To assess time of onset of treatment effects of onabotulinumtoxinA relative to placebo on reduction of headache days/week and migraine days/week from baseline in an exploratory pooled analysis of PREEMPT 1 and 2.

Lack of efficacy, adverse effects, and delayed onset of action contribute to poor adherence to current oral medications in individuals with chronic migraine.

Individuals were randomized 1:1 to onabotulinumtoxinA (155-195 U) or placebo given every 12 weeks for 2 cycles in the 24-week, double-blind phase of the trials, followed by 3 cycles of onabotulinumtoxinA (155-195 U) in the 32-week open-label phase. The primary efficacy variable for the pooled analysis was mean (SD) change from baseline in headache days/28 days at week 24. Additional analyses included mean (SD) change from baseline in headache days/week and migraine days/week.

1384 adults received onabotulinumtoxinA (n=688) or placebo (n=696). Baseline values were similar for mean (SD) headache days/week (onabotulinumtoxinA: 4.8 [1.6]; placebo: 4.8 [1.6]; P=0.699) and migraine days/week (onabotulinumtoxinA: 4.6 [1.7]; placebo: 4.6 [1.7]; P=0.722). Pooled analyses demonstrated a significant decrease from baseline in mean headache days/28 days, favoring onabotulinumtoxinA over placebo at the week-24 primary endpoint (−8.4 vs −6.6; P<0.001) and the end of the open-label period (onabotulinumtoxinA/onabotulinumtoxinA: –11.7 vs placebo/onabotulinumtoxinA: –10.8; P=0.019). One week after the first treatment, onabotulinumtoxinA reduced headache days/week by –0.9 (2.2) vs –0.7 (2.1) in placebo (P=0.046) and migraine days/week by –1.0 (2.4) vs –0.7 (2.2) in placebo (P=0.031); this effect persisted from week 3 of the first treatment cycle over 5 treatment cycles.

OnabotulinumtoxinA treatment was associated with significantly greater efficacy than placebo as early as week 1. This improvement was persistent and progressive from week 3 of the first treatment cycle over the course of the 56-week trials, indicating that peak benefit may require multiple treatments.