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

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

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

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

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)

TCC

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

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

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

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

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

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

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

Migraine prevention: what is new -ish Neurostimulation: Cefaly stms GammaCore

Cefaly

Transcutaneous electrical stimulation of the supra-orbital and trochlear nerves

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

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

Cefaly 4% > 1 AE Paraesthesia Sleepiness Headache Skin rash

gammacore

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

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

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

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

Single-pulse Transcranial Magnetic Stimulation stms

Cortical Spreading depression CSD

stms TMS blocks triggered CSD Inhibits firing rate of VPM neurons

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

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

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

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

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

Drop out rate Rx EM/CM Drop out (%) Erenumab EM 2.1 Fremenezumab CM 1.8 Topiramate EM 26.7 Botox CM 3.2

CGRP-mabs Alder Novartis Lilly TEVA Name Eptinezumab Erenumab Gacenezumab Fremenzumab Agianst CGRP Receptor CGRP CGRP Route/dose IV/ 12 weeks SC/ 4 weeks SC/ 4 weeks SC/ 4 weeks

Erenumab (70mg) in episodic migraine STRIVE ARISE Active Placebo Active Placebo Migraine days -3.2-1.8 - - Headache days - - -2.9-1.8 50% responder 43.3% 26.6% 39.7% 29.5%

Erenumab (70mg) for chronic migraine Active Placebo Headache days -6.6-4.2 50% responder 40% 23% Adverse event 44% 47%

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

Thank you