Reducing the Physical, Social, and Emotional Impact of Episodic Migraine

Results From Erenumab STRIVE and ARISE Phase III Randomized Trials

Ariane K. Kawata PhD; Mary Kate Ladd MA; Richard B. Lipton MD; Dawn C. Buse PhD; Mark Bensink PhD; Shweta Shah PhD; Asha Hareendran MA, PhD; Sally Mannix BA; Daniel Mikol MD, PhD

Disclosures

Headache. 2022;62(2):159-168. 

In This Article

Abstract and Introduction

Abstract

Objective: The purpose of this study was to examine changes in the functional impact of migraine following treatment with erenumab, as measured by the Migraine Functional Impact Questionnaire (MFIQ).

Background: The MFIQ, a novel patient-reported outcome (PRO) measuring the impact of migraine on four domains (physical function, social function, and emotional function [PF, SF, and EF]; usual activities [UAs]) and a single item assessing overall impact on UA, was included in phase III trials evaluating erenumab 70 and 140 mg monthly for migraine prevention among people with episodic migraine (EM).

Methods: In the ARISE study, 577 patients with EM were randomized to erenumab 70 mg or placebo. In the STRIVE study, 955 patients with EM were randomized to erenumab, 70 mg or 140 mg or placebo. Pairwise comparisons of least-squares mean (LSM) change from baseline in MFIQ scores (with associated 95% confidence interval [CI]) were assessed for each active treatment versus placebo.

Results: In ARISE, greater reductions from baseline to month 3 were observed for 70 mg versus placebo for PF (LSM [95% CI]: −3.2 [−6.4 to −0.1]; p = 0.046) and EF (−4.0 [−7.3 to −0.7]; p = 0.019) domain scores. In STRIVE, between-group differences also reflected reductions from baseline to the average of months 4–6 that favored erenumab on all four MFIQ domain scores. Reductions in impact for 70 mg compared to placebo were −4.3 (95% CI: −6.8 to −1.7; p < 0.001) for PF, −4.0 (−6.3 to −1.7; p < 0.001) for UA, −3.7 (−6.1 to −1.2; p = 0.003) for SF, and −5.3 (−7.9 to −2.6; p < 0.001) for EF domain scores. Improvements were also observed for 140 mg versus placebo with between-group differences of −5.7 (95% CI: −8.2 to −3.2; p < 0.001) in PF, −5.1 (−7.5 to −2.8; p < 0.001) in UA, −5.0 (−7.4 to −2.6; p < 0.001) in SF, and −7.2 (−9.9 to −4.5; p < 0.001) in EF domain scores. There were also greater improvements in the overall impact on UA score for 70 mg (LSM [95% CI]: −4.3 [−7.0 to −1.7]; p = 0.001) and 140 mg (−5.3 [−8.5 to −3.2]; p < 0.001) versus placebo.

Conclusions: The MFIQ measures the frequency of impacts and level of difficulty on multiple functional domains that provide a more complete picture of the effects of migraine. MFIQ scores showed that in comparison with placebo, patients treated with erenumab had greater reductions in the functional impact of migraine, providing insight into treatment benefits that extend beyond improvements in clinical status and health-related quality of life previously reported based on clinical end points and other PROs.

Introduction

Migraine is a chronic disease that can be associated with substantial disability.[1] Individuals living with migraine experience disruptions of physical and emotional functioning as well as occupational, academic, social, family, and leisure activities.[2,3] In addition, individuals living with migraine may experience effects between attacks (interictal burden), including anxiety and avoidance of activities due to fear of an upcoming migraine attack.[3,4] Specific examples of the impact of migraine were found in a qualitative study of individuals with migraine where 97% reported psychological effects, 91% reported substantial interference with social and leisure functioning, 78% reported an impact on everyday activities (EAs), and more than 50% reported decrements in physical functioning, especially when experiencing a migraine attack.[2]

Preventive treatment for migraine is intended to reduce the frequency and severity of attacks, but also to restore a patient's ability to function and improve their quality of life.[5,6] Previous research has shown that preventive therapies, both pharmacologic and nonpharmacologic, can reduce migraine attacks and headache days, improve quality of life, and reduce functional impact.[7] Traditional oral pharmacologic therapies for migraine prevention were developed for other indications, are less than completely effective, sometimes poorly tolerated, and often discontinued.[8,9] Recently, preventive migraine treatments targeting the calcitonin gene-related peptide pathway, which is pathophysiologically relevant in migraine, have been approved by the US Food and Drug Administration and other regulatory agencies for migraine prevention; approved agents include erenumab,[10] fremanezumab,[11] galcanezumab,[12] and eptinezumab.[13] Erenumab is a fully human monoclonal antibody that selectively blocks the calcitonin gene-related peptide receptor,[14] and reduces migraine frequency in individuals with episodic migraine (EM)[15,16] and chronic migraine.[17]

Guidelines for the evaluation of migraine treatments emphasize the importance of understanding the impact of migraine on functioning.[18] In addition to migraine diaries that capture the severity and frequency of headaches, guidelines recommend the use of patient-reported outcome (PRO) instruments to assess the patient perspective.[18,19] Patient-centric outcome assessments that measure the effect of treatment on functional capacity, disability, and quality of life, including the Migraine Functional Impact Questionnaire (MFIQ), are important for evaluation in clinical trials and for guiding clinical treatment decisions.[20] Measures, like the MFIQ, that include multiple domains allow for the evaluation of the impact of migraine on physical, social, and psychological functioning.[5,21]

The MFIQ was constructed based on best practices for the development of PRO measures to support product labeling claims in the United States.[22–24] Qualitative research was conducted with adults with migraine to develop the MFIQ: concept elicitation interviews were conducted to identify concepts and develop the initial item pool[2] and cognitive interviews were conducted to explore the comprehensiveness of the content and participants' understanding of the items, instructions, and response options.[5] The MFIQ was developed in parallel with the Migraine Physical Function Impact Diary (MPFID), a daily diary focused specifically on the impact of migraine on physical functioning and EAs.[25,26] In contrast to the MPFID, the MFIQ is a comprehensive measure that covers multiple domains, including physical function (PF), social function (SF), and emotional function (EF), and usual activities (UAs), using a 7-day recall period. By collecting data about a range of functional impacts of migraine, the MFIQ offers a more complete disease-specific measurement compared to the PRO instruments that are most commonly used in migraine prevention trials[27] (e.g., Headache Impact Test [HIT-6],[28,29] Migraine Disability Assessment Scale [MIDAS],[30] or Migraine-Specific Quality-of-Life Questionnaire version 2.1 [MSQ v2.1][31]). By virtue of its 1-week recall, the MFIQ is far easier to administer and less burdensome for participants than a daily diary.

The MPFID and MFIQ ask individuals about the impact of migraine on PF in terms of both everyday acts as well as tasks (as conceptualized by Badley and colleagues[32,33])1 that are experienced on migraine and non-migraine days.[25] Measurement of the level of impact of migraine on acts (e.g., difficulty moving the body) is not widely captured by PRO instruments commonly used in migraine.[25] The MFIQ also assesses difficulty in performing particular acts and tasks, as they attempt to "power through" their activities. This additional aspect of level of difficulty is not captured in measures assessing the frequency of restrictions to tasks and how often some activities are avoided, such as the MSQ.

The MFIQ was included in two phase III trials (ARISE and STRIVE) of erenumab in patients with EM. Previously published results from these two trials demonstrated that patients treated with erenumab had statistically significant decreases versus placebo in the number of monthly migraine days, reduction in physical impairment (PI) (based on MPFID), and improvements in health-related quality of life (based on the MSQ).[15,16,34] It is believed that patients treated with erenumab may also experience greater functional improvements in physical, social, and emotional impacts than placebo, as measured by the MFIQ. In this paper, we report an exploratory, post hoc analysis to examine changes in MFIQ scores, to produce additional information from the patient perspective about the impact of migraine, and the ability of erenumab to reduce this impact on physical, social, and emotional functioning.

1The World Health Organization's (WHO) International Classification of Functioning, Disability and Health (ICF) provides a conceptual basis for assessing functioning (WHO 2001). Bradley (2008) conceptualized two key facets of physical functioning: acts (things that an individual can do independent of context or purpose) and tasks (things people do in daily life in a specific context, with purpose)

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