Eptinezumab Infusion During a Migraine Attack Provides Rapid Relief of Migraine Pain and Symptoms

July 2022

Several monoclonal antibodies against calcitonin gene-related peptide or its receptor have been approved by the US Food and Drug Administration for preventing migraines. Previous clinical trials of eptinezumab, an antibody that targets the peptide, have suggested efficacy in preventing migraine attacks as soon as 1 day after infusion. In the latest study, investigators asked whether eptinezumab could be effective as an acute therapy when administered during a migraine attack.

RELIEF, a phase 3, double-blind, randomized clinical trial, enrolled adults with a history of migraine with or without aura for more than 1 year. Participants were required to have had migraines for 4 to 15 days a month in the 3 months before screening, and to have used triptans as an acute therapy for migraines.

When participants had a migraine attack after being headache-free for 24 hours, they received an infusion of eptinezumab or placebo for 30 to 45 minutes within 1 to 6 hours of migraine onset. A total of 238 patients received eptinezumab and 242 received placebo during a migraine attack.

The primary end points were time to freedom from headache pain and time to absence of the most bothersome symptom. Patients chose their most bothersome symptom from among nausea, photophobia, and phonophobia. Secondary outcomes were use of a rescue medication within 24 hours and freedom from headache pain and most bothersome symptom at specific time points.

The results for the primary end points favored eptinezumab. For patients receiving eptinezumab, the median time to freedom from headache pain was 4 hours, compared with 9 hours for patients receiving the placebo (P <.001). The median time to absence of the most bothersome symptom in the eptinezumab group was 2 hours compared with 3 hours in the placebo group (P <.001).

Similarly, secondary end points favored eptinezumab. Freedom from headache pain at 2 hours was achieved by 23.5% of patients receiving eptinezumab versus 12.0% of patients receiving placebo (P <.001). Absence of the most bothersome symptom at 2 hours was achieved by 55.5% of patients with eptinezumab versus 35.8% of patients with placebo (P <.001). Approximately twice as many patients who received the placebo used a rescue medication during the migraine, compared with those who received eptinezumab (59.9% vs 31.5%, respectively; P <.001).

No serious adverse events occurred, but 5 hypersensitivity events occurred in the eptinezumab group, 1 of which was severe.

The investigators concluded that their results showed that eptinezumab shortened the time to relief from a migraine attack. It is unclear, however, whether infusion is a feasible way to deliver an acute therapy. “The practical challenges of delivering eptinezumab during an acute migraine attack (eg, access to an infusion center, insurance coverage issues) may be a limitation to the clinical usefulness of this study,” the investigators acknowledged.


Winner PK, McAllister P, Chakhava G, et al. Effects of intravenous eptinezumab vs placebo on headache pain and most bothersome symptom when initiated during a migraine attack: a randomized clinical trial. JAMA. 2021;325(23):2348-2356.

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