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.

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.