Objective.—To describe the prevalence, sociodemographic profile, and the burden of migraine in the United States in 1999 and to compare results with the original American Migraine Study, a 1989 ...population‐based study employing identical methods.
Methods.—A validated, self‐administered questionnaire was mailed to a sample of 20 000 households in the United States. Each household member with severe headache was asked to respond to questions about symptoms, frequency, and severity of headaches and about headache‐related disability. Diagnostic criteria for migraine were based on those of the International Headache Society. This report is restricted to individuals 12 years and older.
Results.—Of the 43 527 age‐eligible individuals, 29 727 responded to the questionnaire for a 68.3% response rate. The prevalence of migraine was 18.2% among females and 6.5% among males. Approximately 23% of households contained at least one member suffering from migraine. Migraine prevalence was higher in whites than in blacks and was inversely related to household income. Prevalence increased from aged 12 years to about aged 40 years and declined thereafter in both sexes. Fifty‐three percent of respondents reported that their severe headaches caused substantial impairment in activities or required bed rest. Approximately 31% missed at least 1 day of work or school in the previous 3 months because of migraine; 51% reported that work or school productivity was reduced by at least 50%.
Conclusions.—Two methodologically identical national surveys in the United States conducted 10 years apart show that the prevalence and distribution of migraine have remained stable over the last decade. Migraine‐associated disability remains substantial and pervasive. The number of migraineurs has increased from 23.6 million in 1989 to 27.9 million in 1999 commensurate with the growth of the population. Migraine is an important target for public health interventions because it is highly prevalent and disabling.
Objective
To evaluate the efficacy, tolerability, and safety of eptinezumab 100 and 300 mg compared with placebo in patients with the dual diagnosis of chronic migraine (CM) and medication‐overuse ...headache (MOH).
Background
Eptinezumab, a humanized monoclonal antibody targeting calcitonin gene‐related peptide, may be effective for treating patients with a dual diagnosis of CM and MOH.
Methods
PROMISE‐2 (NCT02974153) was a double‐blind, randomized, placebo‐controlled, phase 3 study that comprised a screening visit, a 28‐day pretreatment period, and a 32‐week study duration. Patients in this exploratory analysis of a prespecified subgroup had confirmed diagnoses of both CM and MOH at screening. Patients were randomly assigned to receive intravenous eptinezumab 100, 300 mg, or placebo every 12 weeks. Efficacy outcomes included mean changes from baseline in monthly migraine days (MMDs) during weeks 1–12, migraine responder rates at week 12, and percentages of patients below International Classification of Headache Disorders thresholds for CM and MOH over weeks 1–24.
Results
There were 431 patients who were diagnosed with CM and MOH as specified in the protocol and received eptinezumab 100 mg (n = 139), 300 mg (n = 147), or placebo (n = 145). During the baseline period, these patients experienced an average of 16.7 migraine days across treatment arms. Over weeks 1–12, eptinezumab‐treated patients experienced greater reductions from baseline in MMDs than placebo patients (100 mg, change from baseline = −8.4, difference from placebo 95% confidence interval (CI) = −3.0 −4.56, −1.52, p < 0.0001 vs. placebo; 300 mg, change from baseline = −8.6, difference from placebo 95% CI = −3.2 −4.66, −1.78, p < 0.0001 vs. placebo; placebo, −5.4). Compared with placebo, more eptinezumab‐treated patients were ≥50% migraine responders (100 mg, 84/139 60.4%; 300 mg, 91/147 61.9%; placebo, 50/145 34.5%) or ≥75% responders (100 mg, 38/139 27.3%; 300 mg, 44/147 29.9%; placebo, 21/145 14.5%) over weeks 1–12. Therapeutic benefits with eptinezumab were observed from day 1 after dosing, and improvements were sustained with an additional dose. For the full 24‐week treatment period, 71/139 (51.1%), 80/147 (54.4%), and 47/145 (32.4%) of 100, 300 mg, and placebo‐treated patients, respectively, were below CM thresholds, and of the patients who provided sufficient acute medication data, 47/93 (50.5%), 53/107 (49.5%), and 26/96 (27.1%), respectively, were below medication‐overuse thresholds.
Conclusions
In patients diagnosed with both CM and MOH, eptinezumab treatment resulted in greater reductions in MMDs, higher responder rates, and fewer patients meeting CM and MOH criteria, thus demonstrating the efficacy and clinical utility of eptinezumab in this patient population.
Objective
This post hoc analysis in patients medically diagnosed with chronic migraine (CM) and medication‐overuse headache (MOH) evaluated reductions in the use of acute headache medication (AHM) ...and sustained changes in the diagnostic status of CM and MOH following eptinezumab treatment in the PROMISE‐2 study.
Background
Eptinezumab, a monoclonal antibody that inhibits calcitonin gene‐related peptide, is approved in the United States for the preventive treatment of migraine. A previous analysis showed that eptinezumab reduced monthly migraine days and was well tolerated in the subgroup of PROMISE‐2 patients diagnosed with both CM and MOH.
Methods
The phase 3, double‐blind, placebo‐controlled PROMISE‐2 study (NCT02974153) randomized adults with CM to eptinezumab 100 mg, 300 mg, or placebo (administered intravenously every 12 weeks for up to two doses). MOH was prospectively diagnosed at screening by trained physicians based on 3 months of medication history and International Classification of Headache Disorders‐3β criteria. This post hoc analysis evaluated changes in total and class‐specific days of AHM usage, the percentage of patients using AHM at or above MOH diagnostic thresholds, and the percentage of patients experiencing monthly headache and migraine day frequency below diagnostic thresholds for MOH and/or CM.
Results
In PROMISE‐2, 431/1072 (40.2%) patients with CM were diagnosed with MOH (eptinezumab 100 mg, n = 139; 300 mg, n = 147; placebo, n = 145) and were included in this analysis. Total monthly AHM use decreased from 20.6 days/month at baseline to 10.6 days/month over 24 weeks of treatment (49% decrease) with eptinezumab 100 mg, from 20.7 to 10.5 days/month (49% decrease) with eptinezumab 300 mg, and from 19.8 to 14.0 days/month (29% decrease) with placebo. Numerically greater decreases from baseline with eptinezumab were also observed for individual drug classes. In each study month, the percentages of patients who were below MOH thresholds were numerically higher for both eptinezumab doses compared with placebo, as were the percentages of patients experiencing headache and migraine frequency below CM thresholds. Of patients with available data across the entire treatment period, 29.0% (58/200) of patients treated with eptinezumab stopped meeting and remained below diagnostic thresholds for both CM and MOH during Weeks 1–24, as well as 6.3% (6/96) of patients who received placebo.
Conclusions
Across 24 weeks of treatment, eptinezumab reduced AHM use in patients diagnosed with CM and MOH. More than one‐fourth (29%) of patients treated with eptinezumab did not meet the diagnostic thresholds for either CM or MOH for the entire treatment period.
Objective.—A population‐based survey was conducted in 1999 to describe the patterns of migraine diagnosis and medication use in a representative sample of the US population and to compare results ...with a methodologically identical study conducted 10 years earlier.
Methods.—A survey mailed to a panel of 20 000 US households identified 3577 individuals with severe headache meeting a case definition for migraine based on the International Headache Society (IHS) criteria. Those with severe headache answered questions regarding physician diagnosis and use of medications for headache as well as headache‐related disability.
Results.—A physician diagnosis of migraine was reported by 48% of survey participants who met IHS criteria for migraine in 1999, compared with 38% in 1989. A total of 41% of IHS‐defined migraineurs used prescription drugs for headaches in 1999, compared with 37% in 1989. The proportion of IHS‐defined migraineurs using only over‐the‐counter medications to treat their headaches was 57% in 1999, compared with 59% in 1989. In 1999, 37% of diagnosed and 21% of undiagnosed migraineurs reported 1 to 2 days of activity restriction per episode (P<.001); 38% of diagnosed and 24% of undiagnosed migraineurs missed at least 1 day of work or school in the previous 3 months (P<.001); 57% of diagnosed and 45% of undiagnosed migraineurs experienced at least a 50% reduction in work/school productivity (P<.001).
Conclusions.— Diagnosis of migraine has increased over the past decade. Nonetheless, approximately half of migraineurs remain undiagnosed, and the increased rates of diagnosis of migraine have been accompanied by only a modest increase in the proportion using prescription medicines. Migraine continues to cause significant disability whether or not there has been a physician diagnosis. Given the availability of effective treatments, public health initiatives to improve patterns of care are warranted.
That migraine is significantly underdiagnosed in the United States and other countries is well established. New data from a follow-up survey to the American Migraine Study II reveal that the presence ...of concomitant headache types and co-morbid conditions significantly affects the ability to detect and diagnose migraine. This article describes these data and explores the contribution of concomitant headache types and co-morbidities to the problem of underdiagnosis of migraine. Migraine continues to be underdiagnosed because of failure to recognize it (missed diagnosis) and because of misdiagnosis of migraine as another headache type. First, a diagnosis of migraine may be missed in the presence of other headache types that occur proportionally more frequently than migraine and thereby overshadow migraine. Second, migraine may be misdiagnosed when health-care providers inappropriately interpret specific symptoms and co-morbid conditions as indicators of the presence of a non-migraine headache type such as sinus or tension. By becoming aware of these diagnostic pitfalls and being more judicious and deliberate in diagnosing migraine and other headache types, health-care providers can improve the diagnosis of migraine and help patients to receive appropriate therapy.
To evaluate the efficacy and tolerability of sumatriptan-naproxen during the mild pain phase of a single menstrual migraine attack associated with dysmenorrhea.
Two replicate randomized, multicenter, ...double-blind, placebo-controlled, trials of adults with menstrual migraine and dysmenorrhea were conducted. Participants treated their menstrual migraine attack during the mild pain phase (within 1 hour of onset) with sumatriptan 85 mg and naproxen sodium 500 mg in a single fixed-dose formulation (sumatriptan-naproxen) or placebo. The primary endpoint was 2-hour pain-free response.
Sumatriptan-naproxen was statistically superior to placebo in both studies (n=311, Study 1; n=310, Study 2) for 2-hour and, 2- to 24-hour sustained pain-free response, use of headache and menstrual rescue medications, and several nonpain menstrual symptom categories. Two-hour pain-free rates were Study 1, 42% compared with 23%, and Study 2, 52% compared with 22%, P<.001. Two- to 24-hour sustained pain-free rates were Study 1, 29% compared with 18%, P=.022; Study 2, 38% compared with 10%, P<.001. Headache and menstrual medication rates were Study 1, 37% compared with 53%, P=.005; Study 2, 31% compared with 69%, P<.001. Women treated with sumatriptan-naproxen continued to be pain free through 48 hours compared with placebo: Study 1, 26% compared with 17%, P=.040; Study 2, 28% compared with 8%, P<.001. No serious adverse events were reported in either study; nausea and dizziness were the most frequently reported adverse events.
Sumatriptan-naproxen provided an effective pain-free response at 2 hours, which was maintained up to 48 hours in menstrual migraineurs with dysmenorrhea. Sumatriptan-naproxen was well-tolerated and resulted in decreased rescue medication use and relief of nonpainful menstrual symptoms.
ClinicalTrials.gov, www.clinicaltrials.gov, NCT00329459 and NCT00329355
I.
Objectives.— To compare the clinical characteristics of menstrually related migraines (MRMs) and nonmenstrually related migraines (nonMRMs) and to investigate the efficacy of almotriptan in the ...treatment of these migraine subtypes.
Design/Methods.— These are post hoc analyses of data from the AXERT® Early miGraine Intervention Study (AEGIS), a multicenter, double‐blind, parallel‐group trial that evaluated adults with IHS‐defined migraine with and without aura. Patients were randomized 1 : 1 to treat 3 consecutive headaches with almotriptan 12.5 mg or matching placebo at the first sign of headache typical of their usual migraine, at any level of pain intensity but within 1 hour of onset. MRMs were defined as those occurring ±2 days of the first day of menstrual flow. Post hoc analyses to describe headache characteristics pooled all migraine attacks experienced by patients who reported ≥1 menses during the study regardless of assigned treatment group. The post hoc efficacy analyses included outcomes of almotriptan treatment compared with placebo treatment for all migraines in patients with a menstrual record.
Results.— Of the 275 women in the AEGIS intent‐to‐treat population, 190 (69.1%; 97 almotriptan, 93 placebo; aged 18‐54 years) reported ≥1 menses during the trial. Of the 506 migraines reported by these patients, 95 (18.8%) occurred ±2 days of the first day of menstrual flow and were defined as MRM. Aura was associated with 11.7% of MRM and 15.0% of nonMRM. Allodynia‐associated symptoms were present with 62.8% of MRM and 57.0% of nonMRM. Prior to treatment, 19.1% of MRM were associated with normal functional ability, 68.1% with disturbed functional ability, and 12.8% required bed rest compared with 18.9%, 68.8%, and 12.3%, respectively, of nonMRM. Pretreatment pain intensity was mild in 40.0%, moderate in 47.4%, and severe in 12.6% of MRM compared with 43.6%, 47.2%, and 9.2%, respectively, of nonMRM. Almotriptan treatment efficacy outcomes for MRM vs nonMRM, respectively, were: 2‐hour pain relief, 77.4% vs 68.3%; 2‐hour pain free, 35.4% vs 35.9%; and sustained pain free, 22.9% vs 23.8%. Almotriptan was similarly effective in relieving migraine‐associated symptoms and improving functional disability associated with both MRM and nonMRM.
Conclusions.— Prior to treatment, the presence of migraine‐associated characteristics including aura, allodynia‐associated symptoms, photophobia, phonophobia, and nausea were similar for both MRM and nonMRM attacks. The pretreatment levels of pain intensity and functional disability were likewise similar across the migraine subtypes. Almotriptan was equally effective in the treatment of both MRM and nonMRM attacks and was associated with an adverse event profile that was similar to placebo treatment.
Migraine is common during pregnancy, but fortunately this combination of conditions obviously exists for only a finite period. The greatest frequency of migraine attacks occurs during the first ...trimester. Accurate diagnosis is a sine qua non in this setting as in any headache patient. It is in the first trimester that the fetus is at greatest risk from abortifacient and teratogenic drugs, and when very early pregnancy may be undiagnosed. Ergot alkaloids (including methysergide) should be avoided during pregnancy because of their teratogenicity, and most other drug classes should be used only when unavoidable. The use of prophylactic agents during pregnancy should be the exception, not the rule, and preferably only during the second and third trimesters; propranolol is probably safest in this situation. De novo headache during pregnancy usually requires expert review of the patient. Treatment tactics for uncomplicated migraine in pregnancy depend on the concurrent clinical situation. Paracetamol (acetaminophen) is the mainstay for the patient whose typical attacks continue into the first trimester. If paracetamol is insufficient, then partial agonist opioids may be used if typical migraine attacks persist in the second and third trimesters (which is uncommon). 'Chronic migraine' in pregnancy, i.e. >or=15 headache days per month, is rare, and is the greatest therapeutic challenge. Co-morbidities such as depression or epilepsy require specialised approaches. The complexities associated with these tactics are discussed in this article, and it is emphasised that none has the specific approval of regulatory authorities. Heightened pharmacovigilance will better inform the future pregnant migraineur. However, this type of information is less likely to be available for novel classes of neuropharmacological agents than for existing ones.
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