The impact of migraine prevention on daily activities: a longitudinal and responder analysis from three topiramate placebo-controlled clinical trials

<p>Abstract</p> <p>Background</p> <p>Topiramate is approved for the prophylaxis (prevention) of migraine headache in adults. The most common adverse events in the three pivotal, randomized, double-blind, placebo-controlled trials were paresthesia, fatigue, cognitive impairment, anorexia, nausea, and taste alteration. In these trials, topiramate 100 mg/d significantly improved Migraine-Specific Questionnaire (MSQ) scores versus placebo (p < 0.001). The MSQ measures how much migraine limits/interrupts daily performance. Pooled analyses of pivotal trial data were conducted to further assess how topiramate 100 mg/d affects daily activities and patient functioning.</p> <p>Methods</p> <p>Mean MSQ and Medical Outcome Study Short Form 36 (SF-36) change scores (baseline to each double-blind assessment point) were calculated for pooled intent-to-treat (ITT) patients. Additionally, pooled ITT patients receiving topiramate 100 mg/d or placebo were combined and divided into two responder groups according to percent reduction in monthly migraine frequency: < 50% responders or ≥ 50% responders. Between-group differences were assessed using analysis of covariance.</p> <p>Results</p> <p>Of 756 patients (mean age 39.8 years, 86% female), 384 received topiramate 100 mg/d and 372 placebo. Topiramate significantly improved all three MSQ domains throughout the double-blind phase versus placebo (p = 0.024 [week 8], p < 0.001 [weeks 16 and 26] for role prevention; p < 0.001 for role restriction and emotional function [all time points]). Topiramate 100 mg/d significantly improved SF-36 physical component scores (PCS) throughout the double-blind phase versus placebo (p < 0.001, all time points) and significantly improved mental component scores (MCS) at week 26 (p = 0.043). The greatest topiramate-associated improvements on SF-36 subscales were seen for bodily pain and general health perceptions (p < 0.05; weeks 8, 16, and 26), and physical functioning, vitality, role-physical, and social functioning (p < 0.05; weeks 16 and 26). Significantly greater improvements in all three MSQ domains, as well as the PCS and MCS of SF-36, were observed for ≥ 50% responders versus < 50% responders (p < 0.001). Significantly greater percentages of topiramate-treated patients were ≥ 50% responders versus placebo (46% versus 23%; p < 0.001).</p> <p>Conclusion</p> <p>Topiramate 100 mg/d significantly improved daily activities and patient functioning at all time points throughout the double-blind phase. Daily function and health status significantly improved for those achieving a ≥ 50% migraine frequency reduction.</p

Migraine Frequency and Health Utilities: Findings from a Multisite Survey

AbstractObjectivesAssess the relationship between migraine frequency and health utility.MethodsPatients aged ≥18 years diagnosed with episodic migraine were enrolled at three US sites representing varied models of health-care delivery. All subjects completed a questionnaire that included demographic and clinical information, a migraine-specific disability questionnaire, and the Health Utilities Index Mark 3 (HUI3). The HUI3 is a generic health status and health-related quality-of-life measure. HUI3 health status data are translated into utility scores anchored by 0 (dead) and 1 (perfect health).ResultsThe study enrolled 150 patients. The mean age was 44 years and 87% were female. Mean (±SD) monthly migraine frequency was 4.4 ± 3.6, with 34% reporting ≤2 migraines per month and 20% reporting >6 migraines per month. The mean (±SD) HUI3 score was 0.62 ± 0.26. After controlling for study center, demographics, comorbidities, migraine characteristics, and level of migraine disruptiveness, migraine frequency was found to be significantly (P < 0.05) and negatively associated with HUI3 scores. Subjects with >6 migraines per month had an adjusted mean HUI3 score of 0.41; the corresponding mean for those reporting ≤2 migraines per month was 0.67. Migraine frequency was positively associated with higher levels of disability for the emotion, cognition, and pain components of the HUI3.ConclusionsAmong this group of care-seeking patients, migraineurs' health utilities were inversely related to headache frequency. Although these data may not be generalizable to the entire migraine population, they may be useful in assessing the comparative cost-effectiveness of preventive migraine therapies

Frictional Instabilities and Carbonation of Basalts Triggered by Injection of Pressurized H2O- and CO2- Rich Fluids

The safe application of geological carbon storage depends also on the seismic hazard associated with fluid injection. In this regard, we performed friction experiments using a rotary shear apparatus on precut basalts with variable degree of hydrothermal alteration by injecting distilled H2O, pure CO2, and H2O + CO2 fluid mixtures under temperature, fluid pressure, and stress conditions relevant for large-scale subsurface CO2 storage reservoirs. In all experiments, seismic slip was preceded by short-lived slip bursts. Seismic slip occurred at equivalent fluid pressures and normal stresses regardless of the fluid injected and degree of alteration of basalts. Injection of fluids caused also carbonation reactions and crystallization of new dolomite grains in the basalt-hosted faults sheared in H2O + CO2 fluid mixtures. Fast mineral carbonation in the experiments might be explained by shear heating during seismic slip, evidencing the high chemical reactivity of basalts to H2O + CO2 mixtures

Eptinezumab for the prevention of chronic migraine: efficacy and safety through 24 weeks of treatment in the phase 3 PROMISE-2 (Prevention of migraine via intravenous ALD403 safety and efficacy-2) study.

BACKGROUND: PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of repeat intravenous (IV) doses of the calcitonin gene-related peptide-targeted monoclonal antibody eptinezumab (ALD403) for migraine prevention in adults with chronic migraine. This report describes the results of PROMISE-2 through 24 weeks of treatment. METHODS: Patients received up to two 30-min IV administrations of eptinezumab 100 mg, 300 mg, or placebo separated by 12 weeks. Patients recorded migraine and headache endpoints in a daily eDiary. Additional assessments, including patient-reported outcomes, were performed at regularly scheduled clinic visits throughout the 32-week study period (screening, day 0, and weeks 2, 4, 8, 12, 16, 20, 24, and 32). RESULTS: A total of 1072 adults received treatment: eptinezumab 100 mg, n = 356; eptinezumab 300 mg, n = 350; placebo, n = 366. The reduction in mean monthly migraine days observed during the first dosing interval (100 mg, - 7.7 days; 300 mg, - 8.2 days; placebo, - 5.6 days) was further decreased after an additional dose (100 mg, - 8.2 days; 300 mg, - 8.8 days; placebo, - 6.2 days), with both doses of eptinezumab demonstrating consistently greater reductions from baseline compared to placebo. The ≥50% and ≥ 75% migraine responder rates (MRRs) increased after a second dose, with more eptinezumab-treated patients experiencing migraine response than placebo patients (≥50% MRRs weeks 13-24: 100 mg, 61.0%; 300 mg, 64.0%; placebo, 44.0%; and ≥ 75% MRRs weeks 13-24: 100 mg, 39.3%; 300 mg, 43.1%; placebo, 23.8%). The percentages of patients who improved on patient-reported outcomes, including the Headache Impact Test and Patient Global Impression of Change, increased following the second dose administration at week 12, and were greater with eptinezumab than with placebo at all time points. No new safety concerns were identified with the second dose regarding the incidence, nature, and severity of treatment-emergent adverse events. CONCLUSION: Eptinezumab 100 mg or 300 mg administered IV at day 0 and repeated at week 12 provided sustained migraine preventive benefit over a full 24 weeks and demonstrated an acceptable safety profile in patients with chronic migraine. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02974153 ). Registered November 23, 2016

Safety and Tolerability Results of Atogepant for the Preventive Treatment of Episodic Migraine From a 40-Week, Open-Label Multicenter Extension of the Phase 3 ADVANCE Trial

Background: Atogepant is a United States Food and Drug Administration-approved oral calcitonin gene-related peptide receptor antagonist for the preventive treatment of episodic migraine. The study objective was to evaluate the long-term safety and tolerability of atogepant in participants who completed the phase 3 ADVANCE trial (NCT03777059). Methods: This 40-week, open-label extension trial (NCT03939312) monitored safety in participants receiving oral atogepant 60 mg once daily, followed by a four-week safety follow-up period. Results: Of the 685 participants taking at least one dose of atogepant, the treatment period was completed by 74.6% of participants with a mean (standard deviation) treatment duration of 233.6 (89.3) days. Treatment-emergent adverse events occurred in 62.5% of participants, with upper respiratory tract infection (5.5%), urinary tract infection (5.3%), nasopharyngitis (4.8%), sinusitis (3.6%), constipation (3.4%), and nausea (3.4%) occurring at ≥3%. Serious adverse events were observed in 3.4% of participants (none were treatment-related), and there were no deaths. Adverse events leading to discontinuation occurring at \u3e0.1% were nausea (0.4%) and abdominal pain, vomiting, weight decrease, dizziness, and migraine (0.3% each). Conclusion: These results are consistent with atogepant\u27s known safety profile and support long-term use of atogepant 60 mg once daily dosing as safe and well tolerated.ClinicalTrials.gov Registration Number: NCT03939312

Headache and migraine biology and management /

There are two crucial issues in the treatment and management of headache patients: More than 50% of individuals experiencing headache have only been treated symptomatically, with no appropriate diagnosis established; and history and neurologic examination are essential to establishing a diagnosis, and thus selecting appropriate therapy. Headache and Migraine Biology and Management is a practical text that addresses these issues, featuring contributions from expert clinical authors. The book covers in detail topics including chronic and episodic migraine, post-traumatic headache, sinus headache, cluster headache, tension headache, and others. Chapters are also dedicated to treatment subjects, including psychiatric and psychological approaches, medication overuse, inpatient treatment, and pediatric issues. This book is an ideal resource for researchers and clinicians, uniting practical discussion of headache biology, current ideas on etiology, future research, and genetic significance and breakthroughs. This resource is useful to those who want to understand headache biology, treat and manage symptoms, and for those performing research in the headache field.Online resource; title from PDF title page (Ebsco, viewed March 18, 2015).Includes bibliographical references and index.There are two crucial issues in the treatment and management of headache patients: More than 50% of individuals experiencing headache have only been treated symptomatically, with no appropriate diagnosis established; and history and neurologic examination are essential to establishing a diagnosis, and thus selecting appropriate therapy. Headache and Migraine Biology and Management is a practical text that addresses these issues, featuring contributions from expert clinical authors. The book covers in detail topics including chronic and episodic migraine, post-traumatic headache, sinus headache, cluster headache, tension headache, and others. Chapters are also dedicated to treatment subjects, including psychiatric and psychological approaches, medication overuse, inpatient treatment, and pediatric issues. This book is an ideal resource for researchers and clinicians, uniting practical discussion of headache biology, current ideas on etiology, future research, and genetic significance and breakthroughs. This resource is useful to those who want to understand headache biology, treat and manage symptoms, and for those performing research in the headache field.Elsevie