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Objective: To assess rates of traversing barriers to care to access optimal clinical outcomes in people with migraine internationally. Background: People in need of medical care for migraine should consult a health care professional knowledgeable in migraine management, obtain an accurate diagnosis, and receive an individualized treatment plan, which includes scientific society guideline-recommended treatments where appropriate. Methods: The Chronic Migraine Epidemiology and Outcomes-International (CaMEO-I) Study was a cross-sectional, web-based survey conducted from July 2021 through March 2022 in Canada, France, Germany, Japan, the United Kingdom, and the United States (US). Respondents who met modified International Classification of Headache Disorders, 3rd edition, criteria for migraine and had Migraine Disability Assessment Scale (MIDAS) scores of ≥ 6 (i.e., mild, moderate, or severe disability) were deemed to need medical care and were included in this analysis. Minimally effective treatment required that participants were currently consulting a health care professional for headache (barrier 1), reported an accurate diagnosis (barrier 2), and reported use of minimally appropriate pharmacologic treatment (barrier 3; based on American Headache Society 2021 Consensus Statement recommendations). Proportions of respondents who successfully traversed each barrier were calculated, and chi-square tests were used to assess overall difference among countries. Results: Among 14,492 respondents with migraine, 8,330 had MIDAS scores of ≥ 6, were deemed in need of medical care, and were included in this analysis. Current headache consultation was reported by 35.1% (2926/8330) of respondents. Compared with the US, consultation rates and diagnosis rates were statistically significantly lower in all other countries except France where they were statistically significantly higher. Total appropriate treatment rates were also statistically significantly lower in all other countries compared with the US except France, which did not differ from the US. All 3 barriers were traversed by only 11.5% (955/8330) of respondents, with differences among countries (P < 0.001). Conclusions: Of people with migraine in need of medical care for migraine, less than 15% traverse all 3 barriers to care. Although rates of consultation, diagnosis, and treatment differed among countries, improvements are needed in all countries studied to reduce the global burden of migraine. Trial registration: NA. [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence and impact of neck pain during headache among respondents with migraine in the multicountry Chronic Migraine Epidemiology and Outcomes – International (CaMEO‐I) Study. Background: Neck pain among individuals with migraine is highly prevalent and contributes to disability. Methods: The CaMEO‐I was a prospective, cross‐sectional, web‐based study conducted in Canada, France, Germany, Japan, United Kingdom, and the United States. A demographically representative sample of participants from each country completed a screening survey to evaluate headache characteristics. Respondents with headache were identified as having migraine or non‐migraine headache based on modified International Classification of Headache Disorders, third edition, criteria; those with migraine completed a detailed survey with migraine‐specific assessments. Results were stratified by the presence or absence of neck pain with headache (NPWH). For these analyses, data were pooled across the six countries. Results: Of 51,969 respondents who reported headache within the past 12 months, 14,492 (27.9%) were classified as having migraine; the remaining 37,477 (72.1%) had non‐migraine headache. Overall, 9896/14,492 (68.3%) of respondents with migraine headache reported NPWH, which was significantly higher (p < 0.001) than the proportion of respondents with non‐migraine headache who reported NPWH (13,536/37,477 [36.1%]). Among respondents with migraine, moderate‐to‐severe disability was significantly more prevalent for those with NPWH versus without (47.7% [4718/9896] vs. 28.9%, p < 0.001). Respondents with NPWH versus without also had significantly greater work productivity losses, at a median (interquartile range [IQR]) of 50.0 (20.0, 71.3) vs. 30.0 (0.0, 60.0) (p < 0.001), lower quality of life (Migraine‐Specific Quality of Life questionnaire version 2.1, median [IQR] Role Function–Restrictive domain score 60.0 [42.9, 74.3] vs. 68.6 [54.3, 82.9], p < 0.001), higher prevalence of depression and anxiety symptoms (depression, 40.2% [3982/9896] vs. 28.2% [1296/4596], p < 0.001); anxiety, 41.2% [4082/9896] vs. 29.2% [1343/4596], p < 0.001), higher prevalence of cutaneous allodynia during headache (54.0% [5345/9896] vs. 36.6% [1681/4596], p < 0.001), and higher prevalence of poor acute treatment optimization (61.1% [5582/9129] vs. 53.3% [2197/4122], p < 0.001). Conclusions: Nearly 70% of respondents with migraine reported NPWH. Individuals with migraine with neck pain during their headaches had greater disability, depression, anxiety, and cutaneous allodynia (during headache) than those without neck pain during their headaches. They also had diminished quality of life and work productivity, and poorer response to acute treatment compared with those without neck pain. Plain Language Summary: We looked at data from a web‐based study of over 51,000 people across Canada, France, Germany, Japan, United Kingdom, and the United States to understand how neck pain affects people with migraine. We found that neck pain is common in people with migraine, and that those who have neck pain during their headaches have more disability, worse symptoms, more anxiety and depression, and poorer quality of life than those without neck pain. Our results show that neck pain is a serious problem for people with migraine, and it can worsen the negative impacts of migraine. [ABSTRACT FROM AUTHOR]

Objective: To characterize the long‐term (56‐week) benefits of continuous onabotulinumtoxinA treatment response in individuals with chronic migraine (CM) who achieved reduction to <15 headache days/month with treatment. Background: There are limited data exploring reductions in monthly headache days to levels consistent with episodic migraine among those experiencing CM. Understanding the impact of sustained preventive treatment response in CM can provide important information about the impact of successful therapy. Methods: The two Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy trials of onabotulinumtoxinA in adults included a 24‐week, randomized, double‐blind, placebo‐controlled phase and a 32‐week open‐label phase. Data were pooled to determine proportions of individuals with <15 headache days/month while on treatment during several time periods in the double‐blind phase (Weeks 21–24; any 12 consecutive weeks; Weeks 13–24) and the entire study (Weeks 53–56; any 12 consecutive weeks; any 4‐week period). We assessed the long‐term impact on mean monthly headache days and changes from baseline on the six‐item Headache Impact Test (HIT‐6) and Migraine‐Specific Quality of Life questionnaire version 2.1 (MSQv2.1). Results: We analyzed 1384 participants with chronic migraine (double‐blind: onabotulinumtoxinA, n = 688; placebo, n = 696; open‐label: n = 688 [onabotulinumtoxinA]). The discontinuation rates prior to the completion of the full 56‐week treatment period for onabotulinumtoxinA and placebo were 25.4% (n = 175) and 29.3% (n = 204), respectively. During Weeks 13–24 of the double‐blind phase, significantly more onabotulinumtoxinA‐treated (386/688 [56.1%]) than placebo‐treated (342/696 [49.1%]) individuals had <15 headache days/month (p = 0.010), with fewer monthly headache days for onabotulinumtoxinA versus placebo responders. The proportions of participants achieving <15 monthly headache days with onabotulinumtoxinA were 60.9% (419/688) at Weeks 25–56, 81.1% (558/688) at Weeks 53–56, and 79.4% (546/688) during any consecutive 12‐week period. Mean changes from baseline on the HIT‐6 and MSQv2.1 questionnaire surpassed within‐group minimal important difference thresholds in all periods. At Week 24, onabotulinumtoxinA‐treated participants who achieved <15 monthly headache days during Weeks 21–24 had a greater mean HIT‐6 score reduction (−6.5 vs. −1.4) and greater mean MSQv2.1 Role‐Function Restrictive score improvements (21.3 vs. 6.4) than those who did not achieve <15 monthly headache days during the same period. Conclusions: Participants who achieved <15 monthly headache days with onabotulinumtoxinA treatment achieved meaningful benefits in headache‐related disability and migraine‐specific quality of life compared with those who remained at or above the 15–monthly headache days threshold. Sustained benefits observed over 56 weeks support long‐term onabotulinumtoxinA use for the prevention of CM. Plain Language Summary: It is not always clear how we should define if a preventive treatment for chronic migraine (CM) is successful. People with CM have ≥15 headache days/month, so we looked at data from two groups of patients who received long‐term treatment with onabotulinumtoxinA: the first group decreased to <15 headache days/month, and the second group continued to have ≥15 headache days/month. We found that the patients whose headaches decreased to <15 headache days/month, which we called the response threshold, said that their headaches impacted their lives much less and that they had better quality of life compared to the group who still met CM diagnostic criteria at the end of treatment. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) risk factors are highly prevalent among Hispanic/Latino adults, while the prevalence of MRI infarcts is not well-documented. We, therefore, sought to examine the relationships between CVD risk factors and infarcts with brain structure among Hispanic/Latino individuals. Methods: Participants included 1,886 Hispanic/Latino adults (50-85 years) who underwent magnetic resonance imaging (MRI) as part of the Study of Latinos--Investigation of Neurocognitive Aging-MRI (SOL-INCA-MRI) study. CVD risk was measured approximately 10.5 years before MRI using the Framingham cardiovascular risk score, a measure of 10-year CVD risk (low (<10%), medium (10 - < 20%), and high (≥20%)). MR infarcts were determined as present or absent. Outcomes included total brain, cerebral and lobar cortical gray matter, hippocampal, lateral ventricle, and total white matter hyperintensity (WMH) volumes. Linear regression models tested associations between CVD risk and infarct with MRI outcomes and for modifications by age and sex. Results: Sixty percent of participants were at medium or high CVD risk. Medium and high CVD risk were associated with lower total brain and frontal gray matter and higher WMH volumes compared to those with low CVD risk. High CVD risk was additionally associated with lower total cortical gray matter and parietal volumes and larger lateral ventricle volumes. Men tended to have greater CVDRF-related differences in total brain volumes than women. The association of CVD risk factors on total brain volumes increased with age, equal to an approximate 7-year increase in total brain aging among the high-CVD-risk group compared to the low-risk group. The presence of infarct(s) was associated with lower total brain volumes, which was equal to an approximate 5-year increase in brain aging compared to individuals without infarcts. Infarcts were also associated with smaller total cortical gray matter, frontal and parietal volumes, and larger lateral ventricle and WMH volumes. Conclusion: The high prevalence of CVD risk among Hispanic/Latino adults may be associated with accelerated brain aging. [ABSTRACT FROM AUTHOR]

Background: Atogepant is an oral calcitonin gene–related peptide receptor antagonist approved for the preventive treatment of migraine in adults. These analyses evaluated the proportions of clinical trial participants who experienced sustained responses to atogepant over 12 or 52 weeks of treatment. Methods: These were post hoc analyses of ADVANCE, a 12-week, double-blind, randomized trial of atogepant 10, 30, and 60 mg once daily vs. placebo for the preventive treatment of episodic migraine, and a separate open-label long-term safety (LTS) trial of atogepant 60 mg once daily over 52 weeks. The 60 mg dose of atogepant was used to detect safety issues. An initial response was defined as ≥50%, ≥75%, or 100% reduction from baseline in MMDs in month 1 for ADVANCE or quarter 1 for the LTS trial. The proportions of participants who continued to experience a response above each response-defining threshold through each subsequent month (for ADVANCE) or each quarter (for LTS) were calculated. Results: In ADVANCE, sustained response rates during months 2 and 3 varied with dose and were as follows: 70.8–81.1% following an initial ≥50% response, 47.3–61.9% following an initial ≥75% response, and 34.8–41.7% following an initial 100% response. Of those who experienced an initial ≥75% or 100% response during month 1, more than 79% continued to experience at least a 50% response during both months 2 and 3. During the LTS trial, sustained response rates through quarters 2, 3, and 4 were 84.7% following an initial ≥50% response, 72.6% following an initial ≥75% response, and 37.8% following an initial 100% response. Of those who experienced an initial ≥75% or 100% response during quarter 1, more than 90% continued to experience at least a 50% response through quarters 2, 3, and 4. Conclusion: Over 70% of participants who experienced an initial response with atogepant treatment had a sustained response with continued treatment. Trial registration: ClinicalTrials.gov: NCT03777059 (submitted: December 13, 2018); NCT03700320 (submitted: September 25, 2018). [ABSTRACT FROM AUTHOR]

Objective: To analyze data from the Chronic Migraine Epidemiology and Outcomes‐International (CaMEO‐I) Study in order to characterize preventive medication use and identify preventive usage gaps among people with migraine across multiple countries. Background: Guidelines for the preventive treatment of migraine are available from scientific organizations in various countries. Although these guidelines differ among countries, eligibility for preventive treatment is generally based on monthly headache day (MHD) frequency and associated disability. The overwhelming majority of people with migraine who are eligible for preventive treatment do not receive it. Methods: The CaMEO‐I Study was a cross‐sectional, observational, web‐based panel survey study performed in six countries: Canada, France, Germany, Japan, the United Kingdom, and the United States. People were invited to complete an online survey in their national language(s) to identify those with migraine according to modified International Classification of Headache Disorders, 3rd edition, criteria. People classified with migraine answered questions about current and ever use of both acute and preventive treatments for migraine. Available preventive medications for migraine differed by country. MHD frequency and associated disability data were collected. The American Headache Society (AHS) 2021 Consensus Statement algorithm was used to determine candidacy for preventive treatment (i.e., ≥3 monthly MHDs with severe disability, ≥4 MHDs with some disability, or ≥6 MHDs regardless of level of disability). Results: Among 90,613 valid completers of the screening survey, 14,492 met criteria for migraine and completed the full survey, with approximately 2400 respondents from each country. Based on the AHS consensus statement preventive treatment candidacy algorithm, averaging across countries, 36.2% (5246/14,492) of respondents with migraine qualified for preventive treatment. Most respondents (84.5% [4431/5246]) who met criteria for preventive treatment according to the AHS consensus statement were not using a preventive medication at the time of the survey. Moreover, 19.3% (2799/14,492) of respondents had ever used preventive medication (ever users); 58.1% (1625/2799) of respondents who reported ever using a preventive medication for migraine were still taking it. Of the respondents who were currently using a preventive medication, 50.2% (815/1625) still met the criteria for needing preventive treatment based on the AHS consensus statement. Conclusions: Most people with migraine who qualify for preventive treatment are not currently taking it. Additionally, many people currently taking preventive pharmacologic treatment still meet the algorithm criteria for needing preventive treatment, suggesting inadequate benefit from their current regimen. Plain Language Summary: People with migraine who experience frequent headaches or some level of disability may benefit from using a preventive medication for migraine. We collected data on the use of preventive medication for migraine in Canada, France, Germany, Japan, the United Kingdom, and the United States. These data demonstrated that many people who qualified for the use of a preventive treatment in the six participating countries were not currently taking a preventive medication for migraine. [ABSTRACT FROM AUTHOR]

The Hispanic/Latino population experiences socioeconomic adversities across the lifespan and is at greater risk of cognitive impairment, yet little is known about the role of life-course socioeconomic position (SEP) in cognitive function in this population. Using baseline data (2008–2011) from adults (aged 45–74 years) of the Hispanic Community Health Study/Study of Latinos, we assessed the association between childhood SEP and socioeconomic mobility with cognitive function, and whether this association was mediated by midlife SEP. Childhood SEP was assessed using parental education. An index combining participants' education and household income represented midlife SEP. Socioeconomic mobility was categorized as stable low, downward or upward mobility, and stable high-SEP. Cognitive function measures were modeled using survey linear regression with inverse-probability weighting, accounting for covariates. We used mediation analysis to estimate the indirect effect of childhood SEP on cognition through midlife SEP. High childhood SEP was associated with global cognition in adulthood (coefficient for parental education beyond high school vs. less than high school = 0.26, 95% confidence interval: 0.15, 0.37). This association was partially mediated through midlife SEP (indirect effect coefficient = 0.16, 95% confidence interval: 0.15, 0.18). Low SEP through the life course was associated with the lowest cognitive function. This study provides evidence that life-course SEP influences cognitive performance in adulthood. [ABSTRACT FROM AUTHOR]

Background: Individuals with migraine frequently experience pre- and post-headache symptoms. This analysis aimed to characterize the relative frequency and burden of pre- and post-headache symptoms in people with migraine using data collected through the Chronic Migraine Epidemiology and Outcomes – International Study. Methods: This cross-sectional, observational, web-based survey was conducted in 2021–2022 in Canada, France, Germany, Japan, the United Kingdom, and the United States. Respondents who met modified International Classification of Headache Disorders, 3rd edition, criteria were offered the opportunity to participate. Information collected included migraine-related disability, depression/anxiety symptoms, cutaneous allodynia, activity limitations, and acute treatment optimization. Respondents indicated how often they had pre- or post-headache symptoms using a 5-point scale, ranging from 0 to 4, with a rating of 2 or higher classified as a pre- or post-headache symptom case. Modeling was used to examine relationships with monthly headache days (MHDs) and activity limitations during pre-headache and post-headache phases. Results: Among a total of 14,492 respondents, pre-headache symptoms were reported by 66.9%, while post-headache symptoms were reported by 60.2%. Both pre-headache and post-headache symptoms were reported by 49.5% of respondents, only pre-headache by 17.4%, only post-headache by 10.7%, and neither pre- nor post-headache symptoms by 22.4%. Compared with respondents who experienced only pre- or post-headache symptoms, respondents who experienced both pre- and post-headache symptoms had the highest rates of 4–7, 8–14, and ≥ 15 monthly headache days (23.1%, 14.1%, and 10.9%, respectively). Of respondents with both pre- and post-headache symptoms, 58.5% reported moderate-to-severe disability, 47.7% reported clinically significant symptoms of depression, 49.0% reported clinically significant symptoms of anxiety, and 63.8% reported cutaneous allodynia with headache (ASC-12). Moderate-to-severe activity limitations were reported during the pre-headache (29.5%) and post-headache phases (27.2%). For all outcomes modeled, after controlling for covariates, having pre-headache symptoms, post-headache symptoms, or both were associated with worse outcomes than having neither. Conclusions: Pre- and post-headache phases of migraine are common, carry unrecognized burden, and may be a target for treatment. [ABSTRACT FROM AUTHOR]

Objective: To characterize the direct impact of monthly headache days (MHDs) on health‐related quality of life (HRQoL) in people with migraine and the potential mediating effects of anxiety, depression, and allodynia. Background: Although the general relationship between increased migraine frequency (i.e., MHDs) and reduced HRQoL is well established, the degree to which reduced HRQoL is due to a direct effect of increased MHDs or attributable to mediating factors remains uncertain. Methods: Cross‐sectional baseline data from participants with migraine who completed the Core and Comorbidities/Endophenotypes modules in the 2012–2013 US Chronic Migraine Epidemiology and Outcomes (CaMEO) study, a longitudinal web‐based survey study, were analyzed. The potential contribution of depression, anxiety, and/or allodynia to the observed effects of MHDs on HRQoL as measured by the Migraine‐Specific Quality‐of‐Life Questionnaire version 2.1 (MSQ) was evaluated. Results: A total of 12,715 respondents were included in the analyses. The MSQ domain scores demonstrated progressive declines with increasing MHD categories (B = −1.23 to −0.60; p < 0.001). The observed HRQoL decrements associated with increasing MHDs were partially mediated by the presence of depression, anxiety, and allodynia. The MHD values predicted 24.0%–32.4% of the observed variation in the MSQ domains. Depression mediated 15.2%–24.3%, allodynia mediated 9.6%–16.1%, and anxiety mediated 2.3%–6.0% of the observed MHD effects on the MSQ. Conclusions: Increased MHD values were associated with lower MSQ scores; the impact of MHDs on the MSQ domain scores was partially mediated by the presence of depression, anxiety, and allodynia. MHDs remain the predominant driver of the MSQ variation; moreover, most of the variation in the MSQ remains unexplained by the variables we analyzed. Future longitudinal analyses and studies may help clarify the contribution of MHDs, comorbidities, and other factors to changes in HRQoL. [ABSTRACT FROM AUTHOR]

Objective: To evaluate an alternative method of defining acute treatment success in migraine by combining multiple indicators into a single dichotomous measure of success. Background: Migraine is characterized by a symptom complex; combining these features as a single endpoint may improve the measurement of treatment effects and better predict patient satisfaction with treatment. Methods: We used a confirmatory latent class model (LCM) with two latent classes interpreted as treatment success and treatment failure. Pooled data for placebo and ubrogepant 50 mg from the ACHIEVE I and ACHIEVE II trials and data for ubrogepant 100 mg from ACHIEVE I were used. LCM inputs included pre‐dose and 2‐h post‐dose measures of pain severity (0–3), the presence/absence of associated symptoms (nausea, photophobia, and phonophobia [0 or 1]), and functional disability (0–3). All definitions were validated against satisfaction with study medication (SWSM) at 24 h post‐dose; results were compared with 2‐hour pain freedom (2hPF). Results: This pooled analysis included 2247 participants. At 2 h post‐dose in the ubrogepant 50 and 100 mg dose groups, 53.2% (472/887) and 54.9% (246/448) of participants, respectively, were classified as achieving treatment success using the LCM‐based approach, compared to 39.0% (356/912) of participants in the placebo group. The results for treatment success using the 2hPF endpoint were 20.7% (184/887) and 21.5% (96/447) in the ubrogepant 50 and 100 mg dose groups, respectively, compared to 12.7% (116/912) for placebo. Using 24‐h SWSM as an external validator, the LCM approach sensitivity and correct classification rates were higher than for 2hPF. Conclusion: The LCM approach led to higher rates of treatment success and greater separation between ubrogepant and placebo and was a more sensitive predictor of treatment satisfaction than the regulatory endpoint of 2hPF. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to characterize the utility of calcitonin gene–related peptide (CGRP) and nerve growth factor (NGF) as potential biomarkers for headache and pain disorders in the post–military deployment setting. Background: The need to improve recognition, assessment, and prognoses of individuals with posttraumatic headache or other pain has increased interest in the potential of CGRP and NGF as biomarkers. Methods: The Warrior Strong Study (NCT01847040) is an observational longitudinal study of United States–based soldiers who had recently returned from deployment to Afghanistan or Iraq from 2009 to 2014. The present nested cross‐sectional analysis uses baseline data collected from soldiers returning to Fort Bragg, North Carolina. Results: In total, 264 soldiers (mean (standard deviation [SD] age 28.1 [6.4] years, 230/264 [87.1%] men, 171/263 [65.0%] White) were analyzed. Mean (SD) plasma levels of CGRP were 1.3 (1.1) pg/mL and mean levels of NGF were 1.4 (0.4) pg/mL. Age was negatively correlated with NGF (−0.01 pg/mL per year, p = 0.007) but was not associated with CGRP. Men had higher mean (SD) CGRP plasma levels than women (1.4 95% confidence interval [CI; 1.2] vs. 0.9 95% CI [0.5] pg/mL, p < 0.002, Kruskal–Wallis test). CGRP levels were lower in participants who had a headache at the time of the blood draw (1.0 [0.6] pg/mL vs. 1.4 [1.2] pg/mL, p = 0.024). NGF was lower in participants with continuous pain (all types; 1.2 [0.4] vs. 1.4 [0.4] pg/mL, p = 0.027) and was lower in participants with traumatic brain injury (TBI) + posttraumatic headache (PTH) versus TBI without PTH (1.3 [0.3] vs. 1.4 [0.4] pg/mL, p = 0.021). Otherwise, CGRP and NGF were not associated with migraine‐like headache, TBI status, or headache burden as measured by the number of medical encounters in crude or adjusted models. Conclusion: In this exploratory study, plasma levels of NGF and CGRP showed promise as biomarkers for headache and other types of pain. These findings need to be replicated in other cohorts. [ABSTRACT FROM AUTHOR]

Background: Individuals using onabotulinumtoxinA as a preventive migraine treatment often use acute treatments for breakthrough attacks. Data on real-world effectiveness of the small-molecule calcitonin gene–related peptide (CGRP) receptor antagonist ubrogepant in combination with onabotulinumtoxinA are limited. Methods: COURAGE, a prospective, multiple attack, observational study, evaluated the real-world effectiveness of ubrogepant (50 or 100 mg) for acute treatment of migraine in people receiving onabotulinumtoxinA, an anti-CGRP monoclonal antibody (mAb), or both. This analysis focused only on onabotulinumtoxinA users. The Migraine Buddy app was used to identify eligible participants and track response to treated attacks. For each ubrogepant-treated attack, meaningful pain relief (MPR) and return to normal function (RNF) at 2 and 4 h post-dose over 30 days was assessed. MPR was defined as a level of relief that is meaningful to the participant, usually occurring before the pain is all gone. After 30 days, satisfaction was reported on a 7-point scale and overall acute treatment optimization was evaluated using the migraine Treatment Optimization Questionnaire-4 (mTOQ-4). Results: This analysis included 122 participants who received ubrogepant and onabotulinumtoxinA and reported on 599 ubrogepant-treated attacks. Following the first ubrogepant-treated attack, MPR was achieved in 53.3% of participants 2 h post-dose and in 76.2% of participants 4 h post-dose. RNF was achieved in 25.4% of participants 2 h post-dose and in 45.9% of participants 4 h post-dose. MPR and RNF results were similar across up to 10 ubrogepant-treated attacks. After 30 days, satisfaction with ubrogepant in combination with onabotulinumtoxinA was reported by 69.8% of participants and acute treatment optimization (defined as mTOQ-4 score ≥ 4) was achieved in 77.6%. Conclusions: In this prospective real-world effectiveness study, ubrogepant treatment in onabotulinumtoxinA users with self-identified migraine was associated with high rates of MPR and RNF at 2 and 4 h as well as satisfaction and acute treatment optimization. Although the lack of a contemporaneous control group limits causal inference, these findings demonstrate the feasibility of using a novel, app-based design to evaluate the real-world effectiveness and satisfaction of treatments. [ABSTRACT FROM AUTHOR]

Background: There is renewed emphasis on including patients in determining, defining, and prioritizing outcomes for migraine treatment. Objectives: To obtain insights directly from people living with migraine on their priorities for treatment. Methods: A total of 40 qualitative interviews were conducted as part of the Migraine Clinical Outcome Assessment System project, a United States Food and Drug Administration grant‐funded program to develop a core set of patient‐centered outcome measures for migraine clinical trials. Interviews included a structured exercise in which participants rank‐ordered pre‐defined lists of potential benefits for acute and preventive migraine therapy. The 40 study participants who reported being diagnosed with migraine by a clinician ranked the benefits and explained their rationale. Results: Study participants consistently ranked either pain relief or absence of pain as their top priority for acute treatment. Relief/absence of other migraine symptoms and improved functioning were also prioritized. For preventive treatment, participants prioritized reductions in migraine frequency, symptom severity, and attack duration. Few differences were found between participants with episodic migraine and those with chronic migraine. However, participants with chronic migraine ranked "increased predictability of attacks" much higher than those with episodic migraine. Participants' rankings were influenced by prior expectations and experiences of migraine treatments, which caused many participants to deprioritize desired benefits as unrealistic. Participants also identified several additional priorities, including limited side‐effects and reliable treatment efficacy in both acute and preventive treatments. Conclusion: The results showed the participants prioritized treatment benefits aligned with existing core clinical outcomes used in migraine research, but also valued benefits that are not typically assessed, such as predictability. Participants also deprioritized important benefits when they believed treatment was unlikely to deliver those outcomes. [ABSTRACT FROM AUTHOR]

The article reports that NPWH is more prevalent in people with migraine compared to those with non-migraine headaches, with significant impacts on disability, depression, anxiety, and work productivity. Topics include the frequency and impact of NPWH in migraine sufferers, its association with increased disease burden and reduced treatment response, and the variation in NPWH impact across different countries, notably Japan.

Objective: Assess the long‐term efficacy and safety of erenumab in patients with chronic migraine with acute medication overuse. Background: Overuse of acute medication in patients with chronic migraine has been linked to greater pain intensity and disability and may diminish the effectiveness of preventive therapies. Methods: This 52‐week open‐label extension study followed a 12‐week double‐blind placebo‐controlled study in which patients with chronic migraine were randomized 3:2:2 to placebo or once‐monthly erenumab 70 mg or 140 mg. Patients were stratified by region and medication overuse status. Patients received erenumab 70 mg or 140 mg throughout or switched from erenumab 70 to 140 mg (based on protocol amendment to augment safety data at higher dose). Efficacy was assessed in patients with and without medication overuse at parent study baseline. Results: Of 609 patients enrolled in the extension study, 252/609 (41.4%) met the criteria for medication overuse at parent study baseline. At Week 52, the mean change in monthly migraine days from parent study baseline was −9.3 (95% confidence interval: −10.4, −8.1 days) in the medication overuse subgroup versus −9.3 (−10.1, −8.5 days) in the non‐medication overuse subgroup (combined erenumab doses); proportion of patients achieving ≥50% reduction in monthly migraine days at Week 52 was 55.9% (90/161; 48.2%, 63.3%) versus 61.3% (136/222; 54.7%, 67.4%), respectively. Among baseline users of acute migraine‐specific medication, the mean change in monthly migraine‐specific medication days at Week 52 was −7.4 (−8.3, −6.4 days) in the medication overuse subgroup versus −5.4 (−6.1, −4.7 days) in the non–medication overuse subgroup. Most patients (197/298; 66.1%) in the medication overuse subgroup transitioned to non‐overuse status by Week 52. Erenumab 140 mg was associated with numerically greater efficacy than erenumab 70 mg across all endpoints. No new safety signals were identified. Conclusion: Long‐term erenumab treatment demonstrated sustained efficacy and safety in patients with chronic migraine with and without acute medication overuse. [ABSTRACT FROM AUTHOR]

Objective: To evaluate changes in interictal burden with galcanezumab versus placebo in patients with episodic (EM) or chronic migraine (CM). Background: The disruptive effects of migraine occur both during attacks (ictal period) and between attacks (interictal period), affecting work, school, family, and social life. Migraine clinical trials typically assess ictal burden endpoints, neglecting interictal burden. Methods: CONQUER was a 3‐month, double‐blind study that randomized adult patients with EM or CM who had experienced failure of two to four standard‐of‐care migraine preventive medication categories to receive monthly galcanezumab (n = 232) or placebo (n = 230), followed by 3 months of open‐label galcanezumab. The mean change in interictal burden, a secondary objective, was measured using the four‐item Migraine Interictal Burden Scale (MIBS‐4). The total score for MIBS‐4 can range from zero to 12, with scores ≥5 indicating severe interictal burden. Post hoc analyses evaluated shifts in MIBS‐4 severity categories and item‐level improvement. Results: The MIBS‐4 total score indicated severe interictal burden at baseline (mean [SD]: all patients, 5.5 [3.5]; EM, 5.0 [3.4]; CM, 6.2 [3.5]). Reductions in the MIBS‐4 score were significantly greater with galcanezumab versus placebo at Month 3 (mean [SE]: all patients −1.9 [0.2] vs. −0.8 [0.2], p < 0.0001; EM, −1.8 [0.3] vs. −1.1 [0.3], p = 0.033; CM, −1.8 [0.4] vs. −0.3 [0.4], p < 0.001), with further improvement at Month 6 after all patients had received galcanezumab (mean [SE]: all patients, −2.4 [0.2] vs. −2.0 [0.2]; EM, −2.3 [0.3] vs. −2.2 [0.3]; CM, −2.1 [0.4] vs. −1.5 [0.4]). The percentage of patients with severe interictal burden decreased substantially for the galcanezumab‐treated patients, from 59% (137/232) at baseline to 27% (58/217) at Month 6 (EM from 51% [70/137] to 23% [30/131]; CM from 71% [67/95] to 33% [28/86]). Conclusion: In addition to the known efficacy of galcanezumab in the ictal period, these findings suggest treatment with galcanezumab results in a significant reduction in interictal burden. [ABSTRACT FROM AUTHOR]

Background: No available studies demonstrate validity and meaningful change thresholds of Work Productivity and Activity Impairment (WPAI) questionnaire in patients with migraine. In this post-hoc analysis, we assessed reliability, validity, responsiveness, and meaningful within-patient change from baseline to Month 3 for Work Productivity and Activity Impairment (WPAI) domain scores in patients with episodic migraine (EM) or chronic migraine (CM). Method: The Phase 3, multicenter, randomized, double-blind, placebo-controlled CONQUER study (NCT03559257, N = 462) enrolled patients with EM or CM who failed two to four categories of prior preventive medication in past ten years. The analyses were performed for WPAI domain scores (absenteeism, presenteeism, overall work productivity, and non-work-related activity impairment). Migraine Specific Quality of Life Questionnaire version 2.1 (MSQv2.1) domain scores (Role Function-Restrictive [RFR] and Role Function-Preventive [RFP]), and monthly migraine headache days were used as anchors. Responder criteria were changes from baseline to Month 3 for each of these anchors and were defined as: increase in MSQ-RFR by ≥ 25.71 points and MSQ-RFP by ≥ 20.00 points and a 50% reduction in monthly migraine headache days. Assessments were performed for overall population, and patients with EM or CM. The meaningful change threshold was determined based on Youden index, Phi coefficient and sensitivity. Results: Of 462 randomized patients, 444 who completed WPAI questionnaire were included in post-hoc analysis. Test–retest reliability over 3 months in a stable subgroup revealed moderate correlations for non-work-related Activity Impairment (ICC = 0.446) presenteeism (ICC = 0.438) and a fair correlation for overall work productivity loss (ICC = 0.360). At baseline, all correlations between WPAI domain scores and continuous anchor variables exceeded recommended threshold of ≥ 0.30, except for WPAI domain scores with number of monthly migraine headache days. Patients achieving pre-specified responsiveness thresholds for monthly migraine headache days, and MSQ-RFP, MSQ-RFR from baseline to Month 3 (responders) showed significant improvements in WPAI domain scores compared with non-responders (P < 0.001). The meaningful change thresholds of -20 (% unit) were identified for WPAI domain scores. Conclusion: In conclusion, WPAI has sufficient validity, reliability, responsiveness, and appropriate interpretation standards to assess the impact of EM or CM on presenteeism and overall work productivity loss and non-work-related activity impairment. Trial registration: NCT number of CONQUER study, NCT03559257. [ABSTRACT FROM AUTHOR]

Aim: To synthesize international findings on the alcohol–dementia relationship, including representation from low‐ and middle‐income countries. Methods: Individual participant data meta‐analysis of 15 prospective epidemiological cohort studies from countries situated in six continents. Cox regression investigated the dementia risk associated with alcohol use in older adults aged over 60 years. Additional analyses assessed the alcohol–dementia relationship in the sample stratified by sex and by continent. Participants included 24 478 community dwelling individuals without a history of dementia at baseline and at least one follow‐up dementia assessment. The main outcome measure was all‐cause dementia as determined by clinical interview. Results: At baseline, the mean age across studies was 71.8 (standard deviation = 7.5, range = 60–102 years), 14 260 (58.3%) were female and 13 269 (54.2%) were current drinkers. During 151 636 person‐years of follow‐up, there were 2124 incident cases of dementia (14.0 per 1000 person‐years). When compared with abstainers, the risk for dementia was lower in occasional [hazard ratio (HR) = 0.78; 95% confidence interval (CI) = 0.68–0.89], light–moderate (HR = 0.78; 95% CI = 0.70–0.87) and moderate–heavy drinkers (HR = 0.62; 95% CI = 0.51–0.77). There was no evidence of differences between life‐time abstainers and former drinkers in terms of dementia risk (HR = 0.98; 95% CI = 0.81–1.18). In dose–response analyses, moderate drinking up to 40 g/day was associated with a lower risk of dementia when compared with lif‐time abstaining. Among current drinkers, there was no consistent evidence for differences in terms of dementia risk. Results were similar when the sample was stratified by sex. When analysed at the continent level, there was considerable heterogeneity in the alcohol–dementia relationship. Conclusions: Abstinence from alcohol appears to be associated with an increased risk for all‐cause dementia. Among current drinkers, there appears to be no consistent evidence to suggest that the amount of alcohol consumed in later life is associated with dementia risk. [ABSTRACT FROM AUTHOR]

Objectives: To capture patients' perspectives on migraine‐related cognitive symptoms during pre‐headache, headache, post‐headache, and interictal periods. Background: Migraine‐related cognitive symptoms are reported by people with migraine both during and between attacks. Associated with disability, they are increasingly viewed as a priority target for treatment. The Migraine Clinical Outcome Assessment System (MiCOAS) project is focused on developing a patient‐centered core set of outcome measures for the evaluation of migraine treatments. The project focuses on incorporating the experience of people living with migraine and the outcomes most meaningful to them. This includes an examination of the presence and functional impact of migraine‐related cognitive symptoms and their perceived impact on quality of life and disability. Methods: Forty individuals with self‐reported medically diagnosed migraine were recruited via iterative purposeful sampling for semi‐structured qualitative interviews conducted using audio‐only web conferencing. Thematic content analysis was performed to identify key concepts around migraine‐related cognitive symptoms. Recruitment continued until concept saturation was achieved. Results: Participants described symptoms consistent with migraine‐related deficits in language/speech, sustained attention, executive function, and memory that manifest during pre‐headache (36/40 [90%] reported ≥1 cognitive feature), headache (35/40 [88%] reported ≥1 cognitive feature), post‐headache (27/40 [68%] reported ≥1 cognitive feature), and interictal periods (13/40 [33%] reported ≥1 cognitive feature). Among participants reporting cognitive symptoms during pre‐headache, 32/40 (81%) endorsed 2–5 cognitive symptoms. Findings were similar during the headache phase. Participants reported language/speech problems consistent with, for example, impairments in receptive language, expressive language, and articulation. Issues with sustained attention included fogginess, confusion/disorientation, and trouble with concentration/focus. Deficits in executive function included difficulty processing information and reduced capacity for planning and decision‐making. Memory issues were reported across all phases of the migraine attack. Conclusions: This patient‐level qualitative study suggests that cognitive symptoms are common for persons with migraine, particularly in the pre‐headache and headache phases. These findings highlight the importance of assessing and ameliorating these cognitive problems. [ABSTRACT FROM AUTHOR]

Objective: To evaluate potential drug–drug interactions of ubrogepant and atogepant. Background: Ubrogepant and atogepant, calcitonin gene‐related peptide (CGRP) receptor antagonists, are recently approved drugs for acute and preventive treatment of migraine, respectively. For patients with migraine who are prescribed atogepant for the preventive treatment of migraine, health care providers could prescribe ubrogepant for the acute treatment of breakthrough migraine attacks. Methods: A phase Ib, multi‐center, open‐label, fixed‐sequence study was conducted in participants diagnosed with migraine for at least 1 year. To assess the primary objective of pharmacokinetic interactions in this phase I trial, the highest United States Food and Drug Administration‐approved individual dose strengths of atogepant (60 mg once daily) and ubrogepant (100 mg) were utilized, with ubrogepant being administered on a fixed‐dose schedule every 3 days, regardless of whether a participant was experiencing a migraine attack. Secondary endpoints included safety and tolerability. Clinical safety measurements were monitored throughout the study. Results: Of the 31 participants enrolled, 26 completed the study. A single dose of ubrogepant had no statistically significant effect on atogepant pharmacokinetics. Co‐administration of ubrogepant with atogepant resulted in a 19% increase (geometric mean ratio 118.80, 90% confidence interval [CI] 108.69–129.84) in the ubrogepant area under the plasma concentration‐time curve and a 26% increase (geometric mean ratio 125.63, 90% CI 105.58–149.48) in the ubrogepant maximum plasma concentration. These statistically significant changes in ubrogepant exposure were not clinically meaningful, and no new safety concerns were identified for the combination. Conclusion: The combination use of atogepant and ubrogepant was safe and well tolerated in adult participants with a history of migraine enrolled in the study. Pharmacokinetic changes during co‐administration were not clinically meaningful. [ABSTRACT FROM AUTHOR]

Objective: To identify predictors of acute treatment optimization for migraine with "over‐the‐counter" (OTC) or prescription nonsteroidal anti‐inflammatory drugs (NSAIDs) as well as other widely used OTCs including acetaminophen, caffeine combination products (CCP), and acetylsalicylic acid (ASA, aspirin) among people with episodic migraine and to develop models that predict treatment response to each class of OTCs. Background: Efficacy of acute OTC medications for migraine varies greatly. Identifying predictors of treatment response to particular classes of medication is a step toward evidence‐based personalized therapy. Methods: For this prediction model development study, we used data from 2224 participants from the American Migraine Prevalence and Prevention (AMPP) study who were aged ≥18 years, met criteria for migraine, had <15 monthly headache days, and reported being on monotherapy for acute migraine attacks with one of the following classes medications: CCP (N = 711), acetaminophen (N = 643), ASA (N = 110), and prescription or OTC NSAIDs (N = 760). The primary outcome measures of treatment optimization were adequate 2‐h pain freedom (2hPF) and adequate 24‐h pain relief (24hPR), which were defined by responses of half the time or more to the relevant items on the Migraine Treatment Optimization Questionnaire‐6. Results: The mean (SD) age of the participants was 46.2 (13.1) years, 79.4% (1765/2224) were female, 43.7% (972/2224) reported adequate 2hPF, and 46.1% (1025/2224) reported adequate 24hPR. Those taking CCP had better 2hPF and 24PR outcomes. For those taking NSAIDs, better outcomes were associated with lower average pain intensity (2hPF: odds ratio [OR] 0.89, 95% confidence interval [CI] 0.80–0.99; 24PR: OR 0.86, 95% CI 0.77–0.96), cutaneous allodynia (2hPF: OR 0.92, 95% CI 0.89–0.96; 24PR: OR 0.91, 95% CI 0.87–0.95), depressive symptoms (2hPF: OR 0.95, 95% CI 0.92–0.98; 24PR: OR 0.95, 95% CI 0.91–0.99), and Migraine Disability Assessment Scale (MIDAS) grade (2hPF: OR 0.76, 95% CI 0.64–0.90; 24PR: OR 0.79, 95% CI 0.65–0.95). Adequate 2hPF for those taking CCP was associated with male gender (OR 1.83, 95% CI 1.21–2.77), lower average pain intensity (OR 0.80, 95% CI 0.70–0.91), lower cutaneous allodynia (OR 0.94, 95% CI 0.90–0.97), and lower Migraine Symptom Severity Scale Score (MSSS; OR 0.91, 95% CI 0.86–0.97). Adequate 24hPR for those taking CCP was associated with lower average pain intensity (OR 0.85, 95% CI 0.75–0.96), lower cutaneous allodynia (OR 0.92, 95% CI 0.89–0.96), and lower MIDAS grade (OR 0.81, 95% CI 0.68–0.96). Participants who were married (OR 1.51, 95% CI 1.05–2.19), had lower average pain intensity (OR 0.79, 95% CI 0.70–0.89), lower MSSS (OR 0.93, 95% CI 0.88–0.99), less depression (OR 0.96, 95% CI 0.93–0.99), and lower MIDAS grade (OR 0.72, 95% CI 0.59–0.87) had adequate 2hPF after taking acetaminophen. Participants who were married (OR 1.50, 95% CI 1.02–2.21), had lower pain intensity (OR 0.78, 95% CI 0.69–0.88), less depression (OR 0.95, 95% CI 0.91–0.98) and lower MIDAS grade (OR 0.53, 95% CI 0.42–0.67) had higher 24hPR following use of acetaminophen. A lower MSSS was the only factor associated with higher 2hPF and 24PR after using ASA (OR 0.78, 95% CI 0.67–0.92 and OR 0.79, 95% CI 0.67–0.93). Predictive models had modest performance in identifying responders to each class of OTC. Conclusion: A large subgroup of people with migraine had an inadequate response to their usual acute OTC migraine treatment 2‐ and 24‐h after dosing. These findings suggest a need to improve OTC treatment for some and to offer prescription acute medications for others. Predictive models identified several factors associated with better treatment‐response in each OTC class. Selecting OTC treatment based on factors predictive of treatment optimization might improve patient outcomes. [ABSTRACT FROM AUTHOR]

Objective: To investigate the links between adolescent migraine and comorbid and co‐occurring conditions using a large, nationally representative longitudinal study. Background: Comorbidities and co‐occurring conditions play an important role in the clinical treatment of individuals with migraine. Research in this area has focused largely on the adult population using cross‐sectional data, but less is known about adolescents and how conditions may co‐occur over time from a broader developmental perspective. The goals of this manuscript were to empirically evaluate the associations between adolescent migraine and several linked conditions and explore the relative timings of onset of these conditions from adolescence to adulthood. Methods: Data came from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a school‐based study of the health‐related behaviors and conditions of adolescents. The present study examined data from Wave 1 (W1, study years: 1994–1995), Wave 4 (W4, study years: 2008–2009), and Wave 5 (W5, study years: 2016–2018). Analyses and visual plots were used to evaluate potential links between parent‐reported adolescent migraine status (PR‐AdMig) at W1 and 15 medical conditions identified based on self‐reported medical diagnoses (SR‐MDs) at W4 and W5. Based on prior literature in adults, we identified 11 conditions predicted to be associated with PR‐AdMig and four conditions predicted not to be associated with PR‐AdMig. The analyses were exploratory and post hoc. Results: The total sample size pooling over all analyses was n = 13,786, but the wave‐specific sample sizes differed due to missing data (W4 analyses, n = 12,692; W5 analyses, n = 10,340); 7243/13,786 (unweighted: 52.5%; weighted: 50.5%) of participants were female, 7640/13,786 (unweighted: 55.4%; weighted: 68.6%) were White, and 1580/13,786 (unweighted: 11.5%; weighted: 12.0%) had PR‐AdMig. The average ages were 15.8 years at W1, 28.7 years at W4, and 37.8 years at W5. Findings showed that PR‐AdMig was associated with anxiety/panic disorder (W4: PR‐AdMig vs. Control weighted %: 17.1% vs. 12.6%, unadjusted odds ratio [OR] = 1.43, 95% confidence interval [CI] 1.18–1.74, p = 0.0003; W5: 31.6% vs. 22.4%, OR = 1.60, 95% CI 1.28–2.02, p < 0.0001), asthma/chronic bronchitis/emphysema (W4: 20.0% vs. 14.7%, OR = 1.45, 95% CI 1.20–1.76, p < 0.001; W5: 21.0% vs. 14.6%, OR = 1.55, 95% CI 1.25–1.94, p < 0.001), attention deficit hyperactivity disorder (W4: 8.3% vs. 5.4%, OR = 1.58, 95% CI 1.18–2.10, p = 0.002), depression (W4: 23.7% vs. 15.4%, OR = 1.71, 95% CI 1.43–2.04, p < 0.0001; W5: 33.8% vs. 25.1%, OR = 1.53, 95% CI 1.22–1.90, p < 0.001), epilepsy/seizure disorder (W4: 2.2% vs. 1.2%, OR = 1.84, 95% CI 1.23–2.76, p = 0.004), migraine (W4: 38.8% vs. 11.9%, OR = 4.7, 95% CI 4.1–5.5, p < 0.001), post‐traumatic stress disorder (W4: 4.1% vs. 2.8%, OR = 1.45, 95% CI 1.01–2.08, p = 0.042; W5: 11.3% vs. 7.1%, OR = 1.67, 95% CI 1.27–2.20, p < 0.001), and sleep apnea (W5: 11.0% vs. 7.6%, OR = 1.51, 95% CI 1.15–1.98, p = 0.003). Among theoretically unlinked conditions, only hepatitis C at W4 was shown to have a relationship with adolescent onset migraine (0.7% vs. 0.2%, OR = 3.63, 95% CI 1.32–10.0, p = 0.013). Visual plots suggested that the retrospective, self‐report timing of onset of specific subsets of co‐occurring conditions tended to group together over time. Conclusions: Consistent with the existing headache literature, results showed that adolescent migraine was associated with other medical and psychological conditions and visual plots suggested that there may be developmental patterns in the occurrence of migraine with other related conditions. [ABSTRACT FROM AUTHOR]

Background: Stigma is increasingly recognized as an important social feature of living with migraine. Methods: Adults with migraine recruited from neurology offices completed the validated Stigma Scale for Chronic Illnesses 8‐item version (SSCI‐8); two outcome measures (the Migraine Disability Assessment [MIDAS] and the Migraine‐Specific Quality of Life Questionnaire v 2.1 [MSQ]); and measures of allodynia (Allodynia Symptom Checklist [ASC‐12]), pain cognition (Pain Catastrophizing Scale [PCS]), and psychiatric symptoms (Patient Reported Measurement Information System Anxiety [PROMIS‐A] and Depression [PROMIS‐D]). Pearson and Spearman correlations evaluated bivariate relationships, and linear (MSQ) and logistic (MIDAS Severe Disability, scores ≥21) regressions evaluated the unique variance associated with SSCI‐8 beyond other study variables. Conditional process analysis evaluated mediation hypotheses between study variables. Results: Participants (n = 121) reported levels of stigma on par with other chronic illnesses (SSCI‐8 M = 53.0, standard deviation [SD] = 7.8), with 25/127 (19.6%) reporting clinically significant levels of stigma (SSCI‐8 T‐score ≥ 60). Higher SSCI‐8 scores were associated with higher monthly headache day frequency (r = 0.35), MIDAS (ρ = 0.41), ASC‐12 (r = 0.24, p < 0.01), PCS (r = 0.46), both PROMIS‐A (r = 0.43) and D (r = 0.42), and lower MSQ subscale scores (Role Restriction r = −0.50; Role Prevention r = −0.48; Emotion Function r = −0.50), all ps <0.001 unless otherwise noted. The SSCI‐8 contributed significantly beyond migraine symptoms and other psychological factors for MSQ Emotion Function (5% unique variance) and MIDAS Severe Disability (6% of unique variance). The SSCI‐8 mediated relationships between headache frequency and the MSQ subscales and MIDAS Severe Disability. The PCS mediated relationships between the SSCI‐8 and MSQ subscales. The PROMIS‐D mediated relationships between the SSCI‐8 and MSQ Role Restriction and MSQ Role Prevention. Conclusions: Migraine stigma has medium to large associations with migraine outcomes and psychiatric symptoms and is independently associated with migraine disability and emotion‐related quality of life. Migraine stigma is an important contributor to the relationship between headache frequency and migraine outcomes. [ABSTRACT FROM AUTHOR]

Objective: Evaluate the efficacy, safety, and tolerability of zavegepant nasal spray in the acute treatment of migraine. Background: Calcitonin gene‐related peptide‐targeting agents are a novel class of therapeutics for migraine, but none are currently available as a nonoral option for acute treatment. Zavegepant, a high‐affinity, selective, and structurally unique calcitonin gene‐related peptide‐receptor antagonist in late‐stage development, is formulated as a nasal spray for the acute treatment of migraine. Methods: This randomized, dose‐ranging, placebo‐controlled, Phase 2/3 trial in adults aged ≥18 years with migraine (NCT03872453) was conducted at US study sites. Participants were randomized by an interactive web response system and treated a single attack of moderate to severe pain intensity with zavegepant nasal spray 5, 10, 20 mg, or placebo. Coprimary efficacy endpoints were pain freedom and freedom from the most bothersome symptom at 2 h postdose. Results: Of the 1673 participants aged 18 to 79 years who were randomized, 1588 were treated with study medication, and 1581 (mean age 40.8 years, 85.5% female) were analyzed for efficacy: zavegepant 5 mg (n = 387), 10 mg (n = 391), 20 mg (n = 402), and placebo (n = 401). Zavegepant 10 and 20 mg were more effective than placebo on the coprimary endpoints of pain freedom at 2 h postdose (placebo: 15.5% [98.3% confidence interval (CI), 11.1, 19.8]; 10 mg: 22.5% [98.3% CI, 17.5, 27.6; p = 0.0113]; 20 mg: 23.1% [98.3% CI, 18.1, 28.2; p = 0.0055]) and freedom from the most bothersome symptom at 2 h postdose (placebo: 33.7% [98.3% CI, 28.0, 39.3]; 10 mg: 41.9% [98.3% CI, 36.0, 47.9; p = 0.0155]; 20 mg: 42.5% [98.3% CI, 36.6, 48.4; p = 0.0094]). Findings for the 5 mg dose were not significant. The most common treatment‐emergent adverse events with zavegepant 10 and 20 mg and placebo were dysgeusia (13.5% to 16.1% vs. 3.5%), nausea (2.7% to 4.1% vs. 0.5%), and nasal discomfort (1.3% to 5.2% vs. 0.2%). Most adverse events were mild or moderate and resolved without treatment. There was no signal of hepatotoxicity. Conclusion: Zavegepant nasal spray, in single doses of 10 or 20 mg, was effective for the acute treatment of migraine, with a favorable safety profile. Additional research is needed to confirm its potential as a nonoral medication for the acute treatment of migraine. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether patients discharged to home after an emergency department (ED) visit for headache face a heightened short‐term risk of stroke. Background: Stroke hospitalizations that occur soon after ED visits for headache complaints may reflect diagnostic error. Methods: We conducted a retrospective cohort study using statewide administrative claims data for all ED visits and admissions at nonfederal hospitals in Florida 2005–2018 and New York 2005–2016. Using standard International Classification of Diseases (ICD) codes, we identified adult patients discharged to home from the ED (treat‐and‐release visit) with a benign headache diagnosis (cohort of interest) as well as those with a diagnosis of renal colic or back pain (negative controls). The primary study outcome was hospitalization within 30 days for stroke (ischemic or hemorrhagic) defined using validated ICD codes. We assess the relationship between index ED visit discharge diagnosis and stroke hospitalization adjusting for patient demographics and vascular comorbidities. Results: We identified 1,502,831 patients with an ED treat‐and‐release headache visit; mean age was 41 (standard deviation: 17) years and 1,044,520 (70%) were female. A total of 2150 (0.14%) patients with headache were hospitalized for stroke within 30 days. In adjusted analysis, stroke risk was higher after headache compared to renal colic (hazard ratio [HR]: 2.69; 95% confidence interval [CI]: 2.29–3.16) or back pain (HR: 4.0; 95% CI: 3.74–4.3). In the subgroup of 26,714 (1.78%) patients with headache who received brain magnetic resonance imaging at index ED visit, stroke risk was only slightly elevated compared to renal colic (HR: 1.47; 95% CI: 1.22–1.78) or back pain (HR: 1.49; 95% CI: 1.24–1.80). Conclusion: Approximately 1 in 700 patients discharged to home from the ED with a headache diagnosis had a stroke in the following month. Stroke risk was three to four times higher after an ED visit for headache compared to renal colic or back pain. [ABSTRACT FROM AUTHOR]

Background: Triptans are the first-line option for the acute treatment of migraine attacks; however, triptans are contraindicated in people with certain underlying cardiovascular risk factors and are associated with inadequate efficacy or poor tolerability in some individuals. Ubrogepant is an oral calcitonin gene–related peptide receptor antagonist approved for the acute treatment of migraine. Methods: This post hoc analysis of the phase 3 ACHIEVE trials examined the impact of ubrogepant on the Functional Disability Scale (FDS), satisfaction with medication, and Patient Global Impression of Change (PGIC) in participants who were self-reported triptan insufficient responders (TIRs), defined as those who are unable to take triptans due to contraindications, tolerability issues, or insufficient efficacy. Responder definitions for the FDS, satisfaction measures, and PGIC were based on qualitative interpretation of the respective response options for the pooled ubrogepant 50 mg and placebo groups. Results: In the pooled analysis population (n = 1799), 451 (25%) participants were TIRs, with most (80%) reporting insufficient efficacy with triptan use. A significantly higher proportion of TIRs treated with ubrogepant vs placebo reported being able to function normally from 2 to 8 h post dose (P < 0.05). Notably, significance was demonstrated at the time of the primary outcome assessments (2 h post dose), where rates of normal function were 38% for ubrogepant vs 29% for placebo (P = 0.048). A greater proportion of TIRs in the ubrogepant arm vs the placebo arm were satisfied with treatment at 2 (33% vs 21%, P = 0.006) and 24 h (58% vs 28%, P < 0.001) and indicated that their migraine improved at 2 h vs placebo (30% vs 18%, P = 0.006). Results were generally similar in the insufficient efficacy subpopulation of TIRs as in the overall TIRs group. Ubrogepant was safe and well tolerated in TIRs, with no new safety signals identified. Conclusions: In people with migraine who are TIRs, individuals treated with ubrogepant had favorable 2-h outcomes, as measured by the FDS, satisfaction with medication, and PGIC, compared with placebo. Trial registration: ClinicalTrials.gov: NCT02828020 (ACHIEVE I), registered July 11, 2016; NCT02867709 (ACHIEVE II), registered August 16, 2016. [ABSTRACT FROM AUTHOR]

Background falls share risk factors with cognitive decline but whether falls predict cognitive decline, pre-dementia syndromes and dementia is poorly understood. Objectives this study aimed to examine if falls are associated with cognitive decline in specific domains and the risk of Motoric Cognitive Risk (MCR) syndrome and dementia. Design cross-sectional study. Methods in older people (age 80.6 ± 5.3 years) free of dementia at baseline, the number of falls (none, one or multiple) during the year before enrolment and the first year of follow-up (exposure) were recorded. Decline in specific cognitive functions (global cognition, episodic verbal memory, verbal fluency, working memory, response inhibition and processing speed-attention), incident MCR and incident dementia were outcome measures. Linear mixed effects models were used to examine the associations between falls and cognitive decline, adjusting for confounders. Cox proportional hazards models were used to determine if falls predicted risk of incident MCR or dementia. Results of 522 eligible participants, 140 had a single fall and 70 had multiple falls. Multiple falls were associated with a greater decline in global cognition, episodic memory, verbal fluency and processing speed-attention compared to those with no falls (P  < 0.05). Over a median follow-up of 1.0 years 36 participants developed MCR and 43 participants developed dementia. Those with multiple falls had a two-fold increased risk of MCR compared to those with no falls, but no increased risk of developing dementia. Conclusions multiple falls may be an important marker to identify older people at greater risk of future cognitive decline and incident MCR. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID‐19) pandemic is an ongoing global health crisis that has had a range of impacts on people living with migraine. Methods: Qualitative interviews performed as part of the Migraine Clinical Outcome Assessment System project, a multi‐stage Food and Drug Administration–grant funded program to develop a patient‐centered core set of outcome measures for use in migraine clinical trials, offered an opportunity to explore the experience of living with migraine during the pandemic as well as to examine whether migraine treatment priorities, symptoms, and associated disability changed due to the pandemic. Semi‐structured interviews were conducted in the United States between the summer and fall of 2020 with 40 individuals with self‐reported, medically diagnosed migraine who self‐reported that they had not tested positive for or been diagnosed with COVID‐19. Results: Seventy percent (n = 28) of the sample reported ≥1 pandemic‐related impact on their life with migraine. Fourteen participants reported both positive and negative impacts, twelve reported negative impacts only, and two reported positive impacts only. Among those reporting ≥1 pandemic‐related impact, nine participants (32%) reported more frequent and five (17%) reported less frequent migraine attacks. Other negative impacts included interrupted medical care (n = 9; 32%), and greater stress (n = 13; 46%). The most frequent positive impact reported was greater access to health care (n = 8; 29%). Ictal and interictal symptoms were not noted to change due to the pandemic, but some respondents reported less disability due to increased flexibility of schedules and reduced expectations. Treatment priorities did not change due to the pandemic. Conclusion: The global COVID‐19 pandemic has resulted in both negative and positive impacts for people living with migraine. Lessons to be considered when moving into a post‐pandemic world include benefits of and satisfaction with telehealth and the benefits and importance of healthy lifestyle habits and flexibility such as improved sleep, reduced stress, and fewer social expectations. [ABSTRACT FROM AUTHOR]

Background: PROMISE-1 and PROMISE-2 evaluated the preventive efficacy, tolerability, and safety of eptinezumab, a calcitonin gene-related peptide–targeted monoclonal antibody, in adults with episodic (EM) and chronic migraine (CM), finding significant reductions in migraine frequency. This post hoc analysis compared patient-reported outcomes (PROs), health-related quality of life (HRQoL) and acute medication use in patients with a ≥ 75% migraine responder rate (MRR) after treatment with eptinezumab to patients with a ≥ 50– < 75% MRR. Methods: PROMISE-1 and PROMISE-2 were phase 3, randomized, double-blind, placebo-controlled studies. This analysis included patients from both studies treated with eptinezumab 100 mg or 300 mg who experienced ≥ 75% and ≥ 50–< 75% MRR over Weeks 1–12 (wks1–12). In both studies, HRQoL was measured by the 36-item Short-Form Health Survey (SF-36) and acute medication usage. PROMISE-2 also included the 6-item Headache Impact Test (HIT-6), patient-identified most bothersome symptom (PI-MBS), and Patient Global Impression of Change (PGIC). Results: In PROMISE-1, a total of 115/443 (26.0%; 100 mg, n = 49, 300 mg, n = 66) and 120/443 (27.0%; 100 mg, n = 61, 300 mg, n = 59) eptinezumab-treated patients achieved ≥ 75% and ≥ 50–< 75% MRR over wks1–12, respectively. In PROMISE-2, a total of 211/706 (30.0%; 100 mg, n = 95; 300 mg, n = 116) and 209/706 (29.6%; 100 mg, n = 110, 300 mg, n = 99) eptinezumab-treated patients achieved ≥ 75% and ≥ 50–< 75% MRR over wks1–12, respectively. EM and CM patients with ≥ 75% and ≥ 50–< 75% MRR over wks1–12 showed reduced use of acute headache medication and increased HRQoL to normative levels across SF-36 domains of bodily pain, social functioning, and physical functioning. In CM patients with ≥ 75% and ≥ 50–< 75% MRR over wks1–12, the mean change in HIT-6 total score with eptinezumab (pooled) was − 11.7 and − 7.6, respectively. "Very much" or "much" improvement responses were reported in 41.8% and 16.5% on PI-MBS and 36.2% and 20.0% on PGIC in ≥ 75% and ≥ 50–< 75% MRR, respectively. Conclusion: Eptinezumab treatment induced a ≥ 75% MRR over wks1–12 in the majority of patients. This patient subgroup reported substantial improvements in PROs associated with headache-related life impact and HRQoL, and reductions in acute headache medication use, which were more marked than those in the ≥ 50–< 75% responders. This study supports the clinical meaningfulness of ≥ 75% MRR for patients with either EM or CM. Trial registration: ClinicalTrials.gov identifiers: NCT02559895 (PROMISE-1), NCT02974153 (PROMISE-2). [ABSTRACT FROM AUTHOR]

Background: Demonstrating therapeutic value from the patient perspective is important in patient-centered migraine management. The objective of this study was to investigate the impact of eptinezumab, a preventive migraine treatment, on patient-reported headache impact, acute medication optimization, and perception of disease change when initiated during a migraine attack. Methods: RELIEF was a randomized, double-blind, placebo-controlled trial conducted between 2019 and 2020 in adults with ≥1-year history of migraine and 4–15 migraine days per month in the 3 months prior to screening. Patients were randomized (1:1) to a 30-min infusion of eptinezumab 100 mg or placebo within 1–6 h of a qualifying migraine attack onset. The 6-item Headache Impact Test (HIT-6) and 6-item Migraine Treatment Optimization Questionnaire (mTOQ-6) were administered at baseline and week 4, and the Patient Global Impression of Change (PGIC) at week 4. A post hoc analysis of these measures was conducted in patients who reported headache pain freedom at 2 h after infusion start. Results: Of 480 patients enrolled and treated, 476 completed the study and are included in this analysis. Mean baseline HIT-6 total scores indicated severe headache impact (eptinezumab, 65.1; placebo, 64.8). At week 4, the eptinezumab-treated group demonstrated clinically meaningful improvement in HIT-6 total score compared with placebo (mean change from baseline: eptinezumab, − 8.7; placebo, − 4.5; mean [95% CI] difference from placebo: − 4.2 [− 5.75, − 2.63], P <.0001), with greater reductions in each item score vs placebo (P <.001 all comparisons). Change in HIT-6 total score in the subgroup with 2-h headache pain freedom was − 13.8 for the eptinezumab group compared with − 4.9 for the placebo group. mTOQ-6 total score mean change from baseline favored eptinezumab (change, 2.1) compared with placebo (1.2; mean [95% CI] difference: 0.9 [0.3, 1.5], P <.01). More eptinezumab-treated patients rated PGIC as much or very much improved than placebo patients (59.3% vs 25.9%). Conclusions: When administered during a migraine attack, eptinezumab significantly improved patient-reported outcomes after 4 weeks compared with placebo, with particularly pronounced effects in patients reporting headache pain freedom at 2 h after infusion start. Trial registration: ClinicalTrials.gov Identifier: NCT04152083. November 5, 2019. [ABSTRACT FROM AUTHOR]

Objective: The ObserVational survey of the Epidemiology, tReatment and Care of MigrainE (OVERCOME; United States) study is a multicohort, longitudinal web survey that assesses symptomatology, consulting, diagnosis, treatment, and impact of migraine in the United States. Background: Regularly updating population‐based views of migraine in the United States provides a method for assessing the quality of ongoing migraine care and identifying unmet needs. Methods: The OVERCOME (US) 2018 migraine cohort involved: (I) creating a demographically representative sample of US adults using quota sampling (n = 97,478), (II) identifying people with active migraine in the past year via a validated migraine diagnostic questionnaire and/or self‐reported medical diagnosis of migraine (n = 24,272), and (III) assessing consultation, diagnosis, and treatment of migraine (n = 21,143). The current manuscript evaluated whether those with low frequency episodic migraine (LFEM; 0–3 monthly headache days) differed from other categories on outcomes of interest. Results: Among the migraine cohort (n = 21,143), 19,888 (94.1%) met our International Classification of Headache Disorders, 3rd edition‐based case definition of migraine and 12,905 (61.0%) self‐reported a medical diagnosis of migraine. Respondents' mean (SD) age was 42.2 (15.0) years; 15,697 (74.2%) were women. Having at least moderate disability was common (n = 8965; 42.4%) and around half (n = 10,783; 51.0%) had consulted a medical professional for migraine care in the past year. Only 4792 (22.7%) of respondents were currently using a triptan. Overall, 8539 (40.4%) were eligible for migraine preventive medication and 3555 (16.8%) were currently using migraine preventive medication. Those with LFEM differed from moderate and high frequency episodic migraine and chronic migraine on nearly all measures of consulting, diagnosis, and treatment. Conclusion: The OVERCOME (US) 2018 cohort revealed slow but steady progress in diagnosis and preventive treatment of migraine. However, despite significant impact among the population, many with migraine have unmet needs related to consulting for migraine, migraine diagnosis, and getting potentially beneficial migraine treatment. Moreover, it demonstrated the heterogeneity and varying unmet needs within episodic migraine. [ABSTRACT FROM AUTHOR]

Background: Delayed diagnosis of cerebrovascular disease (CVD) among patients can result in substantial harm. If diagnostic process failures can be identified at emergency department (ED) visits that precede CVD hospitalization, interventions to improve diagnostic accuracy can be developed. Methods: We conducted a nested case–control study using a cohort of adult ED patients discharged from a single medical center with a benign headache diagnosis from October 1, 2015 to March 31, 2018. Hospitalizations for CVD within 1 year of index ED visit were identified using a regional health information exchange. Patients with subsequent CVD hospitalization (cases) were individually matched to patients without subsequent hospitalization (controls) using patient age and visit date. Demographic, clinical, and ED process characteristics were assessed via detailed chart review. McNemar's test for categorical and paired t‐test for continuous variables were used with statistical significance set at ≤0.05. Results: Of the 9157 patients with ED headache visits, 57 (0.6%, 95% confidence interval [CI] = 0.5–0.8) had a subsequent CVD hospitalization. Median time from ED visit to hospitalization was 107 days. In 25 patients (43.9%, 25/57) the CVD hospitalization and the index ED visit were at different hospitals. Fifty‐three cases and 53 matched controls were included in the final study analysis. Cases and controls had similar baseline demographic and headache characteristics. Cases more often had a history of stroke (32.1% vs. 13.2%, p = 0.02) and neurosurgery (13.2% vs. 1.9%, p = 0.03) prior to the index ED visit. Cases more often had less than two components of the neurologic examination documented (30.2% vs. 11.3%, p = 0.03). Conclusion: We found that 0.6% of patients with an ED headache visit had subsequent CVD hospitalization, often at another medical center. ED visits for headache complaints among patients with prior stroke or neurosurgical procedures may be important opportunities for CVD prevention. Documented neurologic examinations were poorer among cases, which may represent an opportunity for ED process improvement. [ABSTRACT FROM AUTHOR]

Background: While pain freedom at 2 h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2 h has rarely been explored. Following lasmiditan treatment of a migraine attack with moderate or severe head pain, we contrast those who achieve pain freedom with those who achieve mild pain but not pain freedom 2 h post dosing. Methods: Patient-level data were pooled across studies and treatment arms from two Phase 3 trials comparing lasmiditan and placebo, SAMURAI and SPARTAN. This post hoc analysis assessed freedom from the most bothersome symptom (MBS), freedom from migraine-related functional disability (disability), and improved patient global impression of change (PGIC) in patients who achieved 2 h pain freedom compared to those who experienced 2 h mild pain. Mild pain differs from pain relief which is defined as either mild pain or pain freedom. Results: Patients who achieved 2 h pain freedom (N = 913), in comparison with those with 2 h mild pain (N = 864), were significantly more likely to experience MBS freedom (91.9% vs. 44.9%), disability freedom (87.1% and 13.4%), and improved PGIC (86.5% and 31.5%) (p < 0.001 for all combinations). In addition, more patients who were pain free experienced both 2 h MBS freedom and 2 h functional disability freedom (83.6%) compared to those with mild pain (10.8%; p < 0.001). The proportion of patients with pain freedom who did not achieve either MBS or disability freedom (4.6%) was lower than in patients with mild pain (52.4%). Lastly, 55.2% of patients experienced mild pain before disability freedom compared to 72.1% who experienced pain freedom and disability freedom at the same time. Conclusions: This study demonstrated that, at 2 h post treatment, patients who were pain free were more likely to achieve other outcomes including freedom from their MBS, freedom from migraine-related functional disability, and improved PGIC compared to those with mild pain, confirming that 2 h pain freedom is more robustly associated with other clinical outcomes than the 2 h mild pain endpoint. Trial Registration: SAMURAI (NCT02439320); SPARTAN (NCT02605174). [ABSTRACT FROM AUTHOR]

Background We examined the efficacy and tolerability of calcitonin gene–related peptide–targeted monoclonal antibodies (CGRP-targeted mAbs) as add-on therapy for patients with chronic migraine (CM) undergoing treatment with onabotulinumtoxinA (onabot) who require additional preventive therapy. Methods We reviewed medical records of patients with CM receiving treatment with onabot who were subsequently prescribed a CGRP-targeted mAb medication. The primary outcome was the change in number of monthly headache days (MHDs) reported. Secondary outcomes were change in headache pain severity, discontinuation due to lack of tolerability, and severe adverse events. Results Of 153 patients, 111 (72.5%) reported a decrease in either MHDs or headache pain severity, with documentation of MHDs in 66 patients. Among these 66 patients, the average number of MHDs before initiation of onabot treatment was 25.7. After onabot treatment, an average decrease of 10.9 MHDs was reported (P  < 0.001). After the addition of a CGRP-targeted mAb medication, patients experienced a further decrease of 5.7 MHDs (P  < 0.001). With combined therapy, patients reported a total decrease of 16.6 MHDs (P  < 0.001). Adverse effects occurred in 13 patients (8.5%) after addition of the CGRP-targeted mAb and included constipation, injection site reaction, and fatigue. No serious adverse events were reported. Conclusion Adding a CGRP-targeted mAb to onabot in patients with CM was associated with further reductions in MHDs without major tolerability issues across a range of mAbs. This retrospective review supports the conduct of a well-designed double-blind study adding a CGRP-targeted mAb or placebo to onabot. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association of psychiatric and cognitive comorbidities with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (TBI). Methods: A total of 100 patients with persistent PTH attributed to mild TBI and 100 age- and gender-matched healthy controls free of mild TBI were enrolled between July 2018 and June 2019. Quality of sleep was evaluated using the Pittsburgh Sleep Quality Index, while symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Cognitive impairment was evaluated using the Montreal Cognitive Assessment questionnaire, while post-traumatic stress disorder (PTSD) was assessed using the Harvard Trauma Questionnaire. Results: In 100 patients with persistent PTH, 85% reported poor quality sleep, compared with 42% of healthy controls (P < 0.01). The relative frequency of probable to high risk of anxiety was 52% in the persistent PTH group vs. 8% in healthy controls (P < 0.01), while the relative frequency of probable to high risk of depression was 42% in the persistent PTH group vs. 2% in healthy controls (P < 0.01). Furthermore, 27% of the patients with persistent PTH had mild cognitive impairment while 10% had probable PTSD. Conclusions: Poor quality of sleep as well as symptoms suggestive of anxiety and depression were more common in patients with persistent PTH than healthy controls. Clinicians should screen patients with persistent PTH for these comorbidities and develop treatment plans that account for their presence. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether the 15‐day threshold of headache days per month adequately reflects substantial differences in disability across the full spectrum of migraine. Background: The monthly frequency of headache days defines migraine subtypes and has crucial implications for epidemiological and clinical research as well as access to care. Methods: The patients with migraine (N = 836) who participated in the American Registry for Migraine Research, which is a multicenter, longitudinal patient registry, between February 2016 and March 2020, were divided into four groups based on monthly headache frequency: Group 1 (0–7 headache days/month, n = 286), Group 2 (8–14 headache days/month, n = 180), Group 3 (15–23 headache days/month, n = 153), Group 4 (≥24 headache days/month, n = 217). Disability (MIDAS), Pain intensity (NRS), Work Productivity and Activity Impairment (WPAI), Pain Interference (PROMIS‐PI), Patient Health Questionnaire‐4 (PHQ‐4), and General Anxiety Disorder‐7 (GAD‐7) scores were compared. Results: Mean (standard deviation [SD]) age was 46 (13) years (87.9% [735/836] female). The proportion of patients in each group was as follows: Group 1 (34.2% [286/836]), Group 2 (21.5% [180/836]), Group 3 (18.3% [153/836]), and Group 4 (26.0% [217/836]). There were significant relationships with increasing disability, lost productive time, and pain interference in higher headache frequency categories. There were no significant differences between Group 2 and Group 3 for most measures (NRS, all WPAI scores, PROMIS‐PI, GAD‐7, and PHQ‐4), although MIDAS scores differed (median [interquartile range (IQR)]; 38 [20–58] vs. 55 [30–90], p < 0.001). Patients in Group 1 had significantly lower MIDAS (median [IQR];16 [7–30], p < 0.001), WPAI‐% total active impairment (mean (SD): Group 1 [30.9 (26.8)] vs. Group 2 [39.2 (24.5), p = 0.017], vs. Group 3 [45.9 (24.1), p < 0.001], vs. Group 4 [55.3 (23.0), p < 0.001], and PROMIS‐PI‐T score (Group 1 [60.3 (7.3)] vs. Group 2 [62.6 (6.4), p = 0.008], vs. Group 3 [64.6 (5.6), p < 0.001], vs. Group 4 [66.8 (5.9), p < 0.001]) compared to all other groups. Patients in Group 4 had significantly higher MIDAS (median (IQR): Group 4 [90 (52–138)] vs. Group 1 [16 (7–30), p < 0.001], vs. Group 2 [38 (20–58), p < 0.001], vs. Group 3 [55 (30–90), p < 0.001], WPAI‐%Presenteeism (Group 4 [50.4 (24.4)] vs. Group 1 [28.8 (24.9), p < 0.001], vs. Group 2 [34.9 (22.3), p < 0.001], vs. Group 3 [40.9 (22.3), p = 0.048], WPAI‐% total work productivity impairment (Group 4 [55.9 (26.1)] vs. Group 1 [32.1 (37.6), p < 0.001], vs. Group 2 [38.3 (24.0), p < 0.001], vs. Group 3 [44.6 (24.4), p = 0.019]), and WPAI‐%Total activity impairment (Group 4 [55.3 (23.0)] vs. Group 1 [30.9 (26.8), p < 0.001], vs. Group 2 [39.2 (24.5), p < 0.001], vs. Group 3 [45.9 (24.1), p = 0.025]) scores compared with all other groups. Conclusion: Our data suggest that the use of a 15 headache day/month threshold to distinguish episodic and chronic migraine does not capture the burden of illness nor reflect the treatment needs of patients. These results have important implications for future refinements in the classification of migraine. [ABSTRACT FROM AUTHOR]

Objective: To better characterize the ways that migraine affects multiple domains of life. Background: Further understanding of migraine burden is needed. Methods: Adults with migraine randomized to mindfulness‐based stress reduction or headache education arms (n = 81) in two separate randomized clinical trials participated in semistructured in‐person qualitative interviews conducted after the interventions. Interviews queried participants on migraine impact on life and were audio‐recorded, transcribed, and summarized into a framework matrix. A master codebook was created until meaning saturation was reached and magnitude coding established code frequency. Themes and subthemes were identified using a constructivist grounded theory approach. Results: Despite most participants being treated with acute and/or prophylactic medications, 90% (73/81) reported migraine had a negative impact on overall life, with 68% (55/81) endorsing specific domains of life impacted and 52% (42/81) describing impact on emotional health. Six main themes of migraine impact emerged: (1) global negative impact on overall life; (2) impact on emotional health; (3) impact on cognitive function; (4) impact on specific domains of life (work/career, family, social); (5) fear and avoidance (pain catastrophizing and anticipatory anxiety); and (6) internalized and externalized stigma. Participants reported how migraine (a) controls life, (b) makes life difficult, and (c) causes disability during attacks, with participants (d) experiencing a lack of control and/or (e) attempting to push through despite migraine. Emotional health was affected through (a) isolation, (b) anxiety, (c) frustration/anger, (d) guilt, (e) mood changes/irritability, and (f) depression/hopelessness. Cognitive function was affected through concentration and communication difficulties. Conclusions: Migraine has a global negative impact on overall life, cognitive and emotional health, work, family, and social life. Migraine contributes to isolation, frustration, guilt, fear, avoidance behavior, and stigma. A greater understanding of the deep burden of this chronic neurological disease is needed to effectively target and treat what is most important to those living with migraine. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of fremanezumab in patients with chronic migraine (CM) and moderate to severe depression. Background: Fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene–related peptide, has been approved for the preventive treatment of migraine in adults. CM and depression are highly comorbid. Methods: The 12‐week, Phase 3 HALO trial randomized patients with CM to fremanezumab quarterly (675 mg/placebo/placebo), fremanezumab monthly (675/225/225 mg), or placebo. Post hoc analyses evaluated the effects of fremanezumab in patients with moderate to severe depression (baseline 9‐item Patient Health Questionnaire sum score ≥10) on monthly number of headache days of at least moderate severity; monthly migraine days; Patient Global Impression of Change (PGIC); 6‐item Headache Impact Test (HIT‐6) scores; and depression. Results: For the 219/1121 (19.5%) patients with moderate to severe depression at baseline, fremanezumab was associated with a significant reduction in monthly number of headache days of at least moderate severity for active treatment versus placebo (least‐squares mean change ± standard error for quarterly dosing: −5.3 ± 0.77; for monthly dosing: −5.5 ± 0.72; and for placebo: −2.2 ± 0.81; both p < 0.001). More patients achieved a ≥50% reduction in headache days of at least moderate severity with fremanezumab (quarterly: 31/78 [39.7%]; monthly: 39/96 [40.6%]) than placebo (9/67 [13.4%]; both p < 0.001). Compared with placebo, fremanezumab improved PGIC and HIT‐6 scores. Conclusions: Fremanezumab demonstrated efficacy in the preventive treatment of CM and reduced headache impact in patients with comorbid depression. [ABSTRACT FROM AUTHOR]

Objectives The purpose of this study was to evaluate the hypothesis that chronic and acculturative stress would be negatively associated with neurocognitive function among middle aged to older Hispanics/Latinos. Method Our analytic sample consisted of 3,265 participants (mean age = 56.7 (±0.24)) from the Hispanic Community Health Study/Study of Latinos who participated in its Sociocultural Ancillary Study. During the baseline phase of this project, participants were assessed on multiple domains of neurocognitive function, and completed self-report measures of chronic and acculturative stress. Results Each standard deviation increase in chronic stress was associated with lower performance in a verbal learning task (B = −.17, 95% CI [−.32, −.01]); this association was no longer significant after adjusting for mental and physical health symptoms, including depression and anxiety symptoms, and cardiovascular health. A standard deviation increase in acculturative stress was associated with poorer performance in all cognitive measures (B s range = −.13 to −1.03). Associations of acculturation stress with psychomotor speed, verbal learning, and word fluency remained significant after adjusting for mental and physical health symptoms. Discussion Our results suggest that mental and physical health may help explain some cross-sectional associations between stress and cognition and highlight the need to examine culture-specific psychosocial stressors to better understand the context of psychosocial risk factors for neurocognitive performance. [ABSTRACT FROM AUTHOR]

Objectives Engaging in mentally challenging activities is associated with reduced risk for cognitive impairment and dementia; however, its association with rates of cognitive decline has been inconsistent. The aim of this study is to test whether working in mentally challenging occupations is related to rates of cognitive change at later older adulthood. Method The sample consisted of 1,520 individuals (baseline mean age = 78.6 ± 5.1, range = 64–100) from the Einstein Aging Study. Occupation information of each participant was collected retrospectively and linked with the substantive complexity of work score from the Dictionary of Occupational Titles. Cognitive changes in memory, speed, and executive function (EF) domains were represented using two time metrics (i.e. time from retirement, time from study enrollment). Results Results from mixed models showed that occupational complexity was associated with significantly faster rates of cognitive decline in speed and EF in the "time from retirement" model but not in the "time from baseline" model. Despite faster cognitive loss, the protective effect of occupational complexity persisted for decades after retirement due to higher initial levels of cognition. Discussion The result suggests that protective factors for cognitive health may be associated with delayed onset but more rapid cognitive decline afterwards at later stages of cognitive aging. [ABSTRACT FROM AUTHOR]

Objective: To assess rates of and factors associated with traversing fundamental barriers to good medical outcomes and pharmacologic care in individuals with episodic migraine (EM) and chronic migraine (CM), including socioeconomic status and race. Background: Barriers to good outcomes in migraine include the lack of appropriate medical consultation, failure to receive an accurate diagnosis, not being offered a regimen with acute and preventive pharmacologic treatments (if indicated), and not avoiding medication overuse. Methods: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study was a longitudinal Internet‐based survey. Respondents who met criteria for migraine consistent with the International Classification of Headache Disorders, 3rd edition, had a Migraine Disability Assessment score ≥ 6, and provided health insurance coverage status were included in this analysis. Successfully traversing each barrier to care and the effects of sociodemographic characteristics were examined. Results: Among 16,789 respondents with migraine, 9184 (54.7%; EM: 7930; CM: 1254) were eligible. Current headache consultation was reported by 27.6% (2187/7930) of EM and 40.8% (512/1254) of CM respondents. Among consulters, 75.7% (1655/2187) with EM and 32.8% (168/512) with CM were accurately diagnosed. Among diagnosed consulters, 59.9% (992/1655) with EM and 54.2% (91/168) with CM reported minimally appropriate acute and preventive pharmacologic treatment. Among diagnosed and treated consulters, in the EM group 31.8% (315/992) and in the CM group 74.7% (68/91) met medication overuse criteria. Only 8.5% (677/7930) of EM and 1.8% (23/1254) of CM respondents traversed all four barriers. Higher income was positively associated with likelihood of traversing each barrier. Blacks and/or African Americans had higher rates of consultation than other racial groups. Blacks and/or African Americans and multiracial people had higher rates of acute medication overuse. Conclusions: Efforts to improve care should focus on increasing consultation and diagnosis rates, improving the delivery of all appropriate guideline‐based treatment, and avoidance of medication overuse. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of two calcitonin gene–related peptide (CGRP)‐targeted monoclonal antibodies (mAbs), erenumab and galcanezumab, on the pharmacokinetic (PK) profile, safety, and tolerability of ubrogepant. Background: People taking CGRP‐targeted mAbs for migraine prevention sometimes take ubrogepant, an oral small‐molecule CGRP receptor antagonist, for acute treatment of breakthrough migraine attacks. Design: In this two‐arm, multicenter, open‐label, phase 1b trial, adults with migraine were randomized to arm 1 (ubrogepant ± erenumab) or arm 2 (ubrogepant ± galcanezumab). The PK profile of ubrogepant was characterized for administration before and 4 days after CGRP‐targeted mAb injection. Participants received single‐dose ubrogepant 100 mg on day 1, subcutaneous erenumab 140 mg (arm 1) or galcanezumab 240 mg (arm 2) on day 8, and ubrogepant 100 mg once daily on days 12–15. In each study arm, serial blood samples were drawn on days 1 and 12 for measurement of plasma ubrogepant concentrations. The primary outcomes were area under the plasma ubrogepant concentration–time curve (AUC) from time 0 to t post‐dose (AUC0–t) and from time 0 to infinity (AUC0–inf), and maximum plasma concentration (Cmax) of ubrogepant when ubrogepant was administered before or after a single dose of erenumab or galcanezumab. Vital signs and laboratory parameters were monitored. Results: Forty participants enrolled (20 per arm; mean [standard deviation] ages, 32.2 [8.9] and 38.4 [8.8] years; 50% [10/20] and 60% [12/20] female in arms 1 and 2, respectively). There were no significant differences in ubrogepant Cmax after versus before erenumab administration (geometric least‐squares mean [LSM] ratio, 1.04 [90% CI, 0.93–1.16]), and no significant differences in AUC0–t (1.06 [0.96–1.16]) or AUC0–inf (1.05 [0.96–1.15]). Similarly, ubrogepant Cmax (1.00 [90% CI, 0.82–1.20]), AUC0–t (1.05 [0.90–1.23]), and AUC0–inf (1.05 [0.90–1.22]) geometric LSM ratios were statistically equivalent after galcanezumab versus ubrogepant alone. Treatment‐emergent adverse events (TEAEs) were similar to those reported with each treatment alone. No serious TEAEs, TEAEs leading to discontinuation, or clinically relevant changes in laboratory parameters or vital signs were reported. Conclusions: The PK profile of ubrogepant was not significantly changed and no safety concerns were identified when ubrogepant was coadministered with erenumab or galcanezumab. [ABSTRACT FROM AUTHOR]

Objective: To investigate between and within‐woman differences in the association between menstruation and migraine days. Background: Prior diary studies have shown that at the population level, aggregating across individuals, the odds of migraine increase during the perimenstrual window (from day −2 to day +3, where +1 is the first day of bleeding). These studies have been neither long nor large enough to assess the association between migraine and menses from an individual perspective. Consequently, existing research on menstrual‐related migraine has largely overlooked between and within‐woman variation that is critical for progressing clinical understanding and practice. Methods: Intensive longitudinal data for the current study were collected in a digital platform (N1‐Headache®) that tracks individual migraine‐related factors daily. Participants for the current study were actively menstruating adult (18+ years old) women who used the platform. Two variables were of primary interest, migraine day (no/yes) and menstrual status (inside or outside the 5‐day perimenstrual window). Results: The sample consisted of 203 women with a mean age of 35.6 (SD = 8.7) years. At baseline, the women reported an average of 30.6 (SD = 23.6) headache days over the last 3 months. Analyses were based on a total of 53,302 days (median of 150 per person), 18,520 of which were migraine days (median of 44 per person), and a total of 2,126 menstrual cycles (median of 7 per person). Results showed that the 5‐day perimenstrual window was associated with a 34% increase in odds of a migraine day compared to other days (OR = 1.34, 95% CI: 1.23–1.45, p < 0.0001). Importantly, there was between and within‐woman variability in the association between menses and migraine days (between‐woman variability: p = 0.002; within‐woman [between‐cycles] variability: p < 0.0001). Exploration of these individual differences demonstrated that relationship between menses and migraine days varied more within‐person across cycles than between women. Discussion: This study supports previous research and demonstrates that the odds of migraine days are elevated from day −2 to day +3 of the menstrual cycle. We also show that the effect of menses on migraine days varies more within‐woman than between‐women. This work provides an initial foundation for better understanding menstrual‐related migraine from the perspective of the individual patient. [ABSTRACT FROM AUTHOR]

Background/Objective: To review the acute migraine clinical trial literature and provide a summary of the endpoints and outcomes used in such trials. Method: A systematic literature review, following a prespecified (but unregistered) protocol developed to adhere to recommendations of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses, was conducted to understand endpoints and outcomes used in acute migraine clinical trials. Predefined terms were searched in PubMed to locate clinical trials assessing acute migraine treatments. Final database search was conducted on October 28, 2019. Identified publications were reviewed against established inclusion and exclusion criteria to determine eligibility. Data related to general trial design characteristics, sample characteristics, and outcomes and endpoints reported in each publication were extracted from eligible publications. Descriptive summaries of design features, sample characteristics, and the endpoints and outcomes employed across publications were constructed. Outcomes are presented within four broad categories: (a) pain‐related outcomes (pain relief, pain freedom, etc.), (b) associated symptoms (nausea, photophobia, etc.), (c) disability/impairment/impact, (d) patient‐reported outcome measures (PROMs, general health and migraine/headache‐specific). Endpoint types were categorized within three broad categories: (a) change from baseline, (b) fixed timepoint, and (c) responder definitions (e.g., 50% reduction). This review focuses on a subset of recent (1998 or later) randomized and blinded publications evaluating drugs or medical devices. Results: Of 1567 publications found through the initial search and reference section reviews, 705 met criteria and were included for data extraction. Inter‐rater agreement kappas for the descriptive variables extracted had an average kappa estimate of 0.86. The more recent, randomized and blinded pharmaceutical and medical device article subset includes 451 publications (451/705, 63.9%). The outcomes and endpoints varied substantially across trials, ranging from pain relief or freedom, freedom from or relief of migraine‐associated symptoms, use of acute or rescue medication, and various other PROMs, including measures of satisfaction and quality of life. Within the recent randomized and blinded article subset, most articles examined ≥1 pain‐related outcome (430/451, 95.3%). Of the publications that examined pain, outcomes most often used were pain relief (310/430, 72.1%), pain freedom (279/430, 64.9%), and headache recurrence (202/43,051, 47.0%) or rescue medication use (278/430, 64.9%). Associated symptoms such as nausea, photophobia, and phonophobia were more frequently measured (299/451, 66.3%) compared to most bothersome associated symptom (16/451, 3.5%), as it is a new addition to regulatory guidance. Over one‐third of eligible publications examined disability/impairment (186/451, 41.2%) or ≥1 PROM (159/451, 35.3%). The definition of the endpoints used (e.g., change from baseline, fixed timepoint comparisons, categorization of "responders" to treatment based on wide variety of "responder definitions") also differed substantially across publications. Conclusion: Acute migraine clinical trials exhibit a large amount of variability in outcomes and endpoints used, in addition to the variability in how outcomes and endpoints were used from trial‐to‐trial. There were some common elements across trials that align with guidance from the International Headache Society, the Food and Drug Administration and other regulatory agencies (e.g., assessing pain and associated symptoms, 2‐hour post‐treatment). Other aspects of acute migraine clinical trial design did not follow guidance. For example, multi‐item PROMs intended to measure constructs (e.g., scales) are rarely used, the use of pain‐related outcomes is inconsistent, some associated symptom assessments are idiosyncratic, and the timing of the assessment of primary endpoints is variable. The development of a core set of outcomes and endpoints for acute migraine clinical trials that are patient‐centered and statistically robust could improve the conduct of individual trials, facilitate cross‐trial comparisons, and better support informed treatment decisions by healthcare professionals and patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the sensitivity and specificity of the 6‐item Identify Chronic Migraine screener (ID‐CM[6]), designed to improve the detection of chronic migraine (CM). Background: CM is often undertreated and underdiagnosed. Survey‐based studies have found that approximately 75–80% of people meeting criteria for CM do not report having received an accurate diagnosis. Methods: This study used claims data of patients enrolled in a large medical group who had at least one medical claim with an International Classification of Diseases 9th/10th revision diagnostic code for migraine in the 12‐month prescreening period. The Identify Chronic Migraine survey was administered by e‐mail, in‐person, or over the telephone to all enrolled patients. A Semi‐Structured Diagnostic Interview (SSDI) was administered by telephone by a trained physician. The ID‐CM(6) and SSDI classifications of CM status were compared to evaluate sensitivity and specificity of the ID‐CM(6) screening tool. Results: The analysis of the ID‐CM(6) screening tool included 109 patients, with 65/109 (59.6%) positive for CM based on the SSDI. The mean (standard deviation) age of the patient sample was 49 (15) years and 100/109 (91.7%) were female. Using the SSDI as the diagnostic gold standard, the ID‐CM(6) had a sensitivity of 70.8% (46/65) and a specificity of 93.2% (41/44). Conclusion: The ID‐CM(6) demonstrated acceptable sensitivity and good specificity in determining CM status. The results of this analysis support the real‐world utility of the ID‐CM(6) as a simple and useful tool to identify patients with CM. [ABSTRACT FROM AUTHOR]

Objective: We sought to assess factors associated with the frequency of self‐reported prescription opioid use in persons with migraine, including demographic variables, comorbidities, headache characteristics, and patterns of consultation. Background: Despite the dose‐dependent effect of opioids on migraine progression and the association with negative outcomes, migraine treatment often includes opioids. The Migraine in America Symptoms and Treatment Study focuses on individuals with migraine who receive prescription acute medications, including those receiving and those not receiving opioids. Methods: This web‐based panel survey identified people in the United States with migraine using a validated screener. This analysis stratified people with migraine into 4 groups based on days of monthly opioid use: non‐opioid users, ≤3 days, 4‒9 days, and ≥10 days per month. Results: Of 15,133 respondents with migraine, 4701 (31%) reported acute prescription medication use for headache/migraine in the previous 3 months (mean age 45 years, 71.6% [3367/4701] female), of whom 32.5% (1528/4701) reported opioid use. About one‐third of respondents with primary care or neurology consults in the prior 6 months reported receiving an opioid, and more than half of respondents (209/391, 53.5%) with a pain clinic consultation did so. Models compared those using opioids ≤3 days/month (879/4701, 18.7%), 4‒9 days/month (304/4701, 6.5%), ≥10 days/month (345/4701, 7.3%) to non‐opioid users (3173/4701, 67.5%). Compared to non‐opioid users, infrequent users (≤3 days/month) were more likely to be male and less likely to have chronic migraine or to screen positive for anxiety and depression; and frequent opioid users (the 4‒9 days/month and the ≥10 days/month groups) were more likely to be male, to smoke, to be obese, to report greater pain interference, to have moderate to severe disability, to have symptoms of anxiety and depression, to use fewer triptans and nonsteroidal anti‐inflammatory drugs, and to have poor acute treatment optimization. Conclusion: Among prescription medication users, this cross‐sectional analysis shows that increasing use of prescription opioids is associated with male gender, chronic migraine, more severe disability, anxiety and depression, poor acute treatment optimization, and treatment in a pain clinic. [ABSTRACT FROM AUTHOR]

Objectives: To describe patterns of perceived stress across stages of the migraine cycle, within and between individuals and migraine episodes as defined for this study. Methods: Individuals with migraine aged ≥18 years, who were registered to use the digital health platform N1‐HeadacheTM, and completed 90 days of daily data entry regarding migraine, headache symptoms, and lifestyle factors were eligible for inclusion. Perceived stress was rated once a day at the participant's chosen time with a single question, "How stressed have you felt today?" with response options graded on a 0‐10 scale. Days were categorized into phases of the migraine cycle: Ppre = pre‐migraine headache (the 2 days prior to the first day with migraine headache), P0 = migraine headache days, Ppost = post‐migraine headache (the 2 days following the last migraine day with migraine headache), and Pi = interictal days (all other days). Episodes, defined as discrete occurrences of migraine with days in all 4 phases, were eligible if there was at least 1 reported daily perceived stress value in each phase. Individuals with ≥5 valid episodes, and ≥75% compliance (tracking 90 days in 120 calendar days or less) were eligible for inclusion in the analysis. Results: Data from 351 participants and 2115 episodes were included in this analysis. Eighty‐six percent of the sample (302/351) were female. The mean number of migraine days per month was 6.1 (range 2‐13, standard deviation = 2.3) and the mean number of episodes was 6.0 (range 5‐10, standard deviation = 1.0) over the 90‐day period. Only 8 (8/351, 2.3%) participants had chronic migraine (defined as 15 or more headache days per month with at least 8 days meeting criteria for migraine). Cluster analysis revealed 3 common patterns of perceived stress variation across the migraine cycle. For cluster 1, the "let down" pattern, perceived stress in the interictal phase (Pi) falls in the pre‐headache phase (Ppre) and then decreases more in the migraine phase (P0) relative to Pi. For cluster 2, the "flat" pattern, perceived stress is relatively unchanging throughout the migraine cycle. For cluster 3, the "stress as a trigger/symptom" pattern, perceived stress in Ppre increases relative to Pi, and increases further in P0 relative to Pi. Episodes were distributed across clusters as follows: cluster 1: 354/2115, 16.7%; cluster 2: 1253/2115, 59.2%, and cluster 3: 508/2115, 24.0%. Twelve participants (12/351, 3.4%) had more than 50% of their episodes fall into cluster 1, 216 participants (216/351, 61.5%) had more than 50% of their episodes fall into cluster 2, and 25 participants (25/351, 7.1%) had more than 50% of their episodes fall into cluster 3. There were 40 participants with ≥90% of their episodes in cluster 2, with no participants having ≥90% of their episodes in cluster 1 or 3. Conclusions: On an aggregate level, perceived stress peaks during the pain phase of the migraine cycle. However, on an individual and episode basis, there are 3 dominant patterns of perceived stress variation across the migraine cycle. Elucidating how patterns of perceived stress vary across the migraine cycle may contribute insights into disease biology, triggers and protective factors, and provide a framework for targeting individualized treatment plans. [ABSTRACT FROM AUTHOR]

Background: Persistent post-traumatic headache (PTH) is a common sequela of mild traumatic brain injury (TBI) and retrospective assessments have found a migraine-like phenotype to be very frequent. This has raised a discussion of shared underlying mechanisms and whether persistent PTH is simply trauma-triggered migraine. Methods: A 28-day prospective diary study with daily entries and acquisition of data on headache characteristics, associated symptoms, and acute medication use. A total of 64 patients with persistent PTH were enrolled from April 2019 to August 2019. Outcomes were the proportion of monthly headache days of any intensity that met the criteria for a migraine-like day or TTH-like day, as well as the corresponding figures for monthly headache days of moderate to severe intensity. Headache phenotypes were initially assigned based on diagnostic evaluation by semi-structured interview, whilst final headache phenotypes were assigned by diary review. Results: After diary review, we found that monthly headache days were exclusively migraine-like in 24 of 64 patients (38%) and exclusively TTH-like days in 8 of 64 patients (13%). Considering only monthly headache days of moderate to severe intensity, the corresponding figures were 35 of 64 patients (55%) for migraine-like days and 8 of 64 patients (13%) for TTH-like days. The following headache phenotypes were assigned based on diary review: chronic migraine-like (n = 47, 73%), combined episodic migraine-like and chronic TTH-like (n = 9, 13%), and 'pure' chronic TTH-like (n = 8, 13%). Conclusions: A migraine-like phenotype is common in patients most adversely affected by persistent PTH, although some patients did have a pure chronic TTH-like phenotype. At minimum, these findings suggest that persistent PTH is – at least in some – not 'trauma-triggered migraine'. [ABSTRACT FROM AUTHOR]

Background: Migraine preventive medications are used to reduce headache frequency, severity, and duration. In patients with chronic migraine (CM), reversion to episodic migraine (EM) is an important treatment goal. Objective: To evaluate the effect of fremanezumab on the rate of reversion from CM to EM. Methods: This phase 3, randomized, double‐blind, placebo‐controlled, parallel‐group trial included a 28‐day pretreatment period and a 3‐month treatment period. Patients with CM received subcutaneous fremanezumab quarterly (675 mg at baseline) or monthly (675 mg at baseline; 225 mg at Weeks 4 and 8), or placebo. Post hoc analyses evaluated the proportion of patients who reverted from CM to EM, defined as either a reduction to an average of <15 headache days per month during the 3‐month treatment period or a reduction to <15 headache days per month in all 3 months of the treatment period. Results: This analysis included data from 1088 CM patients (quarterly, n = 366; monthly, n = 365; placebo, n = 357). More fremanezumab‐treated patients with CM reverted to EM using either the monthly average number of headache days criteria for reversion (quarterly: 50.5% [185/366], P =.108; monthly: 53.7% [196/365], P =.012; vs placebo: 44.5% [159/357]) or the monthly headache day count at Months 1, 2, and 3 criteria for reversion (quarterly: 31.2% [114/366], P =.008; monthly: 33.7% [123/365], P =.001; vs placebo: 22.4% [80/357]). Patients with CM who reported previous topiramate or onabotulinumtoxinA use, concomitant preventive medication use, or medication overuse were less likely to revert to EM. Conclusions: Fremanezumab may offer the benefit of reversion from CM to EM, based on a reduction in the number of headache days over 3 months of treatment. [ABSTRACT FROM AUTHOR]

Objective: Scalable, accessible forms of behavioral therapy for migraine prevention are needed. We assessed the feasibility and acceptability of progressive muscle relaxation (PMR) delivered by a smartphone application (app) in the Primary Care setting. Methods: This pilot study was a non‐blinded, randomized, parallel‐arm controlled trial of adults with migraine and 4+ headache days/month. Eligible participants spoke English and owned a smartphone. All participants were given the RELAXaHEAD app which includes an electronic headache diary. Participants were randomized to receive 1 of the 2 versions of the app‐one with PMR and the other without PMR. The primary outcomes were measures of feasibility (adherence to the intervention and diary entries during the 90‐day interval) and acceptability (satisfaction levels). We conducted exploratory analyses to determine whether there was a change in Migraine Disability Assessment Scale (MIDAS) scores or a change in headache days. Results: Of 139 participants (77 PMR, 62 control), 116 (83%) were female, mean age was 41.7 ± 12.8 years. Most patients 108/139 (78%) had moderate‐severe disability. Using a 1‐5 Likert scale, participants found the app easy to use (mean 4.2 ± 0.7) and stated that they would be happy to engage in the PMR intervention again (mean 4.3 ± 0.6). For the first 6 weeks, participants practiced PMR 2‐4 days/week. Mean per session duration was 11.1 ± 8.3 minutes. Relative to the diary‐only group, the PMR group showed a greater non‐significant decline in mean MIDAS scores (−8.7 vs −22.7, P =.100) corresponding to a small‐moderate mean effect size (Cohen's d = 0.38). Conclusion: Smartphone‐delivered PMR may be an acceptable, accessible form of therapy for migraine. Mean effects show a small‐moderate mean effect size in disability scores. [ABSTRACT FROM AUTHOR]