Early improvements in function with atogepant as assessed by the Activity Impairment in Migraine–Diary: Post hoc analyses of three randomized, phase 3 clinical trials of atogepant for the preventive treatment of migraine

Abstract Objective Evaluate early functional improvements with the preventive migraine treatment atogepant using Activity Impairment in Migraine–Diary (AIM‐D) individual and activity limitation items, and complete improvement in AIM‐D Performance of Daily Activities (PDA) and Physical Impairment (PI) domain scores assessed weekly during the first 4 weeks of three phase 3 trials. Background Patient‐reported functional outcomes are critical for assessing response to preventive migraine treatments, yet analyses of treatment effects on function at early timepoints are limited. Methods Post hoc analyses assessed AIM‐D data in three multicenter, placebo‐controlled, double‐blind, parallel‐group, 12‐week, randomized clinical trials in participants who received once‐daily atogepant 60 mg or placebo: ADVANCE (episodic migraine [EM], 4–14 monthly migraine days [MMDs]; United States trial, December 14, 2018–June 19, 2020), ELEVATE (EM with prior failure to two to four classes of oral preventive migraine treatments; international trial, March 5, 2021–August 4, 2022), and PROGRESS (chronic migraine [CM]; ≥15 monthly headache days, including ≥8 MMDs; international trial, March 11, 2019–January 20, 2022). A separate activity limitation item was included in the daily eDiary to assess limitation of activity over the past 24 h. The percent change from baseline in each AIM‐D item score and the activity limitation item score, and the proportions of participants achieving complete improvement (i.e., scores of zero) in AIM‐D PDA or PI domain scores, were evaluated at weeks 1 through 4. A mixed model for repeated measures analysis compared least squares mean change from baseline in individual AIM‐D items and activity limitation. A generalized linear mixed model compared the relative odds of achieving complete improvement. Results In ADVANCE, ELEVATE, and PROGRESS, participants treated with atogepant versus placebo generally had a greater reduction in the individual AIM‐D item scores at weeks 1 (ADVANCE, p: <0.001–0.14; ELEVATE, all items p: <0.001; PROGRESS, p: <0.001–0.003), 2 (ADVANCE, p: <0.001–0.018; ELEVATE, p: <0.001–0.002; PROGRESS, p: 0.006–0.192), 3 (ADVANCE, p: <0.001–0.001; ELEVATE, p: <0.001–0.003; PROGRESS, p: 0.004–0.460), and 4 (ADVANCE, p: <0.001–0.028; ELEVATE, p: <0.001–0.050; PROGRESS, p: <0.001–0.067). At weeks 1 through 4, participants in ADVANCE and ELEVATE showed greater improvements in the activity limitation item scores with atogepant versus placebo (all p ≤ 0.001). There were higher odds of achieving complete improvement in the PDA and PI domain scores at weeks 1–4 with atogepant versus placebo across all trials (odds ratios: ADVANCE, 1.614–3.089; ELEVATE, 2.298–5.363; PROGRESS, 2.106–7.617). Conclusions For preventive migraine treatment, atogepant once daily versus placebo was associated with early improvements in AIM‐D individual and activity limitation items and with higher odds of achieving complete improvement for AIM‐D domain scores in people with EM and CM, demonstrating early functional improvements across the migraine spectrum.