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

Abstract

Introduction: The 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.

Methods: A 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.

Results: In 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.

Conclusions: Relative 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.

Trial registration: ClinicalTrials.gov identifiers, NCT00156910 (PREEMPT 1) and NCT00168428 (PREEMPT 2).

Keywords: Botulinum toxin type A; Chronic migraine; Headache; Quality of life.

Fig. 1

Mean (SE) change from baseline in moderate-to-severe headache days. *P < 0.05; **P < 0.01; ***P < 0.001; P values for between-treatment comparisons (e.g., placebo responder vs. onabotulinumtoxinA-treated responder). P < 0.001 for all within-treatment comparisons (responder vs. nonresponder). SE standard error

Fig. 2

Mean (SE) change from baseline in total HIT-6 scores. *P < 0.05; **P < 0.01; ***P < 0.001; P values for between-treatment comparisons (e.g., placebo responder vs. onabotulinumtoxinA-treated responder). P < 0.001 for all within-treatment comparisons (responder vs. nonresponder). HIT-6 6-item Headache Impact Test, SE standard error

Fig. 3

Mean (SE) change from baseline in MSQv2.1 domain scores: a Role Function-Restrictive, b Role Function-Preventive, and c Emotional Function. *P < 0.05; **P < 0.01; ***P < 0.001; P values for between-treatment comparisons (e.g., placebo responder vs. onabotulinumtoxinA-treated responder). MSQv2.1 Migraine-Specific Quality of Life Questionnaire version 2.1, SE standard error