Goadsby PJ, Reuter U, Hallström Y, Broessner G, Bonner JH,
Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. A Controlled Trial of Erenumab
for Episodic Migraine. N Engl J Med. 2017 Nov 30;377(22):2123-2132.
BACKGROUND
We tested erenumab, a fully human monoclonal antibody that
inhibits the calcitonin gene–related peptide receptor, for the prevention of
episodic migraine.
METHODS
We randomly assigned patients to receive a subcutaneous
injection of either erenumab, at a dose of 70 mg or 140 mg, or placebo monthly
for 6 months. The primary end point was the change from baseline to months 4
through 6 in the mean number of migraine days per month. Secondary end points
were a 50% or greater reduction in mean migraine days per month, change in the
number of days of use of acute migraine–specific medication, and change in
scores on the physical-impairment and everyday-activities domains of the
Migraine Physical Function Impact Diary (scale transformed to 0 to 100, with
higher scores representing greater migraine burden on functioning).
RESULTS
A total of 955 patients underwent randomization: 317 were
assigned to the 70-mg erenumab group, 319 to the 140-mg erenumab group, and 319
to the placebo group. The mean number of migraine days per month at baseline
was 8.3 in the overall population; by months 4 through 6, the number of days
was reduced by 3.2 in the 70-mg erenumab group and by 3.7 in the 140-mg
erenumab group, as compared with 1.8 days in the placebo group (P<0.001 for
each dose vs. placebo). A 50% or greater reduction in the mean number of
migraine days per month was achieved for 43.3% of patients in the 70-mg
erenumab group and 50.0% of patients in the 140-mg erenumab group, as compared
with 26.6% in the placebo group (P<0.001 for each dose vs. placebo), and the
number of days of use of acute migraine–specific medication was reduced by 1.1
days in the 70-mg erenumab group and by 1.6 days in the 140-mg erenumab group,
as compared with 0.2 days in the placebo group (P<0.001 for each dose vs.
placebo). Physical-impairment scores improved by 4.2 and 4.8 points in the
70-mg and 140-mg erenumab groups, respectively, as compared with 2.4 points in
the placebo group (P<0.001 for each dose vs. placebo), and
everyday-activities scores improved by 5.5 and 5.9 points in the 70-mg and
140-mg erenumab groups, respectively, as compared with 3.3 points in the
placebo group (P<0.001 for each dose vs. placebo). The rates of adverse
events were similar between erenumab and placebo.
CONCLUSIONS
Erenumab administered subcutaneously at a monthly dose of 70
mg or 140 mg significantly reduced migraine frequency, the effects of migraines
on daily activities, and the use of acute migraine–specific medication over a
period of 6 months. The long-term safety and durability of the effect of
erenumab require further study. (Funded by Amgen and Novartis; STRIVE
ClinicalTrials.gov number, NCT02456740.)
Silberstein SD, Dodick DW, Bigal ME, Yeung PP, Goadsby PJ,
Blankenbiller T, Grozinski-Wolff M, Yang R, Ma Y, Aycardi E. Fremanezumab for
the Preventive Treatment of Chronic Migraine. N Engl J Med. 2017 Nov
30;377(22):2113-2122
BACKGROUND
Fremanezumab, a humanized monoclonal antibody targeting
calcitonin gene–related peptide (CGRP), is being investigated as a preventive
treatment for migraine. We compared two fremanezumab dose regimens with placebo
for the prevention of chronic migraine.
METHODS
In this phase 3 trial, we randomly assigned patients with
chronic migraine (defined as headache of any duration or severity on ≥15 days
per month and migraine on ≥8 days per month) in a 1:1:1 ratio to receive
fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at
weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4
and 8), or matching placebo. Both fremanezumab and placebo were administered by
means of subcutaneous injection. The primary end point was the mean change from
baseline in the average number of headache days (defined as days in which
headache pain lasted ≥4 consecutive hours and had a peak severity of at least a
moderate level or days in which acute migraine–specific medication [triptans or
ergots] was used to treat a headache of any severity or duration) per month
during the 12 weeks after the first dose.
.
RESULTS
Of 1130 patients enrolled, 376 were randomly assigned to
fremanezumab quarterly, 379 to fremanezumab monthly, and 375 to placebo. The
mean number of baseline headache days (as defined above) per month was 13.2,
12.8, and 13.3, respectively. The least-squares mean (±SE) reduction in the
average number of headache days per month was 4.3±0.3 with fremanezumab
quarterly, 4.6±0.3 with fremanezumab monthly, and 2.5±0.3 with placebo (P<0.001
for both comparisons with placebo). The percentage of patients with a reduction
of at least 50% in the average number of headache days per month was 38% in the
fremanezumab-quarterly group, 41% in the fremanezumab-monthly group, and 18% in
the placebo group (P<0.001 for both comparisons with placebo). Abnormalities
of hepatic function occurred in 5 patients in each fremanezumab group (1%) and
3 patients in the placebo group (<1%).
CONCLUSIONS
Fremanezumab as a preventive treatment for chronic migraine
resulted in a lower frequency of headache than placebo in this 12-week trial.
Injection-site reactions to the drug were common. The long-term durability and
safety of fremanezumab require further study. (Funded by Teva Pharmaceuticals;
ClinicalTrials.gov number, NCT02621931.)