Atogepant Improves Quality of Life in Individuals with Chronic, Episodic Migraine

Christopher Gottschalk, MD:

Credit: Yale Medicine

Phase 3 data shows taking atogepant 60 mg as a preventive migraine treatment improves migraine-related quality of life and functioning in participants with different headache frequencies.¹

The trial ADVANCE previously reported that people with episodic migraines who were treated with atogepant demonstrated improvements in their quality of life, and these benefits lasted for a full year, with significant improvement in MSQv2.1 scores, HIT-6 total score, and AIM-D scores.² Going off this study, investigators sought to assess the effects of preventive migraine treatment with atogepant compared with placebo on self-reported quality of life and functioning among different populations of migraine patients across several randomized controlled trials^.1

“The present analysis expands on earlier findings by demonstrating that atogepant also improved QoL, headache-related impairment and daily functioning among people with [episodic migraine] failed by prior preventive treatment, as well as those with [high-frequency episodic migraine], who are at risk of transformation to [chronic migraine] in the absence of effective treatment,” wrote investigators, led by Christopher Gottschalk, MD, from Yale Medicine. “These PROM data are an important complement to the efficacy and safety data underpinning the American Headache Society's endorsement of atogepant and other [calcitonin gene-related peptide]- targeted agents as first-line preventive migraine treatments and reflect the rapid improvement in well-being for patients who respond to atogepant.”

Gottschalk and colleagues analyzed 3 12-week, randomized, placebo-controlled trials to evaluate preventive migraine treatment with atogepant 60 mg once-daily: ADVANCE, PROGRESS, and ELEVATE.^3,4

The ADVANCE trial focused on episodic migraine, 4 to 8 migraine days, and high-frequency episodic migraine with 8 to 12 monthly migraine days. PROGRESS examined chronic migraine. Lastly, ELEVATE, focused on episodic migraine in individuals who previously failed 2 to 4 classes of oral preventive treatments.

“These analyses demonstrated that MSQv2.1 and HIT-6 responder rates favored atogepant in the overall population, but did not reach statistical significance for atogepant vs. placebo among those with [high-frequency episodic migraine],” investigators wrote.¹ “A likely explanation for these findings is the fact that [low-frequency and high-frequency episodic migraine] subgroup analyses were not adequately powered in the ADVANCE trial.”

Compared with placebo, participants on atogepant had a greater change from baseline to week 12 in the Migraine-Specific Quality of Life questionnaire Role Function-Restrictive domain scores (P < .05). This was seen in ADVANCE for low-frequency episodic migraine (least squares mean difference, 12.0; 95% confidence interval [CI], 6.0 to 18.0) and high-frequency episodic migraine (9.9; 95% CI, 3.4 to 16.4), as well as in PROGRESS (6.2; 95% CI, 2.5 to 9.8) and ELEVATE (17.7; 95% CI, 13.1 to 22.3).

Participants on atogepant also had a greater change from baseline to week 12 in Headache Impact Test-6 total scores, shown in ADVANCE for low-frequency episodic migraine (-4.7; 95% CI, -6.7 to -2.7) and high-frequency episodic migraine (-3.4; 95% CI, -5.5 to -1.2), PROGRESS (-2.8; 95% CI, -4.1 to -1.4), and ELEVATE (-6.5; 95% CI, -8.3 to -4.7). Once again, for Activity Impairment in Migraine–Diary-Performance of Daily Activities scores across 12 weeks, participants on atogepant had a greater change from baseline than placebo, demonstrated in the trials ADVANCE (low-frequency episodic migraine: -2.3; 95% CI, -3.9 to -0.7; high-frequency episodic migraine: -4.5; 95% CI, -6.9 to -2.2), PROGRESS (-3.4; 95% CI, 5.3 to -1.5), and ELEVATE (-4.7; 95% CI, -6.4 to -3.1).

“Atogepant 60 mg once-daily improved quality of life, daily functioning, and headache-related impairment among participants with migraine, including those with low- or high-frequency episodic migraine, chronic migraine, or multiple preventive treatment failures,” investigators wrote. “These results demonstrate the value of preventive treatment with atogepant for reducing migraine-attributed impacts on multiple aspects of daily life, health, and well-being across the spectrum of people with migraine.”

References

1. ^{Gottschalk C, Gandhi P, Pozo-Rosich P, Christie S, Tassorelli C, Stokes J, Liu Y, Luo L, Nagy K, Trugman JM, Lipton RB. Effect of preventive treatment with atogepant on quality of life, daily functioning, and headache impact across the spectrum of migraine: Findings from three double-blind, randomized, phase 3 trials. Cephalalgia. 2024 Dec;44(12):3331024241300305. doi: 10.1177/03331024241300305. PMID: 39648617.}
2. ^{Ailani J, Lipton RB, Goadsby PJ, Guo H, Miceli R, Severt L, Finnegan M, Trugman JM; ADVANCE Study Group. Atogepant for the Preventive Treatment of Migraine. N Engl J Med. 2021 Aug 19;385(8):695-706. doi: 10.1056/NEJMoa2035908. PMID: 34407343.}
3. ^{Ashina M, Tepper SJ, Reuter U, Blumenfeld AM, Hutchinson S, Xia J, Miceli R, Severt L, Finnegan M, Trugman JM. Once-daily oral atogepant for the long-term preventive treatment of migraine: Findings from a multicenter, randomized, open-label, phase 3 trial. Headache. 2023 Jan;63(1):79-88. doi: 10.1111/head.14439. Epub 2023 Jan 18. Erratum in: Headache. 2024 Mar;64(3):329. doi: 10.1111/head.14691. PMID: 36651532; PMCID: PMC10107835.}
4. ^{Pozo-Rosich P, Ailani J, Ashina M, Goadsby PJ, Lipton RB, Reuter U, Guo H, Schwefel B, Lu K, Boinpally R, Miceli R, De Abreu Ferreira R, McCusker E, Yu SY, Severt L, Finnegan M, Trugman JM. Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Sep 2;402(10404):775-785. doi: 10.1016/S0140-6736(23)01049-8. Epub 2023 Jul 26. Erratum in: Lancet. 2023 Sep 2;402(10404):774. doi: 10.1016/S0140-6736(23)01812-3. Erratum in: Lancet. 2023 Oct 14;402(10410):1328. doi: 10.1016/S0140-6736(23)02236-5. PMID: 37516125.}