache was associated with two core circadian genes (CLOCK and REV-ERB–alpha), and five of the nine genes that increase the likelihood of having cluster headache are genes with a circadian pattern of expression.

Migraine headache was associated with lower urinary melatonin levels and with the core circadian genes, CK1-delta and ROR-alpha, and 110 of the 168 genes associated with migraine were clock-controlled genes.

“The data suggest that both of these headache disorders are highly circadian at multiple levels, especially cluster headache,” Dr. Burish said in a release.

“This reinforces the importance of the hypothalamus – the area of the brain that houses the primary biological clock – and its role in cluster headache and migraine. It also raises the question of the genetics of triggers such as sleep changes that are known triggers for migraine and are cues for the body’s circadian rhythm,” Dr. Burish said.

“We hope that future research will look into circadian medications as a new treatment option for migraine and cluster headache patients,” Dr. Burish told this news organization.
 

Importance of sleep regulation

The authors of an accompanying editorial note that even though the study doesn’t have immediate clinical implications, it offers a better understanding of the way chronobiologic factors may influence treatment.

“At a minimum, interventions known to regulate and improve sleep (e.g., melatonin, cognitive behavioral therapy), and which are safe and straightforward to introduce, may be useful in some individuals susceptible to circadian misalignment or sleep disorders,” write Heidi Sutherland, PhD, and Lyn Griffiths, PhD, with Queensland University of Technology, Brisbane, Australia.

“Treatment of comorbidities (e.g., insomnia) that result in sleep disturbances may also help headache management. Furthermore, chronobiological aspects of any pharmacological interventions should be considered, as some frequently used headache and migraine drugs can modulate circadian cycles and influence the expression of circadian genes (e.g., verapamil), or have sleep-related side effects,” they add.

A limitation of the study was the lack of information on factors that could influence the circadian cycle, such as medications; other disorders, such as bipolar disorder; or circadian rhythm issues, such as night-shift work.

The study was supported by grants from the Japan Society for the Promotion of Science, the National Institutes of Health, The Welch Foundation, and The Will Erwin Headache Research Foundation. Dr. Burish is an unpaid member of the medical advisory board of Clusterbusters, and a site investigator for a cluster headache clinical trial funded by Lundbeck. Dr. Sutherland has received grant funding from the U.S. Migraine Research Foundation, and received institute support from Queensland University of Technology for genetics research. Dr. Griffiths has received grant funding from the Australian NHMRC, U.S. Department of Defense, and the U.S. Migraine Research Foundation, and consultancy funding from TEVA.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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