Encouraging Response Trajectories for Eptinezumab for Chronic Migraine

December 2022

Newer therapies for prevention of migraines that block the calcitonin gene-related peptide, such as the monoclonal antibody eptinezumab, reach efficacy sooner than previous therapies. However, whether early responses are maintained over time is unclear.

To evaluate whether the response to treatment is maintained, researchers compared migraine frequency in the first month of treatment to that of the subsequent 5 months using the results from previous trials for eptinezumab. They obtained the data from PROMISE-2, a phase 3 randomized clinical trial for eptinezumab in adults with chronic migraines. Patients enrolled in the trial had migraines for ≥8 days and headaches for 15 to 26 days during the 4 weeks before treatment. Patients were randomized to 1 of 3 groups to receive 100 mg or 300 mg of eptinezumab or placebo by infusion at the start of the trial and again after 12 weeks.

The reduction in number of migraine days in each month of the study was compared with the 4 weeks before treatment, and patients were classified by migraine responder rates. More than one-quarter of patients had a reduction in the number of monthly migraine days of ≥75% during the first month of treatment. Of these patients with a ≥75% migraine responder rate, 81% were in the eptinezumab groups. Among poor responders (responder rate of <25%), more patients were in the placebo group (42%) than in the 100 mg eptinezumab group (29%) or the 300 mg eptinezumab group (23%).

The strong responders in month 1 tended to maintain a strong response regardless of whether they received eptinezumab or placebo. At least two-thirds of each treatment group with a migraine responder rate of ≥75% maintained this level of response for an additional ≥3 months. Two-thirds of the strong responders in month 1 had a responder rate of ≥50% in each of the following 5 months, and 43% had a responder rate of ≥75% in each of the following 5 months.

Some patients who had poorer responses in month 1 had stronger responses in subsequent months. For patients who had a 25% to <50% migraine responder rate in month 1, approximately half of each treatment group still had ≥3 additional months with a ≥50% response.

Stronger responses in later months were found more often in patients taking eptinezumab than placebo. More patients receiving eptinezumab than placebo in the 25% to 50% responder rate group at month 1 were able to achieve a ≥50% response in each of the following 5 months. Among those with a migraine responder rate of <25% in the first month, approximately one-quarter of the patients in the eptinezumab groups were able to achieve a ≥50% response for ≥3 months compared with 14% of the placebo group.

Self-reported ratings of condition paralleled the migraine response results. Most patients who rated their condition as “much improved” or “very much improved” in month 1 gave similar ratings for each of the following months.

According to the researchers, the study “revealed that an early response was generally predictive of a sustained response, with many patients experiencing consistent benefits during the subsequent months.” They suggested that patients and clinicians should be able to predict whether eptinezumab will work after 1 month of therapy for those who respond well. However, some patients who had poor responses in the first month were still able to achieve a 50% reduction in migraine frequency for ≥3 of the following 5 months. “These findings could help clinicians and patients set realistic treatment expectations and accelerate appropriate management decisions,” the researchers suggested.

Study limitations were the post hoc design, the natural variation in migraine frequency, and the high placebo response. Funding for the study was from H. Lundbeck A/S.


Buse DC, Winner PK, Charleston L 4th, et al. Early response to eptinezumab indicates high likelihood of continued response in patients with chronic migraine. J Headache Pain. 2022;23(1):29.

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