Galcanezumab in patients with episodic migraine: results from the open-label period of the phase 3 PERSIST study.

BACKGROUND: The phase 3 randomized PERSIST study demonstrated the efficacy and tolerability of galcanezumab, a humanized anti-calcitonin gene-related peptide (CGRP) monoclonal antibody for prevention of episodic migraines. We present findings from the open-label extension (OLE) of PERSIST, which evaluated the long-term efficacy and safety of galcanezumab in patients from China, India, and Russia. METHODS: Patients completing the 3-month double-blind period of PERSIST were eligible for the 3-month OLE. Patients previously randomized to galcanezumab (GMB/GMB group) continued to receive galcanezumab 120 mg at all three visits during the OLE whereas patients randomized to placebo received a 240 mg loading dose of galcanezumab and then two 120 mg doses (PBO/GMB group). The primary outcome was the mean change (from double-blind baseline) in the number of monthly migraine headache days (MHDs) to month 6. Other endpoints included percent reduction in monthly MHDs from double-blind baseline to month 6, functional outcomes, safety and tolerability. RESULTS: Overall, 99% of patients completing the double-blind period entered the OLE, and 96% completed through month 6. Patients in the GMB/GMB group achieved continued improvements in efficacy, with the reduction from baseline in the mean number of monthly MHDs, and slightly increasing from 4.01 days at the end of the double-blind period to 4.62 at the end of the OLE. Of patients who were ≥ 50% responders to galcanezumab at month 3, 66% maintained this response through to month 6. Patients in the PBO/GMB group experienced a rapid reduction in the number of monthly MHDs after initiation of galcanezumab, with a mean reduction from baseline of 4.56 days by month 6. The long-term benefits of galcanezumab were also supported by improvements in other efficacy and functional endpoints. All safety findings were consistent with the known long-term safety profile of galcanezumab; no patients experienced a treatment-related serious adverse event. CONCLUSIONS: Galcanezumab was efficacious and well-tolerated in patients with episodic migraine from China, India and Russia, for up to 6 months. TRIAL REGISTRATION: ClinicalTrisABSTRACT_pals.gov NCT03963232, registered May 24, 2019.

Diagnosis and management of migraine in ten steps.

Migraine is a disabling primary headache disorder that directly affects more than one billion people worldwide. Despite its widespread prevalence, migraine remains under-diagnosed and under-treated. To support clinical decision-making, we convened a European panel of experts to develop a ten-step approach to the diagnosis and management of migraine. Each step was established by expert consensus and supported by a review of current literature, and the Consensus Statement is endorsed by the European Headache Federation and the European Academy of Neurology. In this Consensus Statement, we introduce typical clinical features, diagnostic criteria and differential diagnoses of migraine. We then emphasize the value of patient centricity and patient education to ensure treatment adherence and satisfaction with care provision. Further, we outline best practices for acute and preventive treatment of migraine in various patient populations, including adults, children and adolescents, pregnant and breastfeeding women, and older people. In addition, we provide recommendations for evaluating treatment response and managing treatment failure. Lastly, we discuss the management of complications and comorbidities as well as the importance of planning long-term follow-up.

Need of guidance in disabling and chronic migraine identification in the primary care setting, results from the european MyLife anamnesis survey.

BACKGROUND: Migraine affects 80.8 million people in Western Europe and is the first cause of disability among people between ages 15 and 49 worldwide. Despite being a highly prevalent and disabling condition, migraine remains under-diagnosed and poorly managed. METHODS: An international, online survey was conducted among 201 general practitioners (GPs) from 5 European countries (France, Germany, Italy, Spain and the UK) who are experienced in the management of headache disorders. RESULTS: The majority of GPs (82%) did not refer patients with chronic migraine (CM) to migraine specialists. Among those patients, the participants estimated that around 55% received preventive medication. Some differences between countries were observed regarding referral rate and prescription of preventive treatment. Most GPs (87%) reported a lack of training or the need to be updated on CM management. Accordingly, 95% of GPs considered that a migraine anamnesis guide could be of use. Overall, more than 95% of GPs favoured the use of a patient diary, a validated diagnostic tool and a validated scale to assess impact of migraine on patients' daily life. Similarly, 96% of the GPs considered that the inclusion of warning features (red flags) in an anamnesis guide would be useful and 90% favoured inclusion of referral recommendations. CONCLUSIONS: The results from this survey indicate that more education on diagnosis and management of CM is needed in primary care. Better knowledge on the recognition and management of migraine in primary care would improve both prognosis and diagnosis and reduce impact of migraine on patients' lives, healthcare utilization and societal burden.

Current clinical practice in disabling and chronic migraine in the primary care setting: results from the European My-LIFE anamnesis survey.

BACKGROUND: Migraine is a prevalent and disabling headache disorder that affects more than 1.04 billion individuals world-wide. It can result in reduction in quality of life, increased disability, and high socio-economic burden. Nevertheless, and despite the availability of evidence-based national and international guidelines, the management of migraine patients often remains suboptimal, especially for chronic migraine (CM) patients. METHODS: My-LIFE anamnesis project surveyed 201 General practitioners (GPs) from 5 European countries (France, Germany, Italy, Spain, and the UK) with the aim of understanding chronic migraine (CM) patients' management in the primary care setting. RESULTS: In our survey, GPs diagnosed episodic migraine (EM) more often than CM (87% vs 61%, p < 0.001). We found that many CM patients were not properly managed or referred to specialists, in contrast to guidelines recommendations. The main tools used by primary-care physicians included clinical interview, anamnesis guide, and patient diary. Tools used at the first visit differed from those used at follow-up visits. Up to 82% of GPs reported being responsible for management of patients diagnosed with disabling or CM and did not refer them to a specialist. Even when the GP had reported referring CM patients to a specialist, 97% of them were responsible for their follow-up. Moreover, the treatment prescribed, both acute and preventive, was not in accordance with local and international recommendations. GPs reported that they evaluated the efficacy of the treatment prescribed mainly through patient perception, and the frequency of follow-up visits was not clearly established in the primary care setting. These results suggest that CM is underdiagnosed and undertreated; thereby its management is suboptimal in the primary care. CONCLUSIONS: There is a need of guidance in the primary care setting to both leverage the management of CM patients and earlier referral to specialists, when appropriate.

Functional connectivity studies in migraine: what have we learned?

BACKGROUND: Resting-state functional connectivity (FC) MRI has widely been used to understand migraine pathophysiology and to identify an imaging marker of the disorder. Here, we review what we have learned from FC studies. METHODS: We performed a literature search on the PubMed website for original articles reporting data obtained from conventional resting-state FC recording in migraine patients compared with healthy controls or during and outside of migraine attacks in the same patients. RESULTS: We found 219 articles and included 28 in this review after screening for inclusion and exclusion criteria. Twenty-five studies compared migraine patients with healthy controls, whereas three studies investigated migraine patients during and outside of attacks. In the studies of interictal migraine more alterations of more than 20 FC networks (including amygdala, caudate nucleus, central executive, cerebellum, cuneus, dorsal attention network, default mode, executive control, fronto-parietal, hypothalamus, insula, neostriatum, nucleus accumbens, occipital lobe, periaqueductal grey, prefrontal cortex, salience, somatosensory cortex I, thalamus and visual) were reported. We found a poor level of reproducibility and no migraine specific pattern across these studies. CONCLUSION: Based on the findings in the present review, it seems very difficult to extract knowledge of migraine pathophysiology or to identify a biomarker of migraine. There is an unmet need of guidelines for resting-state FC studies in migraine, which promote the use of homogenous terminology, public availability of protocol and the a priori hypothesis in line with for instance randomized clinical trial guidelines.

Headache service quality: evaluation of quality indicators in 14 specialist-care centres.

BACKGROUND: The study was a collaboration between Lifting The Burden (LTB) and the European Headache Federation (EHF). Its aim was to evaluate the implementation of quality indicators for headache care Europe-wide in specialist headache centres (level-3 according to the EHF/LTB standard). METHODS: Employing previously-developed instruments in 14 such centres, we made enquiries, in each, of health-care providers (doctors, nurses, psychologists, physiotherapists) and 50 patients, and analysed the medical records of 50 other patients. Enquiries were in 9 domains: diagnostic accuracy, individualized management, referral pathways, patient's education and reassurance, convenience and comfort, patient's satisfaction, equity and efficiency of the headache care, outcome assessment and safety. RESULTS: Our study showed that highly experienced headache centres treated their patients in general very well. The centres were content with their work and their patients were content with their treatment. Including disability and quality-of-life evaluations in clinical assessments, and protocols regarding safety, proved problematic: better standards for these are needed. Some centres had problems with follow-up: many specialised centres operated in one-touch systems, without possibility of controlling long-term management or the success of treatments dependent on this. CONCLUSIONS: This first Europe-wide quality study showed that the quality indicators were workable in specialist care. They demonstrated common trends, producing evidence of what is majority practice. They also uncovered deficits that might be remedied in order to improve quality. They offer the means of setting benchmarks against which service quality may be judged. The next step is to take the evaluation process into non-specialist care (EHF/LTB levels 1 and 2).

Biomarkers of migraine: Part 1 - Genetic markers.

BACKGROUND: Migraine is a multifactorial socially significant disease affecting the peripheral and central nervous system. The diagnosis of "migraine" is still the only clinical, and additional methods of inspection are only required to avoid secondary headaches if certain "signs of danger". Accordingly, the search for biomarkers of migraine, confirming the diagnosis, rather than refuting others, is the leading vector in this scientific field. AIM: In this paper we have analyzed the literature data on the genetic markers associated with migraine. METHODS: List of genes was compiled using Pathway Studio 10® software and abstract database ResNet12 ® made by Elsevier. Addition search (last time on 15 March 2016) was performed by using PubMed or TargetInsights. Information about 185 polymorphic loci in 98 genes associated with migraine was extracted and described. RESULTS: The genes associated with migraine could be classified into 8 major groups: homeostasis of blood vessels - 26.5%, metabolism of neurotransmitters - 11.2%, transport and reception of neurotransmitters - 24.5%, neurogenesis - 5.1%, inflammation - 8.2%, sex hormones - 5.1%, ion channels and membrane potential - 11.2%, other - 8.2%. CONCLUSION: These findings parallel the range of mechanisms implicated in migraine pathogenesis.

Effects of MTHFR gene polymorphism on the clinical and electrophysiological characteristics of migraine.

BACKGROUND: It was previously shown that the MTHFR gene polymorphism correlated with an increased risk of migraine, particularly migraine with aura. The substitution of cytosine for thymine at the position 677 of the MTHFR gene leads to formation of the thermolabile form of the protein and development of hyperhomocysteinemia, which increases the probability of migraine. The purpose of this study was to determine whether the replacement of C677T in the gene MTHFR influenced any particular symptoms of the disease. METHODS: We have analyzed clinical and electrophysiological characteristics of 83 patients with migraine (migraine with aura (MA), 19 patients, and migraine without aura (MO), 64 patients, according to the ICHD-II (2003)) taking into account their genotypes of C677T variant of MTHFR. RESULTS: We have shown that MA was significantly more prevalent among the T-allele carriers (37.2%), as compared to the СС genotype patients (0%), р < 0.0001. Patients with TT genotype were not only more likely to have accompanying symptoms (significant differences were found only for photophobia), but also more sensitive to migraine attack triggers. In RP-VEP test results we observed a trend that the T-allele carriers were presented with the decreased N75/P100 amplitudes and a positive habituation index, as compared to the СС genotype patients. CONCLUSIONS: Thus, according to our data, the MTHFR genotypes are associated with several clinical and electrophysiological characteristics of migraine.