1. Results w the CI

2. Results

3. Results 140mg seems to act faster but then 70mg catches up?
Already benefit at 1 mo

4. Results – Safety
572 (90.4%) of pts who received at least 1 erenumab and 278 (87.1%) of pts who received at least 1 placebo got all 6 doses
Frequency and severity of adverse events similar btw groups
No difference in EKG, LFTs, Cr, VS, WBC
35 (5.6%) of 628 pts who got tested for anti-erenumab binding Abs were + (8% in 70mg, 3.2 in the 140mg)

5. Limitations Exclusion criteria include:
“no therapeutic response to more than two migraine-preventive treatment categories” – are we excluding the refractory patients?
However, could be included if prior preventive discontinued for partial or unsustained response
No hemiplegic migraine – why?
Stratified randomization according to region (North Am vs other) and according to other preventive medication?
prevents imbalance btw treatment groups for known factors that influence prognosis or treatment responsiveness
Harmless bcuz doesn’t cause greater imbalance than expected by chance, unless there is a small # pts
Useful because reduces type I and II errors, improves trial efficiency
Migraine Physical Function Impact Diary (MPFID): what is it?

6. Summary
Erenumab subQ at monthly doses of 70mg or 140mg decreases migraine frequency, decreases use of abortive, and improves daily function
Strength of the study: includes impact on every day activity function
Similar safety than placebo, 3% withdrew from trial 2/2 adverse events
Further studies are needed to assess long term safety and durability of the effect

7. References
Ho TW, Edvinsson L, Goadsby PJ. CGRP and its receptors provide new insights into migraine pathophysiology. Nat Rev Neurol Oct;6(10):573-82
Kawata AK, Hsieh R, Bender R, et al.Psychometric Evaluation of a Novel Instrument Assessing the Impact of Migraine on Physical Functioning: The Migraine Physical Function Impact Diary. Headache Oct;57(9):
Kernan WN, Viscoli CM, Makuch RW, et al. Stratified Randomization for Clinical Trials. J of Clin Epi (52):1: 1999: 19-26
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Novartis. Bretz F, Xun X. Introduction to Multiplicity in Cilnical Trials.
Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 2017; 16:
Shi L, Lehto SG, Zhu DX, et al. Pharmacologic characterization of AMG 334, a potent and selective human monoclonal antibody against the calcitonin gene- related peptide receptor. J Pharmacol Exp Ther 2016;356:
Sun H, Dodick DW, Silberstein S, et al. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol 2016;15: