Patient-identified Most Bothersome Symptom As a Driver of Health-Related Quality of Life Experienced by Patients with Migraine (P8-12.010)

Objective: To identify efficacy measures mediating eptinezumab’s effect on health-related quality of life (HRQoL) improvements in patients with migraine. Background: DELIVER (NCT04418765) was a randomized, double-blind, placebo-controlled trial exploring eptinezumab’s safety and efficacy in patients with migraine and 2–4 prior preventive migraine treatment failures. At Weeks 12 and 24, eptinezumab resulted in significantly larger Migraine Specific Quality of Life Questionnaire (MSQ, v2.1) domain score improvements versus placebo. Design/Methods: A latent variable (HRQoL improvement) was constructed to summarize improvement in patient-reported MSQ Emotional-Function, Role-Preventive, and Role-Restrictive domain scores. After determining goodness of fit, two models were used to identify potential effect mediators from treatment (eptinezumab 100mg and 300mg pooled vs. placebo) on HRQoL. In Model 1, changes in migraine frequency (monthly migraine days [MMDs]), proportion of severe migraine attacks, and proportion of migraine attacks with cardinal symptoms (nausea, light sensitivity, and pulsating headache) were included as mediators. In Model 2, only changes in MMDs and patient-identified most bothersome symptom (PI-MBS) were included as mediators. Each model included treatment as the exogeneous variable and the HRQoL latent construct as the dependent variable. Analyses were conducted on DELIVER data from all patients in the double-blind period (Weeks 1–24), using the LAVAAN package for R. Results: Reductions in MMDs and proportion of migraine attacks with cardinal symptoms (including severity) accounted for 35% and 25% of HRQoL improvement, respectively, with 40% of the observed improvement with eptinezumab unexplained by mediators (“direct treatment effect”) (Model 1). Substantial improvement in HRQoL (86%) with eptinezumab is due to MMD reduction and change in PIMBS, with change in PI-MBS contributing more than MMD reduction (69% vs 18%) (Model 2). Conclusions: The burden placed on patients’ HRQoL is driven by efficacy measures beyond migraine frequency. Physicians should discuss improvements in patients’ most bothersome symptom associated with migraine, as this may impact HRQoL. Disclosure: Prof. Jonsson has received personal compensation for serving as an employee of H. Lundbeck A/S. The institution of Prof. Jonsson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for H. Lundbeck. Dr. Awad has nothing to disclose. Mr. Regnier has received personal compensation for serving as an employee of Lundbeck. Mr. Regnier has received personal compensation for serving as an employee of Novartis. Mr. Regnier has stock in Novartis. Dr. Talon has nothing to disclose. Steven Kymes has received personal compensation for serving as an employee of Lundbeck. Steven Kymes has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Journal of Ophthalmology. Steven Kymes has received research support from Emmes Corporation. Ms. Lee has received personal compensation for serving as an employee of Lundbeck A/S. Dr. Goadsby has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aeon BioPharmaceuticals. Dr. Goadsby has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven Pharmaceuticals. Dr. Goadsby has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eli-Lilly. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epalex. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Impel Neuropharma. Dr. Goadsby has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva Pharmaceuticals. Dr. Goadsby has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Praxis. Dr. Goadsby has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dr Reddys. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biodelivery Sciences International. Dr. Goadsby has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aeon Biopharma. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Massachusetts Medical Society. The institution of Dr. Goadsby has received research support from Celgene. The institution of Dr. Goadsby has received research support from Eli-Lilly. The institution of Dr. Goadsby has received research support from Visual Snow Initiative. Dr. Goadsby has received publishing royalties from a publication relating to health care. Dr. Goadsby has received publishing royalties from a publication relating to health care. Dr. Goadsby has a non-compensated relationship as a Trustee with Migraine Trust that is relevant to AAN interests or activities. Dr. Goadsby has a non-compensated relationship as a Trustee with Organisation for Understanding Cluster Headache (UK) that is relevant to AAN interests or activities. Dr. Goadsby has a non-compensated relationship as a Executive roles with American Headache Society that is relevant to AAN interests or activities. Dr. Goadsby has a non-compensated relationship as a Scientific Officer with British Association for the Study of Headache that is relevant to AAN interests or activities. Dr. Goadsby has a non-compensated relationship as a Director with American Migraine Foundation that is relevant to AAN interests or activities.