Post Hoc Analysis of ADVANCE Trial Reveals Atogepant Improves Functional Outcomes in Migraine

Andrew Blumenfeld, MD

(Credit: BNL Health)

A post hoc analysis of the ADVANCE trial (NCT03777059) revealed that 60 mg once daily of atogepant (Qulipta; AbbVie) led to significant improvements in functional outcomes in patients with episodic migraine. This study examined data from completers who received atogepant or placebo, with the results showing clear benefits across multiple migraine-specific quality of life and activity impairment measures.¹

The analysis focused on participants who completed at least 84 days of treatment and had valid data for all study visits. Presented at the 2025 American Academy of Neurology (AAN) Annual Meeting, held April 5-9, in San Diego, California, a total of 176 participants in the atogepant group and 178 in the placebo group were included. All told, atogepant was associated with significant improvements in several key outcomes, including the Migraine-Specific Quality of Life Questionnaire v2.1 (MSQv2.1), Headache Impact Test-6 (HIT-6), and Activity Impairment in Migraine-Diary (AIM-D), with benefits observed from week 4 to week 12.

The study reported that participants receiving atogepant showed greater improvements from baseline in the MSQv2.1 domains compared with placebo at week 4. Notable improvements included Role Function Restrictive (LSMD change from baseline, 14.25; 95% CI, 9.70-18.81), Role Function Preventive (LSMD, 10.19; 95% CI, 6.01-14.37), and Emotional Function (LSMD, 12.15; 95% CI, 7.22; 17.09), all with nominal p-values of less than .0001. A significant reduction in the HIT-6 score was also seen in the atogepant group at week 4 (LSMD, -3.63; 95% CI, -5.09 to -2.17), further supporting its efficacy in improving migraine-related outcomes.

At week 8 and 12, the improvements in the MSQv2.1 domains and HIT-6 were consistent with those seen at week 4, highlighting the sustained benefits of atogepant. In terms of activity impairment, atogepant demonstrated significant reductions in both Performance of Daily Activities and Physical Impairment domains of the AIM-D, with improvements of -4.30 (95% CI, -5.86 to -2.74) and -3.14 (95% CI, -4.41 to -1.87) at weeks 1-4, respectively. These improvements persisted through weeks 5-8 and weeks 9-12.

Led by Andrew Blumenfeld, MD, director of The Headache Center of Southern California, San Diego and co-director of BNL Health, these findings confirm that atogepant 60 mg once daily leads to significant improvements in functional outcomes for patients with episodic migraine across multiple domains, with effects evident throughout the 12-week study period.

READ MORE: Ubrogepant During Migraine Prodrome Shows Significant Benefits in Patient-Reported Outcomes

Following the post hoc results of the ADVANCE trial, a meta-analysis also presented at AAN 2025 provided further evidence supporting the efficacy of atogepant for migraine prevention. The analysis showed that atogepant not only reduced the frequency of migraines but also enhanced quality of life for patients, despite some adverse effects like constipation and nausea.²

The meta-analysis pooled data from 4 randomized controlled trials involving 2813 patients, with 1354 receiving atogepant. The trials collectively showed that atogepant significantly reduced monthly migraine days (SMD, -0.39; 95% CI, -0.49 to -0.29) and monthly headache days (SMD, -0.40; 95% CI, -0.51 to -0.30). Participants also reported decreased acute medication use (SMD, -0.44; 95% CI, -0.70 to -0.18), and a greater 50% responder rate (RR, 1.84; 95% CI, 1.40- 2.42) in the atogepant group compared with placebo. All in all, these results highlighted atogepant’s significant impact on reducing both the frequency and severity of migraine attacks.

Atogepant also demonstrated improvements in quality of life, particularly in the areas of role function–restrictive (SMD, 0.46; 95% CI, 0.27; 0.66), daily activities (SMD, -0.37; 95% CI, -0.47 to -0.27), and physical impairment (SMD, -0.34; 95% CI, -0.44 to -0.24). Additionally, patients reported a reduction in headache impact (SMD, -0.46; 95% CI, -0.61 to -0.32), further confirming its role in enhancing functional outcomes for those with chronic migraine.

Subgroup analyses showed that atogepant was particularly beneficial for patients who had failed prior oral preventive treatments, underscoring its potential as an effective option for harder-to-treat patients. Despite some reports of mild adverse effects, the trial sequential analysis confirmed the robustness of the findings. Moving forward, long-term safety studies, as well as studies focusing on chronic migraine, may be needed to further confirm these results and assess the long-term benefits and risks of atogepant for a broader patient population.

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REFERENCES
1. Blumenfeld A, Gandhi P, Najib U, et al. Impact of Atogepant on Functional Outcomes in Trial Completers for the Preventive Treatment of Episodic Migraine: A Post-Hoc Analysis of the ADVANCE Trial. Presented at: 2025 AAN Annual Meeting; April 5-9; San Diego, CA.
2. Chochoł P, Koppanatham A, Quednow EV, et al. Comparative Efficacy and Safety of Atogepant as Prophylaxis for Chronic and Episodic Migraine in Adults: a Systematic Review with Meta-Analysis and Trial Sequential Analysis. Presented at: 2025 AAN Annual Meeting; April 5-9; San Diego, CA.