Impact of fremanezumab on disability outcomes in patients with episodic and chronic migraine: a pooled analysis of phase 3 studies

Abstract

Background: Migraine is the second leading cause of disability worldwide. Although many preventive treatments reduce migraine frequency and severity, it is unclear whether these treatments reduce migraine-related disability in a clinically meaningful way. This pooled analysis evaluated the ability of fremanezumab to reduce migraine-related disability, based on responses and shifts in severity in patient-reported disability outcomes.

Methods: This pooled analysis included 3 double-blind phase 3 trials (HALO EM, HALO CM, FOCUS) in which patients with episodic or chronic migraine were randomly assigned 1:1:1 to quarterly or monthly fremanezumab or matched placebo for 12 weeks. Migraine-related disability was assessed using the 6-item Headache Impact Test (HIT-6) and Migraine Disability Assessment (MIDAS) questionnaires. A clinically meaningful improvement in disability was defined per American Headache Society guidelines: for HIT-6, a ≥ 5-point reduction; for MIDAS, a ≥ 5-point reduction when baseline score was 11 to 20 or ≥ 30% reduction when baseline score was > 20. Proportions of patients who demonstrated shifts in severity for each outcome were also evaluated.

Results: For patients with baseline MIDAS scores of 11 to 20 (n = 234), significantly higher proportions achieved 5-point reductions from baseline in MIDAS scores with fremanezumab (quarterly, 71%; monthly, 70%) compared with placebo (49%; both P ≤ 0.01). For patients with baseline MIDAS scores of > 20 (n = 1266), proportions achieving ≥30% reduction from baseline in MIDAS scores were also significantly higher with fremanezumab (quarterly, 69%; monthly, 79%) compared with placebo (58%; both P < 0.001). For HIT-6 scores, proportions of patients achieving 5-point reductions from baseline were significantly higher with fremanezumab (quarterly, 53%; monthly, 55%) compared with placebo (39%; both P < 0.0001). Proportions of patients with shifts of 1 to 3 grades down in MIDAS or HIT-6 disability severity were significantly greater with quarterly and monthly fremanezumab compared with placebo (all P < 0.0001).

Conclusion: Fremanezumab demonstrated clinically meaningful improvements in disability severity in this pooled analysis.

Trial registrations: HALO CM, NCT02621931 ; HALO EM, NCT02629861 ; FOCUS, NCT03308968 .

Keywords: Disability; Fremanezumab; HIT-6; MIDAS; Migraine; Preventive.

Conflict of interest statement

P. McAllister has received research support from and serves as a consultant for Alder Pharmaceuticals, Amgen, Eli Lilly, Novartis, and Teva Pharmaceuticals. J.M. Cohen is a former employee of Teva Pharmaceuticals. V Ramirez Campos, X. Ning, L. Janka, and S. Barash are employees of Teva Pharmaceuticals.

© 2022. The Author(s).

Figures

Fig. 1

Severity of A) headache impact (HIT-6)a and B) migraine-related disability (MIDAS)b at study baseline. HIT-6, 6-item Headache Impact Test; MIDAS, Migraine Disability Assessment. aHIT-6 score categories: ≤49 = little or no impact; 50–55 = some impact; 56–59 = substantial impact; 60–78 = severe impact. bMIDAS score grades: 0–5 = minimal or infrequent disability; 6–10 = mild or infrequent disability; 11–20 = moderate disability; ≥21 = severe disability

Fig. 2

Proportion of patients experiencing A) clinically meaningful (≥5-point) reduction in HIT-6 and B) clinically meaningful reductions in MIDAS scores during 12 weeks of treatment. HIT-6, 6-item Headache Impact Test; MIDAS, Migraine Disability Assessment. MIDAS: severe baseline disability = baseline MIDAS score, > 20; moderate baseline disability = baseline MIDAS score, 11–20; clinically meaningful reduction in MIDAS score = ≥30% reduction for severe disability and ≥ 5-point reduction for moderate disability. n values shown are the number of patients with data available for analysis of change in HIT-6 or MIDAS scores at the end of treatment. aP < 0.0001 versus placebo. bP = 0.0006 versus placebo. cP = 0.0093 versus placebo. dP = 0.0137 versus placebo

Fig. 3

Proportion of patients experiencing downward shifts in A) HIT-6 severity categories and B) MIDAS severity grades during 12 weeks of treatment. HIT-6, 6-item Headache Impact Test; MIDAS, Migraine Disability Assessment. n values shown are the number of patients with data available for analysis of shift in disability severity category in HIT-6 or MIDAS scores at the end of treatment. Total proportion of patients with a downward shift of 1, 2, or 3 categories or grades (as shown at the top of each bar) may differ from the sum of the proportions of patients with downward shifts of 1, 2, or 3 categories or grades due to rounding. aP < 0.0001 versus placebo