CGRP Antagonist Atogepant Improves Patient-Reported Outcomes as Migraine Preventive

In a post-hoc analysis of the ADVANCE trial, atogepant 30 and 60 mg produced significant improvements in outcomes on Migraine-Specific Quality of Life Questionnaire and Activity Impairment in Migraine-Diary domains.

Richard B. Lipton, MD, director of the Montefiore Headache Center

Richard B. Lipton, MD

Recently published findings showed that atogepant (Qulipta; AbbVie), an FDA-approved preventive for episodic migraine, significantly improved patient-reported outcomes (PROs) that assessed functioning in daily social and work-related activities, as well as emotional impact, physical impairment, and overall impact of headaches.1

The phase 3 study—ADVANCE (NCT02848326)— included a modified intent-to-treat population of 873 adults with 4-14 migraine days/month who were randomly assigned to either atogepant 10 mg (n = 214), 30 mg (n = 223), 60 mg (n = 222), or placebo (n = 214). Atogepant, an oral calcitonin gene-related peptide (CGRP) receptor, was approved in 2021 based on data from a clinical program that included almost 2000 patients with episodic migraine, which included ADVANCE.

Led by Richard B. Lipton, MD, director of the Montefiore Headache Center, the post-hoc analysis specifically focused on several PROs, including the Migraine-Specific Quality of Life Questionnaire v2.1 (MSQ v2.1), Activity Impairment in Migraine-Diary (AIM-D), and Headache Impact Test-6 (HIT-6). The study was designed with a 4-week baseline period, 12-week double-blind treatment period, and 4-week safety follow-up period. Each patient took treatment once daily, orally, at approximately the same time each day.

In the mITT population, the mean age was 41.7 years, and most participants were female (89%) and White (84%). After 12 weeks of treatment, patients demonstrated statistically significant changes in MSQ v2.1 and clinically meaningful improvements in the impact of migraine on daily social and work-related activities in all atogepant groups relative to placebo (P <.0001 for all). Nominally greater improvements were seen in exploratory MSQ v2.1 end points, including Role Function-Restrictive (RFR), Role Function-Preventive (RFP), and Emotional Function (EF) scores.

"The early onset of improved functioning is important to patients, as well as payers,” Lipton et al wrote. "Together, these results reinforce the beneficial effects of atogepant as a promising new treatment for the prevention of migraine."

Despite similar baseline mean AIM-D domain scores, atogepant 30 mg and 60 mg groups continued to show statistically significant improvements in mean monthly AIM-D Performance of Daily Activities (PDA) and Physical Impairment (PI) scores over the 12-week treatment period (P ≤ .002). The 10 mg group also showed an improvement in both AIM-D domains; however, this was not statistically significant compared with placebo.

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Mean baseline HIT-5 total scores were similar among treatment groups and reflective of a severe impact of headaches. Relative to placebo, all atogepant groups showed a nominal improvement (P ≤.006) in HIT-6 total score at the earliest point assessed (week 4) and throughout the double-blind treatment period. Notably, there were a higher proportion of HIT-6 responders—considered at least a 6-point improvement—with all atogepant doses at weeks 4, 8, and 12 (P ≤.03), with the exception of the atogepant 30 mg group at week 4 (P = .07).

When it was approved, atogepant became the first oral CGRP receptor antagonist, specifically for the preventive treatment of episode migraine. It joined Rimegepant (Nurtec ODT; Biohaven) as the second overall member of the gepant class to receive FDA approval. In the original findings of ADVANCE, atogepant met its primary end point, with decreases in mean monthly headache days of 3.7, 3.9, and 4.2 days, respectively, in the 10 mg, 30 mg, and 60 mg atogepant groups compared with a 2.5-day decline in the placebo arm.

Additionally, atogepant demonstrated an ability to improve several prespecified, multiplicity-controlled secondary end points across the 12-week period. Those in the atogepant 10-, 30-, and 60-mg dose groups experienced decreases in mean monthly headache days of 3.9 (baseline, 8.4), 4.0 (baseline, 8.8), and 4.2 (baseline, 9.0) days vs a 2.5-day (baseline, 8.4) decline in the placebo arm (<.0001 for all doses). These translated to 56%, 59%, and 61% of patients in the 10-mg, 30-mg, 60-mg dose groups, respectively, compared with 29% of patients in the placebo arm.

REFERENCES
1. Lipton RB, Pozo-Rosich P, Blumenfeld A, et al. Effect of atogepant for preventive migraine treatment on patient-reported outcomes in the randomized, double-blind, phase 3 ADVANCE trial. Neurology. Published online November 17, 2022. doi:10.1212/WNL.0000000000201568
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