Atogepant reduces migraine days in patients with episodic migraine

Treatment with atogepant significantly reduces the number of migraine days compared with placebo in patients with episodic migraine, according to the ADVANCE* study.

This phase III, double-blind trial involved 873 adults (mean age 41.6 years, 88.8 percent female) with episodic migraine who had an average of 7.4 migraine days per month. Participants were randomized to receive oral atogepant 10 mg (n=214), 30 mg (n=223), or 60 mg (n=222), or placebo (n=214) once daily for 12 weeks. Activity Impairment in Migraine-Diary (AIM-D) scores were used to assess the effect of migraine on daily activities. [N Engl J Med 2021;385:695-706]

At 12 weeks, patients treated with atogepant experienced a significant reduction in the number of monthly migraine days compared with placebo (mean change from baseline, -3.7 days [10 mg], -3.9 days [30 mg], and -4.2 days [60 mg] vs -2.5 days; adjusted p<0.001).

At week 12, atogepant recipients also achieved a significantly reduced number of headache days per month (mean change from baseline, -3.9 days [10 mg], -4.0 days [30 mg], and -4.2 days [60 mg] vs -2.5 days; adjusted p<0.001) compared with the placebo recipients.

Patients in the atogepant arm also demonstrated a reduction in the mean number of days of medication use per month for the treatment of migraine attacks than patients in the placebo arm (-3.7 days [10 mg], -3.7 days [30 mg], and -3.9 days [60 mg] vs -2.4 days; adjusted p<0.001).

Significantly more patients treated with atogepant than placebo achieved a ≥50 percent reduction in the 3-month average of migraine days per month (55.6 percent, 58.7 percent, and 60.8 percent vs 29.0 percent; adjusted p<0.001).

Patients treated with either atogepant 30 or 60 mg achieved a significant decrease in AIM-D scores for performance of daily activities (difference, -2.5 and -3.3, respectively; adjusted p<0.001 for both) and physical impairment (difference, -2.0; adjusted p=0.002 and difference, -2.5; adjusted p<0.001; respectively) at week 12 compared with placebo.

“[Moreover, with regard to secondary endpoints,] significant differences between all three atogepant doses and placebo were observed, … with the exception of the [AIM-D] scores … for the 10-mg dose,” the researchers noted.

The rate of adverse events (AEs) was comparable between the atogepant and the placebo treatment arms (52.9 percent [10 mg], 52.2 percent [30 mg], and 53.7 percent [60 mg] vs 56.8 percent), with only four serious AEs occurring in the atogepant 10 mg and placebo arms (two events in each arm).

Constipation (6.9–7.7 percent) and nausea (4.4–6.1 percent) were the most common AEs reported across all doses of atogepant. Constipation rates were higher in the atogepant vs the placebo group. “Although no serious cases of constipation were reported in this trial, continued monitoring and evaluation for this AE in clinical practice will be appropriate,” the researchers noted.

“[In conclusion, oral] atogepant once daily was effective … and resulted in significantly greater reductions in the number of migraine … and headache days in the prevention treatment of migraine over 12 weeks,” said the researchers.

“[As] the 12-week treatment duration is not adequate to assess the long-term safety and side effects of atogepant, … longer and larger trials are needed to determine the effect and safety of atogepant for migraine prevention,” they added.

*ADVANCE: 12-week placebo-controlled study of atogepant for the preventive treatment of migraine in participants with episodic migraine