Session 1

Future of migraine management

Unmet needs in migraine management

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Jan Versijpt,
MD, PhD Neurologist, UZ Brussel, Belgium

Migraine management is not fully meeting the needs of patients and clinicians in three important areas: the role of monoclonal antibodies targeting CGRP, understanding the clinical role of neuromodulation and the development of biomarkers for migraine.
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Calcitonin family of peptides in migraine - beyond the CGRP

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Hashmat Ghanizada,
MD and PhD Fellow, Danish Headache Center, Rigshospitalet, Glostrup, Denmark

CGRP is one of a family of peptides which share varying degrees of affinity with their receptors. Treatments to prevent migraine are not effective in all patients; this may be due to the effects of other calcitonin peptides in the trigeminal ganglion, including amylin and adrenomedullin.
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Role of ion channels in the trigeminal system - relation to CGRP signalling

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Lars Edvinsson,
MD, DMSci Professor, of Internal Medicine, Lund University, Lund, Sweden, and Copenhagen University, Denmark

CGRP appears to induce pain by modulating the activity of Aδ fibres at the nodes of Ranvier, where they occur in close proximity to C fibres. It is likely that CGRP induces cAMP and protein kinase A (PKA), resulting in inhibition/activation of K+ channels. This may offer a new therapeutic target for future migraine treatments.
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Session 2 A

Medication overuse and aCGRP mAbs (Two views)

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Due to difference in Nordic compliance rules, session 2 is not available for Danish viewers

Migraine patients with MO can be treated with aCGRP mAbs without withdrawal

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Hans Christopher Diener,
Professor of Neurology and Chairman of the Department of Neurology, University Duisberg-Essen, Germany

A 2019 review of the prevention and treatment of medication overuse headache recommended that treatment for migraine attacks should be withdrawn, eliminating the use of acute medication for 2–4 weeks, reducing the frequency of acute medication to less than 2 days per week and switching from triptans or combination analgesics to NSAIDs.1 This, in light of what is now known about the efficacy safety of the anti-CGRP monoclonal antibodies, is outdated advice.
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Migraine patients with MO can be treated with aCGRP mAbs after withdrawal

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Rigmor Højland Jensen,
Dr Med, Professor of Neurology, Director of Danish Headache Center

Medication overuse headache (MOH) presents a therapeutic challenge. It is relatively common, with an overall prevalence in the general population of 1—2% but up to 50% in specialised headache clinics, and the cost of management is three times greater than for migraine. It is associated with depression and anxiety, disability and impaired quality of life.1 However, although this challenge is recognised there is uncertainty about the best management strategy.
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Session 2 B

Medication overuse headache

New EAN treatment guidelines on medication overuse headache

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Signe Bruun Munksgaard,
MD, PhD, Danish Headache Center, Rigshospitalet Glostrup, Denmark

The European Academy of Neurology guideline on the management of medication overuse headache (MOH) updates the 2011 guideline from the European Federation of Neurological Societies with new research and new diagnostic criteria.
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Comparison of three treatment strategies of medication overuse headache - a randomized clinical trial

Louise Ninett Carlsen,
MD, PhD student, Danish Headache Center, Rigshospitalet Glostrup, Denmark

Three strategies are effective in reducing headache days in patients with MOH. These were compared in a non-blinded randomized trial in 120 patients with MOH associated with migraine or tensiontype headache: withdrawal plus preventive therapy from the outset, preventive therapy alone with no advice on withdrawal, and withdrawal alone (with an option to start preventive therapy after two months). 6
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Session 3

Case reports – risk factors for anti-CGRP targeting treatments

Cardiovascular disease

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Marja-Liisa Sumelahti,
MD, PhD, Specialist in Neurology, Faculty of Medicine and Health Technology, Tampere University, Finland

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an hereditary angiopathy caused by mutations in the NOTCH3 gene. It is rare, with a prevalence of 5 per 100,000; it is associated with an increased risk of transient ischaemic attack, cognitive defects and migraine developing after age 45, and has a highly variable progressive clinical course.
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Comorbidity of migraine and epilepsy: a case report

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Annelies Van Dycke,
MD, PhD Neurologist, AZ Sint-Jan, Bruges, Belgium

The prevalence of epilepsy is 0.5—1.0% and that of migraine is 15—18% in women, 6% in men and 4% in children. Epidemiological studies show that comorbidity between these disorders is high, with migraine occurring in about 25% of people with epilepsy and epilepsy reported in 1—2% of people with migraine.
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Pregnancy (and lactation)

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Anne Christine Poole,
General Practitioner and Headache Specialist, Oslo Headache Centre

This case study describes the challenges of counselling patients with migraine about the safety of treatment during pregnancy and while they are breast feeding.
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Session 4

Migraine in women

Pharmacology of monoclonal antibodies and gepants

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Eili Tranheim Kase,
PhD, Associate Professor, Department of Pharmacy, University of Oslo

Anti-CGRP monoclonal antibodies probably cross the placenta but there is no evidence of harm in humans as a result; levels in breast milk are very low, especially after one week. There are no data on human exposure to gepants during pregnancy but animal studies at doses comparable with clinical doses suggest any risk is low.
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Migraine management during pregnancy and breastfeeding

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Mattias Linde,
MD, PhD, Professor of Neurology, Norwegian Advisory Unit for Headaches and NTNU Consultant Neurologist, Tjörn Headache Clinic

The group of people most highly burdened by migraine are women of childbearing age, with about 1 in 5 of 30- to 39-year-olds affected.1 The challenge of treatment and prevention during pregnancy and while breast feeding is therefore a frequent one. Fortunately, the frequency of migraine attacks declines towards the time of delivery; however, there is often a marked increase during the puerperium.
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Session 5

Challenges using aCGRP treatment

Current preventative migraine treatments and the risk of infections

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Marja-Liisa Sumelahti,
MD, PhD, Specialist in Neurology, Faculty of Medicine and Health Technology, Tampere University, Finland

There has been concern during the Covid pandemic that the immunosuppressive effects of medicines may increase the risk of infection. Little is known about the effect of migraine preventive medication on immune function but laboratory evidence of immunosuppression has not been reflected in clinical practice. Despite theoretical concerns, CGRP antagonists may confer some degree of protection against the complications of Covid.
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Follow-up of migraine treatment in the days of pandemic outbreak - is telehealth the answer?

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Gürdal Sahin,
MD, PhD, Specialist in Neurology and Head of the Skåneuro Private Headache and Movement Disorders Clinic, Institution for Clinical Sciences, Lund University

Social distancing during the Covid pandemic has limited clinicians’ ability to provide face-to-face care and disrupted the assessment, monitoring and supervision normally provided in outpatient clinics. Telemedicine is an option for providing care remotely that offers service continuity, with some success in the management of headache.1-3 Its uptake during the pandemic may foretell a wider role in the future.
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Session 6

Nordic reimbursement guidelines for aCGRP treatment


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Ingela Nilsson Remahl,
MD, PhD, Head of the Headache Center, Karolinska University Hospital

An anti-CGRP monoclonal antibody may be prescribed for patients with chronic migraine for whom at least two preventive treatments have proved unsuccessful. Patients must keep a migraine diary for the 2–3 months preceding and following initiation using the Swedish Headache Register. Treatment may only be prescribed by a neurologist or physician working at a headache clinic who has experience of treating patients with severe migraine. Treatment must be evaluated after three months and continued only when a ≥30% reduction in migraine days has been achieved. It should then be re-evaluated every 12–18 months. Galcanezumab is recommended as the agent of first choice (at the time of this presentation, 28 November 2020).

In Sweden, all residents have a right to treatment regardless of where they live, their income or their social status but how this obligation is implemented varies between the six health care regions and 21 councils, and also between hospitals. Patients pay the first 2,350 SEK per year of medicines costs, after which they receive full reimbursement. The Swedish Headache Society is currently developing uniform treatment criteria to ensure equal access across Sweden.
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Lars Bendtsen,
MD, PhD, Associate Professor, Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup, University of Copenhagen, Denmark

In Denmark, anti-CGRP monoclonal antibodies can only be prescribed by neurologists working in a Danish hospital (not private practice). Treatment is free for patients and costs are met by the hospital.

Anti-CGRP monoclonal antibodies are prescribed according to national guidelines developed by the Medicinrådet. Eligible patients have chronic migraine that has not responded to treatment with at least one antihypertensive agent and at least one anti-epileptic drug. Medication overuse must be treated before starting therapy and treatment with onabotulinum toxin A must be stopped. The least expensive anti-CGRP monoclonal antibody is the agent of choice unless there are strong reasons for prescribing an alternative. Patients must be closely followed up and headache days, headache severity and use of acute medications must be documented. Treatment must be reviewed after three months and continued only if moderate/severe headache days have been reduced by ≥30%. Effectiveness and adverse effects should be reviewed every three months. Treatment should be paused after one year to determine whether it is still necessary.
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Lars Jacob Stovner
MD, PhD, Professor of Neurology, Norwegian University of Science and Technology and Norwegian Advisory Unit on Headaches, St. Olavs Hospital, Trondheim, Norwayk

The Norwegian Health Economic Administration (HELFO) administers the ‘Blue Prescription’ national insurance scheme under which the costs of medicines are reimbursed. Unlike other migraine treatments, anti-CGRP monoclonal antibodies are not covered by this scheme. Instead, their cost is reimbursed on individual application which must be renewed annually. The application can be made by a neurologist or a doctor working at the neurology department, or a doctor in a private hospital employing at least one neurologist. Treatment of patients aged under 18 is an unlicensed use but the same doctors and also a pediatrician are eligible to make the application.

Eligible patients have chronic migraine according to ICHD-3 criteria. The application must document migraine severity (monthly migraine headache days), previous preventive therapy, evidence of medication overuse headache and state that discontinuation of acute treatments has been attempted. Previous treatment with one of at least three pharmacological classes must have been unsuccessful. This may have been due to lack of effectiveness or adverse effects but contraindication is not considered a valid reason for not attempting treatment. For patients who have chronic migraine despite treatment with onabotulinum toxin A and who wish to start with an anti-CGRP monoclonal antibody it is recommended that this is done at least 4 months after the last injection, but if an increase in migraine cannot be tolerated, it can also be done immediately. Either way, if CGRP antibodies seem to work, one should try to discontinue onabotulinum toxin A, but in some cases both medicines may be necessary.

The patient must keep a headache diary. Treatment should be reviewed after 3 months and continued only if headache days (severity 2–3 on a scale of 0–4) were reduced by ≥30% during the previous 4 weeks. Clinicians are allowed discretion when interpreting the effectiveness criteria – for example, effectiveness may mean the patient manages with less acute medication, migraine
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Marja-Liisa Sumelahti
MD, PhD, Specialist in Neurology, Faculty of Medicine and Health Technology, Tampere University, Finland

The Finland national health insurance scheme (KELA) reimburses patients at 40% of the cost of erenumab, fremanezumab and galcanezumab. Eligibility is determined by statements from a neurologist (the first and the second statement) or a physician having experience in migraine treatment (the third statement). Eligible patients must have at least 8 migraine days a month on average during a 3-month period with at least two preventive medications proving unsuccessful due to lack of effectiveness or they are not tolerated or they are contraindicated.

The statement procedure has two steps. After the first statement, the patient must achieve a ≥50% reduction in monthly migraine days over a 12-week period during the first 6 months. The response has to be evaluated at weeks 9-12. The second statement has to be submitted if the response is achieved and then the reimbursement will be continued for a further 2 years. A third statement is then granted if the improvement in monthly migraine days was sustained for the 2-year period. The first two statements must be made by a neurologist but any physician can make the third statement.
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