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11/10/2017
1
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
11/10/2017
2
• 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
11/10/2017
3
• 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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4
• 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.
11/10/2017
5
Research with promising
translational implications
11/10/2017
6
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
11/10/2017
7
Headache/Migraine: Biomarkers and
Natural History
11/10/2017
8
Female sex, no overuse of pain medication and lower
headache frequency were associated with remission.
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9
11/10/2017
10
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
11/10/2017
11
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
11/10/2017
12
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
11/10/2017
13
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
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