A real-world prospective observational study of eptinezumab in Asian patients with migraine.

OBJECTIVE: To evaluate the real-world effectiveness of eptinezumab for migraine prevention in Asian patients. BACKGROUND: Eptinezumab is a monoclonal antibody that targets calcitonin gene-related peptide (CGRP), a potent vasodilator with an important role in migraine pathophysiology. Although there is robust clinical evidence from pivotal Phase 3 placebo-controlled trials of the efficacy of eptinezumab for migraine prevention, there are limited data on the real-world effectiveness of eptinezumab in Asian patient cohorts. METHODS: This was a non-interventional, prospective, multisite cohort study of adults with migraine (International Classification of Headache Disorders, 3rd edition criteria) in Singapore who were prescribed eptinezumab (100 mg at baseline and Month 3, administered intravenously) and were followed until Month 6. The primary endpoint was change from baseline in monthly migraine days (MMDs) at Month 3 and Month 6. Secondary endpoints were ≥30% and ≥50% responder rates, and change from baseline in the Headache Impact Test-6 (HIT-6), Migraine Disability Assessment (MIDAS), Migraine-Specific Quality of Life (MSQ), patient-identified most bothersome symptom (PI-MBS), acute medication use at Month 3 and Month 6, and safety. RESULTS: Enrolled patients (completed = 29/30) had on average 3.4 (SD 2.9) previous preventive treatments; 29/30 of the patients had trialed at least one previous preventive treatment without benefit. Most had previously trialed oral preventives (87%, 26/30) and anti-CGRP (70%, 21/30). Relative to baseline, mean MMDs decreased by 4.3 days (95% CI 2.1-6.4; p < 0.001) at Month 3 and 4.9 days (95% CI 2.1-7.7; p < 0.001) at Month 6. At Month 3 and Month 6, 14/30 (47%) and 15/29 (52%) of the patients were ≥30% responders, and 6/30 (20%) and 8/29 (28%) patients were ≥50% responders, respectively. The number of patients with severe life impairment based on the HIT-6 score (total score 60-78) decreased from 24/30 (80%) at baseline to 19/30 (63%) at Month 3 and 19/29 (66%) at Month 6. The mean MIDAS score decreased by 24.6 points (95% CI 2.82-46.38; p = 0.028) at Month 6, and the mean MSQ score increased by 12.2 points (95% CI 5.18-19.20; p = 0.001) at Month 3 and 13.6 points (95% CI 4.58-22.66; p = 0.004) at Month 6. Most patients reported improvement in the PI-MBS at Month 3 (73%, 22/30) and Month 6 (55%, 16/29). Acute medication use for headache relief decreased by 3.3 days/month (95% CI 1.0-5.6; p = 0.007) at Month 3 and 4.7 days/month (95% CI 1.7-7.7; p = 0.003) at Month 6. Treatment-emergent adverse events (TEAEs) were reported in 16/30 (54%) patients, mostly mild/moderate in severity. No serious TEAEs led to treatment discontinuation. CONCLUSION: Quarterly eptinezumab administration was effective and well-tolerated in Asian patients with chronic migraine.

Migraine and atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Patients with migraines, particularly those with auras, may present with stroke. Atrial fibrillation is a known risk factor for stroke. With common pathophysiological factors between migraines and atrial fibrillation, we aimed to clarify the association between migraine and atrial fibrillation in this systematic review and meta-analysis. METHODS: A literature search was conducted in EMBASE, PubMed, Scopus and Cochrane electronic bibliographic databases from inception to 5 September 2022 with the following inclusion criteria: (a) cohort or cross-sectional studies; (b) studies that included only patients aged ≥18 years; and (c) studies that examined the association between atrial fibrillation and migraines. Exclusion criteria were case-control studies and the studies that included patients with previous diagnosis of atrial fibrillation or nonmigrainous headache. The Newcastle-Ottawa Scale was used to assess the quality of studies. RESULTS: Six studies were included, demonstrating a pooled prevalence of atrial fibrillation of 1.61% (95% confidence interval [CI] 0.51, 3.29) in migraine with aura and 1.32% (95% CI 0.17, 3.41) in migraine without aura. The overall prevalence of atrial fibrillation in migraine was 1.39% (95% CI 0.24, 3.46). CONCLUSION: In this systematic review and meta-analysis, the overall prevalence of atrial fibrillation in patients with migraine was low. Further studies are needed to clarify this relationship.

The adult patient with headache.

Headaches are common in primary care. For safe assessment and management of the patient with headache, a focused history and physical examination are important to identify secondary headache, and find out whether an immediate referral to the emergency department or a non-emergent referral to the neurologist is warranted. The majority of patients with primary headache may be safely managed in the outpatient setting. Key steps include proper categorisation of the primary headache, attention to lifestyle and psychosocial factors, prescription of analgesics for acute pain relief, and the use of preventive medication when indicated. The patient with a cluster headache, a headache of uncertain diagnosis and/or poor response to preventive strategies or a migraine with persistent aura, or a headache with associated motor weakness, should be referred to a neurologist. Secondary headache and the diagnosis of medication overuse headache should be considered in a patient on long-term analgesics with unremitting headache.

Recent Advances in Pharmacotherapy for Migraine Prevention: From Pathophysiology to New Drugs.

Migraine is a common and disabling neurological disorder, with a significant socioeconomic burden. Its pathophysiology involves abnormalities in complex neuronal networks, interacting at different levels of the central and peripheral nervous system, resulting in the constellation of symptoms characteristic of a migraine attack. Management of migraine is individualised and often necessitates the commencement of preventive medication. Recent advancements in the understanding of the neurobiology of migraine have begun to account for some parts of the symptomatology, which has led to the development of novel target-based therapies that may revolutionise how migraine is treated in the future. This review will explore recent advances in the understanding of migraine pathophysiology, and pharmacotherapeutic developments for migraine prevention, with particular emphasis on novel treatments targeted at the calcitonin gene-related peptide (CGRP) pathway.

Correction to: Migraine Treatment: Current Acute Medications and Their Potential Mechanisms of Action.

This article was updated to correct an error in figure 1 introduced during the production process.

Migraine Treatment: Current Acute Medications and Their Potential Mechanisms of Action.

Migraine is a common and disabling primary headache disorder with a significant socioeconomic burden. The management of migraine is multifaceted and is generally dichotomized into acute and preventive strategies, with several treatment modalities. The aims of acute pharmacological treatment are to rapidly restore function with minimal recurrence, with the avoidance of side effects. The choice of pharmacological treatment is individualized, and is based on the consideration of the characteristics of the migraine attack, the patient's concomitant medical problems, and treatment preferences. Notwithstanding, a good understanding of the pharmacodynamic and pharmacokinetic properties of the various drug options is essential to guide therapy. The current approach and concepts relevant to the acute pharmacological treatment of migraine will be explored in this review.

Medical Undergraduate Survey on Headache Education in Singapore: Knowledge, Perceptions, and Assessment of Unmet Needs.

BACKGROUND: There have been no prior studies assessing the status of undergraduate headache training and education in Singapore. Unmet needs of undergraduate medical students in terms of knowledge-practice gaps pertaining to diagnosis and management of headache disorders are unknown. The possible underemphasis of this aspect of the curriculum as compared to other chronic conditions such as diabetes mellitus has also not been ascertained. OBJECTIVE: The aim of this article is to assess the knowledge base and perceptions, thereby identifying the unmet needs of headache disorder education in undergraduate medical students. Students reported their perceived time that was devoted to the subject matter and this was recorded and reported. In order to provide a comparative indication on the level of prioritization, the total duration within the syllabus dedicated to headache education vs other chronic diseases (using diabetes mellitus as a surrogate) was sought. METHODS: A comprehensive survey consisting of questions assessing the headache curriculum, knowledge, and perceptions was developed. The questionnaire was distributed to final year medical students attending a full-day Neurology review course in their last semester. Attendees were given the duration of the course to complete the questionnaire, and forms were collected at the end of the day. RESULTS: About 127 final year medical students completed our survey. More than half (55.1%) did not receive formal teaching on how to take a complete headache history. The majority (90.6%) have not attended a headache sub-specialty clinic. The mean total number of hours exposed to headache disorders was 5.69h (SD ± 5.19). The vast majority (96.1%) were unfamiliar with locally published clinical practice guidelines, and a significant proportion (74.0%) were unfamiliar with the third edition (beta) of the International Classification of Headache Disorders. Nearly half (47.2%) were unfamiliar with 'medication overuse headache' as a disease entity. Only one (0.8%) respondent was able to correctly classify all listed primary and secondary headache disorders correctly. Only 37.0% were able to identify all 4 indications (headaches that were new, worsening, and unresponsive to treatment or associated with neurological symptoms) that warranted neuroimaging in a patient with a pre-existing diagnosis of migraine. The antidepressants were the most frequently reported incorrect option for the abortive treatment of migraine (16.5%). Nearly one-fifth (18.9%) were unable to name a single abortive treatment correctly, while a significant proportion (39.4%) could not identify a single correct prophylactic migraine treatment. A large proportion (62.2%) opined that their exposure to 'headache diagnosis and management' was inadequate, with a minority (3.1%) being 'very comfortable' in the diagnosing migraine. A significant proportion felt uncomfortable in treating special population groups diagnosed with migraine - pregnant (79.5%), elderly (48.0%), those with cardiac conditions (51.2%). CONCLUSIONS: The current medical undergraduate curriculum on headache disorders in Singapore may harbor significant unmet needs. A review of the syllabus to increase headache education may be one method to address this gap. Further studies in this area are required.