Novel Therapy Combo for Migraine and Medication Overuse Headache

Results from the phase 4 RESOLUTION clinical trial (NCT05452239) show that Vyepti (eptinezumab; Lundbeck, Copenhagen, Denmark) treatment reduced migraine frequency, acute medication use, and pain severity among adults with chronic migraine (CM) and medication-overuse headache (MOH) when combined with a brief educational intervention about MOH. These results were presented at the 67th Annual Scientific Meeting of the American Headache Society (AHS).

The multinational, randomized, double-blind, placebo-controlled trial included 596 adults with CM and MOH who had a history of ≥15 monthly headache days (MHDs), ≥8 monthly migraine days (MMDs), and regular overuse of acute medication. Individuals with opioid-overuse headache were excluded. Participants were randomized 1:1 to receive a single infusion of Vyepti 100 mg or placebo, with all participants receiving a brief educational intervention about MOH before infusion. The primary end point was change in MMDs during weeks 1 through 4, and key secondary end points included sustained changes in MMDs, rates of remission from CM and MOH, pain severity, and acute medication use in weeks 1 through 12.

In terms of key findings:

• Mean reduction in MMDs: -6.9 with Vyepti vs -3.7 with placebo during weeks 1 through 4, and -7.4 vs -4.5 during weeks 1 through12 (both P<.0001)
• Remission from both CM and MOH: 37.8% with Vyepti vs 18.1% with placebo during weeks 1 through 4, and 27.2% vs 12.7% during weeks 1 through 12 (both P<.0001)
• Reduction in average daily pain on a 3-point scale: -.6 with Vyepti vs -.3 with placebo during weeks 1 through 2 (P<.0001)
• Reduction in monthly days of acute medication use: -11.3 with Vyepti vs -7.7 with placebo during weeks 1 through 4, and -11.2 vs -7.8 during weeks 1 through 12 (both P<.0001)
• Rates of treatment-emergent adverse events (TEAEs): 41.9% with Vyepti vs. 36.9% with placebo. Nasopharyngitis was the most common in both groups.

Source: Jensen R, Lundqvist C, Schytz HW, et al. Eptinezumab and patient education in chronic migraine and medication-overuse headache: results from the randomized, placebo-controlled RESOLUTION trial. Presented at: Presented at: Annual Scientific Meeting of the American Headache Society; June 19–22, 2025; Minneapolis, MN.