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Migraine Disorders: HELP
Articles from London, EN
Based on 407 articles published since 2010

These are the 407 published articles about Migraine Disorders that originated from London, EN during 2010-2020.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13 · 14 · 15 · 16 · 17
101 Review Aspirin for acute migraine headaches in adults. 2013

Kirthi, Varo / Derry, Sheena / Moore, R Andrew / McQuay, Henry. ·Royal College of Physicians, 11 St Andrew Place Regent's Park, London NW1 4LE, UK. varo.kirthi@gmail.com ·J Neurol Neurosurg Psychiatry · Pubmed #22832741.

ABSTRACT: -- No abstract --

102 Review Neurological perspectives on voltage-gated sodium channels. 2012

Eijkelkamp, Niels / Linley, John E / Baker, Mark D / Minett, Michael S / Cregg, Roman / Werdehausen, Robert / Rugiero, François / Wood, John N. ·Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK. n.eijkelkamp@ucl.ac.uk ·Brain · Pubmed #22961543.

ABSTRACT: The activity of voltage-gated sodium channels has long been linked to disorders of neuronal excitability such as epilepsy and chronic pain. Recent genetic studies have now expanded the role of sodium channels in health and disease, to include autism, migraine, multiple sclerosis, cancer as well as muscle and immune system disorders. Transgenic mouse models have proved useful in understanding the physiological role of individual sodium channels, and there has been significant progress in the development of subtype selective inhibitors of sodium channels. This review will outline the functions and roles of specific sodium channels in electrical signalling and disease, focusing on neurological aspects. We also discuss recent advances in the development of selective sodium channel inhibitors.

103 Review Classification of perimenstrual headache: clinical relevance. 2012

MacGregor, E Anne. ·Barts Sexual Health Centre, Kenton and Lucas Block, St Bartholomew's Hospital, London, UK. e.macgregor@qmul.ac.uk ·Curr Pain Headache Rep · Pubmed #22653664.

ABSTRACT: Although more than 50% of women with migraine report an association between migraine and menstruation, menstruation has generally considered to be no more than one of a variety of different migraine triggers. In 2004, the second edition of the International Classification of Headache Disorders introduced specific diagnostic criteria for menstrual migraine. Results from research undertaken subsequently lend support to the clinical impression that menstrual migraine should be seen as a distinct clinical entity. This paper reviews the recent research and provides specific recommendations for consideration in future editions of the classification.

104 Review Traumatic head injury in cluster headache: cause or effect? 2012

Lambru, Giorgio / Matharu, Manjit. ·Headache Group, Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. ·Curr Pain Headache Rep · Pubmed #22274664.

ABSTRACT: Post-traumatic headache (PTH) is a common and well-recognized entity. Tension-type headache and migraine are the commonest phenotypes that can result from head trauma, while the onset of cluster headache (CH) in close temporal relation to a head trauma has only been described in rare cases. Nevertheless, CH patients seem to incur more frequent traumatic head injuries during their lifetimes when compared to migraine controls and the general population. The basis of this association remains unclear, since only a limited number of methodologically robust studies have examined it. However, three main hypotheses can be proposed to explain this association: head trauma is the direct cause of CH; head trauma is a risk factor for the future development of CH; and head trauma is a consequence of a CH trait. A better understanding of the association between head trauma and CH may provide important insights into both the pathophysiology of CH and the mechanisms by which traumatic head injury predisposes patients to developing headaches.

105 Review Perimenopausal migraine in women with vasomotor symptoms. 2012

MacGregor, E Anne. ·Centre for Neuroscience and Trauma, Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, United Kingdom. e.macgregor@qmul.ac.uk ·Maturitas · Pubmed #22115567.

ABSTRACT: Migraine is affected by fluctuating estrogen levels so it is not surprising that the perimenopause is a time of peak rate of change of migraine prevalence in women. Evidence supports estrogen 'withdrawal' as one of the important triggers of menstrual attacks of migraine without aura, while high levels are associated with migraine aura. This mini review addresses the issues of diagnosing migraine, treating the symptoms of migraine, and controlling co-morbid migraine and hot flushes with hormonal and non-hormonal options. Maintaining a stable estrogen environment is the most effective treatment for vasomotor symptoms and can also benefit estrogen-withdrawal migraine. Using only the lowest doses necessary to control symptoms minimizes the risk of unwanted side effects. Non-hormonal options for both conditions are limited but there is evidence of efficacy for fluoxetine and venflaxine, with less evidence for gabapentin.

106 Review Neurological complications of sclerotherapy for varicose veins. 2012

Sarvananthan, Tharsi / Shepherd, Amanda Claire / Willenberg, Torsten / Davies, Alun Huw. ·Academic Section of Vascular Surgery, Imperial College School of Medicine, Charing Cross Hospital, London, United Kingdom. ·J Vasc Surg · Pubmed #21840152.

ABSTRACT: BACKGROUND: Sclerotherapy has been shown to be an effective and increasingly popular therapeutic strategy for the treatment of varicose veins. However, recent reports of serious side effects, including cerebrovascular accidents (CVA) and transient ischemic attacks (TIA), as well as speech and visual disturbances, have caused serious concern regarding its use. This review evaluated the reported incidences of neurological side effects associated with the use of sclerotherapy. METHODS: A systematic search of the data bases MEDLINE, OVID Embase, and Google Scholar was undertaken by two independent reviewers. Articles reporting neurological side effects in humans following foam and liquid sclerotherapy were included; animal studies, laboratory studies, and review articles were excluded. Additional references were also obtained using the related articles function. RESULTS: The search yielded 1023 articles, of which 41 studies were found to meet the inclusion criteria. A total of 10,819 patients undergoing sclerotherapy were reviewed. There were 12 case reports of CVA with confirmatory brain imaging and nine reports of TIA. There were 97 (0.90%) reports of neurological events overall, including TIA, visual and speech disturbances, and 29 cases of reported migraine (0.27%). Symptoms occurred at times ranging from minutes to several days following sclerotherapy. Eleven patients with TIA or CVA were found to have a right to left cardiac shunt, usually a patent foramen ovale. CONCLUSIONS: Neurological side effects following sclerotherapy are a rare occurrence; however, CVA associated with the use of sclerotherapy is clearly documented. The pathologic mechanisms resulting in CVA are likely to be different to those leading to migraine and visual disturbances; however, care should be exercised in patient selection, particularly in those with known cardiac defects.

107 Review New directions in migraine. 2011

Weir, Greg A / Cader, M Zameel. ·Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, UK. ·BMC Med · Pubmed #22027350.

ABSTRACT: Migraine is a highly prevalent neurological disorder imparting a major burden on health care around the world. The primary pathology may be a state of hyperresponsiveness of the nervous system, but the molecular mechanisms are yet to be fully elucidated. We could now be at a watershed moment in this respect, as the genetic loci associated with typical forms of migraine are being revealed. The genetic discoveries are the latest step in the evolution of our understanding of migraine, which was initially considered a cerebrovascular condition, then a neuroinflammatory process and now primarily a neurogenic disorder. Indeed, the genetic findings, which have revealed ion channels and transporter mutations as causative of migraine, are a powerful argument for the neurogenic basis of migraine. Modulations of ion channels leading to amelioration of the migraine 'hyperresponsive' brain represent attractive targets for drug discovery. There lies ahead an exciting and rapidly progressing phase of migraine translational research, and in this review we highlight recent genetic findings and consider how these may affect the future of migraine neurobiology and therapy.

108 Review Sex-related differences in epidemiological and clinic-based headache studies. 2011

Macgregor, E Anne / Rosenberg, Jason D / Kurth, Tobias. ·City of London Migraine Clinic, London, UK. Anne.MacGregor@MigraineClinic.org.uk ·Headache · Pubmed #21631472.

ABSTRACT: This manuscript discusses sex-related differences in headache prevalence, the symptoms and natural history of migraine, associated disability, and co-morbid disorders. The role of sex hormones is discussed with reference to the effects of hormonal events across the reproductive years and the specific effects of the menstrual cycle on migraine. Differences between the sexes were identified across all parameters reviewed. Future research should ensure that data are analyzed separately for men and women to ensure that differences between the sexes are identified.

109 Review Migraine-like visual aura due to focal cerebral lesions: case series and review. 2011

Shams, Pari N / Plant, Gordon T. ·The National Hospital for Neurology & Neurosurgery, London, UK. pari.shams@gmail.com ·Surv Ophthalmol · Pubmed #21335146.

ABSTRACT: Visual aura is a common presenting symptom of migraine to both neurologists and ophthalmologists. Features such as photopsia, fortification spectra, and the slow propagation of a scintillating scotoma across the visual field are usually considered diagnostic features of the visual aura of migraine. In the vast majority of cases, the diagnosis can be made without the need for further investigations. We present 9 patients and a further 31 cases from the literature who experienced visual aura fulfilling the diagnostic criteria for migraines but caused by focal occipital pathology. Key clinical features that could help to differentiate between the visual aura of migraine and those suggestive of a structural lesion are outlined. We review current scientific theories into the pathophysiology of visual aura, drawing on clinical and basic science research, including human functional imaging studies of migraine aura and advances in the genetic characterization of familial channelopathies, in order to explain the overlap which occurs in the clinical features of visual aura associated with migraine, cortical lesions, and epilepsy. We conclude that any disease process that is able to create a state of neuronal hyperexcitability can therefore increase an individual's susceptibility to the development of cortical spreading depression, the electrophysiological correlate of the visual aura.

110 Review Serotonergic agents in the management of cluster headache. 2011

Lambru, Giorgio / Matharu, Manjit. ·Headache Group, Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N3BG, UK. ·Curr Pain Headache Rep · Pubmed #21271306.

ABSTRACT: Cluster headache is a highly disabling primary headache disorder, characterized by unilateral headache attacks occurring in association with cranial autonomic symptoms. Serotonergic agents, such as the ergot alkaloids, have traditionally been used for the acute and preventive treatment of cluster headache and other primary headaches. Although it initially was thought that their efficacy was due solely to the vasoconstriction of extracranial cerebral vessels, new mechanisms of action of these drugs have been ascertained as a consequence of advances in elucidation of the pathogenesis of primary headaches and the development of triptans. This article reviews the current knowledge about serotonergic agonists and antagonists used in the management of cluster headache, focusing on their mechanisms of action and on the possible role of serotonin system dysfunction in this complex disorder.

111 Review The bedside assessment of vertigo. 2010

Kaski, Diego / Seemungal, Barry M. ·Department of Neuro-otology, Imperial College London, Charing Cross Hospital. d.kaski@ic.ac.uk ·Clin Med (Lond) · Pubmed #20849021.

ABSTRACT: -- No abstract --

112 Review Prevention and treatment of menstrual migraine. 2010

MacGregor, E Anne. ·The City of London Migraine Clinic, England, UK. anne.macgregor@migraineclinic.org.uk ·Drugs · Pubmed #20836574.

ABSTRACT: Migraine is a prevalent headache disorder affecting three times more women than men during the reproductive years. Menstruation is a significant risk factor for migraine, with attacks most likely to occur on or between 2 days before the onset of menstruation and the first 3 days of bleeding. Although menstrual migraine has been recognized for many years, diagnostic criteria have only recently been published. These have enabled better comparison of the efficacy of drugs for this condition. Acute treatment, if effective, may be all that is necessary for control. Evidence of efficacy, with acceptable safety and tolerability, exists for sumatriptan 50 and 100 mg, mefenamic acid 500 mg, rizatriptan 10 mg and combination sumatriptan/naproxen 85 mg/500 mg. However, there is evidence that menstrual attacks are more severe, longer, less responsive to treatment, more likely to relapse and associated with greater disability than attacks at other times of the cycle. Prophylactic strategies can reduce the frequency and severity of attacks and acute treatment is more effective. Predictable menstrual attacks offer the opportunity for perimenstrual prophylaxis taken only during the time of increased migraine incidence. There is grade B evidence of efficacy for short-term prophylaxis with transcutaneous estradiol 1.5 mg, frovatriptan 2.5 mg twice daily and naratriptan 1 mg twice daily. Contraceptive strategies offer the opportunity for treating menstrual migraine in women who also require effective contraception.

113 Review Glutamatergic fine tuning with ADX-10059: a novel therapeutic approach for migraine? 2010

Marin, Juana C A / Goadsby, Peter J. ·The National Hospital for Neurology and Neurosurgery, Institute of Neurology, Headache Group, Queen Square, London, UK. ·Expert Opin Investig Drugs · Pubmed #20218930.

ABSTRACT: IMPORTANCE OF THE FIELD: Migraine is an episodic, substantially inherited brain disorder affecting 15% of adults in Western Europe and North America, and is one of the commonest reasons for patients to see their physicians. While the World Health Organization considers that severe migraine can be as disabling as quadriplegia, unfortunately the condition remains undertreated. Until the 1990s, specific migraine therapies were limited to ergot derivatives. AREAS COVERED IN THIS REVIEW: The triptans, serotonin 5-HT(1B/1D) receptor agonists, revolutionized the acute management of migraine patients. However, although the triptans are generally effective and safe, not all patients can take them and many do not respond especially to oral therapies. Recently, progress has been made on the therapeutic front, particularly with new acute treatments. This review will focus on the therapeutic potential of ADX10059, a metabotropic glutamate receptor 5, negative allosteric modulator (mGluR5 NAM), in migraine. Data from a proof-of-concept study in episodic migraineurs demonstrated a significant improvement following acute treatment. A large European multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study is currently investigating the efficacy, safety and tolerability of the compound for migraine prevention. WHAT THE READER WILL GAIN: The reader will have the basic principles of migraine management and the potential for glutamate-targeted approaches. TAKE HOME MESSAGE: Targeting glutamatergic transmission in migraine may provide a novel preventive therapy that is effective and well-tolerated.

114 Review Pain channelopathies. 2010

Cregg, Roman / Momin, Aliakmal / Rugiero, Francois / Wood, John N / Zhao, Jing. ·Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK. ·J Physiol · Pubmed #20142270.

ABSTRACT: Pain remains a major clinical challenge, severely afflicting around 6% of the population at any one time. Channelopathies that underlie monogenic human pain syndromes are of great clinical relevance, as cell surface ion channels are tractable drug targets. The recent discovery that loss-of-function mutations in the sodium channel Nav1.7 underlie a recessive pain-free state in otherwise normal people is particularly significant. Deletion of channel-encoding genes in mice has also provided insights into mammalian pain mechanisms. Ion channels expressed by immune system cells (e.g. P2X7) have been shown to play a pivotal role in changing pain thresholds, whilst channels involved in sensory transduction (e.g. TRPV1), the regulation of neuronal excitability (potassium channels), action potential propagation (sodium channels) and neurotransmitter release (calcium channels) have all been shown to be potentially selective analgesic drug targets in some animal pain models. Migraine and visceral pain have also been associated with voltage-gated ion channel mutations. Insights into such channelopathies thus provide us with a number of potential targets to control pain.

115 Review Management of the patient with chronic dizziness. 2010

Bronstein, A M / Lempert, Th. ·Neuro-otology Unit, Division of Neuroscience and Mental Health, Imperial College London, Charing Cross Hospital, London, UK. a.bronstein@imperial.ac.uk ·Restor Neurol Neurosci · Pubmed #20086285.

ABSTRACT: In this review we present a pragmatic approach to the patient with chronic vestibular symptoms. Even in the chronic patient a retrospective diagnosis should be attempted, in order to establish how the patient reached the current situation. Simple questions are likely to establish if the chronic dizzy symptoms started as benign paroxysmal positional vertigo (BPPV), vestibular neuritis, vestibular migraine, Meniere's disease or as a brainstem stroke. Then it is important to establish if the original symptoms are still present, in which case they need to be treated (e.g. repositioning maenouvres for BPPV, migraine prophylaxis) or if you are only dealing with chronic dizzy symptoms. In addition the doctor or physiotherapist needs to establish if the process of central vestibular compensation has been impeded due to additional clinical problems, e.g. visual problems (squints, cataract operation), proprioceptive deficit (neuropathy due to diabetes or alcohol), additional neurological or orthopaedic problems, lack of mobility or confidence, such as fear of falling or psychological disorders. A general neurological examination should also be conducted, amongst other reasons to make sure your patient's ;chronic dizziness' is not due to a neurological gait disorder. Treatment of the syndrome of chronic dizziness is multidisciplinary but rehabilitation and simple counselling should be available to all patients. In contrast, vestibular suppressants or tranquilisers should be reduced or, if possible, stopped.

116 Clinical Trial Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. 2019

Croop, Robert / Goadsby, Peter J / Stock, David A / Conway, Charles M / Forshaw, Micaela / Stock, Elyse G / Coric, Vladimir / Lipton, Richard B. ·Biohaven Pharmaceuticals, New Haven, CT, USA. Electronic address: robert.croop@biohavenpharma.com. · NIHR-Wellcome Trust King's Clinical Research Facility, King's College Hospital/SLaM Biomedical Research Centre, King's College London, UK; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. · Biohaven Pharmaceuticals, New Haven, CT, USA. · Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA. ·Lancet · Pubmed #31311674.

ABSTRACT: BACKGROUND: Rimegepant, a small molecule calcitonin gene-related peptide receptor antagonist, has shown efficacy in the acute treatment of migraine using a standard tablet formulation. The objective of this trial was to compare the efficacy, safety, and tolerability of a novel orally disintegrating tablet formulation of rimegepant at 75 mg with placebo in the acute treatment of migraine. METHODS: In this double-blind, randomised, placebo-controlled, multicentre phase 3 trial, adults aged 18 years or older with history of migraine of at least 1 year were recruited to 69 study centres in the USA. Participants were randomly assigned to receive rimegepant (75 mg orally disintegrating tablet) or placebo and instructed to treat a single migraine attack of moderate or severe pain intensity. The randomisation was stratified by the use of prophylactic medication (yes or no), and was carried out using an interactive web response system that was accessed by each clinical site. All participants, investigators, and the sponsor were masked to treatment group assignment. The coprimary endpoints were freedom from pain and freedom from the most bothersome symptom at 2 h postdose. The efficacy analyses used the modified intention-to-treat population, which included all patients who were randomly assigned, had a migraine attack with pain of moderate or severe intensity, took a dose of rimegepant or placebo, and had at least one efficacy assessment after administration of the dose. The safety analyses included all randomly assigned participants who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, number NCT03461757, and is closed to accrual. FINDINGS: Between Feb 27 and Aug 28, 2018, 1811 participants were recruited and assessed for eligibility. 1466 participants were randomly assigned to the rimegepant (n=732) or placebo (n=734) groups, of whom 1375 received treatment with rimegepant (n=682) or placebo (n=693), and 1351 were evaluated for efficacy (rimegepant n=669, placebo n=682). At 2 h postdose, rimegepant orally disintegrating tablet was superior to placebo for freedom from pain (21% vs 11%, p<0·0001; risk difference 10, 95% CI 6-14) and freedom from the most bothersome symptom (35% vs 27%, p=0·0009; risk difference 8, 95% CI 3-13). The most common adverse events were nausea (rimegepant n=11 [2%]; placebo n=3 [<1%]) and urinary tract infection (rimegepant n=10 [1%]; placebo n=4 [1%]). One participant in each treatment group had a transaminase concentration of more than 3 × the upper limit of normal; neither was related to study medication, and no elevations in bilirubin greater than 2 × the upper limit of normal were reported. Treated participants reported no serious adverse events. INTERPRETATION: In the acute treatment of migraine, a single 75 mg dose of rimegepant in an orally disintegrating tablet formulation was more effective than placebo. Tolerability was similar to placebo, with no safety concerns. FUNDING: Biohaven Pharmaceuticals.

117 Clinical Trial Rimegepant, an Oral Calcitonin Gene-Related Peptide Receptor Antagonist, for Migraine. 2019

Lipton, Richard B / Croop, Robert / Stock, Elyse G / Stock, David A / Morris, Beth A / Frost, Marianne / Dubowchik, Gene M / Conway, Charles M / Coric, Vladimir / Goadsby, Peter J. ·From the Departments of Neurology and Epidemiology and Population Health, Albert Einstein College of Medicine, and Montefiore Medical Center - both in Bronx, NY (R.B.L.) · Biohaven Pharmaceuticals, New Haven, CT (R.C., E.G.S., D.A.S., B.A.M., M.F., G.M.D., C.M.C., V.C.) · NIHR-Wellcome Trust King's Clinical Research Facility, King's College Hospital-South London and Maudsley Biomedical Research Centre, King's College London, London (P.J.G.) · and the University of California, San Francisco, San Francisco (P.J.G.). ·N Engl J Med · Pubmed #31291516.

ABSTRACT: BACKGROUND: Calcitonin gene-related peptide receptor has been implicated in the pathogenesis of migraine. Rimegepant is an orally administered, small-molecule, calcitonin gene-related peptide receptor antagonist that may be effective in acute migraine treatment. METHODS: In a multicenter, double-blind, phase 3 trial, we randomly assigned adults with at least a 1-year history of migraine and two to eight migraine attacks of moderate or severe intensity per month to receive rimegepant orally at a dose of 75 mg or matching placebo for the treatment of a single migraine attack. The primary end points were freedom from pain and freedom from the most bothersome symptom (other than pain) identified by the patient, both of which were assessed 2 hours after the dose of rimegepant or placebo was administered. RESULTS: A total of 1186 patients were randomly assigned to receive rimegepant (594 patients) or placebo (592 patients); of these, 537 patients in the rimegepant group and 535 patients in the placebo group could be evaluated for efficacy. The overall mean age of the patients evaluated for efficacy was 40.6 years, and 88.7% were women. In a modified intention-to-treat analysis, the percentage of patients who were pain-free 2 hours after receiving the dose was 19.6% in the rimegepant group and 12.0% in the placebo group (absolute difference, 7.6 percentage points; 95% confidence interval [CI], 3.3 to 11.9; P<0.001). The percentage of patients who were free from their most bothersome symptom 2 hours after the dose was 37.6% in the rimegepant group and 25.2% in the placebo group (absolute difference, 12.4 percentage points; 95% CI, 6.9 to 17.9; P<0.001). The most common adverse events were nausea and urinary tract infection. CONCLUSIONS: Treatment of a migraine attack with the oral calcitonin gene-related peptide receptor antagonist rimegepant resulted in a higher percentage of patients who were free of pain and free from their most bothersome symptom than placebo. (Funded by Biohaven Pharmaceuticals; ClinicalTrials.gov number, NCT03237845.).

118 Clinical Trial Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. 2018

Reuter, Uwe / Goadsby, Peter J / Lanteri-Minet, Michel / Wen, Shihua / Hours-Zesiger, Peggy / Ferrari, Michel D / Klatt, Jan. ·Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany. Electronic address: uwe.reuter@charite.de. · NIHR-Wellcome Trust, King's Clinical Research Facility, King's College London, London, UK. · Pain Department and FHU InvoPain, CHU Nice-Université Côte d'Azur, Nice, France; INSERM U1107 Migraine and Trigeminal Pain, Auvergne University, Clermont-Ferrand, France. · Novartis, East Hanover, NJ, USA. · Novartis Pharma, Basel, Switzerland. · Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands. ·Lancet · Pubmed #30360965.

ABSTRACT: BACKGROUND: A substantial proportion of patients with migraine does not respond to, or cannot tolerate, oral preventive treatments. Erenumab is a novel CGRP-receptor antibody with preventive efficacy in migraine. We assessed its efficacy and tolerability in patients with episodic migraine in whom previous treatment with two-to-four migraine preventives had been unsuccessful. METHODS: LIBERTY was a 12-week, double-blind, placebo-controlled randomised study at 59 sites in 16 countries. Eligible patients were aged 18-65 years and had a history of episodic migraine with or without aura for at least 12 months, had migraine for an average of 4-14 days per month during the 3 months before screening, and had been treated unsuccessfully (in terms of either efficacy or tolerability, or both) with between two and four preventive treatments. Eligible participants were randomly assigned (1:1) to receive either erenumab 140 mg (via two 70 mg injections) or placebo every 4 weeks subcutaneously for 12 weeks. Randomisation was by interactive response technology and was stratified by monthly frequency of migraine headache (4-7 vs 8-14 migraine days per month) during the baseline phase. Cenduit generated the randomisation list and assigned participants to groups. Participants, investigators, people doing various assessments, and the study sponsor were masked to treatment assignment. The primary endpoint was the proportion of patients achieving a 50% or greater reduction in the mean number of monthly migraine days during weeks 9-12. Efficacy was measured in the full analysis set, which included all randomly assigned patients who started their assigned treatment and completed at least one post-baseline monthly migraine day measurement. Safety and tolerability were assessed by recording adverse events and by physical examination, assessment of vital signs, clinical laboratory assessments, and electrocardiography. Safety was assessed in all randomly assigned patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT03096834. The trial is closed to new participants, but the open-label extension phase is ongoing. FINDINGS: Between March 20, 2017, and Oct 27, 2017, 246 participants were randomly assigned, 121 to the erenumab group and 125 to the placebo group. 95 of 246 (39%) participants had previously unsuccessfully tried two preventive drugs, 93 (38%) had tried three, and 56 (23%) had tried four. At week 12, 36 (30%) patients in the erenumab had a 50% or greater reduction from baseline in the mean number of monthly migraine days, compared with 17 (14%) in the placebo group (odds ratio 2·7 [95% CI 1·4-5·2]; p=0·002). The tolerability and safety profiles of erenumab and placebo were similar. The most frequent treatment-emergent adverse event was injection site pain, which occurred in seven (6%) participants in both groups. INTERPRETATION: Compared with placebo, erenumab was efficacious in patients with episodic migraine who previously did not respond to or tolerate between two and four previous migraine preventive treatments. Erenumab might be an option for patients with difficult-to-treat migraine who have high unmet needs and few treatment options. FUNDING: Novartis Pharma.

119 Clinical Trial Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial. 2018

Skljarevski, Vladimir / Matharu, Manjit / Millen, Brian A / Ossipov, Michael H / Kim, Byung-Kun / Yang, Jyun Yan. ·1 Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA. · 2 National Hospital for Neurology and Neurosurgery, London, United Kingdom. · 3 Clinical Division, Syneos Health, Raleigh, NC, USA. · 4 Eulji General Hospital, Seoul, Republic of Korea. ·Cephalalgia · Pubmed #29848108.

ABSTRACT: Introduction Galcanezumab is a humanized monoclonal antibody binding calcitonin gene-related peptide, used for migraine prevention. Methods A global, double-blind, 6-month study of patients with episodic migraine was undertaken with 915 intent-to-treat patients randomized to monthly galcanezumab 120 mg (n = 231) or 240 mg (n = 223) or placebo (n = 461) subcutaneous injections. Primary endpoint was overall mean change from baseline in monthly migraine headache days. Key secondary endpoints were ≥50%,  ≥ 75%, and 100% response rates; monthly migraine headache days with acute migraine medication use; Patient Global Impression of Severity rating; the Role Function-Restrictive score of the Migraine-Specific Quality of Life Questionnaire. Results Mean monthly migraine headache days were reduced by 4.3 and 4.2 days by galcanezumab 120 and 240 mg, respectively, and 2.3 days by placebo. The group differences (95% CIs) versus placebo were 2.0 (-2.6, -1.5) and 1.9 (-2.4, -1.4), respectively. Both doses were superior to placebo for all key secondary endpoints. Injection site pain was the most common treatment-emergent adverse event, reported at similar rates in all treatment groups. Both galcanezumab doses had significantly more injection site reactions and injection site pruritus, and the 240 mg group had significantly more injection site erythema versus placebo. Conclusions Galcanezumab 120 or 240 mg given once monthly was efficacious, safe, and well tolerated. Study identification EVOLVE-2; NCT02614196; https://clinicaltrials.gov/ct2/show/NCT02614196 . Trial Registration NCT02614196.

120 Clinical Trial Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine: A Randomized Clinical Trial. 2018

Dodick, David W / Silberstein, Stephen D / Bigal, Marcelo E / Yeung, Paul P / Goadsby, Peter J / Blankenbiller, Tricia / Grozinski-Wolff, Melissa / Yang, Ronghua / Ma, Yuju / Aycardi, Ernesto. ·Mayo Clinic Arizona, Phoenix. · Jefferson Headache Center, Thomas Jefferson University, Philadelphia, Pennsylvania. · Teva Pharmaceuticals, Frazer, Pennsylvania. · NIHR-Wellcome Trust King's Clinical Research Facility, King's College London, London, England. ·JAMA · Pubmed #29800211.

ABSTRACT: Importance: Fremanezumab, a fully humanized monoclonal antibody that targets calcitonin gene-related peptide, may be effective for treating episodic migraine. Objective: To assess the efficacy of fremanezumab compared with placebo for prevention of episodic migraine with a monthly dosing regimen or a single higher dose. Design and Setting: Randomized, double-blind, placebo-controlled, parallel-group trial conducted at 123 sites in 9 countries from March 23, 2016 (first patient randomized), to April 10, 2017, consisting of a screening visit, 28-day pretreatment period, 12-week treatment period, and final evaluation at week 12. Participants: Study participants were aged 18 to 70 years with episodic migraine (6-14 headache days, with at least 4 migraine days, during 28-day pretreatment period). Patients who had previous treatment failure with 2 classes of migraine-preventive medication were excluded. Interventions: Patients were randomized 1:1:1 to receive subcutaneous monthly dosing of fremanezumab (n = 290; 225 mg at baseline, week 4, and week 8); a single higher dose of fremanezumab, as intended to support a quarterly dose regimen (n = 291; 675 mg of fremanezumab at baseline; placebo at weeks 4 and 8); or placebo (n = 294; at baseline, week 4, and week 8). Main Outcomes and Measures: The primary end point was mean change in mean number of monthly migraine days during the 12-week period after the first dose. Results: Among 875 patients who were randomized (mean age, 41.8 [SD, 12.1] years; 742 women [85%]), 791 (90.4%) completed the trial. From baseline to 12 weeks, mean migraine days per month decreased from 8.9 days to 4.9 days in the fremanezumab monthly dosing group, from 9.2 days to 5.3 days in the fremanezumab single-higher-dose group, and from 9.1 days to 6.5 days in the placebo group. This resulted in a difference with monthly dosing vs placebo of -1.5 days (95% CI, -2.01 to -0.93 days; P < .001) and with single higher dosing vs placebo of -1.3 days (95% CI, -1.79 to -0.72 days; P < .001). The most common adverse events that led to discontinuation were injection site erythema (n = 3), injection site induration (n = 2), diarrhea (n = 2), anxiety (n = 2), and depression (n = 2). Conclusions and Relevance: Among patients with episodic migraine in whom multiple medication classes had not previously failed, subcutaneous fremanezumab, compared with placebo, resulted in a statistically significant 1.3- to 1.5-day reduction in the mean number of monthly migraine days over a 12-week period. Further research is needed to assess effectiveness against other preventive medications and in patients in whom multiple preventive drug classes have failed and to determine long-term safety and efficacy. Trial Registration: clinicaltrials.gov Identifier: NCT02629861.

121 Clinical Trial Effect of Different Doses of Galcanezumab vs Placebo for Episodic Migraine Prevention: A Randomized Clinical Trial. 2018

Skljarevski, Vladimir / Oakes, Tina M / Zhang, Qi / Ferguson, Margaret B / Martinez, James / Camporeale, Angelo / Johnson, Kirk W / Shan, Qiuling / Carter, Jeffrey / Schacht, Aaron / Goadsby, Peter J / Dodick, David W. ·Eli Lilly and Company, Indianapolis, Indiana. · Eli Lilly Italia, Sesto Fiorentino, Italy. · National Institute for Health Research-Wellcome Trust King's Clinical Research Facility, King's College London, London, UK. · Department of Neurology, University of California, San Francisco. · Department of Neurology, Mayo Clinic, Scottsdale, Arizona. ·JAMA Neurol · Pubmed #29255900.

ABSTRACT: Importance: Galcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention. Objective: To assess whether at least 1 dose of galcanezumab was superior to placebo for episodic migraine prevention. Design, Setting, and Participants: A randomized clinical trial was conducted in the United States (July 7, 2014, to August 19, 2015) in clinics of 37 licensed physicians with a specialty including, but not limited to, psychiatry, neurology, internal medicine, and primary care. Subcutaneous injections of galcanezumab, 5, 50, 120, or 300 mg, or placebo were given monthly during the 3-month treatment period. A total of 936 patients were assessed; 526 did not meet study entry or baseline criteria and 410 patients were randomly assigned to receive placebo or galcanezumab. Analyses were conducted on an intent-to-treat population, which included all patients who were randomized and received at least 1 dose of study drug. Interventions: Short-term migraine treatments were allowed as needed except for opioids or barbiturates. Main Outcomes and Measures: To determine if at least 1 of the 4 doses of galcanezumab tested was superior to placebo for migraine prevention measured by the mean change from baseline in the number of migraine headache days 9 weeks to 12 weeks after randomization. Results: Of the 936 patients assessed, 410 met entry criteria (aged 18-65 years with 4-14 migraine headache days per month and migraine onset prior to age 50 years) and were randomized to receive placebo or galcanezumab. For the primary end point, galcanezumab, 120 mg, significantly reduced migraine headache days compared with placebo (99.6% posterior probability -4.8 days; 90% BCI, -5.4 to -4.2 days vs 95% superiority threshold [Bayesian analysis] -3.7 days; 90% BCI, -4.1 to -3.2 days). Adverse events reported by 5% or more of patients in at least 1 galcanezumab dose group and more frequently than placebo included injection-site pain, upper respiratory tract infection, nasopharyngitis, dysmenorrhea, and nausea. Conclusions and Relevance: Monthly subcutaneous injections of galcanezumab, both 120 mg and 300 mg, demonstrated efficacy (repeated-measures analysis) for the preventive treatment of migraine and support further development in larger phase 3 studies. All dosages were safe and well tolerated for the preventive treatment of episodic migraine. Trial Registration: clinicaltrials.gov Identifier: NCT02163993.

122 Clinical Trial Non-invasive vagus nerve stimulation for the management of refractory primary chronic headaches: A real-world experience. 2018

Trimboli, Michele / Al-Kaisy, Adnan / Andreou, Anna P / Murphy, Madeleine / Lambru, Giorgio. ·1 The Headache Centre, Guy's and St Thomas' NHS Foundation Trust, London, UK. · 2 Pain Management and Neuromodulation Centre, Guy's and St Thomas' NHS Foundation Trust, London, UK. · 3 Headache Research, Wolfson CARD, Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, UK. ·Cephalalgia · Pubmed #28899205.

ABSTRACT: Background Non-invasive vagus nerve stimulation has initial evidence of efficacy in migraine and cluster headache. However, little is known about its role in the management of refractory chronic headaches. Methods We evaluated the preventive and abortive effects of non-invasive vagus nerve stimulation in 41 consecutive patients with refractory primary chronic headaches in an open-label prospective clinical audit. Headache diaries were used to collect clinical information. Those who obtained at least 30% reduction in headache days/episodes after three months of treatment were considered responders and were offered treatment continuation. Results Twenty-three patients with chronic migraine, 12 with chronic cluster headache, four with hemicrania continua and two with short-lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA) were treated. Two of 23 chronic migraine patients, one of 12 chronic cluster headache patients, and two of four hemicrania continua patients were considered responders. None of the patients with SUNA benefited from the therapy. Two chronic migraine patients were able to reduce the pain severity of moderate migraines with non-invasive vagus nerve stimulation. Conclusion Non-invasive vagus nerve stimulation may not constitute an effective acute nor preventive treatment in refractory chronic primary headaches. The encouraging effect in hemicrania continua warrants further evaluation in larger studies.

123 Clinical Trial A Controlled Trial of Erenumab for Episodic Migraine. 2017

Goadsby, Peter J / Reuter, Uwe / Hallström, Yngve / Broessner, Gregor / Bonner, Jo H / Zhang, Feng / Sapra, Sandhya / Picard, Hernan / Mikol, Daniel D / Lenz, Robert A. ·From the National Institute for Health Research-Wellcome Trust King's Clinical Research Facility, King's College Hospital, London (P.J.G.) · the Department of Neurology, Charité Universitätsmedizin Berlin, Berlin (U.R.) · the Neuro Center, St. Göran Hospital, Stockholm (Y.H.) · the Department of Neurology, Headache Outpatient Clinic, Medical University of Innsbruck, Innsbruck, Austria (G.B.) · Mercy Research, St. Louis (J.H.B.) · and the Departments of Global Biostatistical Science (F.Z.), Global Health Economics (S.S.), and Global Development (H.P., D.D.M., R.A.L.), Amgen, Thousand Oaks, CA. ·N Engl J Med · Pubmed #29171821.

ABSTRACT: BACKGROUND: We tested erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, for the prevention of episodic migraine. METHODS: We randomly assigned patients to receive a subcutaneous injection of either erenumab, at a dose of 70 mg or 140 mg, or placebo monthly for 6 months. The primary end point was the change from baseline to months 4 through 6 in the mean number of migraine days per month. Secondary end points were a 50% or greater reduction in mean migraine days per month, change in the number of days of use of acute migraine-specific medication, and change in scores on the physical-impairment and everyday-activities domains of the Migraine Physical Function Impact Diary (scale transformed to 0 to 100, with higher scores representing greater migraine burden on functioning). RESULTS: A total of 955 patients underwent randomization: 317 were assigned to the 70-mg erenumab group, 319 to the 140-mg erenumab group, and 319 to the placebo group. The mean number of migraine days per month at baseline was 8.3 in the overall population; by months 4 through 6, the number of days was reduced by 3.2 in the 70-mg erenumab group and by 3.7 in the 140-mg erenumab group, as compared with 1.8 days in the placebo group (P<0.001 for each dose vs. placebo). A 50% or greater reduction in the mean number of migraine days per month was achieved for 43.3% of patients in the 70-mg erenumab group and 50.0% of patients in the 140-mg erenumab group, as compared with 26.6% in the placebo group (P<0.001 for each dose vs. placebo), and the number of days of use of acute migraine-specific medication was reduced by 1.1 days in the 70-mg erenumab group and by 1.6 days in the 140-mg erenumab group, as compared with 0.2 days in the placebo group (P<0.001 for each dose vs. placebo). Physical-impairment scores improved by 4.2 and 4.8 points in the 70-mg and 140-mg erenumab groups, respectively, as compared with 2.4 points in the placebo group (P<0.001 for each dose vs. placebo), and everyday-activities scores improved by 5.5 and 5.9 points in the 70-mg and 140-mg erenumab groups, respectively, as compared with 3.3 points in the placebo group (P<0.001 for each dose vs. placebo). The rates of adverse events were similar between erenumab and placebo. CONCLUSIONS: Erenumab administered subcutaneously at a monthly dose of 70 mg or 140 mg significantly reduced migraine frequency, the effects of migraines on daily activities, and the use of acute migraine-specific medication over a period of 6 months. The long-term safety and durability of the effect of erenumab require further study. (Funded by Amgen and Novartis; STRIVE ClinicalTrials.gov number, NCT02456740 .).

124 Clinical Trial Fremanezumab for the Preventive Treatment of Chronic Migraine. 2017

Silberstein, Stephen D / Dodick, David W / Bigal, Marcelo E / Yeung, Paul P / Goadsby, Peter J / Blankenbiller, Tricia / Grozinski-Wolff, Melissa / Yang, Ronghua / Ma, Yuju / Aycardi, Ernesto. ·From the Jefferson Headache Center, Thomas Jefferson University, Philadelphia (S.D.S.), and Teva Pharmaceuticals, Frazer (M.E.B., P.P.Y., T.B., M.G.-W., R.Y., Y.M., E.A.) - both in Pennsylvania · Mayo Clinic Arizona, Phoenix (D.W.D.) · and National Institute for Health Research-Wellcome Trust King's Clinical Research Facility, King's College London, London (P.J.G.). ·N Engl J Med · Pubmed #29171818.

ABSTRACT: BACKGROUND: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine. METHODS: In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on ≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), or matching placebo. Both fremanezumab and placebo were administered by means of subcutaneous injection. The primary end point was the mean change from baseline in the average number of headache days (defined as days in which headache pain lasted ≥4 consecutive hours and had a peak severity of at least a moderate level or days in which acute migraine-specific medication [triptans or ergots] was used to treat a headache of any severity or duration) per month during the 12 weeks after the first dose. RESULTS: Of 1130 patients enrolled, 376 were randomly assigned to fremanezumab quarterly, 379 to fremanezumab monthly, and 375 to placebo. The mean number of baseline headache days (as defined above) per month was 13.2, 12.8, and 13.3, respectively. The least-squares mean (±SE) reduction in the average number of headache days per month was 4.3±0.3 with fremanezumab quarterly, 4.6±0.3 with fremanezumab monthly, and 2.5±0.3 with placebo (P<0.001 for both comparisons with placebo). The percentage of patients with a reduction of at least 50% in the average number of headache days per month was 38% in the fremanezumab-quarterly group, 41% in the fremanezumab-monthly group, and 18% in the placebo group (P<0.001 for both comparisons with placebo). Abnormalities of hepatic function occurred in 5 patients in each fremanezumab group (1%) and 3 patients in the placebo group (<1%). CONCLUSIONS: Fremanezumab as a preventive treatment for chronic migraine resulted in a lower frequency of headache than placebo in this 12-week trial. Injection-site reactions to the drug were common. The long-term durability and safety of fremanezumab require further study. (Funded by Teva Pharmaceuticals; ClinicalTrials.gov number, NCT02621931 .).

125 Clinical Trial Erenumab (AMG 334) in episodic migraine: Interim analysis of an ongoing open-label study. 2017

Ashina, Messoud / Dodick, David / Goadsby, Peter J / Reuter, Uwe / Silberstein, Stephen / Zhang, Feng / Gage, Julia R / Cheng, Sunfa / Mikol, Daniel D / Lenz, Robert A. ·From the Department of Neurology (M.A.), Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark · Department of Neurology (D.D.), Mayo Clinic, Scottsdale, AZ · NIHR-Wellcome Trust King's Clinical Research Facility (P.J.G.), Kings College London, UK · Department of Neurology (U.R.), Charité Universitätsmedizin Berlin, Germany · Jefferson Headache Center (S.S.), Thomas Jefferson University, Philadelphia, PA · Amgen Inc. (F.Z., S.C., D.D.M., R.A.L.), Thousand Oaks · and Gage Medical Writing, LLC (J.R.G.), Moorpark, CA. ·Neurology · Pubmed #28835404.

ABSTRACT: OBJECTIVE: To assess long-term safety and efficacy of anti-calcitonin gene-related peptide receptor erenumab in patients with episodic migraine (EM). METHODS: Patients enrolled in a 12-week, double-blind, placebo-controlled clinical trial (NCT01952574) who continued in an open-label extension (OLE) study will receive erenumab 70 mg every 4 weeks for up to 5 years. This preplanned interim analysis, conducted after all participants had completed the 1-year open-label follow-up, evaluated changes in monthly migraine days (MMD), achievement of ≥50%, ≥75%, and 100% reductions, Headache Impact Test (HIT-6) score, Migraine-Specific Quality of Life (MSQ), Migraine Disability Assessment (MIDAS), and safety. Data reported as observed without imputation for missing data. RESULTS: Of 472 patients enrolled in the parent study, 383 continued in the OLE with a median exposure to erenumab of 575 days (range 28-822 days). Mean (SD) MMD were 8.8 (2.6) at parent study baseline, 6.3 (4.2) at week 12 (beginning of OLE), and 3.7 (4.0) at week 64 (mean change from baseline [reduction] of 5.0 days). At week 64, 65%, 42%, and 26% achieved ≥50%, ≥75%, and 100% reduction in MMD, respectively. Mean HIT-6 scores were 60.2 (6.3) at baseline and 51.7 (9.2) at week 64. MSQ and MIDAS improvements from baseline were maintained through week 64. Safety profiles during the OLE were similar to those in the double-blind phase, which overall were similar to placebo. CONCLUSIONS: One-year efficacy, supported by functional improvements and favorable safety and tolerability profiles, supports further investigation of erenumab as a preventive treatment in patients with EM. CLINICALTRIALSGOV IDENTIFIER: NCT01952574. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with episodic migraine, erenumab reduces long-term MMD and improves headache-related disability and migraine-specific quality of life.

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