Migraine ICYMI

Key clinical point: Erenumab may serve as an effective and well-tolerated therapeutic agent for migraine prophylaxis.

Major finding: Compared with placebo, 28 mg (mean difference [MD] −1.1; P = .02), 70 mg (MD −1.4; P < .001), and 140 mg (MD −1.8; P < .001) erenumab led to significant reductions in monthly migraine days at 12 weeks, with each erenumab dose being associated with a significantly higher proportion of patients achieving ≥50% reduction in migraine days (all P < .001) and similar risk for adverse events.

Study details: This was a systematic review and meta-analysis of eight randomized controlled trials including 4860 patients with migraine who received erenumab (7, 21, 28, 70, or 140 mg) or placebo.

Disclosures: This study was funded by the Jiangsu Province Key Research and Development Program, National Natural Science Foundation of China, and Natural Science Foundation of Jiangsu Province. The authors declared no conflicts of interest.

Source: Gui T, Li H et al. Different dosage regimens of erenumab for the treatment of migraine: A systematic review and meta-analysis of the efficacy and safety of randomized controlled trials. Headache. 2022;62(10):1281-1292 (Nov 14). Doi: 10.1111/head.14423

Key clinical point: Erenumab may serve as an effective and well-tolerated therapeutic agent for migraine prophylaxis.

Major finding: Compared with placebo, 28 mg (mean difference [MD] −1.1; P = .02), 70 mg (MD −1.4; P < .001), and 140 mg (MD −1.8; P < .001) erenumab led to significant reductions in monthly migraine days at 12 weeks, with each erenumab dose being associated with a significantly higher proportion of patients achieving ≥50% reduction in migraine days (all P < .001) and similar risk for adverse events.

Study details: This was a systematic review and meta-analysis of eight randomized controlled trials including 4860 patients with migraine who received erenumab (7, 21, 28, 70, or 140 mg) or placebo.

Disclosures: This study was funded by the Jiangsu Province Key Research and Development Program, National Natural Science Foundation of China, and Natural Science Foundation of Jiangsu Province. The authors declared no conflicts of interest.

Source: Gui T, Li H et al. Different dosage regimens of erenumab for the treatment of migraine: A systematic review and meta-analysis of the efficacy and safety of randomized controlled trials. Headache. 2022;62(10):1281-1292 (Nov 14). Doi: 10.1111/head.14423

Key clinical point: Erenumab may serve as an effective and well-tolerated therapeutic agent for migraine prophylaxis.

Major finding: Compared with placebo, 28 mg (mean difference [MD] −1.1; P = .02), 70 mg (MD −1.4; P < .001), and 140 mg (MD −1.8; P < .001) erenumab led to significant reductions in monthly migraine days at 12 weeks, with each erenumab dose being associated with a significantly higher proportion of patients achieving ≥50% reduction in migraine days (all P < .001) and similar risk for adverse events.

Study details: This was a systematic review and meta-analysis of eight randomized controlled trials including 4860 patients with migraine who received erenumab (7, 21, 28, 70, or 140 mg) or placebo.

Disclosures: This study was funded by the Jiangsu Province Key Research and Development Program, National Natural Science Foundation of China, and Natural Science Foundation of Jiangsu Province. The authors declared no conflicts of interest.

Source: Gui T, Li H et al. Different dosage regimens of erenumab for the treatment of migraine: A systematic review and meta-analysis of the efficacy and safety of randomized controlled trials. Headache. 2022;62(10):1281-1292 (Nov 14). Doi: 10.1111/head.14423

Key clinical point: High quality diet and higher total intake of phytochemicals and polyphenols are significantly associated with lower migraine severity in patients with episodic migraine.

Major finding: Migraine severity was negatively correlated with the intake of good quality diet (correlation coefficient [r] −0.37; P = .0003) and higher intake of phytochemicals (r −0.37; P = .0003) and phenolic components, such as flavanones (r −0.27; P = .01) and lignans (r −0.27; P = .01). The total intake of phenols and flavonoids from olive oil, oil, and fruits was also significantly negatively correlated with migraine severity (each P ≤ .04).

Study details: This questionnaire-based study included 90 patients with episodic migraine who were assessed for their migraine characteristics and dietary phytochemical and polyphenol intake.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Bakırhan H et al. Migraine severity, disability, and duration: Is a good diet quality, high intake of phytochemicals and polyphenols important? Front Nutr. 2022;9:1041907 (Nov 21). Doi: 10.3389/fnut.2022.1041907

Key clinical point: High quality diet and higher total intake of phytochemicals and polyphenols are significantly associated with lower migraine severity in patients with episodic migraine.

Major finding: Migraine severity was negatively correlated with the intake of good quality diet (correlation coefficient [r] −0.37; P = .0003) and higher intake of phytochemicals (r −0.37; P = .0003) and phenolic components, such as flavanones (r −0.27; P = .01) and lignans (r −0.27; P = .01). The total intake of phenols and flavonoids from olive oil, oil, and fruits was also significantly negatively correlated with migraine severity (each P ≤ .04).

Study details: This questionnaire-based study included 90 patients with episodic migraine who were assessed for their migraine characteristics and dietary phytochemical and polyphenol intake.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Bakırhan H et al. Migraine severity, disability, and duration: Is a good diet quality, high intake of phytochemicals and polyphenols important? Front Nutr. 2022;9:1041907 (Nov 21). Doi: 10.3389/fnut.2022.1041907

Key clinical point: High quality diet and higher total intake of phytochemicals and polyphenols are significantly associated with lower migraine severity in patients with episodic migraine.

Major finding: Migraine severity was negatively correlated with the intake of good quality diet (correlation coefficient [r] −0.37; P = .0003) and higher intake of phytochemicals (r −0.37; P = .0003) and phenolic components, such as flavanones (r −0.27; P = .01) and lignans (r −0.27; P = .01). The total intake of phenols and flavonoids from olive oil, oil, and fruits was also significantly negatively correlated with migraine severity (each P ≤ .04).

Study details: This questionnaire-based study included 90 patients with episodic migraine who were assessed for their migraine characteristics and dietary phytochemical and polyphenol intake.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Bakırhan H et al. Migraine severity, disability, and duration: Is a good diet quality, high intake of phytochemicals and polyphenols important? Front Nutr. 2022;9:1041907 (Nov 21). Doi: 10.3389/fnut.2022.1041907

Key clinical point: The first two administrations of onabotulinum toxin A (onabotA) were well-tolerated in patients with chronic migraine, with adverse events (AE) being mostly mild and tolerability to onabotA not being correlated with AE or clinical response.

Major finding: The mean tolerability scores were 7.8/10 and 7.2/10 in the first and second onabotA administration sessions, respectively, with no association being observed between tolerability and AE occurrence or clinical response. The AE were mostly mild and were reported by 71.4% and 68.6% of patients after the first and second onabotA administration sessions, respectively; 49.5% of patients showed a 50% response rate between weeks 20 and 24.

Study details: This was an observational prospective cohort study including 105 patients with chronic migraine who had received onabotA for the first time.

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

Source: García-Azorín D et al. Real-world evaluation of the tolerability to onabotulinum toxin A: The RETO study. Toxins (Basel). 2022;14(12),850 (Dec 3). Doi: 10.3390/toxins14120850.

Key clinical point: The first two administrations of onabotulinum toxin A (onabotA) were well-tolerated in patients with chronic migraine, with adverse events (AE) being mostly mild and tolerability to onabotA not being correlated with AE or clinical response.

Major finding: The mean tolerability scores were 7.8/10 and 7.2/10 in the first and second onabotA administration sessions, respectively, with no association being observed between tolerability and AE occurrence or clinical response. The AE were mostly mild and were reported by 71.4% and 68.6% of patients after the first and second onabotA administration sessions, respectively; 49.5% of patients showed a 50% response rate between weeks 20 and 24.

Study details: This was an observational prospective cohort study including 105 patients with chronic migraine who had received onabotA for the first time.

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

Source: García-Azorín D et al. Real-world evaluation of the tolerability to onabotulinum toxin A: The RETO study. Toxins (Basel). 2022;14(12),850 (Dec 3). Doi: 10.3390/toxins14120850.

Key clinical point: The first two administrations of onabotulinum toxin A (onabotA) were well-tolerated in patients with chronic migraine, with adverse events (AE) being mostly mild and tolerability to onabotA not being correlated with AE or clinical response.

Major finding: The mean tolerability scores were 7.8/10 and 7.2/10 in the first and second onabotA administration sessions, respectively, with no association being observed between tolerability and AE occurrence or clinical response. The AE were mostly mild and were reported by 71.4% and 68.6% of patients after the first and second onabotA administration sessions, respectively; 49.5% of patients showed a 50% response rate between weeks 20 and 24.

Study details: This was an observational prospective cohort study including 105 patients with chronic migraine who had received onabotA for the first time.

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

Source: García-Azorín D et al. Real-world evaluation of the tolerability to onabotulinum toxin A: The RETO study. Toxins (Basel). 2022;14(12),850 (Dec 3). Doi: 10.3390/toxins14120850.

Key clinical point: Erenumab demonstrated an early onset of and superior efficacy in achieving ≥50% reduction in monthly migraine days (MMD) than topiramate in patients with migraine.

Major finding: A significantly higher proportion of patients receiving erenumab vs topiramate reported ≥50% reduction in MMD at 1 month (39.2% vs 24.0%) and during the last 3 months (60.3% vs 43.3%) of treatment (both P < .001). Reductions in MMD over last 3 months were significantly higher with erenumab vs topiramate (mean difference −1.24 days; P < .001).

Study details: This post hoc analysis of the phase 4 HER-MES trial included 776 patients with migraine who were naive to migraine prophylactics or had failed or were ill-suited for metoprolol/propranolol, amitriptyline, or flunarizine and were randomized to receive erenumab (70 or 140 mg/month) or topiramate (50-100 mg/day).

Disclosures: This study was funded by Novartis Pharma GmbH, Germany. Four authors, including the first author, declared being employees of and holding stocks in Novartis. U Reuter reported receiving grants, personal fees, and other supports from Novartis and various other sources.

Source: Ehrlich M et al. Erenumab versus topiramate: Post hoc efficacy analysis from the HER‑MES study. J Headache Pain. 2022;23:141 (Nov 15). Doi: 10.1186/s10194-022-01511-y

Key clinical point: Erenumab demonstrated an early onset of and superior efficacy in achieving ≥50% reduction in monthly migraine days (MMD) than topiramate in patients with migraine.

Major finding: A significantly higher proportion of patients receiving erenumab vs topiramate reported ≥50% reduction in MMD at 1 month (39.2% vs 24.0%) and during the last 3 months (60.3% vs 43.3%) of treatment (both P < .001). Reductions in MMD over last 3 months were significantly higher with erenumab vs topiramate (mean difference −1.24 days; P < .001).

Study details: This post hoc analysis of the phase 4 HER-MES trial included 776 patients with migraine who were naive to migraine prophylactics or had failed or were ill-suited for metoprolol/propranolol, amitriptyline, or flunarizine and were randomized to receive erenumab (70 or 140 mg/month) or topiramate (50-100 mg/day).

Disclosures: This study was funded by Novartis Pharma GmbH, Germany. Four authors, including the first author, declared being employees of and holding stocks in Novartis. U Reuter reported receiving grants, personal fees, and other supports from Novartis and various other sources.

Source: Ehrlich M et al. Erenumab versus topiramate: Post hoc efficacy analysis from the HER‑MES study. J Headache Pain. 2022;23:141 (Nov 15). Doi: 10.1186/s10194-022-01511-y

Key clinical point: Erenumab demonstrated an early onset of and superior efficacy in achieving ≥50% reduction in monthly migraine days (MMD) than topiramate in patients with migraine.

Major finding: A significantly higher proportion of patients receiving erenumab vs topiramate reported ≥50% reduction in MMD at 1 month (39.2% vs 24.0%) and during the last 3 months (60.3% vs 43.3%) of treatment (both P < .001). Reductions in MMD over last 3 months were significantly higher with erenumab vs topiramate (mean difference −1.24 days; P < .001).

Study details: This post hoc analysis of the phase 4 HER-MES trial included 776 patients with migraine who were naive to migraine prophylactics or had failed or were ill-suited for metoprolol/propranolol, amitriptyline, or flunarizine and were randomized to receive erenumab (70 or 140 mg/month) or topiramate (50-100 mg/day).

Disclosures: This study was funded by Novartis Pharma GmbH, Germany. Four authors, including the first author, declared being employees of and holding stocks in Novartis. U Reuter reported receiving grants, personal fees, and other supports from Novartis and various other sources.

Source: Ehrlich M et al. Erenumab versus topiramate: Post hoc efficacy analysis from the HER‑MES study. J Headache Pain. 2022;23:141 (Nov 15). Doi: 10.1186/s10194-022-01511-y

Key clinical point: Monthly erenumab demonstrated promising short-term clinical effectiveness in patients with difficult-to-treat chronic migraine; however, less than one-fourth of the patients sustained efficacy over 2 years.

Major finding: The monthly migraine days (MMD) reduced significantly after 6 months of erenumab treatment (mean reduction [MR] 7.5 days; P < .001), with 48% of patients achieving ≥30% reduction in MMD. At months 12 and 24, 38% and 23% of patients remained ≥30% responders, respectively.

Study details: Findings are from a 2-year real-world prospective analysis of a clinical audit including 160 patients with difficult-to-treat chronic migraine who failed an average of 8.3 preventive treatments and received monthly erenumab.

Disclosures: This study did not receive any funding. Three authors declared receiving honoraria for speaking or participation in advisory boards or funding for travel from various sources.

Source: Andreou AP et al. Two-year effectiveness of erenumab in resistant chronic migraine: a prospective real-world analysis. J Headache Pain. 2022;23:139 (Nov 4). Doi: 10.1186/s10194-022-01507-8

Key clinical point: Monthly erenumab demonstrated promising short-term clinical effectiveness in patients with difficult-to-treat chronic migraine; however, less than one-fourth of the patients sustained efficacy over 2 years.

Major finding: The monthly migraine days (MMD) reduced significantly after 6 months of erenumab treatment (mean reduction [MR] 7.5 days; P < .001), with 48% of patients achieving ≥30% reduction in MMD. At months 12 and 24, 38% and 23% of patients remained ≥30% responders, respectively.

Study details: Findings are from a 2-year real-world prospective analysis of a clinical audit including 160 patients with difficult-to-treat chronic migraine who failed an average of 8.3 preventive treatments and received monthly erenumab.

Disclosures: This study did not receive any funding. Three authors declared receiving honoraria for speaking or participation in advisory boards or funding for travel from various sources.

Source: Andreou AP et al. Two-year effectiveness of erenumab in resistant chronic migraine: a prospective real-world analysis. J Headache Pain. 2022;23:139 (Nov 4). Doi: 10.1186/s10194-022-01507-8

Key clinical point: Monthly erenumab demonstrated promising short-term clinical effectiveness in patients with difficult-to-treat chronic migraine; however, less than one-fourth of the patients sustained efficacy over 2 years.

Major finding: The monthly migraine days (MMD) reduced significantly after 6 months of erenumab treatment (mean reduction [MR] 7.5 days; P < .001), with 48% of patients achieving ≥30% reduction in MMD. At months 12 and 24, 38% and 23% of patients remained ≥30% responders, respectively.

Study details: Findings are from a 2-year real-world prospective analysis of a clinical audit including 160 patients with difficult-to-treat chronic migraine who failed an average of 8.3 preventive treatments and received monthly erenumab.

Disclosures: This study did not receive any funding. Three authors declared receiving honoraria for speaking or participation in advisory boards or funding for travel from various sources.

Source: Andreou AP et al. Two-year effectiveness of erenumab in resistant chronic migraine: a prospective real-world analysis. J Headache Pain. 2022;23:139 (Nov 4). Doi: 10.1186/s10194-022-01507-8

Key clinical point: Prior use of proton pump inhibitors (PPI) increased the risk for incident migraine with or without aura irrespective of the history and duration of use.

Major finding: Compared with non-use, past and current use of PPI increased the odds of migraine by 2.56-fold (P < .001) and 4.66-fold (P < .001), respectively, with the risk being persistent for migraine with or without aura (P < .001) and higher with PPI use for ≥30 (adjusted odds ratio [aOR] 4.41; P < .001) vs <30 (aOR 2.49; P < .001) days.

Study details: This retrospective, nested case-control study included 28,159 patients with incident migraine with or without aura and 112,636 propensity score-matched control participants.

Disclosures: This study was funded by the National Research Foundation of Korea from the Korean Ministry of Science and ICT. The authors declared no conflicts of interest.

Source: Kang HS et al. Association between migraines and prior proton pump inhibitor use: A nested case-control study using a national health screening cohort. Pharmaceuticals (Basel). 2022;15(11):1385 (Nov 10). Doi: 10.3390/ph15111385

Key clinical point: Prior use of proton pump inhibitors (PPI) increased the risk for incident migraine with or without aura irrespective of the history and duration of use.

Major finding: Compared with non-use, past and current use of PPI increased the odds of migraine by 2.56-fold (P < .001) and 4.66-fold (P < .001), respectively, with the risk being persistent for migraine with or without aura (P < .001) and higher with PPI use for ≥30 (adjusted odds ratio [aOR] 4.41; P < .001) vs <30 (aOR 2.49; P < .001) days.

Study details: This retrospective, nested case-control study included 28,159 patients with incident migraine with or without aura and 112,636 propensity score-matched control participants.

Disclosures: This study was funded by the National Research Foundation of Korea from the Korean Ministry of Science and ICT. The authors declared no conflicts of interest.

Source: Kang HS et al. Association between migraines and prior proton pump inhibitor use: A nested case-control study using a national health screening cohort. Pharmaceuticals (Basel). 2022;15(11):1385 (Nov 10). Doi: 10.3390/ph15111385

Key clinical point: Prior use of proton pump inhibitors (PPI) increased the risk for incident migraine with or without aura irrespective of the history and duration of use.

Major finding: Compared with non-use, past and current use of PPI increased the odds of migraine by 2.56-fold (P < .001) and 4.66-fold (P < .001), respectively, with the risk being persistent for migraine with or without aura (P < .001) and higher with PPI use for ≥30 (adjusted odds ratio [aOR] 4.41; P < .001) vs <30 (aOR 2.49; P < .001) days.

Study details: This retrospective, nested case-control study included 28,159 patients with incident migraine with or without aura and 112,636 propensity score-matched control participants.

Disclosures: This study was funded by the National Research Foundation of Korea from the Korean Ministry of Science and ICT. The authors declared no conflicts of interest.

Source: Kang HS et al. Association between migraines and prior proton pump inhibitor use: A nested case-control study using a national health screening cohort. Pharmaceuticals (Basel). 2022;15(11):1385 (Nov 10). Doi: 10.3390/ph15111385

Key clinical point: Alcohol intake slightly reduced the likelihood of migraine attacks 48 hours after consumption in an English-speaking cohort of patients with episodic migraine who identified themselves as mostly low-dose alcohol consumers.

Major finding: The probability of migraine attack 48 hours after consuming alcohol was 25% lower than that after no alcohol consumption (adjusted odds ratio 0.75; 95% CI 0.68-0.82); however, alcohol consumption had no significant effect on migraine probability 24 hours after consumption.

Study details: This observational prospective cohort study included 487 patients with episodic migraine who reported 5913 migraine attacks and were alcohol consumers.

Disclosures: The study was partially funded by Curelator, Inc. M Vives-Mestres and A Casanova declared receiving consulting fees and holding stock options in Curelator, Inc. N Rosen reported ties with a headache society, journals, and various other sources.

Source: Vives-Mestres M et al. Alcohol as a trigger of migraine attacks in people with migraine. Results from a large prospective cohort study in English-speaking countries. Headache. 2022;62:1329-1338. (Nov 27). Doi: 10.1111/head.14428

Key clinical point: Alcohol intake slightly reduced the likelihood of migraine attacks 48 hours after consumption in an English-speaking cohort of patients with episodic migraine who identified themselves as mostly low-dose alcohol consumers.

Major finding: The probability of migraine attack 48 hours after consuming alcohol was 25% lower than that after no alcohol consumption (adjusted odds ratio 0.75; 95% CI 0.68-0.82); however, alcohol consumption had no significant effect on migraine probability 24 hours after consumption.

Study details: This observational prospective cohort study included 487 patients with episodic migraine who reported 5913 migraine attacks and were alcohol consumers.

Disclosures: The study was partially funded by Curelator, Inc. M Vives-Mestres and A Casanova declared receiving consulting fees and holding stock options in Curelator, Inc. N Rosen reported ties with a headache society, journals, and various other sources.

Source: Vives-Mestres M et al. Alcohol as a trigger of migraine attacks in people with migraine. Results from a large prospective cohort study in English-speaking countries. Headache. 2022;62:1329-1338. (Nov 27). Doi: 10.1111/head.14428

Key clinical point: Alcohol intake slightly reduced the likelihood of migraine attacks 48 hours after consumption in an English-speaking cohort of patients with episodic migraine who identified themselves as mostly low-dose alcohol consumers.

Major finding: The probability of migraine attack 48 hours after consuming alcohol was 25% lower than that after no alcohol consumption (adjusted odds ratio 0.75; 95% CI 0.68-0.82); however, alcohol consumption had no significant effect on migraine probability 24 hours after consumption.

Study details: This observational prospective cohort study included 487 patients with episodic migraine who reported 5913 migraine attacks and were alcohol consumers.

Disclosures: The study was partially funded by Curelator, Inc. M Vives-Mestres and A Casanova declared receiving consulting fees and holding stock options in Curelator, Inc. N Rosen reported ties with a headache society, journals, and various other sources.

Source: Vives-Mestres M et al. Alcohol as a trigger of migraine attacks in people with migraine. Results from a large prospective cohort study in English-speaking countries. Headache. 2022;62:1329-1338. (Nov 27). Doi: 10.1111/head.14428

Key clinical point: Once-daily atogepant at doses of 30 and 60 mg significantly improved the performance of social, work-related, and daily activities compared with placebo in patients with episodic migraine.

Major finding: At week 12, atogepant (30 and 60 mg) vs placebo significantly improved Migraine-Specific Quality of Life Questionnaire version 2.1 Role Function-Restrictive (least-squares mean difference [LSMD] 10.08 and 10.8, respectively; both P < .0001). Atogepant at doses of 30 and 60 mg significantly improved monthly Activity Impairment in Migraine-Diary Performance of Daily Activities (P = .0003 and P < .0001, respectively) and Physical Impairment (P = .001 and P < .0001, respectively) scores across the 12-week treatment.

Study details: Findings are from the phase 3, ADVANCE trial including 873 patients with episodic migraine who were randomly assigned to receive once-daily atogepant (10, 30, or 60 mg) or placebo.

Disclosures: This study was sponsored by AbbVie/Allergan. Four authors declared being current or former employees of or holding stocks in AbbVie. The lead author and several other authors reported ties with various sources, including AbbVie.

Source: Lipton RB et al. Effect of atogepant for preventive migraine treatment on patient-reported outcomes in the randomized, double-blind, phase 3 ADVANCE trial. Neurology. 2022 (Nov 17). Doi: 10.1212/WNL.0000000000201568

Key clinical point: Once-daily atogepant at doses of 30 and 60 mg significantly improved the performance of social, work-related, and daily activities compared with placebo in patients with episodic migraine.

Major finding: At week 12, atogepant (30 and 60 mg) vs placebo significantly improved Migraine-Specific Quality of Life Questionnaire version 2.1 Role Function-Restrictive (least-squares mean difference [LSMD] 10.08 and 10.8, respectively; both P < .0001). Atogepant at doses of 30 and 60 mg significantly improved monthly Activity Impairment in Migraine-Diary Performance of Daily Activities (P = .0003 and P < .0001, respectively) and Physical Impairment (P = .001 and P < .0001, respectively) scores across the 12-week treatment.

Study details: Findings are from the phase 3, ADVANCE trial including 873 patients with episodic migraine who were randomly assigned to receive once-daily atogepant (10, 30, or 60 mg) or placebo.

Disclosures: This study was sponsored by AbbVie/Allergan. Four authors declared being current or former employees of or holding stocks in AbbVie. The lead author and several other authors reported ties with various sources, including AbbVie.

Source: Lipton RB et al. Effect of atogepant for preventive migraine treatment on patient-reported outcomes in the randomized, double-blind, phase 3 ADVANCE trial. Neurology. 2022 (Nov 17). Doi: 10.1212/WNL.0000000000201568

Key clinical point: Once-daily atogepant at doses of 30 and 60 mg significantly improved the performance of social, work-related, and daily activities compared with placebo in patients with episodic migraine.

Major finding: At week 12, atogepant (30 and 60 mg) vs placebo significantly improved Migraine-Specific Quality of Life Questionnaire version 2.1 Role Function-Restrictive (least-squares mean difference [LSMD] 10.08 and 10.8, respectively; both P < .0001). Atogepant at doses of 30 and 60 mg significantly improved monthly Activity Impairment in Migraine-Diary Performance of Daily Activities (P = .0003 and P < .0001, respectively) and Physical Impairment (P = .001 and P < .0001, respectively) scores across the 12-week treatment.

Study details: Findings are from the phase 3, ADVANCE trial including 873 patients with episodic migraine who were randomly assigned to receive once-daily atogepant (10, 30, or 60 mg) or placebo.

Disclosures: This study was sponsored by AbbVie/Allergan. Four authors declared being current or former employees of or holding stocks in AbbVie. The lead author and several other authors reported ties with various sources, including AbbVie.

Source: Lipton RB et al. Effect of atogepant for preventive migraine treatment on patient-reported outcomes in the randomized, double-blind, phase 3 ADVANCE trial. Neurology. 2022 (Nov 17). Doi: 10.1212/WNL.0000000000201568

Because of the high out-of-pocket costs of new-to-market neurologic drugs that are of similar benefit as older agents, only a small percentage of patients with neurologic disorders have access to these cutting-edge medications, new research shows.

“Our study of people with neurologic conditions found that fewer than 20% were being treated with new medications,” study author Brian C. Callaghan, MD, with University of Michigan Health in Ann Arbor, said in a statement.

“For new, high-cost medications that have similar effectiveness to older drugs, limited use is likely appropriate. However, future studies are needed to look into whether the high costs are barriers to those new medications that can really make a difference for people living with neurologic disease,” Dr. Callaghan said.

The study was published online in Neurology.
 

Most expensive drugs

Using insurance claims data, the investigators compared the utilization and costs of new-to-market drugs from 2014 to 2018 with those for existing guideline-supported medications for treating 11 neurologic conditions.

The new drugs included:

• erenumab, fremanezumab, and galcanezumab for migraine.
• ocrelizumab and peginterferon beta-1a for multiple sclerosis (MS).
• pimavanserin and safinamide for Parkinson’s disease.
• droxidopa for orthostatic hypertension.
• eculizumab for myasthenia gravis (MG).
• edaravone for amyotrophic lateral sclerosis (ALS).
• deutetrabenazine and valbenazine for Huntington’s disease and tardive dyskinesia.
• patisiran and inotersen for transthyretin amyloidosis (ATTR).
• eteplirsen and deflazacort for Duchenne disease.
• nusinersen for spinal muscular atrophy (SMA).

Utilization of new drugs was modest – they accounted for one in five prescriptions for every condition except tardive dyskinesia (32% for valbenazine), the researchers noted.

Mean out-of-pocket costs were significantly higher for the new medications, although there was large variability among individual drugs.

The two most expensive drugs were edaravone, for ALS, with a mean out-of-pocket cost of $713 for a 30-day supply, and eculizumab, for MG, which costs $91 per month.

“For new-to-market medications, the distribution of out-of-pocket costs were highly variable and the trends over time were unpredictable compared with existing guideline-supported medications,” the authors reported.

They noted that potential reasons for low utilization of newer agents include delay in provider uptake and prescriber and/or patient avoidance because of high cost.

Given that most of the new neurologic agents offer little advantage compared with existing treatments – exceptions being new drugs for SMA and ATTR – drug costs should be a key consideration in prescribing decisions, Dr. Callaghan and colleagues concluded.

One limitation of the study is that follow-up time was short for some of the recently approved medications. Another limitation is that the number of people in the study who had rare diseases was small.
 

Revolution in neurotherapeutics

“We are living in a time when new treatments bring hope to people with neurologic diseases and disorders,” Orly Avitzur, MD, president of the American Academy of Neurology, said in a statement.

“However, even existing prescription medication can be expensive and drug prices continue to rise. In order for neurologists to provide people with the highest quality care, it is imperative that new drugs are accessible and affordable to the people who need them,” Dr. Avitzur added.

Writing in a linked editorial, A. Gordon Smith, MD, professor and chair, department of neurology, Virginia Commonwealth University, Richmond, said there is a revolution in neurotherapeutics, with particularly robust growth in new drug approvals for orphan diseases (those affecting < 200,000 Americans).

“This study adds to a growing literature indicating rising drug prices are a threat to the health care system. No matter how effective a disease-modifying therapy may be, if a patient cannot afford the cost, it doesn’t work,” Dr. Smith wrote.

He added that neurologists must be “diligent in assessing for financial toxicity and appropriately tailor individual treatment recommendations. We must insist on development of point-of-care tools to accurately estimate each patient’s potential financial toxicity including RTBT [real-time benefit tools].

“Neurologists’ primary obligation is to the individual patient, but we are also compelled to support access to high-quality care for all people, which requires advocacy for appropriate policy reforms to ensure value based and fair drug pricing and treatment success,” Dr. Smith added.

The study was funded by the American Academy of Neurology Health Services Research Subcommittee. Dr. Callaghan consults for a PCORI grant, DynaMed, receives research support from the American Academy of Neurology, and performs medical/legal consultations, including consultations for the Vaccine Injury Compensation Program. Dr. Smith has disclosed no relevant financial relationships.

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

Because of the high out-of-pocket costs of new-to-market neurologic drugs that are of similar benefit as older agents, only a small percentage of patients with neurologic disorders have access to these cutting-edge medications, new research shows.

“Our study of people with neurologic conditions found that fewer than 20% were being treated with new medications,” study author Brian C. Callaghan, MD, with University of Michigan Health in Ann Arbor, said in a statement.

“For new, high-cost medications that have similar effectiveness to older drugs, limited use is likely appropriate. However, future studies are needed to look into whether the high costs are barriers to those new medications that can really make a difference for people living with neurologic disease,” Dr. Callaghan said.

The study was published online in Neurology.
 

Most expensive drugs

Using insurance claims data, the investigators compared the utilization and costs of new-to-market drugs from 2014 to 2018 with those for existing guideline-supported medications for treating 11 neurologic conditions.

The new drugs included:

• erenumab, fremanezumab, and galcanezumab for migraine.
• ocrelizumab and peginterferon beta-1a for multiple sclerosis (MS).
• pimavanserin and safinamide for Parkinson’s disease.
• droxidopa for orthostatic hypertension.
• eculizumab for myasthenia gravis (MG).
• edaravone for amyotrophic lateral sclerosis (ALS).
• deutetrabenazine and valbenazine for Huntington’s disease and tardive dyskinesia.
• patisiran and inotersen for transthyretin amyloidosis (ATTR).
• eteplirsen and deflazacort for Duchenne disease.
• nusinersen for spinal muscular atrophy (SMA).

Utilization of new drugs was modest – they accounted for one in five prescriptions for every condition except tardive dyskinesia (32% for valbenazine), the researchers noted.

Mean out-of-pocket costs were significantly higher for the new medications, although there was large variability among individual drugs.

The two most expensive drugs were edaravone, for ALS, with a mean out-of-pocket cost of $713 for a 30-day supply, and eculizumab, for MG, which costs $91 per month.

“For new-to-market medications, the distribution of out-of-pocket costs were highly variable and the trends over time were unpredictable compared with existing guideline-supported medications,” the authors reported.

They noted that potential reasons for low utilization of newer agents include delay in provider uptake and prescriber and/or patient avoidance because of high cost.

Given that most of the new neurologic agents offer little advantage compared with existing treatments – exceptions being new drugs for SMA and ATTR – drug costs should be a key consideration in prescribing decisions, Dr. Callaghan and colleagues concluded.

One limitation of the study is that follow-up time was short for some of the recently approved medications. Another limitation is that the number of people in the study who had rare diseases was small.
 

Revolution in neurotherapeutics

“We are living in a time when new treatments bring hope to people with neurologic diseases and disorders,” Orly Avitzur, MD, president of the American Academy of Neurology, said in a statement.

“However, even existing prescription medication can be expensive and drug prices continue to rise. In order for neurologists to provide people with the highest quality care, it is imperative that new drugs are accessible and affordable to the people who need them,” Dr. Avitzur added.

Writing in a linked editorial, A. Gordon Smith, MD, professor and chair, department of neurology, Virginia Commonwealth University, Richmond, said there is a revolution in neurotherapeutics, with particularly robust growth in new drug approvals for orphan diseases (those affecting < 200,000 Americans).

“This study adds to a growing literature indicating rising drug prices are a threat to the health care system. No matter how effective a disease-modifying therapy may be, if a patient cannot afford the cost, it doesn’t work,” Dr. Smith wrote.

He added that neurologists must be “diligent in assessing for financial toxicity and appropriately tailor individual treatment recommendations. We must insist on development of point-of-care tools to accurately estimate each patient’s potential financial toxicity including RTBT [real-time benefit tools].

“Neurologists’ primary obligation is to the individual patient, but we are also compelled to support access to high-quality care for all people, which requires advocacy for appropriate policy reforms to ensure value based and fair drug pricing and treatment success,” Dr. Smith added.

The study was funded by the American Academy of Neurology Health Services Research Subcommittee. Dr. Callaghan consults for a PCORI grant, DynaMed, receives research support from the American Academy of Neurology, and performs medical/legal consultations, including consultations for the Vaccine Injury Compensation Program. Dr. Smith has disclosed no relevant financial relationships.

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

Because of the high out-of-pocket costs of new-to-market neurologic drugs that are of similar benefit as older agents, only a small percentage of patients with neurologic disorders have access to these cutting-edge medications, new research shows.

“Our study of people with neurologic conditions found that fewer than 20% were being treated with new medications,” study author Brian C. Callaghan, MD, with University of Michigan Health in Ann Arbor, said in a statement.

“For new, high-cost medications that have similar effectiveness to older drugs, limited use is likely appropriate. However, future studies are needed to look into whether the high costs are barriers to those new medications that can really make a difference for people living with neurologic disease,” Dr. Callaghan said.

The study was published online in Neurology.
 

Most expensive drugs

Using insurance claims data, the investigators compared the utilization and costs of new-to-market drugs from 2014 to 2018 with those for existing guideline-supported medications for treating 11 neurologic conditions.

The new drugs included:

• erenumab, fremanezumab, and galcanezumab for migraine.
• ocrelizumab and peginterferon beta-1a for multiple sclerosis (MS).
• pimavanserin and safinamide for Parkinson’s disease.
• droxidopa for orthostatic hypertension.
• eculizumab for myasthenia gravis (MG).
• edaravone for amyotrophic lateral sclerosis (ALS).
• deutetrabenazine and valbenazine for Huntington’s disease and tardive dyskinesia.
• patisiran and inotersen for transthyretin amyloidosis (ATTR).
• eteplirsen and deflazacort for Duchenne disease.
• nusinersen for spinal muscular atrophy (SMA).

Utilization of new drugs was modest – they accounted for one in five prescriptions for every condition except tardive dyskinesia (32% for valbenazine), the researchers noted.

Mean out-of-pocket costs were significantly higher for the new medications, although there was large variability among individual drugs.

The two most expensive drugs were edaravone, for ALS, with a mean out-of-pocket cost of $713 for a 30-day supply, and eculizumab, for MG, which costs $91 per month.

“For new-to-market medications, the distribution of out-of-pocket costs were highly variable and the trends over time were unpredictable compared with existing guideline-supported medications,” the authors reported.

They noted that potential reasons for low utilization of newer agents include delay in provider uptake and prescriber and/or patient avoidance because of high cost.

Given that most of the new neurologic agents offer little advantage compared with existing treatments – exceptions being new drugs for SMA and ATTR – drug costs should be a key consideration in prescribing decisions, Dr. Callaghan and colleagues concluded.

One limitation of the study is that follow-up time was short for some of the recently approved medications. Another limitation is that the number of people in the study who had rare diseases was small.
 

Revolution in neurotherapeutics

“We are living in a time when new treatments bring hope to people with neurologic diseases and disorders,” Orly Avitzur, MD, president of the American Academy of Neurology, said in a statement.

“However, even existing prescription medication can be expensive and drug prices continue to rise. In order for neurologists to provide people with the highest quality care, it is imperative that new drugs are accessible and affordable to the people who need them,” Dr. Avitzur added.

Writing in a linked editorial, A. Gordon Smith, MD, professor and chair, department of neurology, Virginia Commonwealth University, Richmond, said there is a revolution in neurotherapeutics, with particularly robust growth in new drug approvals for orphan diseases (those affecting < 200,000 Americans).

“This study adds to a growing literature indicating rising drug prices are a threat to the health care system. No matter how effective a disease-modifying therapy may be, if a patient cannot afford the cost, it doesn’t work,” Dr. Smith wrote.

He added that neurologists must be “diligent in assessing for financial toxicity and appropriately tailor individual treatment recommendations. We must insist on development of point-of-care tools to accurately estimate each patient’s potential financial toxicity including RTBT [real-time benefit tools].

“Neurologists’ primary obligation is to the individual patient, but we are also compelled to support access to high-quality care for all people, which requires advocacy for appropriate policy reforms to ensure value based and fair drug pricing and treatment success,” Dr. Smith added.

The study was funded by the American Academy of Neurology Health Services Research Subcommittee. Dr. Callaghan consults for a PCORI grant, DynaMed, receives research support from the American Academy of Neurology, and performs medical/legal consultations, including consultations for the Vaccine Injury Compensation Program. Dr. Smith has disclosed no relevant financial relationships.

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

This month, we will take a look at three new studies investigating risk factors and treatments for headache in children.

Stress has long been noted to be one of the most consistent triggers for migraine attacks. Much has been written and studied regarding the effect of migraine on mood in adults; however, few studies have done the same in the pediatric and adolescent population. Childhood trauma has been associated with the development of chronic migraine as an adult, and behavioral treatments, such as cognitive-behavioral therapy and biofeedback, are considered as effective or more effective for migraine prevention in children compared with preventive medications. Falla and colleagues have quantified the risk for anxiety and depression in children and adolescents with migraine.

The "internalization of symptoms" is defined by the authors as an individual's tendency to react to stress with physical symptoms, including anxiety and depression. These are thought to be elevated in children and adolescents with many effects, including migraine. However, no correlation has yet been shown. Beyond the internalization of symptoms, specific psychiatric diagnoses may also be more prominent in this population.

This study was a meta-analysis of data pooled from studies that assessed migraine-related symptoms as they relate to disorders on the spectrum of anxiety, depression, and trauma-related disorders. Any studies with participants older than 18 years were excluded from this analysis. A total of 80 studies were included. Anxiety symptoms were seen to be significantly higher in children and adolescents with migraine compared to controls and the odds of having an anxiety disorder were higher among those with migraine compared with controls. Depressive symptoms were also significantly higher; however, this effect size was much smaller. The incidence of migraine was not different than that of other headache disorders.

Many patients describe stress as a trigger for migraine and other headache attacks. Mood disorders and childhood trauma are associated with the development of chronic migraine as an adult. This study reveals a two-way connection between mood disorders and headache diagnoses in children. Screening for the underlying symptoms of depression and anxiety should be done when evaluating children and adolescents for headache disorders, and there should be a focus on the treatment of these conditions in addition to treating the headache symptoms.

There are, unfortunately, very few acute pediatric migraine trials. Only a handful of medications have actually been investigated for the treatment of migraine in children younger than 12 years, and only one migraine-specific medication, rizatriptan, is approved in the United States for pediatric use. Because of this, many argue that children and adolescents with migraines end up overusing over-the-counter medication options, increasing the risk for medication overuse headache. In addition, many patients need nonoral acute migraine treatments due to nausea and vomiting or rapid onset migraine attacks.

Yonker and colleagues conducted a phase 3, randomized, double-blind, multicenter trial that only enrolled patients aged 6-11 years, all of whom had a diagnosis of episodic migraine (< 15 days of migraine per month). Children that weighed < 50 kg were given a randomly assigned lower dose of 1 mg or 2.5 mg zolmitriptan nasal spray, and those who weighed > 50 kg were randomly assigned to either 2.5 mg or 5 mg, which is the standard adult dose.

The primary outcome was a standard 2-hour pain freedom level; secondary outcomes included the proportion of improvement at 0.5, 1, and 24 hours post-dose, as well as sustained headache response for the following 2-24 hours and time to rescue medication use. Although 300 patients were enrolled and taken through the run-in process, 114 were discontinued either due to placebo response or because they had no treated migraine during the run-in phase. The mean age was 9.2 years and half of the patients were girls (of note, this is considered an appropriate proportion for pediatric migraine).

The primary endpoint of 2-hour pain freedom was not met; however, more patients in the high-dose treatment group were pain-free after 2 hours than in the placebo group. Several secondary endpoints did achieve statistical significance, including pain-free status at 1 hour post-dose, as well as headache response at 0.5, 1, and 2 hours — all of which were lower in the high-dose treatment group. The lower-dose treatment group was statistically similar to placebo for all the timepoints noted above. Treatment-related adverse events were rare in all groups.

This study did not meet its primary efficacy endpoint. However, it does show safety and effectiveness, enough at least to broaden the use of zolmitriptan for pediatric migraine. Many more effective medications for migraine treatment in adults should follow the lead of this group to find better and more specific treatments for children with migraine.

As we noted above, childhood trauma is associated with the development of chronic migraine in adulthood. Prior studies have defined childhood trauma as physical or emotional abuse primarily, and the correlation between childhood illnesses and headache disorder has not previously been determined. Davidsson and colleagues published a study in the Journal of Cancer Epidemiology that reviewed nationwide database registers longitudinally to better understand this potential risk factor.

The Danish Cancer Register was reviewed for the purpose of identifying anyone in the general Danish population who developed a diagnosis of cancer before age 20 years. The individual identification numbers in that register were linked to data in other nationwide registers for the purpose of determining whether those individuals initiated migraine-specific medications or were admitted for an inpatient hospitalization for migraine. Study participants were also grouped based on cancer type, specifically hematologic cancers involving chemotherapy and central nervous system-directed therapies, brain tumors needing intracranial surgery or radiation to the brain, blastomas or other solid tumors outside of the central nervous system, sarcomas treated with an alkylating chemotherapy, and all other carcinomas.

Among all individuals diagnosed with a childhood cancer, there was a significant increase in overall risk for the need to initiate antimigraine medication. Of interest, this was higher in those diagnosed in their teenage years. Migraine hospitalization was also noted to be higher in nearly all strata, with the exception of those diagnosed with cancer prior to the age of 5 years. The highest risk was also noted in individuals with hematologic cancers, blastomas, and brain tumors as opposed to those with sarcomas and other carcinomas. The highest cumulative risk for migraine remains in those who were diagnosed with cancer between ages 15 and 19 years.

This month, we will take a look at three new studies investigating risk factors and treatments for headache in children.

Stress has long been noted to be one of the most consistent triggers for migraine attacks. Much has been written and studied regarding the effect of migraine on mood in adults; however, few studies have done the same in the pediatric and adolescent population. Childhood trauma has been associated with the development of chronic migraine as an adult, and behavioral treatments, such as cognitive-behavioral therapy and biofeedback, are considered as effective or more effective for migraine prevention in children compared with preventive medications. Falla and colleagues have quantified the risk for anxiety and depression in children and adolescents with migraine.

The "internalization of symptoms" is defined by the authors as an individual's tendency to react to stress with physical symptoms, including anxiety and depression. These are thought to be elevated in children and adolescents with many effects, including migraine. However, no correlation has yet been shown. Beyond the internalization of symptoms, specific psychiatric diagnoses may also be more prominent in this population.

This study was a meta-analysis of data pooled from studies that assessed migraine-related symptoms as they relate to disorders on the spectrum of anxiety, depression, and trauma-related disorders. Any studies with participants older than 18 years were excluded from this analysis. A total of 80 studies were included. Anxiety symptoms were seen to be significantly higher in children and adolescents with migraine compared to controls and the odds of having an anxiety disorder were higher among those with migraine compared with controls. Depressive symptoms were also significantly higher; however, this effect size was much smaller. The incidence of migraine was not different than that of other headache disorders.

Many patients describe stress as a trigger for migraine and other headache attacks. Mood disorders and childhood trauma are associated with the development of chronic migraine as an adult. This study reveals a two-way connection between mood disorders and headache diagnoses in children. Screening for the underlying symptoms of depression and anxiety should be done when evaluating children and adolescents for headache disorders, and there should be a focus on the treatment of these conditions in addition to treating the headache symptoms.

There are, unfortunately, very few acute pediatric migraine trials. Only a handful of medications have actually been investigated for the treatment of migraine in children younger than 12 years, and only one migraine-specific medication, rizatriptan, is approved in the United States for pediatric use. Because of this, many argue that children and adolescents with migraines end up overusing over-the-counter medication options, increasing the risk for medication overuse headache. In addition, many patients need nonoral acute migraine treatments due to nausea and vomiting or rapid onset migraine attacks.

Yonker and colleagues conducted a phase 3, randomized, double-blind, multicenter trial that only enrolled patients aged 6-11 years, all of whom had a diagnosis of episodic migraine (< 15 days of migraine per month). Children that weighed < 50 kg were given a randomly assigned lower dose of 1 mg or 2.5 mg zolmitriptan nasal spray, and those who weighed > 50 kg were randomly assigned to either 2.5 mg or 5 mg, which is the standard adult dose.

The primary outcome was a standard 2-hour pain freedom level; secondary outcomes included the proportion of improvement at 0.5, 1, and 24 hours post-dose, as well as sustained headache response for the following 2-24 hours and time to rescue medication use. Although 300 patients were enrolled and taken through the run-in process, 114 were discontinued either due to placebo response or because they had no treated migraine during the run-in phase. The mean age was 9.2 years and half of the patients were girls (of note, this is considered an appropriate proportion for pediatric migraine).

The primary endpoint of 2-hour pain freedom was not met; however, more patients in the high-dose treatment group were pain-free after 2 hours than in the placebo group. Several secondary endpoints did achieve statistical significance, including pain-free status at 1 hour post-dose, as well as headache response at 0.5, 1, and 2 hours — all of which were lower in the high-dose treatment group. The lower-dose treatment group was statistically similar to placebo for all the timepoints noted above. Treatment-related adverse events were rare in all groups.

This study did not meet its primary efficacy endpoint. However, it does show safety and effectiveness, enough at least to broaden the use of zolmitriptan for pediatric migraine. Many more effective medications for migraine treatment in adults should follow the lead of this group to find better and more specific treatments for children with migraine.

As we noted above, childhood trauma is associated with the development of chronic migraine in adulthood. Prior studies have defined childhood trauma as physical or emotional abuse primarily, and the correlation between childhood illnesses and headache disorder has not previously been determined. Davidsson and colleagues published a study in the Journal of Cancer Epidemiology that reviewed nationwide database registers longitudinally to better understand this potential risk factor.

The Danish Cancer Register was reviewed for the purpose of identifying anyone in the general Danish population who developed a diagnosis of cancer before age 20 years. The individual identification numbers in that register were linked to data in other nationwide registers for the purpose of determining whether those individuals initiated migraine-specific medications or were admitted for an inpatient hospitalization for migraine. Study participants were also grouped based on cancer type, specifically hematologic cancers involving chemotherapy and central nervous system-directed therapies, brain tumors needing intracranial surgery or radiation to the brain, blastomas or other solid tumors outside of the central nervous system, sarcomas treated with an alkylating chemotherapy, and all other carcinomas.

Among all individuals diagnosed with a childhood cancer, there was a significant increase in overall risk for the need to initiate antimigraine medication. Of interest, this was higher in those diagnosed in their teenage years. Migraine hospitalization was also noted to be higher in nearly all strata, with the exception of those diagnosed with cancer prior to the age of 5 years. The highest risk was also noted in individuals with hematologic cancers, blastomas, and brain tumors as opposed to those with sarcomas and other carcinomas. The highest cumulative risk for migraine remains in those who were diagnosed with cancer between ages 15 and 19 years.

This month, we will take a look at three new studies investigating risk factors and treatments for headache in children.

Stress has long been noted to be one of the most consistent triggers for migraine attacks. Much has been written and studied regarding the effect of migraine on mood in adults; however, few studies have done the same in the pediatric and adolescent population. Childhood trauma has been associated with the development of chronic migraine as an adult, and behavioral treatments, such as cognitive-behavioral therapy and biofeedback, are considered as effective or more effective for migraine prevention in children compared with preventive medications. Falla and colleagues have quantified the risk for anxiety and depression in children and adolescents with migraine.

The "internalization of symptoms" is defined by the authors as an individual's tendency to react to stress with physical symptoms, including anxiety and depression. These are thought to be elevated in children and adolescents with many effects, including migraine. However, no correlation has yet been shown. Beyond the internalization of symptoms, specific psychiatric diagnoses may also be more prominent in this population.

This study was a meta-analysis of data pooled from studies that assessed migraine-related symptoms as they relate to disorders on the spectrum of anxiety, depression, and trauma-related disorders. Any studies with participants older than 18 years were excluded from this analysis. A total of 80 studies were included. Anxiety symptoms were seen to be significantly higher in children and adolescents with migraine compared to controls and the odds of having an anxiety disorder were higher among those with migraine compared with controls. Depressive symptoms were also significantly higher; however, this effect size was much smaller. The incidence of migraine was not different than that of other headache disorders.

Many patients describe stress as a trigger for migraine and other headache attacks. Mood disorders and childhood trauma are associated with the development of chronic migraine as an adult. This study reveals a two-way connection between mood disorders and headache diagnoses in children. Screening for the underlying symptoms of depression and anxiety should be done when evaluating children and adolescents for headache disorders, and there should be a focus on the treatment of these conditions in addition to treating the headache symptoms.

There are, unfortunately, very few acute pediatric migraine trials. Only a handful of medications have actually been investigated for the treatment of migraine in children younger than 12 years, and only one migraine-specific medication, rizatriptan, is approved in the United States for pediatric use. Because of this, many argue that children and adolescents with migraines end up overusing over-the-counter medication options, increasing the risk for medication overuse headache. In addition, many patients need nonoral acute migraine treatments due to nausea and vomiting or rapid onset migraine attacks.

Yonker and colleagues conducted a phase 3, randomized, double-blind, multicenter trial that only enrolled patients aged 6-11 years, all of whom had a diagnosis of episodic migraine (< 15 days of migraine per month). Children that weighed < 50 kg were given a randomly assigned lower dose of 1 mg or 2.5 mg zolmitriptan nasal spray, and those who weighed > 50 kg were randomly assigned to either 2.5 mg or 5 mg, which is the standard adult dose.

The primary outcome was a standard 2-hour pain freedom level; secondary outcomes included the proportion of improvement at 0.5, 1, and 24 hours post-dose, as well as sustained headache response for the following 2-24 hours and time to rescue medication use. Although 300 patients were enrolled and taken through the run-in process, 114 were discontinued either due to placebo response or because they had no treated migraine during the run-in phase. The mean age was 9.2 years and half of the patients were girls (of note, this is considered an appropriate proportion for pediatric migraine).

The primary endpoint of 2-hour pain freedom was not met; however, more patients in the high-dose treatment group were pain-free after 2 hours than in the placebo group. Several secondary endpoints did achieve statistical significance, including pain-free status at 1 hour post-dose, as well as headache response at 0.5, 1, and 2 hours — all of which were lower in the high-dose treatment group. The lower-dose treatment group was statistically similar to placebo for all the timepoints noted above. Treatment-related adverse events were rare in all groups.

This study did not meet its primary efficacy endpoint. However, it does show safety and effectiveness, enough at least to broaden the use of zolmitriptan for pediatric migraine. Many more effective medications for migraine treatment in adults should follow the lead of this group to find better and more specific treatments for children with migraine.

As we noted above, childhood trauma is associated with the development of chronic migraine in adulthood. Prior studies have defined childhood trauma as physical or emotional abuse primarily, and the correlation between childhood illnesses and headache disorder has not previously been determined. Davidsson and colleagues published a study in the Journal of Cancer Epidemiology that reviewed nationwide database registers longitudinally to better understand this potential risk factor.

The Danish Cancer Register was reviewed for the purpose of identifying anyone in the general Danish population who developed a diagnosis of cancer before age 20 years. The individual identification numbers in that register were linked to data in other nationwide registers for the purpose of determining whether those individuals initiated migraine-specific medications or were admitted for an inpatient hospitalization for migraine. Study participants were also grouped based on cancer type, specifically hematologic cancers involving chemotherapy and central nervous system-directed therapies, brain tumors needing intracranial surgery or radiation to the brain, blastomas or other solid tumors outside of the central nervous system, sarcomas treated with an alkylating chemotherapy, and all other carcinomas.

Among all individuals diagnosed with a childhood cancer, there was a significant increase in overall risk for the need to initiate antimigraine medication. Of interest, this was higher in those diagnosed in their teenage years. Migraine hospitalization was also noted to be higher in nearly all strata, with the exception of those diagnosed with cancer prior to the age of 5 years. The highest risk was also noted in individuals with hematologic cancers, blastomas, and brain tumors as opposed to those with sarcomas and other carcinomas. The highest cumulative risk for migraine remains in those who were diagnosed with cancer between ages 15 and 19 years.