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The Best and Most Interesting Research from

Last Year

Cephalalgia

David W. Dodick, M.D.

Department of Neurology

Mayo Clinic

Scottsdale Arizona

Disclosure

• Consulting services: Acorda, Allergan, Amgen, Alder, Promius, eNeura, Eli Lilly & Company, Insys therapeutics, Autonomic

Technologies, Teva, Xenon, Tonix, Trigemina, Nocira, Colucid, Zosano, Laydenburg Thalmann, Biocentric, Biohaven, Magellan,

Charleston Laboratories.

• Royalties: Oxford University Press and Cambridge University Press (Book Royalty).

• Editorial/honoraria: UpToDate, Chameleon Communications, Medscape, WebMD, Academy for Continued Healthcare

Learning, Haymarket Medical Education, Global Scientific Communications, HealthLogix, Academy for Continued Healthcare

Learning, MeetingLogiX, Wiley Blackwell, Oxford University Press, Cambridge University Press.

• Stock/options: Nocira, Epien, Healint, Theranica, and Mobile Health.

• Consulting use agreement: NAS.

• Board position: King-Devick, Epien.

Learning ObjectivesAt the conclusion of this presentation, participants should be better able to:

•Discuss the advances in the basic and clinical science of headache as published

in Cephalalgia in 2017

•Describe the translational implications of scientific advances and the clinical

implications of the treatment advances in headache as published in Cephalalgia

in 2017

•Develop a patient-specific diagnostic plan based on differential diagnosis

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• 432 pregnant women exposed to triptans in German

Embryotox System

• Compared to a non-migraine cohort no increase in:

– major birth defects (ORadj 0.84; 95% CI 0.4–1.9)

– Spontaneous abortions (ORadj 1.20; 95% CI 0.9–1.7),

– preterm delivery (ORadj 1.01; 95% CI 0.7–1.5),

– preeclampsia (ORadj 1.33; 95% CI 0.7–2.5)

• Triptans are not major teratogens.

• Sumatriptan best studied triptan appears acceptable

treatment option.

• A detailed fetal ultrasound should be offered in cases of first

trimester exposure to less well-studied triptans.

Trigeminal Autonomic Cephalalgias

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• LF stimulation of the SPG induced autonomic symptoms,

but no CH attacks.

• Increased parasympathetic outflow is not sufficient to

induce CH attacks in patients.

• Activation of afferent or efferent arms of trigeminal-autonomic reflex

is insufficient to trigger CH

• Brain drives CH

• Does not exclude therapeutic

actions being either outside or inside CNS.

Responder rate: 77%

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• 100 patients (35 CM, 33 CCH, 20 SUNCT and 12 HC)

• Response rate of the cohort was 48%.

• Multivariate analysis: SUNCT (OR 6.71; 95% CI 1.49–30.05; p 0.013) and prior response

to GON block (OR 4.22; 95% CI 1.35–13.21; p 0.013) were associated with increased likelihood of response.

• Presence of occipital pain (OR 0.27; 95% CI 0.09–0.76; p 0.014) and the presence of severe anxiety and/or

depression at time of implantation

• (OR 0.32; 95% CI 0.11–0.91; p 0.032) were associated with reduced likelihood of response.

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Research with promising

translational implications

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Migraine, Stroke and White Matter

Hyperintense Lesions

• WMHs are more common in patients with migraine than in healthy controls.

• Increased aortic stiffness or central systolic blood pressure in the presence of low intracranial artery

resistance may predispose patients with migraine to WMH formation

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Headache/Migraine: Biomarkers and

Natural History

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Female sex, no overuse of pain medication and lower

headache frequency were associated with remission.

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Cephalalgia Abstracts Presented at 2017

International Headache Congress

Increased Odds of ≥ 50%

Response in Patients With Prior Treatment Failure

Goadsby et al. Cephalalgia 2017;37

Ac

hie

ve

me

nt

of ≥

50

% r

ed

uc

tio

n in

mo

nth

ly

mig

rain

e d

ays

fro

m b

as

eli

ne

Odds ratio

2.13**

Odds ratio

2.81**

Odds ratio

2.93**

Odds

ratio

3.06**

Odds

ratio

2.89*

Odds ratio

4.54*

Overall population ≥1 prior treatment failures ≥2 prior treatment failures

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Erenumab on Exercise Time During a

Treadmill Test in Patients with Stable Angina

Christophe Depre,1 Lubomir Antalik,2 Amaal Starling,3

Michael Koren,4 Osaro Eisele,1 Yumi Kubo,1 Robert A

Lenz,1 Daniel D Mikol1

1Amgen Inc., Thousand Oaks, CA, USA; 2Regional Hospital, Cardiological Department, Slovakia; 3Mayo Clinic, Scottsdale, AZ; 4Jacksonville Center for Clinical Research, Jacksonville, FL

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Multicenter, Randomized, Double-blind,

Placebo-controlled Study

ClinicalTrials.gov #NCT02575833

Key Inclusion Criteria

•History of ischemic heart disease

•History of chronic stable angina for ≥ 3 months prior to screening, with ≥ 1 angina episode/month, on average

Primary endpoint

Change from baseline in exercise duration as measured by TET

Secondary endpoints

Time to onset of ≥ 1 mm ST-segment depression

Time to onset of exercise-induced angina during the ETTMikol D, et al. IHC 2017, Vancouver Canada, Sept 2017

Erenumab in Patients with Cardiovascular Disease

Placebo

(N = 44)

Erenumab 140 mg

(N = 45)

Age (years), median (Q1, Q3) 65.0 (58.5, 69.5) 64.0 (56.0, 70.0)

Female, n (%) 11 (25) 9 (20)

White, n (%) 37 (84) 43 (95)

Cardiovascular history, n (%)

Coronary artery disease (CAD) 44 (100) 45 (100)

Myocardial infarction 20 (46) 16 (36)

Coronary artery bypass 15 (34) 14 (31)

Percutaneous coronary artery intervention 28 (64) 27 (60)

Cerebrovascular or peripheral arterial disease 10 (23) 11 (24)

Transient ischemic attack 2 (5) 2 (4)

Cerebrovascular accident 2 (5) 1 (2)

Carotid or vertebra-basilar artery disease 2 (5) 6 (13)

Other cerebrovascular conditions 3 (7) 2 (4)

Peripheral artery disease 5 (11) 4 (9)

Data represent mean (SD) unless otherwise indicated. Randomization analyses set; all patients randomized.

Mikol D, et al. IHC 2017, Vancouver Canada, Sept 2017

No Difference in Total Treadmill

Exercise TimeTime to Onset of ≥ 1 mm ST-segment

Depression

Mikol D, et al. IHC 2017, Vancouver Canada, Sept 2017

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Time to Onset of Exercise-induced Angina

Mikol D, et al. IHC 2017, Vancouver Canada, Sept 2017

Summary of Adverse Events – 12-week Follow Up

Placebo

(N = 44)

Erenumab 140

mg

(N = 44)

Adverse events, n (%)

Any 14 (32) 12 (27)

Serious 1 (2) 0 (0)

Leading to discontinuation of

study drug

0 (0) 0 (0)

Fatal 0 (0) 0 (0)

Mikol D, et al. IHC 2017, Vancouver Canada, Sept 2017

Summary and Conclusion

• Erenumab did not adversely affect exercise capacity, a surrogate of

underlying myocardial ischemia

• Compared to placebo:

– Change from baseline in total exercise time was non-inferior in the

erenumab group

– No difference was observed in the time to onset of ≥1 mm ST-

segment depression

– No difference was observed in the time to onset of exercise-induced

angina

– No difference in adverse events reported

• These results support that inhibition of the CGRP receptor does not

aggravate myocardial ischemia in an at-risk population of patients with

stable angina

Mikol D, et al. IHC 2017, Vancouver Canada, Sept 2017

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Episodic Migraine & CGRP Monoclonal Antibodies: Phase 3 Results

1. Saper et al. IHC 2017 poster

2. Goadsby et al. Headache 2017; 57 (Suppl 3): 128, abs IOR04

3. Dodick et al. Headache 2017; 57 (Suppl 3): 191, abs PS21

4. Stauffer et al. Headache 2017; 57

5. Conley et al. Headache 2017; 57

6. Aycardi et al. IHC 2017

≥5

0%

re

spo

nd

ers

(%

)

N =

316 312 318 288 282 425 210 208 450 226 220 290 287 288

Dose: 100/300mg, iv 70/140mg, sc 70mg, sc 120/240mg, sc 120/240mg, sc 225/675mg, sc

(1) (2) (3) (4) (5) (6)

*

*

*

**

*

*Statistically significant difference vs placebo

222 223 224

Chronic Migraine and CGRP mAbs Phase II/III Results

Compared to Current Therapy

N = 116 114 281 187 375 379 538 274 696 688 153 153

≥5

0%

re

sp

onse

mig

rain

e d

ays

Dose- 300mg, IV (1) 140mg, sc (2) 675//225mg 240mg, sc (4) PREEMPT (5) 100mg daily (6)

(3)

** *

*

*

*

1. Baker et al. Headache 2017; 57: late breaking abstract

2. Tepper et al. Lancet Neurol 2017 16 : 425-4343. Aycardi et al. Headache 2017; 57: late breaking abstract

4. Detke et al. Headache 2017; 57:

5. Dodick et al. Headache 2010; 51:1358-13736. Silberstein et al. Headache 2009;46:1153

*Statistically significant difference vs placebo

** *

*

*

Lasmiditan in Acute Migraine

SAMURAI: Aurora et al. Headache 2017; in press

(late-breaking AHS abstract)http://www.medscape.com/viewarticle/881835

Patients

(%

)

N = 488 503 518

• Treatment-

Emergent Adverse Events- Dizziness,

paresthesia, and

somnolence

Pain Free 2 hr

SPARTAN: Wietecha et al. Cephalalgia 2017; 37: in press

(late-breaking IHC abstract)Poster P0-02-180

N = 540 556 532 528

*All doses

significantvs placebo