Fremanezumab, administered once monthly or once quarterly, is associated with greater reductions in monthly average migraine days than placebo in patients with difficult-to-treat migraine who did not respond to ≥2 of 4 classes of migraine preventative medications, according to research published in the Lancet.

Results were compiled from the FOCUS trial ( identifier: NCT03308968), a phase 3b study that randomly assigned patients with difficult-to-treat episodic or chronic migraine to subcutaneously administered quarterly fremanezumab (month 1, 675 mg; months 2 and 3, placebo [n=276]), monthly fremanezumab (month 1, 225 mg in episodic migraine and 675 mg in chronic migraine; months 2 and 3, 225 mg in both migraine subgroups [n=283]), or matched placebo (n=279). Primary outcome comprised mean change in the monthly average number of migraine days from baseline to 12 weeks.

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Difficult-to-treat patients with migraine were determined on the basis of a documented failure to ≥2 of 4 classes of migraine-preventative medications in the previous 10 years. Classes of treatment included β blockers (propranolol, metoprolol, atenolol, or bisoprolol), anticonvulsants (topiramate), tricyclic antidepressants (amitriptyline), calcium channel blockers (flunarizine), angiotensin II receptor antagonists (candesartan), onabotulinumtoxinA, or valproic acid.

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During the 12-week treatment period, there were greater reductions in the monthly average migraine days from baseline with quarterly fremanezumab (least-squares mean [LSM] change, −3.7 [0.3]; LSM difference vs placebo, −3.1 [95% CI, −3.8 to −2.4]; P <.0001) and monthly fremanezumab (LSM change, −4.1 [0.3]; LSM difference vs placebo, −3.5 [95% CI, −4.2 to −2.8]; P <.0001). No differences were observed between placebo and fremanezumab in regard to adverse events. A similar proportion of serious adverse events were observed with placebo (1%), quarterly fremanezumab (<1%), and monthly fremanezumab (1%).

Study limitations included the short follow-up period and the inclusion of patients with an average age of 46 years, as individuals aged 30 to 39 years are most likely to have migraine.

Researchers concluded that “patients with difficult-to-treat episodic or chronic migraine, who previously did not respond to up to four pharmacological classes of migraine preventive medications, can still achieve clinically significant improvement with fremanezumab.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Ferrari MD, Diener HC, Ning X, et al. Fremanezumab versus placebo for migraine prevention in patients with documented failure to up to four migraine preventive medication classes (FOCUS): a randomised, double-blind, placebo-controlled, phase 3b trial. Lancet. 2019;394(10203):1030-1040.