Headache & Migraine

Key clinical point: When administered prophylactically, propranolol, topiramate, flunarizine, and cyproheptadine are effective at improving the health-related quality of life in pediatric patients with migraine.

Main finding: The before vs. after mean Pediatric Migraine Disability Assessment scores showed significant improvement with prophylactic topiramate (11.33 ± 13.82 vs. 33.50 ± 13.97), propranolol (12.58 ± 15.67 vs. 30.16 ± 22.97), cyproheptadine (17.00 ± 17.43 vs. 27.33 ± 19.22), or flunarizine (17.50 ± 20.14 vs. 29.89 ± 21.53; all P < .001).

Study details: The data are derived from a retrospective review study including 186 pediatric patients (aged 6 to 18 years) with migraine who were being treated prophylactically for at least 6 months with either topiramate (n = 30), cyproheptadine (n = 45), propranolol (n = 55), or flunarizine (n = 56).

Disclosures: The authors did not receive any financial aid for the study. No conflicts of interest were reported.

Source: Tekin H et al. Pediatr Int. 2021 (Dec 14). Doi: 10.1111/ped.15094.

Key clinical point: When administered prophylactically, propranolol, topiramate, flunarizine, and cyproheptadine are effective at improving the health-related quality of life in pediatric patients with migraine.

Main finding: The before vs. after mean Pediatric Migraine Disability Assessment scores showed significant improvement with prophylactic topiramate (11.33 ± 13.82 vs. 33.50 ± 13.97), propranolol (12.58 ± 15.67 vs. 30.16 ± 22.97), cyproheptadine (17.00 ± 17.43 vs. 27.33 ± 19.22), or flunarizine (17.50 ± 20.14 vs. 29.89 ± 21.53; all P < .001).

Study details: The data are derived from a retrospective review study including 186 pediatric patients (aged 6 to 18 years) with migraine who were being treated prophylactically for at least 6 months with either topiramate (n = 30), cyproheptadine (n = 45), propranolol (n = 55), or flunarizine (n = 56).

Disclosures: The authors did not receive any financial aid for the study. No conflicts of interest were reported.

Source: Tekin H et al. Pediatr Int. 2021 (Dec 14). Doi: 10.1111/ped.15094.

Key clinical point: When administered prophylactically, propranolol, topiramate, flunarizine, and cyproheptadine are effective at improving the health-related quality of life in pediatric patients with migraine.

Main finding: The before vs. after mean Pediatric Migraine Disability Assessment scores showed significant improvement with prophylactic topiramate (11.33 ± 13.82 vs. 33.50 ± 13.97), propranolol (12.58 ± 15.67 vs. 30.16 ± 22.97), cyproheptadine (17.00 ± 17.43 vs. 27.33 ± 19.22), or flunarizine (17.50 ± 20.14 vs. 29.89 ± 21.53; all P < .001).

Study details: The data are derived from a retrospective review study including 186 pediatric patients (aged 6 to 18 years) with migraine who were being treated prophylactically for at least 6 months with either topiramate (n = 30), cyproheptadine (n = 45), propranolol (n = 55), or flunarizine (n = 56).

Disclosures: The authors did not receive any financial aid for the study. No conflicts of interest were reported.

Source: Tekin H et al. Pediatr Int. 2021 (Dec 14). Doi: 10.1111/ped.15094.

Key clinical point: Alpha-lipoic acid (ALA) supplementation may serve as a potential adjunct treatment option for migraine.

Main finding: ALA supplementation vs. placebo over 3 months caused a significant decrease in baseline mean headache severity (−3.59 vs. −0.70; P < .001), frequency of attacks/month (−2.55 vs. −0.40; P = .001), headache diary result (−158.79 vs. −38.63; P = .003), headache impact test-6 (HIT-6) score (−20.09 vs. −2.83; P < .001), and migraine headache index score (MHIS, −65.32 vs. −0.33; P < .001).

Study details: This was a randomized, double-blind trial including 92 female patients aged 20-50 years with episodic migraine who were randomly assigned to receive ALA (n = 47) or placebo (n = 45) for 3 months.

Disclosures: The study received financial support from the Isfahan University of Medical Sciences, Isfahan, Iran. The authors reported no potential conflict of interests.

Source: Kelishadi MR et al. Sci Rep. 2022;12:271 (Jan 7). Doi: 10.1038/s41598-021-04397-z.

Key clinical point: Alpha-lipoic acid (ALA) supplementation may serve as a potential adjunct treatment option for migraine.

Main finding: ALA supplementation vs. placebo over 3 months caused a significant decrease in baseline mean headache severity (−3.59 vs. −0.70; P < .001), frequency of attacks/month (−2.55 vs. −0.40; P = .001), headache diary result (−158.79 vs. −38.63; P = .003), headache impact test-6 (HIT-6) score (−20.09 vs. −2.83; P < .001), and migraine headache index score (MHIS, −65.32 vs. −0.33; P < .001).

Study details: This was a randomized, double-blind trial including 92 female patients aged 20-50 years with episodic migraine who were randomly assigned to receive ALA (n = 47) or placebo (n = 45) for 3 months.

Disclosures: The study received financial support from the Isfahan University of Medical Sciences, Isfahan, Iran. The authors reported no potential conflict of interests.

Source: Kelishadi MR et al. Sci Rep. 2022;12:271 (Jan 7). Doi: 10.1038/s41598-021-04397-z.

Key clinical point: Alpha-lipoic acid (ALA) supplementation may serve as a potential adjunct treatment option for migraine.

Main finding: ALA supplementation vs. placebo over 3 months caused a significant decrease in baseline mean headache severity (−3.59 vs. −0.70; P < .001), frequency of attacks/month (−2.55 vs. −0.40; P = .001), headache diary result (−158.79 vs. −38.63; P = .003), headache impact test-6 (HIT-6) score (−20.09 vs. −2.83; P < .001), and migraine headache index score (MHIS, −65.32 vs. −0.33; P < .001).

Study details: This was a randomized, double-blind trial including 92 female patients aged 20-50 years with episodic migraine who were randomly assigned to receive ALA (n = 47) or placebo (n = 45) for 3 months.

Disclosures: The study received financial support from the Isfahan University of Medical Sciences, Isfahan, Iran. The authors reported no potential conflict of interests.

Source: Kelishadi MR et al. Sci Rep. 2022;12:271 (Jan 7). Doi: 10.1038/s41598-021-04397-z.

Key clinical point: Patients with migraine are at an increased risk of myocardial infarction (MI) and stroke, and those with migraine with aura are also at an increased risk of overall cardiovascular mortality.

Main finding: Migraine showed a positive association with MI (hazard ratio [HR] 1.36; P < .001), unspecified stroke (HR 1.30; P = .01), ischemic stroke (HR 1.35; P = .03), and hemorrhagic stroke (HR 1.43; P = .02). Migraine with aura was positively associated with cardiovascular mortality (HR 1.27; P < .001).

Study details: Findings are from a meta-analysis of 18 prospective cohort studies including 362,434 patients with migraine and 1,323,714 control participants.

Disclosures: BYQ Tan declared receiving the Ministry of Health Healthcare Research Scholarship, Singapore, and the Chan Heng Leong Research Award. CH Sia received financial support from the National University of Singapore Yong Loo Lin School of Medicine’s Junior Academic Faculty Scheme. The authors declared no competing interests.

Source: Ng CYH et al. J Neurol. 2022 (Jan 8). Doi: 10.1007/s00415-021-10930-x.

Key clinical point: Patients with migraine are at an increased risk of myocardial infarction (MI) and stroke, and those with migraine with aura are also at an increased risk of overall cardiovascular mortality.

Main finding: Migraine showed a positive association with MI (hazard ratio [HR] 1.36; P < .001), unspecified stroke (HR 1.30; P = .01), ischemic stroke (HR 1.35; P = .03), and hemorrhagic stroke (HR 1.43; P = .02). Migraine with aura was positively associated with cardiovascular mortality (HR 1.27; P < .001).

Study details: Findings are from a meta-analysis of 18 prospective cohort studies including 362,434 patients with migraine and 1,323,714 control participants.

Disclosures: BYQ Tan declared receiving the Ministry of Health Healthcare Research Scholarship, Singapore, and the Chan Heng Leong Research Award. CH Sia received financial support from the National University of Singapore Yong Loo Lin School of Medicine’s Junior Academic Faculty Scheme. The authors declared no competing interests.

Source: Ng CYH et al. J Neurol. 2022 (Jan 8). Doi: 10.1007/s00415-021-10930-x.

Key clinical point: Patients with migraine are at an increased risk of myocardial infarction (MI) and stroke, and those with migraine with aura are also at an increased risk of overall cardiovascular mortality.

Main finding: Migraine showed a positive association with MI (hazard ratio [HR] 1.36; P < .001), unspecified stroke (HR 1.30; P = .01), ischemic stroke (HR 1.35; P = .03), and hemorrhagic stroke (HR 1.43; P = .02). Migraine with aura was positively associated with cardiovascular mortality (HR 1.27; P < .001).

Study details: Findings are from a meta-analysis of 18 prospective cohort studies including 362,434 patients with migraine and 1,323,714 control participants.

Disclosures: BYQ Tan declared receiving the Ministry of Health Healthcare Research Scholarship, Singapore, and the Chan Heng Leong Research Award. CH Sia received financial support from the National University of Singapore Yong Loo Lin School of Medicine’s Junior Academic Faculty Scheme. The authors declared no competing interests.

Source: Ng CYH et al. J Neurol. 2022 (Jan 8). Doi: 10.1007/s00415-021-10930-x.

Key clinical point: Cessation of calcitonin gene‐related peptide-receptor (CGRP-R) monoclonal antibody (mAb) prophylaxis worsens headache impact and health-related quality of life in patients with migraine.

Main finding: After 16 weeks from the last mAb injection, the mean Headache Impact Test-6 sum score increased by 3.69 (P < .001), mean EuroQol-5-Dimension-5-level declined by −0.07 (P = .013) and mean physical and mental component summary of Short Form-12 score deteriorated by −4.04 (P = .013) and −2.73 (P = .003), respectively.

Study details: This was a longitudinal, prospective cohort study involving 61 adult patients with episodic/chronic migraine receiving prophylaxis with a CGRP-R mAb (erenumab, n = 29; galcanezumab/fremanezumab, n = 32) for ≥8 months before a planned treatment cessation attempt.

Disclosures: The authors did not receive any financial support for the study. Some of the authors, including the lead author, reported serving on the advisory board of or receiving personal fees, speaker/consultant honoraria, and research grants from various organizations.

Source: Terhart M et al. J Headache Pain. 2021;22:158 (Dec 31). Doi: 10.1186/s10194-021-01368-7.

Key clinical point: Cessation of calcitonin gene‐related peptide-receptor (CGRP-R) monoclonal antibody (mAb) prophylaxis worsens headache impact and health-related quality of life in patients with migraine.

Main finding: After 16 weeks from the last mAb injection, the mean Headache Impact Test-6 sum score increased by 3.69 (P < .001), mean EuroQol-5-Dimension-5-level declined by −0.07 (P = .013) and mean physical and mental component summary of Short Form-12 score deteriorated by −4.04 (P = .013) and −2.73 (P = .003), respectively.

Study details: This was a longitudinal, prospective cohort study involving 61 adult patients with episodic/chronic migraine receiving prophylaxis with a CGRP-R mAb (erenumab, n = 29; galcanezumab/fremanezumab, n = 32) for ≥8 months before a planned treatment cessation attempt.

Disclosures: The authors did not receive any financial support for the study. Some of the authors, including the lead author, reported serving on the advisory board of or receiving personal fees, speaker/consultant honoraria, and research grants from various organizations.

Source: Terhart M et al. J Headache Pain. 2021;22:158 (Dec 31). Doi: 10.1186/s10194-021-01368-7.

Key clinical point: Cessation of calcitonin gene‐related peptide-receptor (CGRP-R) monoclonal antibody (mAb) prophylaxis worsens headache impact and health-related quality of life in patients with migraine.

Main finding: After 16 weeks from the last mAb injection, the mean Headache Impact Test-6 sum score increased by 3.69 (P < .001), mean EuroQol-5-Dimension-5-level declined by −0.07 (P = .013) and mean physical and mental component summary of Short Form-12 score deteriorated by −4.04 (P = .013) and −2.73 (P = .003), respectively.

Study details: This was a longitudinal, prospective cohort study involving 61 adult patients with episodic/chronic migraine receiving prophylaxis with a CGRP-R mAb (erenumab, n = 29; galcanezumab/fremanezumab, n = 32) for ≥8 months before a planned treatment cessation attempt.

Disclosures: The authors did not receive any financial support for the study. Some of the authors, including the lead author, reported serving on the advisory board of or receiving personal fees, speaker/consultant honoraria, and research grants from various organizations.

Source: Terhart M et al. J Headache Pain. 2021;22:158 (Dec 31). Doi: 10.1186/s10194-021-01368-7.

Key clinical point: Fremanezumab therapy led to significant reductions in patient-reported headache frequency and migraine pain intensity in patients with migraine.

Main finding: After fremanezumab initiation, the mean number of headache days/month reduced from 22.24 days preindex to 8.24 days postindex (P < .0001) and the mean visual analog scale pain score from 5.47 preindex to 4.51 postindex (P = .014).

Study details: This was a retrospective, observational cohort study including 172 adult patients with migraine who received fremanezumab (index event), had ≥6 months of enrollment/treatment history preindex and ≥1 month postindex along with no pregnancy event during the study.

Disclosures: The study was sponsored by Teva Branded Pharmaceutical Products R&D, Inc. The lead author received research support from and served as a consultant for various organizations including Teva. Some of the authors are current/former employees of Teva.

Source: McAllister P et al. J Headache Pain. 2021;22:156 (Dec 20). Doi: 10.1186/s10194-021-01358-9.

Key clinical point: Fremanezumab therapy led to significant reductions in patient-reported headache frequency and migraine pain intensity in patients with migraine.

Main finding: After fremanezumab initiation, the mean number of headache days/month reduced from 22.24 days preindex to 8.24 days postindex (P < .0001) and the mean visual analog scale pain score from 5.47 preindex to 4.51 postindex (P = .014).

Study details: This was a retrospective, observational cohort study including 172 adult patients with migraine who received fremanezumab (index event), had ≥6 months of enrollment/treatment history preindex and ≥1 month postindex along with no pregnancy event during the study.

Disclosures: The study was sponsored by Teva Branded Pharmaceutical Products R&D, Inc. The lead author received research support from and served as a consultant for various organizations including Teva. Some of the authors are current/former employees of Teva.

Source: McAllister P et al. J Headache Pain. 2021;22:156 (Dec 20). Doi: 10.1186/s10194-021-01358-9.

Key clinical point: Fremanezumab therapy led to significant reductions in patient-reported headache frequency and migraine pain intensity in patients with migraine.

Main finding: After fremanezumab initiation, the mean number of headache days/month reduced from 22.24 days preindex to 8.24 days postindex (P < .0001) and the mean visual analog scale pain score from 5.47 preindex to 4.51 postindex (P = .014).

Study details: This was a retrospective, observational cohort study including 172 adult patients with migraine who received fremanezumab (index event), had ≥6 months of enrollment/treatment history preindex and ≥1 month postindex along with no pregnancy event during the study.

Disclosures: The study was sponsored by Teva Branded Pharmaceutical Products R&D, Inc. The lead author received research support from and served as a consultant for various organizations including Teva. Some of the authors are current/former employees of Teva.

Source: McAllister P et al. J Headache Pain. 2021;22:156 (Dec 20). Doi: 10.1186/s10194-021-01358-9.

Key clinical point: The efficacy of fremanezumab for preventive treatment of difficult-to-treat migraine remains unaffected by age or sex.

Main finding: At week 12, quarterly and monthly fremanezumab reduced the monthly average of migraine days irrespective of age (18-45 years: quarterly, −4.1 days; monthly, −4.7 days; placebo, −0.9 days; >45 years: quarterly, −3.6 days; monthly, −3.7 days; placebo, −0.3 days; both P < .001) and sex (men: quarterly, −4.1 days; monthly, −4.6 days; placebo, −0.3 days; women: quarterly, −3.6 days; monthly, −3.9 days; placebo, −0.6 days; both P < .001).

Study details: This post hoc analysis of the phase 3b FOCUS trial included 837 adult patients with chronic/episodic migraine and an inadequate response to multiple alternative therapies, who were randomly assigned to quarterly fremanezumab, monthly fremanezumab, or placebo over 12 weeks.

Disclosures: The study was sponsored by Teva Branded Pharmaceutical Products R&D, Inc., PA. Some of the authors, including the lead author, received research funds or consultancy/speaker fees from various sources including Teva, which the rest were employees/stock owners of.

Source: MaassenVanDenBrink A et al. J Headache Pain. 2021;22:152 (Dec 18). Doi: 10.1186/s10194-021-01336-1.

Key clinical point: The efficacy of fremanezumab for preventive treatment of difficult-to-treat migraine remains unaffected by age or sex.

Main finding: At week 12, quarterly and monthly fremanezumab reduced the monthly average of migraine days irrespective of age (18-45 years: quarterly, −4.1 days; monthly, −4.7 days; placebo, −0.9 days; >45 years: quarterly, −3.6 days; monthly, −3.7 days; placebo, −0.3 days; both P < .001) and sex (men: quarterly, −4.1 days; monthly, −4.6 days; placebo, −0.3 days; women: quarterly, −3.6 days; monthly, −3.9 days; placebo, −0.6 days; both P < .001).

Study details: This post hoc analysis of the phase 3b FOCUS trial included 837 adult patients with chronic/episodic migraine and an inadequate response to multiple alternative therapies, who were randomly assigned to quarterly fremanezumab, monthly fremanezumab, or placebo over 12 weeks.

Disclosures: The study was sponsored by Teva Branded Pharmaceutical Products R&D, Inc., PA. Some of the authors, including the lead author, received research funds or consultancy/speaker fees from various sources including Teva, which the rest were employees/stock owners of.

Source: MaassenVanDenBrink A et al. J Headache Pain. 2021;22:152 (Dec 18). Doi: 10.1186/s10194-021-01336-1.

Key clinical point: The efficacy of fremanezumab for preventive treatment of difficult-to-treat migraine remains unaffected by age or sex.

Main finding: At week 12, quarterly and monthly fremanezumab reduced the monthly average of migraine days irrespective of age (18-45 years: quarterly, −4.1 days; monthly, −4.7 days; placebo, −0.9 days; >45 years: quarterly, −3.6 days; monthly, −3.7 days; placebo, −0.3 days; both P < .001) and sex (men: quarterly, −4.1 days; monthly, −4.6 days; placebo, −0.3 days; women: quarterly, −3.6 days; monthly, −3.9 days; placebo, −0.6 days; both P < .001).

Study details: This post hoc analysis of the phase 3b FOCUS trial included 837 adult patients with chronic/episodic migraine and an inadequate response to multiple alternative therapies, who were randomly assigned to quarterly fremanezumab, monthly fremanezumab, or placebo over 12 weeks.

Disclosures: The study was sponsored by Teva Branded Pharmaceutical Products R&D, Inc., PA. Some of the authors, including the lead author, received research funds or consultancy/speaker fees from various sources including Teva, which the rest were employees/stock owners of.

Source: MaassenVanDenBrink A et al. J Headache Pain. 2021;22:152 (Dec 18). Doi: 10.1186/s10194-021-01336-1.

Key clinical point: Routine clinical management of migraine using erenumab in occupationally active patients reduces the number of sick leave days and healthcare visits.

Main finding: Compared with the 12-month period before treatment initiation, a significant reduction in the number of headache-related sick leave days (4.9 vs. 1.3 sick leave days per patient-year; P = .035) and headache-related healthcare visits (4.9 vs. 2.7 visits per patient-year; P < .001) was observed over 12 months after treatment initiation.

Study details: This real-world retrospective registry analysis included 82 occupationally active patients with migraine who had 2 or more unique erenumab prescriptions and did not switch to an alternative calcitonin gene-related peptide inhibitor.

Disclosures: The study was supported by Novartis Finland Oy, Espoo, Finland. A few of the authors, including the lead author, declared serving as employees of Novartis Finland Oy while conducting the study. Amgen and Novartis have co-developed erenumab.

Source: Autio H et al. Neurol Ther. 2021 Dec 10. doi: 10.1007/s40120-021-00303-x.

Key clinical point: Routine clinical management of migraine using erenumab in occupationally active patients reduces the number of sick leave days and healthcare visits.

Main finding: Compared with the 12-month period before treatment initiation, a significant reduction in the number of headache-related sick leave days (4.9 vs. 1.3 sick leave days per patient-year; P = .035) and headache-related healthcare visits (4.9 vs. 2.7 visits per patient-year; P < .001) was observed over 12 months after treatment initiation.

Study details: This real-world retrospective registry analysis included 82 occupationally active patients with migraine who had 2 or more unique erenumab prescriptions and did not switch to an alternative calcitonin gene-related peptide inhibitor.

Disclosures: The study was supported by Novartis Finland Oy, Espoo, Finland. A few of the authors, including the lead author, declared serving as employees of Novartis Finland Oy while conducting the study. Amgen and Novartis have co-developed erenumab.

Source: Autio H et al. Neurol Ther. 2021 Dec 10. doi: 10.1007/s40120-021-00303-x.

Key clinical point: Routine clinical management of migraine using erenumab in occupationally active patients reduces the number of sick leave days and healthcare visits.

Main finding: Compared with the 12-month period before treatment initiation, a significant reduction in the number of headache-related sick leave days (4.9 vs. 1.3 sick leave days per patient-year; P = .035) and headache-related healthcare visits (4.9 vs. 2.7 visits per patient-year; P < .001) was observed over 12 months after treatment initiation.

Study details: This real-world retrospective registry analysis included 82 occupationally active patients with migraine who had 2 or more unique erenumab prescriptions and did not switch to an alternative calcitonin gene-related peptide inhibitor.

Disclosures: The study was supported by Novartis Finland Oy, Espoo, Finland. A few of the authors, including the lead author, declared serving as employees of Novartis Finland Oy while conducting the study. Amgen and Novartis have co-developed erenumab.

Source: Autio H et al. Neurol Ther. 2021 Dec 10. doi: 10.1007/s40120-021-00303-x.

Key clinical point: Noninvasive vagus nerve stimulation (nVNS) is an effective therapeutic option for preventing migraine.

Main finding: nVNS led to a greater mean reduction in monthly migraine days from baseline (3.12 days vs. 2.29 days; P = .2329) and a higher percentage of patients achieving ≥50% reduction in the number of migraine days (44.87% vs. 26.81%; P = .0481) compared to sham stimulation.

Study details: Findings are from the multicenter PREMIUM II trial wherein 231 adults with episodic or chronic migraine (with or without aura) were randomly assigned to receive nVNS (n = 114) or sham stimulation (n = 117) over 12 weeks. Of these, 113 (nVNS, n = 56; sham, n = 57) constituted the modified intention-to-treat population.

Disclosures: The study was sponsored by electroCore, Inc. Some of the authors, including the lead author, reported serving as a consultant/advisor/speaker for and receiving research grants from various organizations, including electroCore. E Liebler is an employee and stockholder of electroCore.

Source: Najib U et al. Cephalalgia. 2022  (Jan 9). Doi: 10.1177/03331024211068813.

Key clinical point: Noninvasive vagus nerve stimulation (nVNS) is an effective therapeutic option for preventing migraine.

Main finding: nVNS led to a greater mean reduction in monthly migraine days from baseline (3.12 days vs. 2.29 days; P = .2329) and a higher percentage of patients achieving ≥50% reduction in the number of migraine days (44.87% vs. 26.81%; P = .0481) compared to sham stimulation.

Study details: Findings are from the multicenter PREMIUM II trial wherein 231 adults with episodic or chronic migraine (with or without aura) were randomly assigned to receive nVNS (n = 114) or sham stimulation (n = 117) over 12 weeks. Of these, 113 (nVNS, n = 56; sham, n = 57) constituted the modified intention-to-treat population.

Disclosures: The study was sponsored by electroCore, Inc. Some of the authors, including the lead author, reported serving as a consultant/advisor/speaker for and receiving research grants from various organizations, including electroCore. E Liebler is an employee and stockholder of electroCore.

Source: Najib U et al. Cephalalgia. 2022  (Jan 9). Doi: 10.1177/03331024211068813.

Key clinical point: Noninvasive vagus nerve stimulation (nVNS) is an effective therapeutic option for preventing migraine.

Main finding: nVNS led to a greater mean reduction in monthly migraine days from baseline (3.12 days vs. 2.29 days; P = .2329) and a higher percentage of patients achieving ≥50% reduction in the number of migraine days (44.87% vs. 26.81%; P = .0481) compared to sham stimulation.

Study details: Findings are from the multicenter PREMIUM II trial wherein 231 adults with episodic or chronic migraine (with or without aura) were randomly assigned to receive nVNS (n = 114) or sham stimulation (n = 117) over 12 weeks. Of these, 113 (nVNS, n = 56; sham, n = 57) constituted the modified intention-to-treat population.

Disclosures: The study was sponsored by electroCore, Inc. Some of the authors, including the lead author, reported serving as a consultant/advisor/speaker for and receiving research grants from various organizations, including electroCore. E Liebler is an employee and stockholder of electroCore.

Source: Najib U et al. Cephalalgia. 2022  (Jan 9). Doi: 10.1177/03331024211068813.

Key clinical point: Erenumab led to decreased migraine frequency in patients with migraine with a history of aura.

Main finding: Compared with placebo, the change in monthly migraine days at week 12 was greater with 70 mg and 140 mg of erenumab in patients with episodic (least-squares mean differences [LSM] −1.1; 95% CI –1.7 to –0.6 and −0.9; 95% CI –1.6 to –0.2; respectively) and chronic (LSM −2.1; 95% CI –3.8 to –0.5 and −3.1; 95% CI –4.8 to –1.4, respectively) migraine with aura.

Study details: This was a post hoc subgroup analysis of 4 double-blind randomized clinical trials involving 2,443 adults with chronic or episodic migraine who received either erenumab (70 or 140 mg; n = 1,400) or placebo (n = 1,043).

Disclosures: Amgen Inc. sponsored the study. M Ashina reported being a principal investigator for ongoing trials for various sources including Amgen and, along with some co-authors, receiving speaking/teaching honoraria, advisory/consultation fees, or research grants from; or being a board member of, various companies. A few authors served as employees and stockholders of Amgen during the study period. Amgen and Novartis have co-developed erenumab.

Source: Ashina M et al. JAMA Neurol. 2021 (Dec 20). Doi: 10.1001/jamaneurol.2021.4678.

Key clinical point: Erenumab led to decreased migraine frequency in patients with migraine with a history of aura.

Main finding: Compared with placebo, the change in monthly migraine days at week 12 was greater with 70 mg and 140 mg of erenumab in patients with episodic (least-squares mean differences [LSM] −1.1; 95% CI –1.7 to –0.6 and −0.9; 95% CI –1.6 to –0.2; respectively) and chronic (LSM −2.1; 95% CI –3.8 to –0.5 and −3.1; 95% CI –4.8 to –1.4, respectively) migraine with aura.

Study details: This was a post hoc subgroup analysis of 4 double-blind randomized clinical trials involving 2,443 adults with chronic or episodic migraine who received either erenumab (70 or 140 mg; n = 1,400) or placebo (n = 1,043).

Disclosures: Amgen Inc. sponsored the study. M Ashina reported being a principal investigator for ongoing trials for various sources including Amgen and, along with some co-authors, receiving speaking/teaching honoraria, advisory/consultation fees, or research grants from; or being a board member of, various companies. A few authors served as employees and stockholders of Amgen during the study period. Amgen and Novartis have co-developed erenumab.

Source: Ashina M et al. JAMA Neurol. 2021 (Dec 20). Doi: 10.1001/jamaneurol.2021.4678.

Key clinical point: Erenumab led to decreased migraine frequency in patients with migraine with a history of aura.

Main finding: Compared with placebo, the change in monthly migraine days at week 12 was greater with 70 mg and 140 mg of erenumab in patients with episodic (least-squares mean differences [LSM] −1.1; 95% CI –1.7 to –0.6 and −0.9; 95% CI –1.6 to –0.2; respectively) and chronic (LSM −2.1; 95% CI –3.8 to –0.5 and −3.1; 95% CI –4.8 to –1.4, respectively) migraine with aura.

Study details: This was a post hoc subgroup analysis of 4 double-blind randomized clinical trials involving 2,443 adults with chronic or episodic migraine who received either erenumab (70 or 140 mg; n = 1,400) or placebo (n = 1,043).

Disclosures: Amgen Inc. sponsored the study. M Ashina reported being a principal investigator for ongoing trials for various sources including Amgen and, along with some co-authors, receiving speaking/teaching honoraria, advisory/consultation fees, or research grants from; or being a board member of, various companies. A few authors served as employees and stockholders of Amgen during the study period. Amgen and Novartis have co-developed erenumab.

Source: Ashina M et al. JAMA Neurol. 2021 (Dec 20). Doi: 10.1001/jamaneurol.2021.4678.

Intranasal ketamine may be a viable treatment option for acute cluster headache attacks, a pilot study has found, though it did not reduce pain intensity as quickly as initially anticipated.

“In clinical practice, intranasal ketamine might be a valuable tool for severely affected patients with insufficient response or intolerance to current first-line treatment,” wrote Anja S. Petersen, MD, of the Danish Headache Center at Rigshospitalet-Glostrup (Denmark) and her coauthors. The study was published online ahead of print in Headache.

To assess ketamine’s safety and efficacy in treating cluster headache attacks, the researchers launched a single-center, open-label, proof-of-concept study of 23 Danish patients with chronic cluster headache. Their average age was 51, 70% were males, and their mean disease duration was 18 years. Twenty of the participants suffered a spontaneous attack while under in-hospital observation and were treated with 15 mg of intranasal ketamine every 6 minutes to a maximum of five times.

Fifteen minutes after ketamine was administered, mean pain intensity (±SD) was reduced from 7.2 (±1.3) to 6.1 (±3.1) on an 11-point numeric rating scale, equivalent to a 15% reduction and well below the primary endpoint of a 50% or greater reduction. Only 4 of the 20 participants had a reduction of 50% or more, and 4 patients chose rescue medication at 15 minutes. However, at 30 minutes pain intensity was reduced by 59% (mean difference 4.3, 95% confidence interval, 2.4-6.2, P > 0.001), with 11 out of 16 participants scoring a 4 or below.

Eight of the 20 participants reported feeling complete relief from the ketamine nasal spray, while 6 participants reported feeling no effects. Half of the patients said they preferred ketamine to oxygen and/or sumatriptan injection. Seventeen patients (83%) reported side effects, but 12 of them classified their side effects as “few.” No serious adverse events were identified, with the most common adverse events being dizziness, lightheadedness, nausea/vomiting, and paresthesia.
 

Debating ketamine’s potential for cluster headache patients

“I’m not crazy about the prospects,” said Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H., in an interview. “It was an admirable proof-of-concept trial, and well worth doing. These are desperate patients. But if the aim was to decrease pain intensity within 15 minutes for cluster patients without side effects, this clearly did not do that,” Dr. Tepper said.

“In a sense, this study was to evaluate whether glutamate might be a target for chronic cluster headache, to determine if blocking NMDA glutamate receptors by ketamine would be effective,” Dr. Tepper said. “And I must say, I’m not very impressed.”

He noted his concerns about the study – including 30 minutes being an “unacceptable” wait for patients undergoing a cluster attack, the 20% of patients who required a rescue at 15 minutes, and the various side effects that come with ketamine in nasal form – and said the results did not sway him to consider ketamine a practical option for cluster headache patients.

“You add all of that up, and I would say this was an equivocal study,” he said. “There might be enough there to be worth studying in episodic cluster rather than chronic cluster; there might be enough to consider a randomized, placebo-controlled trial. But it’s not something that I would ring the bell at Wall Street about.”

“The acute treatment of a patient with chronic cluster headache is a real problem for us headache specialists,” added Alan Rapoport, MD, professor of neurology at University of California, Los Angeles, and past president of the International Headache Society, in an interview. “Cluster headache is probably the worst pain we deal with; women who’ve gone through childbirth say that cluster headache is worse. So it’s very reasonable to have tried.”

“It’s not an impressive finding,” he said, “but it does indicate that there’s some value here. Maybe they need to change the dose; maybe they need to get it in faster by doing something tricky like combining the drug with another substance that will make it attach to the nasal mucosa better. I urge them to study it again, and I hope that they come up with better results the next time, because what they attempted to study is absolutely vital.”

The authors acknowledged their study’s limitations, including a homogeneous patient population and the lack of placebo-controlled verification of effect after 30 minutes. They added, however, that a pilot study like this provides “critical information and paves the way for subsequent placebo-controlled studies.” They also admitted that “daily usage [of ketamine] seems suboptimal” because of the potential of patients becoming addicted.

The study was funded by CCH Pharmaceuticals. Several authors reported receiving speaker’s fees and being subinvestigators in trials run by various pharmaceutical companies, including CCH Pharmaceuticals.

Intranasal ketamine may be a viable treatment option for acute cluster headache attacks, a pilot study has found, though it did not reduce pain intensity as quickly as initially anticipated.

“In clinical practice, intranasal ketamine might be a valuable tool for severely affected patients with insufficient response or intolerance to current first-line treatment,” wrote Anja S. Petersen, MD, of the Danish Headache Center at Rigshospitalet-Glostrup (Denmark) and her coauthors. The study was published online ahead of print in Headache.

To assess ketamine’s safety and efficacy in treating cluster headache attacks, the researchers launched a single-center, open-label, proof-of-concept study of 23 Danish patients with chronic cluster headache. Their average age was 51, 70% were males, and their mean disease duration was 18 years. Twenty of the participants suffered a spontaneous attack while under in-hospital observation and were treated with 15 mg of intranasal ketamine every 6 minutes to a maximum of five times.

Fifteen minutes after ketamine was administered, mean pain intensity (±SD) was reduced from 7.2 (±1.3) to 6.1 (±3.1) on an 11-point numeric rating scale, equivalent to a 15% reduction and well below the primary endpoint of a 50% or greater reduction. Only 4 of the 20 participants had a reduction of 50% or more, and 4 patients chose rescue medication at 15 minutes. However, at 30 minutes pain intensity was reduced by 59% (mean difference 4.3, 95% confidence interval, 2.4-6.2, P > 0.001), with 11 out of 16 participants scoring a 4 or below.

Eight of the 20 participants reported feeling complete relief from the ketamine nasal spray, while 6 participants reported feeling no effects. Half of the patients said they preferred ketamine to oxygen and/or sumatriptan injection. Seventeen patients (83%) reported side effects, but 12 of them classified their side effects as “few.” No serious adverse events were identified, with the most common adverse events being dizziness, lightheadedness, nausea/vomiting, and paresthesia.
 

Debating ketamine’s potential for cluster headache patients

“I’m not crazy about the prospects,” said Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H., in an interview. “It was an admirable proof-of-concept trial, and well worth doing. These are desperate patients. But if the aim was to decrease pain intensity within 15 minutes for cluster patients without side effects, this clearly did not do that,” Dr. Tepper said.

“In a sense, this study was to evaluate whether glutamate might be a target for chronic cluster headache, to determine if blocking NMDA glutamate receptors by ketamine would be effective,” Dr. Tepper said. “And I must say, I’m not very impressed.”

He noted his concerns about the study – including 30 minutes being an “unacceptable” wait for patients undergoing a cluster attack, the 20% of patients who required a rescue at 15 minutes, and the various side effects that come with ketamine in nasal form – and said the results did not sway him to consider ketamine a practical option for cluster headache patients.

“You add all of that up, and I would say this was an equivocal study,” he said. “There might be enough there to be worth studying in episodic cluster rather than chronic cluster; there might be enough to consider a randomized, placebo-controlled trial. But it’s not something that I would ring the bell at Wall Street about.”

“The acute treatment of a patient with chronic cluster headache is a real problem for us headache specialists,” added Alan Rapoport, MD, professor of neurology at University of California, Los Angeles, and past president of the International Headache Society, in an interview. “Cluster headache is probably the worst pain we deal with; women who’ve gone through childbirth say that cluster headache is worse. So it’s very reasonable to have tried.”

“It’s not an impressive finding,” he said, “but it does indicate that there’s some value here. Maybe they need to change the dose; maybe they need to get it in faster by doing something tricky like combining the drug with another substance that will make it attach to the nasal mucosa better. I urge them to study it again, and I hope that they come up with better results the next time, because what they attempted to study is absolutely vital.”

The authors acknowledged their study’s limitations, including a homogeneous patient population and the lack of placebo-controlled verification of effect after 30 minutes. They added, however, that a pilot study like this provides “critical information and paves the way for subsequent placebo-controlled studies.” They also admitted that “daily usage [of ketamine] seems suboptimal” because of the potential of patients becoming addicted.

The study was funded by CCH Pharmaceuticals. Several authors reported receiving speaker’s fees and being subinvestigators in trials run by various pharmaceutical companies, including CCH Pharmaceuticals.

Intranasal ketamine may be a viable treatment option for acute cluster headache attacks, a pilot study has found, though it did not reduce pain intensity as quickly as initially anticipated.

“In clinical practice, intranasal ketamine might be a valuable tool for severely affected patients with insufficient response or intolerance to current first-line treatment,” wrote Anja S. Petersen, MD, of the Danish Headache Center at Rigshospitalet-Glostrup (Denmark) and her coauthors. The study was published online ahead of print in Headache.

To assess ketamine’s safety and efficacy in treating cluster headache attacks, the researchers launched a single-center, open-label, proof-of-concept study of 23 Danish patients with chronic cluster headache. Their average age was 51, 70% were males, and their mean disease duration was 18 years. Twenty of the participants suffered a spontaneous attack while under in-hospital observation and were treated with 15 mg of intranasal ketamine every 6 minutes to a maximum of five times.

Fifteen minutes after ketamine was administered, mean pain intensity (±SD) was reduced from 7.2 (±1.3) to 6.1 (±3.1) on an 11-point numeric rating scale, equivalent to a 15% reduction and well below the primary endpoint of a 50% or greater reduction. Only 4 of the 20 participants had a reduction of 50% or more, and 4 patients chose rescue medication at 15 minutes. However, at 30 minutes pain intensity was reduced by 59% (mean difference 4.3, 95% confidence interval, 2.4-6.2, P > 0.001), with 11 out of 16 participants scoring a 4 or below.

Eight of the 20 participants reported feeling complete relief from the ketamine nasal spray, while 6 participants reported feeling no effects. Half of the patients said they preferred ketamine to oxygen and/or sumatriptan injection. Seventeen patients (83%) reported side effects, but 12 of them classified their side effects as “few.” No serious adverse events were identified, with the most common adverse events being dizziness, lightheadedness, nausea/vomiting, and paresthesia.
 

Debating ketamine’s potential for cluster headache patients

“I’m not crazy about the prospects,” said Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H., in an interview. “It was an admirable proof-of-concept trial, and well worth doing. These are desperate patients. But if the aim was to decrease pain intensity within 15 minutes for cluster patients without side effects, this clearly did not do that,” Dr. Tepper said.

“In a sense, this study was to evaluate whether glutamate might be a target for chronic cluster headache, to determine if blocking NMDA glutamate receptors by ketamine would be effective,” Dr. Tepper said. “And I must say, I’m not very impressed.”

He noted his concerns about the study – including 30 minutes being an “unacceptable” wait for patients undergoing a cluster attack, the 20% of patients who required a rescue at 15 minutes, and the various side effects that come with ketamine in nasal form – and said the results did not sway him to consider ketamine a practical option for cluster headache patients.

“You add all of that up, and I would say this was an equivocal study,” he said. “There might be enough there to be worth studying in episodic cluster rather than chronic cluster; there might be enough to consider a randomized, placebo-controlled trial. But it’s not something that I would ring the bell at Wall Street about.”

“The acute treatment of a patient with chronic cluster headache is a real problem for us headache specialists,” added Alan Rapoport, MD, professor of neurology at University of California, Los Angeles, and past president of the International Headache Society, in an interview. “Cluster headache is probably the worst pain we deal with; women who’ve gone through childbirth say that cluster headache is worse. So it’s very reasonable to have tried.”

“It’s not an impressive finding,” he said, “but it does indicate that there’s some value here. Maybe they need to change the dose; maybe they need to get it in faster by doing something tricky like combining the drug with another substance that will make it attach to the nasal mucosa better. I urge them to study it again, and I hope that they come up with better results the next time, because what they attempted to study is absolutely vital.”

The authors acknowledged their study’s limitations, including a homogeneous patient population and the lack of placebo-controlled verification of effect after 30 minutes. They added, however, that a pilot study like this provides “critical information and paves the way for subsequent placebo-controlled studies.” They also admitted that “daily usage [of ketamine] seems suboptimal” because of the potential of patients becoming addicted.

The study was funded by CCH Pharmaceuticals. Several authors reported receiving speaker’s fees and being subinvestigators in trials run by various pharmaceutical companies, including CCH Pharmaceuticals.