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Original Investigation
May 15, 2018

Effect of Fremanezumab Compared With Placebo for Prevention of Episodic MigraineA Randomized Clinical Trial

Author Affiliations
  • 1Mayo Clinic Arizona, Phoenix
  • 2Jefferson Headache Center, Thomas Jefferson University, Philadelphia, Pennsylvania
  • 3Teva Pharmaceuticals, Frazer, Pennsylvania
  • 4NIHR-Wellcome Trust King’s Clinical Research Facility, King’s College London, London, England
JAMA. 2018;319(19):1999-2008. doi:10.1001/jama.2018.4853
Key Points

Question  Is the monoclonal antibody fremanezumab effective in preventing episodic migraine?

Findings  In this randomized clinical trial that included 875 adults with episodic migraine in whom multiple medication classes had not previously failed, fremanezumab compared with placebo resulted in significantly fewer monthly migraine days with monthly dosing (–1.5 days) and with a single higher dose at baseline (–1.3 days) over 12 weeks.

Meaning  Fremanezumab as a preventive treatment for episodic migraine reduced the mean number of monthly migraine days over a 12-week period compared with placebo. 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.

Abstract

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 dose.

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

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