Discussion
migraine, long-term reductions, days/month of acute migraine, disability
MIGRAINE, DISEASE
The long-term extension phase of the DELIVER trial shows that the benefits of eptinezumab treatment in reducing migraine frequency and impact are sustained for up to 18 months in patients with migraine and 2–4 prior preventive treatment failures. Patients who were originally randomized to placebo during the double-blind phase experienced an immediate decrease in MMDs with the first dose of eptinezumab in the extension phase that was a similar level of MMDs experienced by those who received eptinezumab during the placebo-controlled phase. The improvements observed over time with each additional infusion suggests a sustained or potentially additive effect of continued treatment, possibly justifying continuing eptinezumab beyond current stopping rules. This is especially important in consideration that a sizable portion of the DELIVER population may meet criteria for resistant or refractory migraine [While the migraine responder rates tended to favor the higher eptinezumab dose (300 mg) in the placebo-controlled phase of the study, the effectiveness of the 100-mg dose approached that of the 300-mg dose with longer-term treatment. The proportion of patients experiencing a ≥ 50% reduction in MMDs during the final 12 weeks of the long-term extension was similar across all 4 treatment groups. The ≥ 75% migraine responder rates, however, continued to favor the higher dose at this timepoint. At present, long-term data beyond 1 year in similar patient populations are available for only one other anti-CGRP monoclonal antibody (erenumab) [Following eptinezumab initiation, patients used ~ 5 fewer days/month of acute migraine medications use when compared to baseline, bringing the average to below thresholds for medication overuse [Improvements in patient-reported outcomes indicate that patients perceived benefits beyond reduced migraine frequency and acute medication use with eptinezumab therapy. Across measures of disease-related functioning, impact, quality of life, and work productivity, patients treated with eptinezumab experienced improvements following the first administration, which demonstrated consistency or further improvement with each subsequent administration. By the end of study, scores indicated that the average patient in DELIVER shifted from experiencing severe headache-related life impact to moderate impact (HIT-6 total score), had clinically meaningful improvement in health-related quality of life (MSQ subscores), experienced much improvement in their most bothersome symptom (PI-MBS) and overall disease state (PGIC), and reported increased work productivity (WPAI:M). These findings are consistent with those of previous eptinezumab studies, which have demonstrated long-term reductions in disability and improvements in functioning and quality of life over periods of up to 2 years (PROMISE-1 [In this long-term study of eptinezumab, there was a low dropout rate, indicating tolerability, and TEAEs with an incidence of ≥ 1.5% were of similar nature to those most commonly reported in previous studies [