Role of Calcitonin Gene-Related Peptide on the Gastrointestinal Symptoms of Migraine-Clinical Considerations: A Narrative Review.

Calcitonin gene-related peptide (CGRP) is involved in several of the pathophysiological processes underpinning migraine attacks. Therapies that target CGRP or its receptor have shown efficacy as preventive or acute treatments for migraine. Two small-molecule CGRP receptor antagonists (rimegepant and ubrogepant) are approved for the acute treatment of migraine, and four monoclonal antibodies (eptinezumab, erenumab, fremanezumab, and galcanezumab) are approved for migraine prevention; erenumab targets the canonical CGRP receptor, the others CGRP ligand. CGRP plays a role in gastrointestinal nociception, inflammation, gastric acid secretion, and motility. Nausea and vomiting are among the gastrointestinal symptoms associated with migraine, but individuals with migraine may also experience functional upper and lower gastrointestinal comorbidities, such as gastroesophageal reflux disease, gastroparesis, functional diarrhea or constipation, and irritable bowel syndrome. Although gastrointestinal symptoms in migraine can be treatment-related, they may also be attributable to increased CGRP. In this review, we summarize the epidemiological evidence for associations between migraine and gastrointestinal disorders, consider the possible physiological role of CGRP in these associations, and review the clinical occurrence of gastrointestinal events in patients with migraine receiving CGRP-based therapies and other migraine treatments. Because patients with migraine are at an increased risk of comorbid and treatment-related gastrointestinal effects, we also propose a patient-management strategy to mitigate these effects.

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.

Unique Aspects of Asthma in Women.

There are many unique aspects of asthma in women. Compared with men, women go through several hormonal stages over the life span-childhood, menarche, reproductive years, pregnancy, menopause, and postmenopause-and each affects asthma. Onset of asthma in women differs from men. Asthma in women is more often associated with obesity and women are over-represented among patients with severe asthma, including those being prescribed biologic therapies. Asthma affects fertility and pregnancy, and female hormone replacement therapy has been found to affect asthma onset as well as asthma severity. We explore the unique aspects of asthma in women.

A narrative review of the importance of pharmacokinetics and drug-drug interactions of preventive therapies in migraine management.

OBJECTIVE: To review the pharmacokinetics of major classes of migraine preventives and the clinical implications of drug-drug interactions (DDIs) with the use of these therapies in migraine management. BACKGROUND: Preventive treatments for migraine are recommended for a large proportion of patients with frequent migraine attacks. These patients often exhibit a number of comorbidities, which may lead to the introduction of multiple concomitant therapies. Potential DDIs must be considered when using polytherapy to avoid increased risk of adverse events (AEs) or inadequate treatment of comorbid conditions. METHODS: A literature search was performed to identify pharmacokinetic properties and potential DDIs of beta-blockers, antiepileptic drugs, antidepressants, calcium channel blockers, gepants, and monoclonal antibody therapies targeting the calcitonin gene-related peptide pathway with medications that may be used for comorbid conditions. RESULTS: Most DDIs occur through alterations in cytochrome P450 isoenzyme activity and may be complicated by genetic polymorphism for metabolic enzymes. Additionally, drug metabolism may be altered by grapefruit juice ingestion and smoking. The use of migraine preventive therapies may exacerbate symptoms of comorbid conditions or increase the risk of AEs associated with comorbid conditions as a result of DDIs. CONCLUSIONS: DDIs are important to consider in patients with migraine who use multiple medications. The development of migraine-specific evidence-based preventive treatments allows for tailored clinical management that reduces the risk of DDIs and associated AEs in patients with comorbidities.

Erenumab prevents the occurrence of migraine attacks and not just migraine days: Post-hoc analyses of a phase III study.

BACKGROUND: This post-hoc analysis was conducted to evaluate the effect of erenumab on monthly migraine days, monthly migraine attacks, and attack duration in patients with episodic migraine to investigate whether erenumab actually prevents the occurrence of migraine attacks and/or shortens them. METHODS: We conducted a post-hoc analysis of the data from the STRIVE study, in 955 patients with episodic migraine. Relative changes from baseline to mean over months 4, 5 and 6 of the double-blind treatment phase in monthly migraine days, monthly migraine attacks and mean migraine attack duration were assessed. RESULTS: Erenumab reduced monthly migraine days and monthly migraine attacks compared with placebo in a similar way. Erenumab had only a minor impact on shortening the duration of migraine attacks. CONCLUSION: These post-hoc analyses demonstrate that the decrease in monthly migraine days by erenumab is mainly driven by a reduction in the frequency of monthly migraine attacks and to a much lesser extent by shortening the duration of migraine attacks.Trial registration: This study is registered at ClinicalTrials.gov (NCT02456740).

Patient Reported Ease-of-Use with a Disposable Autoinjector in Individuals with Migraine.

PURPOSE: Erenumab-aooe (erenumab, Aimovig®)-a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide (CGRP) receptor-is approved for the prevention of migraine in adults in a number of countries. The approved monthly dosage of erenumab (70 and/or 140 mg, depending on the country) is available as a single, prefilled autoinjector for subcutaneous administration in most countries where it is approved. This study evaluated the patient-reported ease-of-use, ability to learn self-injection, confidence in performing a simulated self-injection, and ergonomics of a prefilled autoinjector device for erenumab (SureClick® autoinjector) in individuals in the US with migraine. PATIENTS AND METHODS: Participants with migraine headaches, all of whom were naïve to the use of an autoinjector for migraine or another condition and CGRP therapy, were recruited from three US-based headache centers. Each participant received a supervised demonstration of the autoinjector during a 30-minute one-on-one session using a standard protocol-driven script. Participants then practiced a simulated injection into an artificial tissue pad using the autoinjector and were asked to rate their agreement with 19 statements about the device on a 5-point Likert scale (1 = completely disagree, 2 = somewhat disagree, 3 = neutral, 4 = somewhat agree, 5 = completely agree). RESULTS: Participants who completed the study and provided responses (n = 204) were between 21 and 85 years of age, inclusive, and 73% were female. More than 90% of the participants completely or somewhat agreed with 16/19 statements relating to the device, including ease-of-use, ability to self-inject, and confidence in using the device, with an average rating of >4.5 on the 5-point Likert scale. Participants rated the size of the device and the compactness of the device as 4.23/5 and 4.26/5, respectively. CONCLUSION: The erenumab-prefilled disposable autoinjector was consistently highly rated across categories by individuals with migraine, with an average rating of >4.5 on the 5-point Likert scale; results were consistent across the three study centers.

Estimating the incidence of the acute coronary syndrome: data from a Danish cohort of 138 290 persons.

BACKGROUND: Estimates of incidence are crucial to the planning of public health measures, but most studies of incidence of, for example, acute myocardial infarction (MI) are troubled by methodological problems such as; (i) selection biases of the patients being included for study, (ii) lack of identification and control of the cohort under observation, (iii) inconsistencies in the use of diagnostic criteria, and (iv) missing data. We aimed to measure directly the incidence of the entire spectrum of the acute coronary syndrome (ACS), consisting of unstable angina pectoris, MI and sudden cardiac death (SCD), by use of the new criteria for MI as proposed in 2000. DESIGN: Cohort study. METHODS: From a cohort of 138 290 residents of the municipality of Aarhus, Denmark, aged 30-69 years, with a demographic structure known at the individual population member level, we prospectively identified all consecutive ACS patients from 1 April 2000 to 31 March 2002. The population was identified from Danish Population Registers. RESULTS: A total of 189 victims of SCD and 457 ACS patients who survived until admission to hospital were present. Consequently, crude incidence rate of ACS was 234 per 100 000 person-years. Unstable angina pectoris constituted for 16.9%, MI for 53.8% and SCD for 29.3% of ACS patients. CONCLUSIONS: Crude incidence rates of ACS were 137 and 331 per 100 000 person years for women and men, respectively. The incidence rate of ACS, as measured directly, was insignificantly 6% higher than expected from Danish administrative databases.