Improvement in most bothersome symptom or monthly migraine days? Which contributes most to quality of life?

Improvement in the most bothersome symptom contributes more to improvement in health-related quality of life than a reduction in monthly migraine days for patients treated with an anti-calcitonin gene-related peptide monoclonal antibody after two to four prior preventive treatment failures. This is the finding of a study presented at AAN 2023.

Anti-calcitonin gene-related peptide monoclonal antibody efficacy mediators

Efficacy mediators were canonical symptoms in Model 1 and patient-identified most bothersome symptom in Model 2

Efficacy measures mediating the effect of an anti-calcitonin gene-related peptide monoclonal antibody (anti-CGRP mAb) on improvement in health-related quality of life (HRQoL) in patients with migraine were analysed using data from DELIVER (NCT04418765). DELIVER was a randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of an anti-CGRP mAb in patients with migraine and two to four prior preventive migraine treatment failures.1

For the analysis it was assumed that the change from baseline in the three Migraine-Specific Quality of Life Questionnaire (MSQ) domain scores — Role-Function Restrictive, Role-Function Preventive, and Emotional Function2 — could be used to estimate the change from baseline in HRQoL.

A reduction in monthly migraine days explained only one-third of the improvement in quality of life in Model 1

Two structural equation models identified potential effect mediators from treatment versus placebo on HRQoL.

  • In Model 1, these mediators were canonical symptoms as defined by International Headache Society diagnostic criteria3 — monthly migraine days (MMD), severe migraine, nausea, light sensitivity, and pulsating headache — a backwards elimination method was used to identify mediators with p values less than 0.05 for the association with HRQoL.

A reduction in monthly migraine days explained only 17% of the improvement in quality of life in Model 2

  • In Model 2, the mediator was patient-identified most bothersome symptom (PI-MBS). PI-MBS categories included nausea, vomiting, light sensitivity, sound sensitivity, mental cloudiness, fatigue, pain with activity, mood changes, and “other.” The most commonly reported categories were pain with activity (24.6%), fatigue (14.1%), and nausea (13.9%).


Improvement in the most bothersome symptom contributed most to improvement in health-related quality of life

The analysis revealed that a reduction in MMD explained only approximately one-third of HRQoL improvement in Model 1. Reductions in MMDs, the percentage of severe migraine attacks, and canonical symptoms insufficiently explained how the anti-CGRP mAb treatment improved patients’ HRQoL.

An improvement in most bothersome symptom explained 69% of the improvement in quality of life in Model 2

In Model 2, 86% of the impact of anti-CGRP mAb treatment on HRQoL was explained by either an improvement in PI-MBS (69%) or a reduction in MMD (17%). The impact due to improvement in PI-MBS was therefore much greater than that of a reduction in MMD.

These results suggest that discussing improvements in a patient’s PI-MBS after starting a preventive migraine treatment provides a fuller picture of the impact of the treatment on the patient’s HRQoL than a discussion on the reduction in MMD.4


This study and poster were sponsored and supported by H. Lundbeck A/S (Copenhagen, Denmark).


AAN : American Academy of Neurology
anti-CGRP mAb : anti-calcitonin gene-related peptide monoclonal antibody
HRQoL : health-related quality of life  MSQ : Migraine-Specific Quality of Life Questionnaire 
MMD : monthly migraine days 
PI-MBS : patient-identified most bothersome symptom 

BE-NOTPR-0324 approval date 07/2023

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

  1. Ashina M, Lanteri-Minet M, Pozo-Rosich P, et al. Safety and efficacy of eptinezumab for migraine prevention in patients with two-to-four previous preventive treatment failures (DELIVER): a multi-arm, randomised, double-blind, placebo-controlled, phase 3b trial. Lancet Neurol. 2022;21(7):597-607. doi:10.1016/S1474-4422(22)00185-5.
  2. Jhingran P, Osterhaus JT, Miller DW, Lee JT, Kirchdoerfer L. Development and validation of the Migraine-Specific Quality of Life Questionnaire. Headache. 1998;38(4):295-302. doi:10.1046/j.1526-4610.1998.3804295.
  3. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1-211. doi:10.1177/0333102417738202.
  4. Jönsson L, Awad SF, Regnier SA, et al. Patient-identified most bothersome symptom as a driver of health-related quality of life experienced by patients with migraine. Poster P8.010 presented at AAN 2023, April 22–27, Boston, MA.
You are leaving Progress in Mind
Please confirm your email
We have just sent you an email, with a confirmation link.
Before you can gain full access - you need to confirm your email.
The information on this site is exclusively intended for health care professionals.
All the information included in the Website is related to diseases, investigations and existing or potential treatment options and, therefore, directed to health professionals . The technical information of the drugs is provided merely informative, being the responsibility of the professionals authorized to prescribe drugs and decide, in each concrete case, the most appropriate treatment to the needs of the patient.
Register for access to Progress in Mind in your country