Better Migraine Response With mMR vs Gepants in Phase 3 EMERGE Trial

Meloxicam and rizatriptan (mMR) are associated with a better response to treatment than gepants among patients with migraine who have an inadequate response to gepants, according to study results presented at the 2025 American Headache Society (AHS) Annual Scientific Meeting, held from June 19-22, in Minneapolis, Minnesota, and virtually.

Meloxicam is a nonsteroidal anti-inflammatory drug and rizatriptan is a selective serotonin receptor agonist. The combinatorial therapy mMR was recently approved by the United States (US) Food and Drug Administration (FDA) as an acute treatment of migraine.

In the EMERGE (ClinicalTrials.gov Identifier: NCT05550207) study, a phase 3, open-label, multicenter trial, researchers evaluated the safety and efficacy of mMR. Patients (N=96) with migraine who had used gepants for 1 month or longer and had inadequate response within 2 hours switched to mMR for their next 4 migraine attacks, up to 8 weeks.

The primary outcome was the change in Migraine Treatment Optimization Questionnaire-4 (mTOQ-4) score from baseline. Inadequate response to gepants was defined as a mTOQ-4 score of 7 or less. The threshold for clinical response was defined as a mTOQ-4 score of 2.

The study participants collectively treated 365 migraine attacks with mMR.

After switching to mMR, patients reported a greater improvement in mTOQ-4 scores than they reported when using gepants (5.2 vs 2.8; P <.001), respectively.

Stratified by TOQ-4 components, a greater rate of clinical response was observed with mMR than gepants for the outcomes of:

• freedom from pain within 2 hours for most attacks (47.9% vs 1.0%; P <.001),
• sustained pain relief through 24 hours after a single dose (47.9% vs 16.7%; P <.001),
• ability to return quickly to normal activities (51.0% vs 11.5%; P <.001), and
• feeling comfortable to plan daily activities (63.5% vs 26.0%; P <.001), respectively.

A quarter of attacks (26.0%) were improved within 30 minutes of taking mMR and two-thirds of attacks (69.2%) were improved within 2 hours of taking mMR, as assessed by the Patient Global Impression of Change.

Patients reported significantly better quality of life outcomes in 3 domains of the Migraine-Specific Quality of Life Questionnaire with mMR than with gepants (all P ≤.003).

The most common adverse events with mMR were fatigue (3.1%), nausea (3.1%), vomiting (2.1%), dizziness (2.1%), and muscle tightness (2.1%).

“These results align with findings from the prior phase 3 studies, providing additional evidence for the efficacy of mMR across a range of migraine patient populations with varying pain intensities and prior responses to acute treatments,” the researchers concluded.

Disclosure: This research was supported by Axsome Therapeutics, Inc. Please see the original reference for a full list of disclosures