Erenumab dosage for migraine prevention: An evidence-based narrative review with recommendations.

BACKGROUND: Therapeutic monoclonal antibodies against the calcitonin gene-related peptide (CGRP) receptor or its ligand have changed the landscape of treatment options for migraine. Erenumab is the first and only fully human monoclonal antibody designed to target and block the CGRP receptor. It is approved by the Food and Drug Administration for preventive treatment of migraine in adults. The recommended dose of erenumab is 70 mg monthly, with guidance that some patients may benefit from the 140 mg monthly dose. There is a need for information to guide clinical practice on the comparative efficacy and safety of these two dosing options. OBJECTIVE: To evaluate therapeutic and tolerability differences between erenumab 70 and 140 mg based on evidence from published literature. METHODS: This narrative review evaluates therapeutic and tolerability differences between erenumab 70 and 140 mg based on a literature search using PubMed interface, Embase and Ovid MEDLINE(R) databases. The key search terms included migraine, AMG 334, AMG334, erenumab, erenumab-aooe, and Aimovig. The search was limited to English language articles or conference abstracts published up to May 2021. RESULTS: From the literature search, we retrieved 23 relevant articles/conference abstracts (19 articles [5 randomized, double-blind studies] and 4 conference abstracts) for inclusion in this narrative review. Although the recommended starting dosage of erenumab is 70 mg, this narrative review of the literature indicates that some patients may benefit from a dosage of 140 mg erenumab once monthly-especially those with difficult-to-treat disease and prior treatment failures. The evidence indicates that erenumab at 140 mg has a numerically better efficacy than 70 mg across a broad spectrum of migraine outcomes, including preventing progression to chronic migraine. CONCLUSION: Cumulative data from the literature support a therapeutic gain with an increase from erenumab 70 to 140 mg and a rationale for initiating 140 mg in selected patients.

Episodic Migraine Comorbidities: Avoiding Pitfalls and Taking Therapeutic Opportunities.

Migraine is a common neurologic disorder. This article will discuss a few factors that influence migraine (mostly episodic) and its treatment, such as sleep, obstructive sleep apnea (OSA), obesity, and affective disorders, as well as autoimmune diseases. Practitioners must be aware of these coexisting conditions (comorbidities) as they affect treatment. It is noted in literature that both the quantity (too much or too few hours) and the quality (OSA related) of sleep may worsen migraine frequency. An associated risk factor for OSA, obesity also increases migraine frequency in episodic migraine cases. A bidirectional relationship with migraine along with depression and anxiety is debated in the literature. Retrospective cohort studies are undecided and lack statistical significance, but prospective studies do show promising results on treatment of anxiety and depression as a means of improving migraine control. Finally, we address the topic of autoimmune diseases and migraine. While few studies exist at this time, there are cohort study groups looking into the association between rheumatoid arthritis, hypothyroidism, and antiphospholipid antibody. There is also evidence for the link between migraine and vascular diseases, including coronary and cerebral diseases. We suggest that these comorbid conditions be taken into account and individualized for each patient along with their pharmaceutical regimen. Physicians should seek a multifactorial treatment plan including diet, exercise, and healthy living to reduce migraine frequency.

Risk of Stroke Associated With Use of Estrogen Containing Contraceptives in Women With Migraine: A Systematic Review.

OBJECTIVE: Migraine with aura has been associated with increased risk of ischemic and hemorrhagic stroke. Prior studies have shown a further increase in risk in women using combined hormonal contraceptives (CHCs). This has led to guidelines recommending against use of CHCs in this population. We sought to assess whether the risk of stroke is associated with the dose of estrogen and whether there is evidence of synergism between migraine and CHCs. We also sought to assess whether an interaction effect exists between migraine and CHCs. METHODS: We searched PubMed, the Cochrane Library, and EMBASE from inception through January 2016 for relevant English-language studies of adults, of any design. We included studies that examined exposure to CHCs and reported outcomes of ischemic or hemorrhagic stroke. Data extraction and assessment of study quality were conducted independently by reviewer pairs and quality was assessed with the GRADE and Newcastle Ottawa scales. RESULTS: Of 2480 records, 15 studies met inclusion criteria and six provided odds ratios for the relevant population. The point estimates for the odds ratios for ischemic stroke in women with migraine who used CHCs with any dose of estrogen ranged from 2.08 to 16.9. Studies were generally small and confidence intervals were wide. No studies reported odds ratios for stroke risk as a function of estrogen dose in women with migraine, largely due to insufficient sample sizes. No interaction effect between migraine and CHCs was seen in the seven studies that assessed this. One study differentiated risk by presence or absence of migraine aura and found an increased risk in the migraine with aura population (OR 6.1; CI 3.1 to 12.1 in migraine with aura vs 1.8; CI 1.1 to 2.9 in the migraine without aura group). Studies generally had high Newcastle Ottawa scores and low GRADE levels of evidence. No studies met all three supplementary quality criteria (assessed migraine subtype, used International Classification of Headache Disorders criteria for diagnosis of migraine, and stratified risk by estrogen dose). CONCLUSIONS: This systematic review shows a lack of good quality studies assessing risk of stroke associated with low dose estrogen use in women with migraine. Further study in this area is needed. The available evidence is consistent with an additive increase in stroke risk with CHC use in women with migraine with aura. Since the absolute risk of stroke is low even in the presence of these risk factors, use of CHCs in women who have migraine with aura should be based on an individualized assessment of harms and benefits.

Impact of Aura and Status Migrainosus on Readmissions for Vascular Events After Migraine Admission.

OBJECTIVE: -To estimate readmission rates for acute ischemic stroke (AIS), transient ischemic attack (TIA), subarachnoid hemorrhage, and intracerebral hemorrhage after an index admission for migraine, using nationally representative data. METHODS: -The Nationwide Readmissions Database was designed to analyze readmissions for all payers and uninsured, with data on >14 million US admissions in 2013. We used International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify index migraine admissions with and without aura or status migrainosus, and readmissions for cerebrovascular events. Cox proportional hazards regression was performed for each outcome with aura and status migrainosus as main predictors, adjusting for age and vascular risk factors. RESULTS: -Out of 12,448 index admissions for migraine, 9972 (80.1%) were women, mean age was 45.5 ± 14.8 years, aura was present in 3038 (24.41%), and status migrainosus in 1798 (14.44%). The 30-day readmission rate (per 100,000 index admissions) was 154 for ischemic stroke, 86 for TIA, 42 for subarachnoid hemorrhage, and 17 for intracranial hemorrhage. In unadjusted models, aura was significantly associated with TIA (hazard ratio 2.43, 95% CI 1.39-4.24), but not AIS (1.26, 0.73-2.18), intracranial hemorrhage (1.86, 0.45-7.79) or subarachnoid hemorrhage (1.85, 0.44-7.75). When adjusting for age and vascular risk factors, aura remained significantly associated with TIA (2.13, 1.22-3.74). Status, in adjusted models, was significantly associated with subarachnoid hemorrhage readmission (4.83, 1.09-21.42). CONCLUSIONS: -In this large, nationally representative retrospective cohort study, migraine admission with aura was independently associated with TIA readmission, and status migrainosus was independently associated with subarachnoid hemorrhage. Further research would clarify the role of misdiagnosis and causal relationships underlying these strong associations.

Headache in Intracranial and Cervical Artery Dissections.

Dissection refers to a tear in the wall of an artery, with the two main types being intracranial or extracranial. Dissections tend to occur most commonly in the young, sometimes secondary to trauma involving the neck. To confirm a dissection, some type of vessel imaging is necessary, including magnetic resonance angiography (MRA), computed tomography angiography (CTA), or angiography. The most common presentation of a dissection (especially extracranial) is pain, usually head and neck pain along with a Horner's syndrome. Patients may also present with ischemic symptoms, including transient ischemic attack (TIA) or stroke, which may also be a complication of a dissection. Although headache is a common presentation, there is little research into phenotype or long-term outcomes. There are a number of case reports detailing the phenotypes of headaches that may be present in dissection, including a migraine-like or hemicrania-like headache. Dissections are usually treated with some type of anti-platelet or anti-coagulation, although there are only a few randomized controlled trials. In a new acute headache, dissection is an important diagnosis to keep in mind.

The prevalence, burden, and treatment of severe, frequent, and migraine headaches in US minority populations: statistics from National Survey studies.

BACKGROUND: The prevalence and burden of migraine and other severe headaches in the US population as a whole is well documented. Prevalence and treatment patterns in US racial and ethnic minorities, however, have received less attention. We sought to assemble and compare this information as identified in large, nationally representative studies. METHODS: We searched for summary statistics from studies performed in the United States between 1989 and 2014. Included studies had to provide population-based, nationally or broadly representative information on the prevalence, burden, or treatment of severe or frequent headache or migraine in adult US Blacks, Hispanics, Native Americans, or Asians. RESULTS: Nine studies were included in the review. Prevalence data from the National Health Interview Survey (NHIS) provide the most comprehensive information for major racial and ethnic groups. The average prevalence of severe headache or migraine from 2005 to 2012 NHIS was 17.7% for Native Americans, 15.5% for Whites, 14.5% for Hispanics, 14.45% for Blacks, and 9.2% for Asians. Severe headache or migraine prevalence was higher in females of all races and ethnic groups compared with males and across all included studies. Female to male prevalence ratios from the 2005-2012 NHIS were 2.1 for Whites, 2.5 for Hispanics, 2.1 for Blacks, and 2.0 for Asians. Among those with chronic migraine (≥15 days of headache per month), prevalence data from the American Migraine Prevalence and Prevention study showed that the prevalence of chronic migraine was highest in Hispanic women (2.26% compared with 1.2% for White females), whereas White males had the lowest prevalence at 0.46%. Data from the National Hospital Ambulatory Care Survey and National Ambulatory Care Survey show that Hispanics make only 89.5 annual ambulatory care visits per 10,000 population at which they receive a diagnosis of migraine, compared with 176.3 for Whites and 133.2 for Blacks. In contrast, visit rates resulting in a diagnosis of nonspecific headache were more comparable across all groups. Only one study obtained information on selected subgroups within Hispanic and Asian populations. This showed that differences among these subgroups, which suggest composite prevalence estimates for broadly defined racial and ethnic groups such as Asians, may conceal meaningful differences in subgroups, such as Vietnamese or Filipinos. CONCLUSIONS: In the United States, migraine prevalence is highest among Native Americans, then Whites, followed closely by Hispanics and Blacks. Asians have the lowest prevalence of severe, frequent headache or migraine of the major racial or ethnic groups. Differences in diagnosis and treatment of headache and migraine may indicate racial and ethnic disparities in access and quality of care for minority patients.

Approach to chronic daily headache.

Chronic daily headaches (CDH) is a descriptive term used for patients who experience headaches on at least 15 days or more out of the month; for at least 3 months, irrespective of the underlying headache etiology. It is a syndrome that affects many people, usually with an underlying primary headache disorder, leading to a reduction in quality of life. The two most common underlying primary headaches are migraines and tension-type headaches. The prevalence is about 4%, and research is emerging on risk factors and comorbidities. The first step when approaching a patient with chronic daily headaches is to rule out secondary causes. Once that is done, the goal is to effectively reduce the days of headache through preventive treatment as well as complementary therapies. This also often involves limiting the use of abortive therapy to avoid medication-overuse headaches (MOH). The pathophysiology, although not fully understood, is thought to be related to central sensitization along with "neurogenic inflammation." Chronic daily headaches can be difficult to treat and at times require a tertiary specialized center.

Clinical aspects of headache in HIV.

BACKGROUND: Headaches are commonly seen in those patients with human immunodeficiency virus (HIV) and are the most common form of pain reported among HIV patients. There have been relatively few studies attempting to determine the rates and phenotypes of the headaches that occur in patients with HIV. DISCUSSION: Patients with HIV are susceptible to a much broader array of secondary headache causes, sometimes with atypical manifestations due to a dampened inflammatory response. The investigation of a headache in the HIV patient should be thorough and focused on making sure that secondary and HIV-specific causes are either ruled out or treated if present. CONCLUSION: An effective treatment plan should incorporate the use of appropriate pharmacological agents along with the integration of non-pharmacological therapies, such as relaxation and lifestyle regulation. When treating for headaches in patients with HIV, it is important to keep in mind comorbidities and other medications, especially combination antiretroviral therapy. For those with complicated headache histories, referral to a specialized headache center may be appropriate.

Reversible cerebral vasoconstriction syndrome: updates and new perspectives.

Reversible cerebral vasoconstriction syndrome (RCVS) is an important cause of headaches that can lead to other neurological complications, including stroke, if not recognized early. Over the past few years, there has been great progress in the recognition of this entity. However, there is still much to be learned about its pathophysiology and optimal treatment strategies. RCVS occurs mostly in middle-aged adults, and there is a female preponderance with an increased incidence during the postpartum period. A consistent, predominating feature is a sudden-onset, severe headache that is frequently recurrent, usually over the span of a week. Less common presentations include seizures or focal neurological symptoms. Important causative factors include vasoactive medications, as well as illicit drugs like marijuana and cocaine. The current underlying pathophysiology is thought to be a disturbance in cerebrovascular tone leading to vasoconstriction. The diagnosis is based on history, physical examination, and cerebrovascular imaging findings that demonstrate multifocal, segmental areas of vasoconstriction in large- and medium-sized arteries. An important criterion for making the diagnosis is the eventual reversibility of symptoms and imaging findings.

Reversible hypohidrosis with topiramate therapy for chronic migraine.

Topiramate is an anticonvulsant medication that is widely used for migraine prophylaxis. Hypohidrosis and hyperthermia are 2 rare adverse effects of topiramate treatment, which have mainly occurred in pediatric epilepsy patients. Herein, we describe the first case of reversible hypohidrosis in an adult patient treated with topiramate for chronic migraine.