ADDITIONAL RESOURCES

LEARNING OBJECTIVESAs a result of participation in this initiative, participants will increase their ability to

1. Apply Apply concepts

in migraine pathophysiology and therapeutic MOA to

treatment discussions.

2. DevelopDevelop treatment plans in line with

current standards of practice and guidelines for the management of

migraine and eCH.

3. Effectively communicate

Effectively communicate with

patients using shared decision making (SDM) to diagnose and treat headache disorders.

4. AnalyzeAnalyze safety and efficacy profiles for new and emerging

therapies in acute and preventive treatment of

migraine and eCH.

5. Discuss Discuss burden of

migraine and eCH and impact to quality

of life (QoL).

Stewart J. Tepper, MD Professor of Neurology,Geisel School of Medicine at DartmouthDirector, Dartmouth Headache CenterDartmouth-Hitchcock Medical CenterLebanon, New Hampshire

Wade M. Cooper, DOAssociate Professor of Neurology,Michigan MedicineDirector, Headache and Neuropathic Pain Program University of Michigan Ann Arbor, Michigan

Merle L. Diamond, MDPresident and Managing Director, Diamond Headache Clinic Chicago, Illinois

PRESENTING FACULTY

LEARNING OBJECTIVE 1 Apply concepts in migraine pathophysiology and therapeutic MOA to treatment discussions.

1. For patients with which of the following headache disorders could an FDA-approved treatment targeting calcitonin gene-related peptide (CGRP) be considered?

A. Episodic migraine

B. Chronic migraine

C. Cluster headache

D. All of the above

ExplanationCGRP is implicated in both migraine and cluster headache pathophysiology. Monoclonal antibodies have shown promising findings in demonstrating efficacy and safety as well as improving headache and QoL.

ReferenceYuan H, Spare NM, Silberstein SD. Targeting CGRP for the prevention of migraine and cluster headache: a narrative review. Headache. 2019;59:20-32.

OUTCOME QUESTIONS: ANSWERS AND EXPLANATIONS

LEARNING OBJECTIVE 2 Develop treatment plans in line with current standards of practice

and guidelines for the management of migraine and eCH

2. A 56-year-old executive has coronary artery disease, peptic ulcer disease, and severe, disabling, episodic migraines. Which of the following FDA-approved acute treatments would be appropriate for her?

A. Sumatriptan or dihydroergotamine

B. Naproxen sodium or rizatriptan

C. Lasmiditan or ubrogepant

D. Galcanezumab or erenumab

ExplanationLasmiditan and ubrogepant are both FDA-approved for acute treatment of migraine in adults and do not have vasoconstrictive or ulcerogenic adverse events associated with use; sumatriptan, dihydroergotamine, and rizatriptan are all vasoconstrictive, naproxen is contraindicated with her peptic ulcer disease, and galcanezumab and erenumab are preventive medications.

ReferencesKuca B, Silberstein SD, Wietecha L, Berg PH, Dozier G, Lipton RB. Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study. Neurology. 2018;91(24):e2222-e2232.

Goadsby PJ, Wietecha LA, Dennehy EB, et al. Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine. Brain. 2019;142(7):1894-1904.

Dodick DW, Lipton RB, Ailani J, et al. Ubrogepant for the treatment of migraine. N Engl J Med. 2019;381(23):2230-2241.

Lipton RB, Dodick DW, Ailani J, et al. Effect of ubrogepant vs placebo on pain and the most bothersome associated symptom in the acute treatment of migraine: the ACHIEVE II randomized clinical trial. JAMA. 2019;322(19):1887-1898.

OUTCOME QUESTIONS: ANSWERS AND EXPLANATIONS

LEARNING OBJECTIVE 3 Effectively communicate with patients using shared decision making (SDM) to diagnose and treat headache disorders.

3. A 30-year-old patient wishes to discuss options for treatment for her migraines. You should A. Evaluate frequency and severity of attacks and recommend optimal acute

and, if indicated, preventive treatments. B. Discuss with her where she is in life (job, plans for pregnancy, etc) and preferences for treatment (medications, neuromodulation, behavioral, etc), then work out a plan together that is mutually acceptable. C. Encourage the patient to read up on migraine through the National Headache Foundation or the American Migraine Foundation websites prior to initiating treatment. D. Use behavioral or neuromodulation treatments, as pregnancy is an issue.

ExplanationExploring aspects of patient preference and matching to clinical need is part of shared decision making.

ReferenceLégaré F, Politi MC, Drolet R, Desroches S, Stacey D, Bekker H; SDM-CPD Team. Training health professionals in shared

decision-making: an international environmental scan. Patient Educ Couns. 2012;88:159-169.

OUTCOME QUESTIONS: ANSWERS AND EXPLANATIONS

LEARNING OBJECTIVE 4 Analyze safety and efficacy profiles for new and emerging therapies in acute and preventive treatment of migraine and eCH.

4. A 48-year-old man has several month cycles of daily side-locked, unilateral, short, disabling attacks with autonomic features and agitation followed by months of remission and normal imaging. He is requesting prevention but only wants FDA- approved preventive therapies. Options for him include

A. Sumatriptan or dihydroergotamine.

B. Verapamil or topiramate

C. Oxygen or lasmiditan

D. Galcanezumab or noninvasive vagal nerve stimulation

ExplanationThis patient with episodic cluster headache has requested the only two therapies that are FDA-approved or -cleared for preventive treatment of cluster headache, galcanezumab (for episodic cluster headache prevention) and noninvasive vagal nerve stimulation (adjunctively for prevention of cluster headache).

ReferencesGoadsby PJ, Dodick DW, Leone M, et al. Trial of galcanezumab in prevention of episodic cluster headache. N Engl J Med. 2019;381(2):132-141.

Gaul C, Diener HC, Silver N, et al. Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): a randomised controlled study. Cephalalgia. 2016;36(6):534-546.

OUTCOME QUESTIONS: ANSWERS AND EXPLANATIONS

LEARNING OBJECTIVE 5 Discuss burden of migraine and eCH and impact to

quality of life (QoL).

5. The 2019 American Headache Society position paper on integrating new treatments into clinical practice recommends one of the following: A. Assessment of impact to quality of life for use of new acute migraine treatments and for evaluation of need for new preventive therapies in low frequency episodic migraine B. Assessment of impact to quality of life in all classes of migraine patients C. Assessment of impact to quality of life in all classes of cluster headache D. Assessment of impact to quality of life in all headache patients

ExplanationThe AHS position paper suggests evaluation of disability or impact for both patients with low frequency episodic migraine when assessing need for new preventive therapies and for all patients with migraine when assessing need for the new acute migraine treatments; patients with high frequency episodic and chronic migraine have such demonstrable disability that additional documentation is not recommended in deciding on new prophylaxis.

ReferenceAmerican Headache Society. The American Headache Society Position Statement on Integrating New Migraine Treatments Into Clinical Practice. Headache. 2019;59(1):1-18.

OUTCOME QUESTIONS: ANSWERS AND EXPLANATIONS

MIXED REALITY EXPERIENCE

Ditan

5HT1B-r on the blood vessel, unbound (triptans bind here)

5HT1D-r on afferent terminal, unbound (triptans bind here)

5HT1F-r, bound (triptans bind here)

Trigeminal Ganglion

Trigeminal ganglion

CGRP mAb Against the Receptor

Scale is reduced 500x relative to the receptor

CGRP-r

CGRP mAb Against the Ligand

Scale is reduced 500x relative to the ligand

CGRP ligand

Triptan

C fiber of trigeminal ganglion, afferent pain signal

A delta fiber of trigeminal ganglion, afferent pain signal Triptans binding

to presynaptic 5-HT receptors

Second order brainstem neurons

Ligand mAbmAb with CGRP (ligand) bound to it

Trigeminal ganglion neurons with satellite cells

Unmyelinated C fiber

Myelinated A-delta fiber

CGRP-r (blue), no CGRP bound

AMY1-r (red), no CGRP bound

Neurovascular Junction

Yellow glow=CGRP binding to the CGRP-r on the blood vessel

A-delta terminals facing the dura

Red glow=action potential, traveling down the A-delta fiber (pain signal)

Terminal of C-fiber (release of neuropeptides)

CGRP-r on the A-delta terminal

CGRP binding to a CGRP-r on a mast cell

GepantCGRP unable to bind to the CGRP-r

Gepant bound to the CGRP-r

CGRP-r

CGRP bound to the AMY1-r

AMY1-r

green glow=therapy binding

American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache. 2019;59(1):1-18.

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Dodick DW, Lipton RB, Ailani J, et al. Ubrogepant for the treatment of migraine. N Engl J Med. 2019;381(23):2230-2241.

Edvinsson L, Haanes KA, Warfvinge K, Krause DN. CGRP as the target of new migraine therapies - successful translation from bench to clinic. Nat Rev Neurol. 2018;14(6):338-350.

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Gaul C, Diener HC, Silver N, et al. Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): a randomised controlled study. Cephalalgia. 2016;36(6):534-546.

Goadsby PJ, Wietecha LA, Dennehy EB, et al. Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine. Brain. 2019;142(7):1894-1904.

Goadsby PJ, de Coo IF, Silver N, et al. Non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: a randomized, double-blind, sham-controlled ACT2 study. Cephalalgia. 2018;38(5):959-969.

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KEY PRESENTATION REFERENCES

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KEY PRESENTATION REFERENCES (CONT.)

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HOLOLENS REFERENCES