Migraine ICYMI

Key clinical point: Women with either migraine or gestational diabetes mellitus (GDM) faced an increased long-term risk for developing major adverse cardiovascular and cerebrovascular events (MACCE) at a premature age (≤60 years), with the risk being significantly higher among those with both conditions.

Major findings: Women with migraine or GDM had a significantly higher 20-year risk for premature MACCE than women without these conditions (adjusted hazard ratio [aHR] 1.65; 95% CI 1.49-1.82 for migraine and aHR 1.64; 95% CI 1.37-1.96 for GDM). The risk was highest among women with both migraine and GDM (aHR 2.35; 95% CI 1.03-5.36).

Study details: This population-based longitudinal cohort study included 1,390,451 women, of which 56,811 had migraine, 24,700 had GDM, 1484 had both migraine and GDM, and 1,307,456 women had neither migraine nor GDM.

Disclosure: The study was funded by Aarhus University. The authors declared no conflicts of interest.

Source: Fuglsang CH, Pedersen L, Schmidt M, et al. The combined impact of migraine and gestational diabetes on long-term risk of premature myocardial infarction and stroke: A population-based cohort study. Headache. 2024 (Aug 28). doi: 10.1111/head.14821 Source

Key clinical point: Women with either migraine or gestational diabetes mellitus (GDM) faced an increased long-term risk for developing major adverse cardiovascular and cerebrovascular events (MACCE) at a premature age (≤60 years), with the risk being significantly higher among those with both conditions.

Major findings: Women with migraine or GDM had a significantly higher 20-year risk for premature MACCE than women without these conditions (adjusted hazard ratio [aHR] 1.65; 95% CI 1.49-1.82 for migraine and aHR 1.64; 95% CI 1.37-1.96 for GDM). The risk was highest among women with both migraine and GDM (aHR 2.35; 95% CI 1.03-5.36).

Study details: This population-based longitudinal cohort study included 1,390,451 women, of which 56,811 had migraine, 24,700 had GDM, 1484 had both migraine and GDM, and 1,307,456 women had neither migraine nor GDM.

Disclosure: The study was funded by Aarhus University. The authors declared no conflicts of interest.

Source: Fuglsang CH, Pedersen L, Schmidt M, et al. The combined impact of migraine and gestational diabetes on long-term risk of premature myocardial infarction and stroke: A population-based cohort study. Headache. 2024 (Aug 28). doi: 10.1111/head.14821 Source

Key clinical point: Women with either migraine or gestational diabetes mellitus (GDM) faced an increased long-term risk for developing major adverse cardiovascular and cerebrovascular events (MACCE) at a premature age (≤60 years), with the risk being significantly higher among those with both conditions.

Major findings: Women with migraine or GDM had a significantly higher 20-year risk for premature MACCE than women without these conditions (adjusted hazard ratio [aHR] 1.65; 95% CI 1.49-1.82 for migraine and aHR 1.64; 95% CI 1.37-1.96 for GDM). The risk was highest among women with both migraine and GDM (aHR 2.35; 95% CI 1.03-5.36).

Study details: This population-based longitudinal cohort study included 1,390,451 women, of which 56,811 had migraine, 24,700 had GDM, 1484 had both migraine and GDM, and 1,307,456 women had neither migraine nor GDM.

Disclosure: The study was funded by Aarhus University. The authors declared no conflicts of interest.

Source: Fuglsang CH, Pedersen L, Schmidt M, et al. The combined impact of migraine and gestational diabetes on long-term risk of premature myocardial infarction and stroke: A population-based cohort study. Headache. 2024 (Aug 28). doi: 10.1111/head.14821 Source

Key clinical point: Patients with migraine experienced considerable neck pain–related disability, with the effect being more prominent among patients with chronic vs episodic migraine.

Major findings: Patients with migraine reported a mean Neck Disability Index (NDI) score of 16.2, indicative of moderate disability. The NDI scores were 12.1 points higher among patients with migraine vs control individuals without headache (P < .001) and 5.5 points higher among patients with chronic vs episodic migraine (P < .001).

Study details: Findings are from a meta-analysis of 33 observational studies including patients with migraine, patients with tension-type headache, and healthy individuals without headache.

Disclosure: The study did not receive any funding. Four authors declared receiving personal fees or honoraria for consultation from or having other ties with various sources; others declared no conflicts of interest.

Source: Al-Khazali HM, Al-Sayegh Z, Younis S, et al. Systematic review and meta-analysis of Neck Disability Index and Numeric Pain Rating Scale in patients with migraine and tension-type headache. Cephalalgia. 2024 (Aug 28). doi: 10.1177/033310242412742 Source

Key clinical point: Patients with migraine experienced considerable neck pain–related disability, with the effect being more prominent among patients with chronic vs episodic migraine.

Major findings: Patients with migraine reported a mean Neck Disability Index (NDI) score of 16.2, indicative of moderate disability. The NDI scores were 12.1 points higher among patients with migraine vs control individuals without headache (P < .001) and 5.5 points higher among patients with chronic vs episodic migraine (P < .001).

Study details: Findings are from a meta-analysis of 33 observational studies including patients with migraine, patients with tension-type headache, and healthy individuals without headache.

Disclosure: The study did not receive any funding. Four authors declared receiving personal fees or honoraria for consultation from or having other ties with various sources; others declared no conflicts of interest.

Source: Al-Khazali HM, Al-Sayegh Z, Younis S, et al. Systematic review and meta-analysis of Neck Disability Index and Numeric Pain Rating Scale in patients with migraine and tension-type headache. Cephalalgia. 2024 (Aug 28). doi: 10.1177/033310242412742 Source

Key clinical point: Patients with migraine experienced considerable neck pain–related disability, with the effect being more prominent among patients with chronic vs episodic migraine.

Major findings: Patients with migraine reported a mean Neck Disability Index (NDI) score of 16.2, indicative of moderate disability. The NDI scores were 12.1 points higher among patients with migraine vs control individuals without headache (P < .001) and 5.5 points higher among patients with chronic vs episodic migraine (P < .001).

Study details: Findings are from a meta-analysis of 33 observational studies including patients with migraine, patients with tension-type headache, and healthy individuals without headache.

Disclosure: The study did not receive any funding. Four authors declared receiving personal fees or honoraria for consultation from or having other ties with various sources; others declared no conflicts of interest.

Source: Al-Khazali HM, Al-Sayegh Z, Younis S, et al. Systematic review and meta-analysis of Neck Disability Index and Numeric Pain Rating Scale in patients with migraine and tension-type headache. Cephalalgia. 2024 (Aug 28). doi: 10.1177/033310242412742 Source

Key clinical point: When administered during the prodrome, ubrogepant was more effective than placebo in improving normal functioning, reducing activity limitations, and increasing treatment satisfaction in patients with acute migraine.

Major findings: A significantly higher proportion of patients were able to function normally as early as 2 hours after receiving ubrogepant vs placebo (odds ratio [OR] 1.76; P = .0001), with the effects being sustained through 24 hours. The patients also experienced reduced activity limitations (OR 2.07; P < .0001) and greater treatment satisfaction (OR 2.32; P < .0001) at 24 hours after receiving ubrogepant vs placebo.

Study details: This PRODROME trial included 477 adult patients with acute migraine who were randomly assigned to receive either placebo followed by 100 mg ubrogepant for the first and second prodrome events, respectively, or vice versa.

Disclosure: The study was funded by AbbVie. Seven authors reported being employees of AbbVie and may hold stock in the company. Other authors declared having other ties with various sources, including AbbVie.

Source: Lipton RB, Harriott AM, Ma JY, et al. Effect of ubrogepant on patient-reported outcomes when administered during the migraine prodrome: Results from the randomized PRODROME trial. Neurology. 2024;103(6):e209745 (Aug 28). doi: 10.1212/WNL.00000000002097 Source

Key clinical point: When administered during the prodrome, ubrogepant was more effective than placebo in improving normal functioning, reducing activity limitations, and increasing treatment satisfaction in patients with acute migraine.

Major findings: A significantly higher proportion of patients were able to function normally as early as 2 hours after receiving ubrogepant vs placebo (odds ratio [OR] 1.76; P = .0001), with the effects being sustained through 24 hours. The patients also experienced reduced activity limitations (OR 2.07; P < .0001) and greater treatment satisfaction (OR 2.32; P < .0001) at 24 hours after receiving ubrogepant vs placebo.

Study details: This PRODROME trial included 477 adult patients with acute migraine who were randomly assigned to receive either placebo followed by 100 mg ubrogepant for the first and second prodrome events, respectively, or vice versa.

Disclosure: The study was funded by AbbVie. Seven authors reported being employees of AbbVie and may hold stock in the company. Other authors declared having other ties with various sources, including AbbVie.

Source: Lipton RB, Harriott AM, Ma JY, et al. Effect of ubrogepant on patient-reported outcomes when administered during the migraine prodrome: Results from the randomized PRODROME trial. Neurology. 2024;103(6):e209745 (Aug 28). doi: 10.1212/WNL.00000000002097 Source

Key clinical point: When administered during the prodrome, ubrogepant was more effective than placebo in improving normal functioning, reducing activity limitations, and increasing treatment satisfaction in patients with acute migraine.

Major findings: A significantly higher proportion of patients were able to function normally as early as 2 hours after receiving ubrogepant vs placebo (odds ratio [OR] 1.76; P = .0001), with the effects being sustained through 24 hours. The patients also experienced reduced activity limitations (OR 2.07; P < .0001) and greater treatment satisfaction (OR 2.32; P < .0001) at 24 hours after receiving ubrogepant vs placebo.

Study details: This PRODROME trial included 477 adult patients with acute migraine who were randomly assigned to receive either placebo followed by 100 mg ubrogepant for the first and second prodrome events, respectively, or vice versa.

Disclosure: The study was funded by AbbVie. Seven authors reported being employees of AbbVie and may hold stock in the company. Other authors declared having other ties with various sources, including AbbVie.

Source: Lipton RB, Harriott AM, Ma JY, et al. Effect of ubrogepant on patient-reported outcomes when administered during the migraine prodrome: Results from the randomized PRODROME trial. Neurology. 2024;103(6):e209745 (Aug 28). doi: 10.1212/WNL.00000000002097 Source

Key clinical point: Middle-aged and older women showed no significant association between migraine, and the risk for Parkinson disease (PD), irrespective of migraine subtypes and frequency.

Major findings: Compared to women with without migraine, those with migraine did not show a risk of PD (adjusted hazard ratio [aHR] 1.07; 95% CI 0.88-1.29) irrespective of the presence of aura. No risk was seen even if patients had monthly migraine frequency (aHR 1.09; 95% CI 0.64-1.87), or a weekly or greater migraine frequency (aHR 1.10; 95% CI 0.44-2.75).

Study details: This study involved 39,312 women (age > 45 years) of whom 7321 had migraines, including 2153 with a history of migraine and 5168 with migraine with or without aura. None had a history of PD.

Disclosure: This study was supported by grants from the US National Cancer Institute and the US National Heart, Lung, and Blood Institute. Two authors declared receiving research grants or personal compensation from various sources.

Source: Schulz RS, Glatz T, Buring Jeet al. Migraine and risk of Parkinson disease in women: A cohort study. Neurology. 2024;103(6):e209747 (Aug 21). doi: 10.1212/WNL.0000000000209747 Source

Key clinical point: Middle-aged and older women showed no significant association between migraine, and the risk for Parkinson disease (PD), irrespective of migraine subtypes and frequency.

Major findings: Compared to women with without migraine, those with migraine did not show a risk of PD (adjusted hazard ratio [aHR] 1.07; 95% CI 0.88-1.29) irrespective of the presence of aura. No risk was seen even if patients had monthly migraine frequency (aHR 1.09; 95% CI 0.64-1.87), or a weekly or greater migraine frequency (aHR 1.10; 95% CI 0.44-2.75).

Study details: This study involved 39,312 women (age > 45 years) of whom 7321 had migraines, including 2153 with a history of migraine and 5168 with migraine with or without aura. None had a history of PD.

Disclosure: This study was supported by grants from the US National Cancer Institute and the US National Heart, Lung, and Blood Institute. Two authors declared receiving research grants or personal compensation from various sources.

Source: Schulz RS, Glatz T, Buring Jeet al. Migraine and risk of Parkinson disease in women: A cohort study. Neurology. 2024;103(6):e209747 (Aug 21). doi: 10.1212/WNL.0000000000209747 Source

Key clinical point: Middle-aged and older women showed no significant association between migraine, and the risk for Parkinson disease (PD), irrespective of migraine subtypes and frequency.

Major findings: Compared to women with without migraine, those with migraine did not show a risk of PD (adjusted hazard ratio [aHR] 1.07; 95% CI 0.88-1.29) irrespective of the presence of aura. No risk was seen even if patients had monthly migraine frequency (aHR 1.09; 95% CI 0.64-1.87), or a weekly or greater migraine frequency (aHR 1.10; 95% CI 0.44-2.75).

Study details: This study involved 39,312 women (age > 45 years) of whom 7321 had migraines, including 2153 with a history of migraine and 5168 with migraine with or without aura. None had a history of PD.

Disclosure: This study was supported by grants from the US National Cancer Institute and the US National Heart, Lung, and Blood Institute. Two authors declared receiving research grants or personal compensation from various sources.

Source: Schulz RS, Glatz T, Buring Jeet al. Migraine and risk of Parkinson disease in women: A cohort study. Neurology. 2024;103(6):e209747 (Aug 21). doi: 10.1212/WNL.0000000000209747 Source

Key clinical point: A single infusion of Lu AG09222, a humanized monoclonal antibody targeting the pituitary adenylate cyclase-activating polypeptide, was more effective than placebo in reducing migraine frequency over 4 weeks in adults with episodic or chronic migraine.

Major findings: Through week 4, a single infusion of 750 mg Lu AG09222 vs placebo led to a significantly greater reduction in monthly migraine days (−6.2 vs −4.2 days; difference −2 days; P = .02). Most adverse events were mild, with COVID-19, nasopharyngitis, and fatigue being more prevalent in those receiving 750 mg Lu AG09222 vs placebo.

Study details: This phase 2 trial included 237 adults with migraine who did not respond to two to four previous treatments and were assigned to receive either Lu AG09222 (750 mg or 100 mg) or placebo for 4 weeks.

Disclosure: The study was supported by H. Lundbeck A/S. Three authors declared being employees of H. Lundbeck A/S, of whom one held stock options. One author reported receiving consulting, speaker, and advisory board fees from various sources, including H. Lundbeck A/S.

Source: Ashina M, Phul R, Khodaie M, et al. A monoclonal antibody to PACAP for migraine prevention. N Engl J Med. 2024;391(9):800-809 (Sept 4). doi: 10.1056/NEJMoa2314577 Source

Key clinical point: A single infusion of Lu AG09222, a humanized monoclonal antibody targeting the pituitary adenylate cyclase-activating polypeptide, was more effective than placebo in reducing migraine frequency over 4 weeks in adults with episodic or chronic migraine.

Major findings: Through week 4, a single infusion of 750 mg Lu AG09222 vs placebo led to a significantly greater reduction in monthly migraine days (−6.2 vs −4.2 days; difference −2 days; P = .02). Most adverse events were mild, with COVID-19, nasopharyngitis, and fatigue being more prevalent in those receiving 750 mg Lu AG09222 vs placebo.

Study details: This phase 2 trial included 237 adults with migraine who did not respond to two to four previous treatments and were assigned to receive either Lu AG09222 (750 mg or 100 mg) or placebo for 4 weeks.

Disclosure: The study was supported by H. Lundbeck A/S. Three authors declared being employees of H. Lundbeck A/S, of whom one held stock options. One author reported receiving consulting, speaker, and advisory board fees from various sources, including H. Lundbeck A/S.

Source: Ashina M, Phul R, Khodaie M, et al. A monoclonal antibody to PACAP for migraine prevention. N Engl J Med. 2024;391(9):800-809 (Sept 4). doi: 10.1056/NEJMoa2314577 Source

Key clinical point: A single infusion of Lu AG09222, a humanized monoclonal antibody targeting the pituitary adenylate cyclase-activating polypeptide, was more effective than placebo in reducing migraine frequency over 4 weeks in adults with episodic or chronic migraine.

Major findings: Through week 4, a single infusion of 750 mg Lu AG09222 vs placebo led to a significantly greater reduction in monthly migraine days (−6.2 vs −4.2 days; difference −2 days; P = .02). Most adverse events were mild, with COVID-19, nasopharyngitis, and fatigue being more prevalent in those receiving 750 mg Lu AG09222 vs placebo.

Study details: This phase 2 trial included 237 adults with migraine who did not respond to two to four previous treatments and were assigned to receive either Lu AG09222 (750 mg or 100 mg) or placebo for 4 weeks.

Disclosure: The study was supported by H. Lundbeck A/S. Three authors declared being employees of H. Lundbeck A/S, of whom one held stock options. One author reported receiving consulting, speaker, and advisory board fees from various sources, including H. Lundbeck A/S.

Source: Ashina M, Phul R, Khodaie M, et al. A monoclonal antibody to PACAP for migraine prevention. N Engl J Med. 2024;391(9):800-809 (Sept 4). doi: 10.1056/NEJMoa2314577 Source

Migraine pathophysiology has been shown to be associated with vascular and inflammatory processes. Diet and lifestyle can have an effect on an individual's inflammatory process, and research regarding the steps between these factors and inflammation is vague and nonspecific. The Dietary Inflammation Score (DIS), which is calculated on the basis of a questionnaire, is used to score the inflammatory potential of an individual's diet. The Dietary and Lifestyle Inflammation Score (DLIS) includes the DIS questions, and also incorporates body mass index (BMI), physical activity, smoking, and alcohol consumption. A recent study, based on a secondary analysis of previous data, examined the correlation between migraine and DIS and DLIS among 285 women, 40% of whom had a chronic migraine diagnosis. Results published in Scientific Reports in July 2024 noted that participants with chronic migraine had a significantly higher DIS and DLIS than those who were not diagnosed with chronic migraine. It is important to note that migraine-associated inflammation can also result from genetic factors. A previous study, published in 2023 in Nature Genetics, described a correlation between genetic markers of inflammatory disorders, such as endometriosis, asthma, and migraine.¹ These results, consistent with our current understanding of the genetic contribution to migraine risk, emphasize that lifestyle modifications alone are not usually adequate for complete management of migraines.

Patients who experience chronic migraine may be inclined to reduce their time spent exercising and engaging in physical activity, as these activities can exacerbate migraine symptoms. Additionally, after recovering from a migraine, patients often need to catch up on tasks and responsibilities, which can squeeze out time for physical activity and exercise (often considered luxuries that can be done during leisure time). Results of a small cross-sectional retrospective study published in Scientific Reports in 2024 suggested a correlation between daily walking steps and response to calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb). According to the study, which included 22 patients who were diagnosed with migraine and treated with CGRP mAb, patients who experienced an improvement of their migraine symptoms also increased their average daily steps by almost 1000 steps per day. The authors suggested that steps can be used as a marker of treatment response in migraine.

Screen time is often blamed as a cause for a number of different ailments, including obesity, anxiety, depression, insomnia, and migraine. An article published in June 2024 in European Journal of Pain described results of a meta-analysis examining the association between sedentary lifestyle and migraine. The authors noted that time spent watching television could be causally associated with an increased risk for migraine.²Another study, with results published in July 2024 in The Journal of Headache and Pain, examined the relationship between migraine and leisure screen time. The researchers used data from 661,399 European individuals from 53 studies to look at genetically predicted leisure screen time, rather than actual leisure screen time. They reported that genetically predicted leisure screen time was associated with a 27.7% increase in migraine risk. While the results are consistent with what is already widely accepted about screen time and migraine, the inclusion of genetic predisposition to screen time is interesting in suggesting that some underlying drive could be contributing to increased screen time among patients who have migraine.

The results of these studies reemphasize the importance of the link between lifestyle factors and migraine but warn against oversimplifying the correlation. There is a bidirectional relationship between migraine and inflammation. We know that inflammation is mediated by diet as well as physical activity. During a migraine, patients may turn to foods that have a high inflammatory potential. Furthermore, migraine can influence a person's inclination to participate in physical activity, as the pain and discomfort can make it difficult engage in exercise. During a migraine, patients may prefer sedentary activities. Screen time can be appealing or relaxing while recovering from a migraine. Genetic predisposition is an interesting additional contributor to this link. Acknowledging genetic predisposition to inflammation or sedentary activity can be a step in helping patients recognize that it could be challenging to overcome these genetically inherent drives or conditions, while providing encouragement regarding the potential benefits of doing so.

Additional References

1. Rahmioglu N, Mortlock S, Ghiasi M, et al. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions. Nat Genet. 2023;55(3):423-436. Doi: 10.1038/s41588-023-01323-z Source

2. Li P, Li J, Zhu H, et al. Causal effects of sedentary behaviours on the risk of migraine: A univariable and multivariable Mendelian randomization study. Eur J Pain. 2024 (Jun 4). Doi: 10.1002/ejp.2296  Source

Migraine pathophysiology has been shown to be associated with vascular and inflammatory processes. Diet and lifestyle can have an effect on an individual's inflammatory process, and research regarding the steps between these factors and inflammation is vague and nonspecific. The Dietary Inflammation Score (DIS), which is calculated on the basis of a questionnaire, is used to score the inflammatory potential of an individual's diet. The Dietary and Lifestyle Inflammation Score (DLIS) includes the DIS questions, and also incorporates body mass index (BMI), physical activity, smoking, and alcohol consumption. A recent study, based on a secondary analysis of previous data, examined the correlation between migraine and DIS and DLIS among 285 women, 40% of whom had a chronic migraine diagnosis. Results published in Scientific Reports in July 2024 noted that participants with chronic migraine had a significantly higher DIS and DLIS than those who were not diagnosed with chronic migraine. It is important to note that migraine-associated inflammation can also result from genetic factors. A previous study, published in 2023 in Nature Genetics, described a correlation between genetic markers of inflammatory disorders, such as endometriosis, asthma, and migraine.¹ These results, consistent with our current understanding of the genetic contribution to migraine risk, emphasize that lifestyle modifications alone are not usually adequate for complete management of migraines.

Patients who experience chronic migraine may be inclined to reduce their time spent exercising and engaging in physical activity, as these activities can exacerbate migraine symptoms. Additionally, after recovering from a migraine, patients often need to catch up on tasks and responsibilities, which can squeeze out time for physical activity and exercise (often considered luxuries that can be done during leisure time). Results of a small cross-sectional retrospective study published in Scientific Reports in 2024 suggested a correlation between daily walking steps and response to calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb). According to the study, which included 22 patients who were diagnosed with migraine and treated with CGRP mAb, patients who experienced an improvement of their migraine symptoms also increased their average daily steps by almost 1000 steps per day. The authors suggested that steps can be used as a marker of treatment response in migraine.

Screen time is often blamed as a cause for a number of different ailments, including obesity, anxiety, depression, insomnia, and migraine. An article published in June 2024 in European Journal of Pain described results of a meta-analysis examining the association between sedentary lifestyle and migraine. The authors noted that time spent watching television could be causally associated with an increased risk for migraine.²Another study, with results published in July 2024 in The Journal of Headache and Pain, examined the relationship between migraine and leisure screen time. The researchers used data from 661,399 European individuals from 53 studies to look at genetically predicted leisure screen time, rather than actual leisure screen time. They reported that genetically predicted leisure screen time was associated with a 27.7% increase in migraine risk. While the results are consistent with what is already widely accepted about screen time and migraine, the inclusion of genetic predisposition to screen time is interesting in suggesting that some underlying drive could be contributing to increased screen time among patients who have migraine.

The results of these studies reemphasize the importance of the link between lifestyle factors and migraine but warn against oversimplifying the correlation. There is a bidirectional relationship between migraine and inflammation. We know that inflammation is mediated by diet as well as physical activity. During a migraine, patients may turn to foods that have a high inflammatory potential. Furthermore, migraine can influence a person's inclination to participate in physical activity, as the pain and discomfort can make it difficult engage in exercise. During a migraine, patients may prefer sedentary activities. Screen time can be appealing or relaxing while recovering from a migraine. Genetic predisposition is an interesting additional contributor to this link. Acknowledging genetic predisposition to inflammation or sedentary activity can be a step in helping patients recognize that it could be challenging to overcome these genetically inherent drives or conditions, while providing encouragement regarding the potential benefits of doing so.

Additional References

1. Rahmioglu N, Mortlock S, Ghiasi M, et al. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions. Nat Genet. 2023;55(3):423-436. Doi: 10.1038/s41588-023-01323-z Source

2. Li P, Li J, Zhu H, et al. Causal effects of sedentary behaviours on the risk of migraine: A univariable and multivariable Mendelian randomization study. Eur J Pain. 2024 (Jun 4). Doi: 10.1002/ejp.2296  Source

Migraine pathophysiology has been shown to be associated with vascular and inflammatory processes. Diet and lifestyle can have an effect on an individual's inflammatory process, and research regarding the steps between these factors and inflammation is vague and nonspecific. The Dietary Inflammation Score (DIS), which is calculated on the basis of a questionnaire, is used to score the inflammatory potential of an individual's diet. The Dietary and Lifestyle Inflammation Score (DLIS) includes the DIS questions, and also incorporates body mass index (BMI), physical activity, smoking, and alcohol consumption. A recent study, based on a secondary analysis of previous data, examined the correlation between migraine and DIS and DLIS among 285 women, 40% of whom had a chronic migraine diagnosis. Results published in Scientific Reports in July 2024 noted that participants with chronic migraine had a significantly higher DIS and DLIS than those who were not diagnosed with chronic migraine. It is important to note that migraine-associated inflammation can also result from genetic factors. A previous study, published in 2023 in Nature Genetics, described a correlation between genetic markers of inflammatory disorders, such as endometriosis, asthma, and migraine.¹ These results, consistent with our current understanding of the genetic contribution to migraine risk, emphasize that lifestyle modifications alone are not usually adequate for complete management of migraines.

Patients who experience chronic migraine may be inclined to reduce their time spent exercising and engaging in physical activity, as these activities can exacerbate migraine symptoms. Additionally, after recovering from a migraine, patients often need to catch up on tasks and responsibilities, which can squeeze out time for physical activity and exercise (often considered luxuries that can be done during leisure time). Results of a small cross-sectional retrospective study published in Scientific Reports in 2024 suggested a correlation between daily walking steps and response to calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb). According to the study, which included 22 patients who were diagnosed with migraine and treated with CGRP mAb, patients who experienced an improvement of their migraine symptoms also increased their average daily steps by almost 1000 steps per day. The authors suggested that steps can be used as a marker of treatment response in migraine.

Screen time is often blamed as a cause for a number of different ailments, including obesity, anxiety, depression, insomnia, and migraine. An article published in June 2024 in European Journal of Pain described results of a meta-analysis examining the association between sedentary lifestyle and migraine. The authors noted that time spent watching television could be causally associated with an increased risk for migraine.²Another study, with results published in July 2024 in The Journal of Headache and Pain, examined the relationship between migraine and leisure screen time. The researchers used data from 661,399 European individuals from 53 studies to look at genetically predicted leisure screen time, rather than actual leisure screen time. They reported that genetically predicted leisure screen time was associated with a 27.7% increase in migraine risk. While the results are consistent with what is already widely accepted about screen time and migraine, the inclusion of genetic predisposition to screen time is interesting in suggesting that some underlying drive could be contributing to increased screen time among patients who have migraine.

The results of these studies reemphasize the importance of the link between lifestyle factors and migraine but warn against oversimplifying the correlation. There is a bidirectional relationship between migraine and inflammation. We know that inflammation is mediated by diet as well as physical activity. During a migraine, patients may turn to foods that have a high inflammatory potential. Furthermore, migraine can influence a person's inclination to participate in physical activity, as the pain and discomfort can make it difficult engage in exercise. During a migraine, patients may prefer sedentary activities. Screen time can be appealing or relaxing while recovering from a migraine. Genetic predisposition is an interesting additional contributor to this link. Acknowledging genetic predisposition to inflammation or sedentary activity can be a step in helping patients recognize that it could be challenging to overcome these genetically inherent drives or conditions, while providing encouragement regarding the potential benefits of doing so.

Additional References

1. Rahmioglu N, Mortlock S, Ghiasi M, et al. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions. Nat Genet. 2023;55(3):423-436. Doi: 10.1038/s41588-023-01323-z Source

2. Li P, Li J, Zhu H, et al. Causal effects of sedentary behaviours on the risk of migraine: A univariable and multivariable Mendelian randomization study. Eur J Pain. 2024 (Jun 4). Doi: 10.1002/ejp.2296  Source

Key clinical point: Rimegepant was more effective than placebo in reducing pain and most bothersome symptoms in patients with moderate to severe migraine, while also showing favorable safety and tolerability.

Major findings: At 2 hours post dose, rimegepant was more effective than placebo in providing freedom from pain (risk difference 4.9; P = .0298) and the most bothersome symptoms (risk difference 8.9; P = .0016). Similar proportions of participants in the rimegepant vs placebo group experienced at least one adverse event (12.6% vs 10.7%), with nausea (0.9% vs 1.1%) and dizziness (0.7% vs 0.4%) being the most common adverse events.

Study details: This randomized, double-blind, placebo-controlled trial (Safety and Efficacy Study in Adult Subjects With Acute Migraines, NCT03235479)  included 1084 patients with migraine with or without aura who were randomly assigned to receive 75 mg rimegepant (n = 543) or placebo (n = 541).

Disclosures: This study was supported by Biohaven Pharmaceuticals (acquired by Pfizer, Inc.). Four authors declared being employees or stockholders of Biohaven Pharmaceuticals, Pfizer, or having other ties with various sources.

Source: Lipton RB, Thiry A, Morris BA, Croop R. Efficacy and safety of rimegepant 75 mg oral tablet, a CGRP receptor antagonist, for the acute treatment of migraine: A randomized, double-blind, placebo-controlled trial. J Pain Res. 2024;17:2431-2441 (Jul 22). Doi: 10.2147/JPR.S453806 Source

Key clinical point: Rimegepant was more effective than placebo in reducing pain and most bothersome symptoms in patients with moderate to severe migraine, while also showing favorable safety and tolerability.

Major findings: At 2 hours post dose, rimegepant was more effective than placebo in providing freedom from pain (risk difference 4.9; P = .0298) and the most bothersome symptoms (risk difference 8.9; P = .0016). Similar proportions of participants in the rimegepant vs placebo group experienced at least one adverse event (12.6% vs 10.7%), with nausea (0.9% vs 1.1%) and dizziness (0.7% vs 0.4%) being the most common adverse events.

Study details: This randomized, double-blind, placebo-controlled trial (Safety and Efficacy Study in Adult Subjects With Acute Migraines, NCT03235479)  included 1084 patients with migraine with or without aura who were randomly assigned to receive 75 mg rimegepant (n = 543) or placebo (n = 541).

Disclosures: This study was supported by Biohaven Pharmaceuticals (acquired by Pfizer, Inc.). Four authors declared being employees or stockholders of Biohaven Pharmaceuticals, Pfizer, or having other ties with various sources.

Source: Lipton RB, Thiry A, Morris BA, Croop R. Efficacy and safety of rimegepant 75 mg oral tablet, a CGRP receptor antagonist, for the acute treatment of migraine: A randomized, double-blind, placebo-controlled trial. J Pain Res. 2024;17:2431-2441 (Jul 22). Doi: 10.2147/JPR.S453806 Source

Key clinical point: Rimegepant was more effective than placebo in reducing pain and most bothersome symptoms in patients with moderate to severe migraine, while also showing favorable safety and tolerability.

Major findings: At 2 hours post dose, rimegepant was more effective than placebo in providing freedom from pain (risk difference 4.9; P = .0298) and the most bothersome symptoms (risk difference 8.9; P = .0016). Similar proportions of participants in the rimegepant vs placebo group experienced at least one adverse event (12.6% vs 10.7%), with nausea (0.9% vs 1.1%) and dizziness (0.7% vs 0.4%) being the most common adverse events.

Study details: This randomized, double-blind, placebo-controlled trial (Safety and Efficacy Study in Adult Subjects With Acute Migraines, NCT03235479)  included 1084 patients with migraine with or without aura who were randomly assigned to receive 75 mg rimegepant (n = 543) or placebo (n = 541).

Disclosures: This study was supported by Biohaven Pharmaceuticals (acquired by Pfizer, Inc.). Four authors declared being employees or stockholders of Biohaven Pharmaceuticals, Pfizer, or having other ties with various sources.

Source: Lipton RB, Thiry A, Morris BA, Croop R. Efficacy and safety of rimegepant 75 mg oral tablet, a CGRP receptor antagonist, for the acute treatment of migraine: A randomized, double-blind, placebo-controlled trial. J Pain Res. 2024;17:2431-2441 (Jul 22). Doi: 10.2147/JPR.S453806 Source

Key clinical point: This Mendelian randomization study showed that leisure screen time (LST) worsens migraine, whereas moderate to vigorous physical activity (MVPA) alleviates it, with hypertension and diastolic blood pressure (DBP) being responsible for the effects of MVPA or LST on migraine.

Major findings: Genetically predicted LST was associated with a significantly increased risk for migraine (odds ratio [OR] 1.28; P < .001), whereas MVPA was linked to a significantly reduced risk (OR 0.73; P = .000006). Hypertension mediated 4.86% and 24.81% of the effects of MVPA and LST on migraine risk, respectively, and DBP accounted for 4.66% of the effects of MVPA on migraine risk.

Study details: This study included 18,477 patients with migraine and 287,837 control individuals without migraine from the FinnGen consortium and 26,052 patients with migraine and 487,214 control individuals without migraine from the large-scale genome-wide association studies.

Disclosures: This study was supported by grants from the National Natural Science Foundation of China and others. The authors declared no conflicts of interest.

Source: Gan Q, Song E, Zhang L, et al. The role of hypertension in the relationship between leisure screen time, physical activity and migraine: A 2-sample Mendelian randomization study. J Headache Pain. 2024;25:122 (Jul 24). Doi: 10.1186/s10194-024-01820-4 Source

Key clinical point: This Mendelian randomization study showed that leisure screen time (LST) worsens migraine, whereas moderate to vigorous physical activity (MVPA) alleviates it, with hypertension and diastolic blood pressure (DBP) being responsible for the effects of MVPA or LST on migraine.

Major findings: Genetically predicted LST was associated with a significantly increased risk for migraine (odds ratio [OR] 1.28; P < .001), whereas MVPA was linked to a significantly reduced risk (OR 0.73; P = .000006). Hypertension mediated 4.86% and 24.81% of the effects of MVPA and LST on migraine risk, respectively, and DBP accounted for 4.66% of the effects of MVPA on migraine risk.

Study details: This study included 18,477 patients with migraine and 287,837 control individuals without migraine from the FinnGen consortium and 26,052 patients with migraine and 487,214 control individuals without migraine from the large-scale genome-wide association studies.

Disclosures: This study was supported by grants from the National Natural Science Foundation of China and others. The authors declared no conflicts of interest.

Source: Gan Q, Song E, Zhang L, et al. The role of hypertension in the relationship between leisure screen time, physical activity and migraine: A 2-sample Mendelian randomization study. J Headache Pain. 2024;25:122 (Jul 24). Doi: 10.1186/s10194-024-01820-4 Source

Key clinical point: This Mendelian randomization study showed that leisure screen time (LST) worsens migraine, whereas moderate to vigorous physical activity (MVPA) alleviates it, with hypertension and diastolic blood pressure (DBP) being responsible for the effects of MVPA or LST on migraine.

Major findings: Genetically predicted LST was associated with a significantly increased risk for migraine (odds ratio [OR] 1.28; P < .001), whereas MVPA was linked to a significantly reduced risk (OR 0.73; P = .000006). Hypertension mediated 4.86% and 24.81% of the effects of MVPA and LST on migraine risk, respectively, and DBP accounted for 4.66% of the effects of MVPA on migraine risk.

Study details: This study included 18,477 patients with migraine and 287,837 control individuals without migraine from the FinnGen consortium and 26,052 patients with migraine and 487,214 control individuals without migraine from the large-scale genome-wide association studies.

Disclosures: This study was supported by grants from the National Natural Science Foundation of China and others. The authors declared no conflicts of interest.

Source: Gan Q, Song E, Zhang L, et al. The role of hypertension in the relationship between leisure screen time, physical activity and migraine: A 2-sample Mendelian randomization study. J Headache Pain. 2024;25:122 (Jul 24). Doi: 10.1186/s10194-024-01820-4 Source

Key clinical point: The meta-analysis showed that atogepant was effective and well tolerated in patients with migraine in a non–dose-dependent manner, with rare incidences of serious treatment-emergent adverse events (TEAE) reported.

Major findings: Atogepant vs placebo led to a significant reduction in monthly migraine days (standardized mean difference [SMD] −0.40; P = .00001) and headache days (SMD −0.39; P = .00001), with consistent results observed across all dosage groups. The risk for TEAE (relative risk [RR] 1.11; P = .02) was significantly higher in the atogepant vs placebo group, with constipation (RR 2.55; P < .00001), nausea (RR 2.19; P < .00001), and urinary tract infection (RR 1.49; P = .03) being the most common.

Study details: This meta-analysis of four randomized controlled trials included 2813 patients with migraine who were treated with atogepant (10 mg, 30 mg, or 60 mg).

Disclosures: This study was supported by the Chongqing Clinical Pharmacy Key Specialties Construction Project, China. The authors declared no conflicts of interest.

Source: Hou M, Luo X, He S, et al. Efficacy and safety of atogepant, a small molecule CGRP receptor antagonist, for the preventive treatment of migraine: A systematic review and meta-analysis. J Headache Pain. 2024;25:116 (Jul 19). Doi: 10.1186/s10194-024-01822-2 Source

Key clinical point: The meta-analysis showed that atogepant was effective and well tolerated in patients with migraine in a non–dose-dependent manner, with rare incidences of serious treatment-emergent adverse events (TEAE) reported.

Major findings: Atogepant vs placebo led to a significant reduction in monthly migraine days (standardized mean difference [SMD] −0.40; P = .00001) and headache days (SMD −0.39; P = .00001), with consistent results observed across all dosage groups. The risk for TEAE (relative risk [RR] 1.11; P = .02) was significantly higher in the atogepant vs placebo group, with constipation (RR 2.55; P < .00001), nausea (RR 2.19; P < .00001), and urinary tract infection (RR 1.49; P = .03) being the most common.

Study details: This meta-analysis of four randomized controlled trials included 2813 patients with migraine who were treated with atogepant (10 mg, 30 mg, or 60 mg).

Disclosures: This study was supported by the Chongqing Clinical Pharmacy Key Specialties Construction Project, China. The authors declared no conflicts of interest.

Source: Hou M, Luo X, He S, et al. Efficacy and safety of atogepant, a small molecule CGRP receptor antagonist, for the preventive treatment of migraine: A systematic review and meta-analysis. J Headache Pain. 2024;25:116 (Jul 19). Doi: 10.1186/s10194-024-01822-2 Source

Key clinical point: The meta-analysis showed that atogepant was effective and well tolerated in patients with migraine in a non–dose-dependent manner, with rare incidences of serious treatment-emergent adverse events (TEAE) reported.

Major findings: Atogepant vs placebo led to a significant reduction in monthly migraine days (standardized mean difference [SMD] −0.40; P = .00001) and headache days (SMD −0.39; P = .00001), with consistent results observed across all dosage groups. The risk for TEAE (relative risk [RR] 1.11; P = .02) was significantly higher in the atogepant vs placebo group, with constipation (RR 2.55; P < .00001), nausea (RR 2.19; P < .00001), and urinary tract infection (RR 1.49; P = .03) being the most common.

Study details: This meta-analysis of four randomized controlled trials included 2813 patients with migraine who were treated with atogepant (10 mg, 30 mg, or 60 mg).

Disclosures: This study was supported by the Chongqing Clinical Pharmacy Key Specialties Construction Project, China. The authors declared no conflicts of interest.

Source: Hou M, Luo X, He S, et al. Efficacy and safety of atogepant, a small molecule CGRP receptor antagonist, for the preventive treatment of migraine: A systematic review and meta-analysis. J Headache Pain. 2024;25:116 (Jul 19). Doi: 10.1186/s10194-024-01822-2 Source

Key clinical point: The presence of migraine aura exacerbated migraine-related disability, mainly due to concurrent non-pain symptoms of migraine rather than the aura itself.

Major findings: The presence of aura on the first day of the migraine episode was significantly associated with increased odds of disability across all migraine days (odds ratio [OR] 1.40; P < .001); and non-pain symptoms, such as allodynia, photophobia, phonophobia, and nausea or vomiting (P < .001 for all). No association was observed between aura and headache-related migraine symptoms.

Study details: This observational prospective cohort study included 554 adults with episodic migraine, with complete data on migraine symptoms and psychological variables collected daily for 90 days using the N-1 Headache™ digital app (N = 11,156 total migraine days).

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

Source: Denney DE, Lee AA, Landy SH, Smitherman TA. Headache-related disability as a function of migraine aura: A daily diary study. Headache. 2024 (Aug 1). Doi: 10.1111/head.14796 Source

Key clinical point: The presence of migraine aura exacerbated migraine-related disability, mainly due to concurrent non-pain symptoms of migraine rather than the aura itself.

Major findings: The presence of aura on the first day of the migraine episode was significantly associated with increased odds of disability across all migraine days (odds ratio [OR] 1.40; P < .001); and non-pain symptoms, such as allodynia, photophobia, phonophobia, and nausea or vomiting (P < .001 for all). No association was observed between aura and headache-related migraine symptoms.

Study details: This observational prospective cohort study included 554 adults with episodic migraine, with complete data on migraine symptoms and psychological variables collected daily for 90 days using the N-1 Headache™ digital app (N = 11,156 total migraine days).

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

Source: Denney DE, Lee AA, Landy SH, Smitherman TA. Headache-related disability as a function of migraine aura: A daily diary study. Headache. 2024 (Aug 1). Doi: 10.1111/head.14796 Source

Key clinical point: The presence of migraine aura exacerbated migraine-related disability, mainly due to concurrent non-pain symptoms of migraine rather than the aura itself.

Major findings: The presence of aura on the first day of the migraine episode was significantly associated with increased odds of disability across all migraine days (odds ratio [OR] 1.40; P < .001); and non-pain symptoms, such as allodynia, photophobia, phonophobia, and nausea or vomiting (P < .001 for all). No association was observed between aura and headache-related migraine symptoms.

Study details: This observational prospective cohort study included 554 adults with episodic migraine, with complete data on migraine symptoms and psychological variables collected daily for 90 days using the N-1 Headache™ digital app (N = 11,156 total migraine days).

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

Source: Denney DE, Lee AA, Landy SH, Smitherman TA. Headache-related disability as a function of migraine aura: A daily diary study. Headache. 2024 (Aug 1). Doi: 10.1111/head.14796 Source