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What is new in the migraine world!

Learn about the latest advancements in understanding and treating migraines from Dr. Modar Khalil, a consultant neurologist at Hull Royal Infirmary. Discover the burden of migraines, commonly used terms, current and upcoming acute and preventive therapies.

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What is new in the migraine world!

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  1. What is new in the migraine world! Modar Khalil Consultant neurologist Hull Royal Infirmary

  2. Overview • Understanding the burden • Commonly used terms • Acute therapy • What we currently have • What we are going to have • Preventive therapy • What we currently have • What we are going to have

  3. Understanding the burden • 10% of population consult their GP each year because of headache • One of the most prevalent worldwide conditions • 324 million people affected worldwide • One of the commonest causes of school absence • 25 million work or school days are missed each year due to migraine

  4. Commonly used terms • Chronic migraine • Episodic migraine • Acute therapy Vs prevention Agonist Vs Antagonist • Double-blind trial Vs Open-label trial • Vascular theory • Trigemino-cervical complex (TCC)

  5. TCC

  6. Acute therapy- What we have: Triptans • Introduced more than 25 years ago • 5-HT 1B/1D receptor agonists • Seven different Triptans • Variety for route of delivery • Oral tablets or melts • Nasal spray • Subcutaneous injection

  7. Issues with triptans • Not effective in 30% • Headache recurrence in up to 40% of patients • Contraindications • High blood pressure, ischemic heart disease • Incidence of Heart attack or stroke in 1:1000000 • SE: • nausea, GI, ‘triptan chest’

  8. Acute therapy: what is new • Lasmiditan • Tablet • Migraine relief without vasoconstriction • 2 positive trials • Migraine freedom at 2 hours (32% Vs 15%) • Ongoing 3rd trial • Mild to moderate side effects

  9. Preventive therapies: what we have! • Tablets: • B-blockers • Topiramate • Amitriptyline • Candesartan • Pizotifen • Gabapentin • Valproate • Memantine • Injections • Greater occipital nerve block • Botox

  10. β-blockers • Overall responder rate: 53% compared with 31% with placebo • SE in 10- 15% • Fatigue (decreased exercise tolerance); dizziness; • insomnia; depression; decreased libido • CI: asthma, COPD, Raynaud’s, PVD

  11. Topiramate • SE common: parasthesiae, fatigue, tremor, weight loss, visual disturbances (incl. glaucoma), kidney stones, cognitive problems (word-finding difficulties, agitation, confusion, depression, psychosis)

  12. Amitriptyline • 1979 small DBRCT AMI 25 mg: responders 55% vs 34% placebo • Traditional first line treatment • SE: fatigue, dry eyes, dry mouth, constipation

  13. Migraine prevention: what is new -ish • Neurostimulation: • Cefaly • sTMS • GammaCore

  14. Cefaly

  15. Transcutaneous electrical stimulation of the supra-orbital and trochlear nerves

  16. Cefaly- prevention • PREMICE trial over 3 months • Prevention of episodic migraine • At least 2 migraines a month (average was 7) • 50% responder rate: 38% verum Vs 12% sham (p=0.023) • Compliance was about 60% Schoenen J, et al. Neurology. 2013;80:697-704

  17. Cefaly- acute • Open label in 30 patients, using Cefaly for 1 hour • Pain intensity was reduced by • 57% after 1 hour (p<0.001) • Just less than 53% after 2 hours (p<0.001) • A third of patient took a painkiller in the 24-hour follow up Chou DE, et al. Neuromodulation. 2017;20:678-83

  18. Cefaly • 4% > 1 AE • Paraesthesia • Sleepiness • Headache • Skin rash

  19. gammaCore

  20. Non-invasive vagal nerve stimulation (VNS) • Invasive VNS is approved for epilepsy • It was found to reduce migraine and depression Courtesy of Dr Kevin Shields

  21. gammaCore- chronic migraine prevention • Two 2-minute stimulations, 5-10 minutes apart, TDS • Randomized for 2 months • Open label for 6 months • No significant reduction in headache days at 2 months • Significant reduction from baseline for completers Silberstein S, et al. Neurology. 2016;87:529-38

  22. gammaCore • Short randomization period • No safety issues • >1 SE in 57% of verum Vs 55%% in sham • Skin irritation • Neck twitching

  23. gammaCore- PRESTO study • Acute therapy in episodic migraine • 248 participants • Significant pain freedom at 30 and 60 minutes but not at 120 minutes • Safe and well-tolerated Tassorelli C, et al. Neurology. 2018,91:e364-e373

  24. Single-pulse Transcranial Magnetic Stimulation sTMS

  25. Cortical Spreading depression CSD

  26. sTMS • TMS blocks triggered CSD • Inhibits firing rate of VPM neurons

  27. sTMS- acute therapy • RCT • 267 adults • Migraine with aura • Pain freedom at 2H were significantly higher (39% Vs 22%, p=0.0179) • Sustained response at 24h (29%) and 48h (27%) post treatment • No serious SE Lipton RB, et al. Lancet Neurol. 2010;9:373-80

  28. sTMS- prevention • Post marketing pilot program in the UK • At 3 months • Reduction in monthly headache days median from 12 to 9 for EM • Reduction in monthly headache days median from 24 to 16 for CM • No serious AE Bhola R, et al. J Headache Pain. 2015;16:535

  29. sTMS- prevention • Prospective, open-label, observational study • Dec 2014- Mar 2016 • Treatment over 3 months • Four pulses, twice daily + acute therapy PRN • Significant reduction in number of headache days and HIT-6 scores Starling AJ, et al. Cephalalgia. 2018;38:1038-48

  30. Migraine prevention: what is new! • CGRP-mab • Erenumab • Galcanezumab • Fremenezumab • Eptinezumab • CGRP antagonist • Gepants

  31. Target specific migraine mechanism • No vasoconstrictive effect • May be suitable for people with angina

  32. Drop out rate

  33. CGRP-mabs

  34. Erenumab (70mg) in episodic migraine

  35. Erenumab (70mg) for chronic migraine

  36. Summary • Migraine can be quite disabling • Although many medications are available but • Lack of efficacy • Side effects and tolerability • Restricted use due to comorbidities • New hope with novel medications • Specific mechanisms • Better tolerated

  37. Thank you

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