Patient-identified most bothersome symptom as a driver of health-related quality of life experienced by patients with migraine
Linus Jonsson1, Susanne F Awad2, Stephane A Regnier2, Brian Talon2, Steven Kymes2, Xin Ying Lee2, Peter J Goadsby3
1Department for Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, 2H. Lundbeck A/S, 3NIHR-King’s Clinical Research Facility, King’s College London
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 PI-MBS, 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.