The Impact of OnabotulinumtoxinA vs. Placebo on Efficacy Outcomes in Headache Day Responder and Nonresponder Patients with Chronic Migraine

摘要

IntroductionThe phase 3 PREEMPT trials demonstrated efficacy and tolerability of onabotulinumtoxinA for headache prevention in adults with chronic migraine. OnabotulinumtoxinA significantly reduced headache frequency from baseline vs. placebo at 24?weeks; however, this measure may not fully capture the benefits of treatment. We evaluated the impact of onabotulinumtoxinA on patient-reported outcomes according to headache responder status.MethodsA post hoc analysis pooled 24-week data from the placebo-controlled, randomized, double-blind treatment phases of the PREEMPT trials. Patients were stratified by randomized treatment (onabotulinumtoxinA vs. placebo) and headache day responder status (responder vs. nonresponder). Headache day responders had a?≥?50% headache day reduction from baseline measured at weeks 21–24. Outcomes evaluated were patient-reported reductions in moderate-to-severe headache days, Headache Impact Test, and Migraine-Specific Quality of Life Questionnaire. Missing values were estimated using a modified last-observation-carried-forward approach.ResultsIn the pooled analysis population ( N =?1384; onabotulinumtoxinA, n =?688; placebo, n =?696), headache day responder rates were 308/688 (45%) for onabotulinumtoxinA- and 238/696 (34%) for placebo-treated patients. At 24?weeks compared with baseline, onabotulinumtoxinA nonresponders showed significantly (all P ?0.01) greater mean (standard error) reductions vs. placebo nonresponders in moderate-to-severe headache days (–?3.5 [0.2] vs. ??2.4 [0.2]) and Headache Impact Test scores (–?2.3 [0.3] vs. –?0.8 [0.2]), and greater mean improvements in Migraine-Specific Quality of Life Questionnaire domains (Restrictive, 8.8 [1.0] vs. 2.9 [0.8]; Preventive, 6.0 [1.0] vs. 1.8 [0.8]; Emotional, 8.5 [1.3] vs. 2.8 [1.1]). Moderate-to-severe headache day and headache impact differences between nonresponder groups were evident at week 4 and sustained through week 24.ConclusionsRelative to placebo nonresponders, onabotulinumtoxinA nonresponders experienced significant reductions in moderate-to-severe headache days and disability and improvement in quality of life, implying that the full benefits of onabotulinumtoxinA are not captured by headache day reduction.