1. JAMA. 2018 May 15;319(19):1999-2008. doi: 10.1001/jama.2018.4853.

Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine:
A Randomized Clinical Trial.

Dodick DW(1), Silberstein SD(2), Bigal ME(3), Yeung PP(3), Goadsby PJ(4),
Blankenbiller T(3), Grozinski-Wolff M(3), Yang R(3), Ma Y(3), Aycardi E(3).

Author information: 
(1)Mayo Clinic Arizona, Phoenix.
(2)Jefferson Headache Center, Thomas Jefferson University, Philadelphia,
(3)Teva Pharmaceuticals, Frazer, Pennsylvania.
(4)NIHR-Wellcome Trust King's Clinical Research Facility, King's College London, 
London, England.

Comment in
    JAMA. 2018 May 15;319(19):1985-1987.

Importance: Fremanezumab, a fully humanized monoclonal antibody that targets
calcitonin gene-related peptide, may be effective for treating episodic migraine.
Objective: To assess the efficacy of fremanezumab compared with placebo for
prevention of episodic migraine with a monthly dosing regimen or a single higher 
Design and Setting: Randomized, double-blind, placebo-controlled, parallel-group 
trial conducted at 123 sites in 9 countries from March 23, 2016 (first patient
randomized), to April 10, 2017, consisting of a screening visit, 28-day
pretreatment period, 12-week treatment period, and final evaluation at week 12.
Participants: Study participants were aged 18 to 70 years with episodic migraine 
(6-14 headache days, with at least 4 migraine days, during 28-day pretreatment
period). Patients who had previous treatment failure with 2 classes of
migraine-preventive medication were excluded.
Interventions: Patients were randomized 1:1:1 to receive subcutaneous monthly
dosing of fremanezumab (n = 290; 225 mg at baseline, week 4, and week 8); a
single higher dose of fremanezumab, as intended to support a quarterly dose
regimen (n = 291; 675 mg of fremanezumab at baseline; placebo at weeks 4 and 8); 
or placebo (n = 294; at baseline, week 4, and week 8).
Main Outcomes and Measures: The primary end point was mean change in mean number 
of monthly migraine days during the 12-week period after the first dose.
Results: Among 875 patients who were randomized (mean age, 41.8 [SD, 12.1] years;
742 women [85%]), 791 (90.4%) completed the trial. From baseline to 12 weeks,
mean migraine days per month decreased from 8.9 days to 4.9 days in the
fremanezumab monthly dosing group, from 9.2 days to 5.3 days in the fremanezumab 
single-higher-dose group, and from 9.1 days to 6.5 days in the placebo group.
This resulted in a difference with monthly dosing vs placebo of -1.5 days (95%
CI, -2.01 to -0.93 days; P < .001) and with single higher dosing vs placebo of
-1.3 days (95% CI, -1.79 to -0.72 days; P < .001). The most common adverse events
that led to discontinuation were injection site erythema (n = 3), injection site 
induration (n = 2), diarrhea (n = 2), anxiety (n = 2), and depression (n = 2).
Conclusions and Relevance: Among patients with episodic migraine in whom multiple
medication classes had not previously failed, subcutaneous fremanezumab, compared
with placebo, resulted in a statistically significant 1.3- to 1.5-day reduction
in the mean number of monthly migraine days over a 12-week period. Further
research is needed to assess effectiveness against other preventive medications
and in patients in whom multiple preventive drug classes have failed and to
determine long-term safety and efficacy.
Trial Registration: clinicaltrials.gov Identifier: NCT02629861.

DOI: 10.1001/jama.2018.4853 
PMID: 29800211  [Indexed for MEDLINE]