Eptinezumab Improved Outcomes in Chronic Migraine with Medication Overuse

Vyepti (eptinezumab-jjmr; Lundbeck, Copenhagen, Denmark) treatment improved migraine and medication-overuse outcomes in adults with chronic migraine (CM) and medication-overuse headache (MOH), according to results from the phase 4 RESOLUTION clinical trial (NCT05452239) published in Neurology. In the randomized, double-blind, placebo-controlled study, Vyepti administered with a brief educational intervention reduced monthly migraine days (MMDs) more than placebo given with the same educational approach.

RESOLUTION was conducted at 76 specialist clinics in 11 countries. Most participants were enrolled in Europe. Adults with both CM and MOH were randomly assigned 1:1 to receive Vyepti 100 mg administered intravenously (n=303) or placebo infusion (n=301). All participants also received a brief educational intervention delivered before infusion at baseline, which included assessment of medication-related dependence behaviors, counseling on the relationship between medication overuse and chronic headache, and a plan to stop overused acute medication. The primary end point was change from baseline in MMDs during weeks 1 to 4. At baseline, participants had a mean of 20.9 MMDs, 21.7 monthly headache days, and 20.1 monthly days with acute migraine medication use.

RESOLUTION Results

• During weeks 1 to 4, MMDs decreased by 6.9 days with Vyepti + education compared with 3.7 days with placebo + education, for a between-group difference of −3.2 days (95% CI, −4.2 to −2.2; P<.0001).
• Across weeks 1 to 12, MMDs decreased by 7.4 days with Vyepti compared with 4.5 days with placebo, a difference of −2.9 days (95% CI, −3.9 to −2.0; P<.0001).
• Monthly headache days were reduced by 6.5 days with Vyepti and 3.4 days with placebo during weeks 1 to 4, and by 7.4 and 4.5 days, respectively, across weeks 1 to 12.
• During weeks 1 to 4, 37.8% of participants treated with Vyepti no longer met threshold criteria for either CM or MOH compared with 18.1% of participants receiving placebo (odds ratio, 3.3; 95% CI, 2.2 to 4.9; P<.0001).
• Across weeks 1 to 12, 27.2% of participants in the Vyepti group no longer met criteria for either CM or MOH compared with 12.7% in the placebo group (odds ratio, 3.1; 95% CI, 1.9 to 4.9; P<.0001).
• Monthly days with acute migraine medication use decreased by 11.3 days with Vyepti and 7.7 days with placebo during weeks 1 to 4, and by 11.2 and 7.8 days, respectively, across weeks 1 to 12.

The study also met multiplicity-controlled secondary end points for monthly headache days, average daily pain score, acute migraine medication use, and combined CM/MOH threshold outcomes. Patient-reported measures also favored Vyepti, including Patient Global Impression of Change scores at weeks 4 and 12 and patient-identified most bothersome symptom scores at week 12.

Treatment-emergent adverse events occurred in 41.9% of participants receiving Vyepti and 36.9% receiving placebo. Most were mild to moderate. Serious treatment-emergent adverse events occurred in 2 participants in the Vyepti group and 1 participant in the placebo group; none were considered treatment-related. No treatment-emergent adverse events led to death. The most common treatment-emergent adverse events occurring in at least 2% of either treatment group were nasopharyngitis, influenza, dizziness, and fatigue.

The investigators noted that the trial design did not include groups receiving Vyepti or placebo without the educational intervention, so the relative contribution of education, medication withdrawal, and Vyepti could not be separated. They also noted limits to generalizability because the trial excluded individuals with prior CGRP-targeted preventive treatment failure, barbiturate or opioid analgesic use for more than 4 days per month, clinically significant psychiatric or cardiovascular disease, or confounding pain syndromes.

Source

Jensen RH, Lundqvist C, Schytz HW, et al. Eptinezumab with patient education for chronic migraine and medication-overuse headache: the randomized, placebo-controlled RESOLUTION trial. Neurology. 2026;106:e214863. doi:10.1212/WNL.0000000000214863