Benefits Beyond Headache Days With OnabotulinumtoxinA Treatment: A Pooled PREEMPT Analysis

Abstract

Introduction: The double-blind, phase 3 PREEMPT trials demonstrated the efficacy and tolerability of onabotulinumtoxinA for headache prevention in adults with chronic migraine. This post hoc analysis evaluated the effect of onabotulinumtoxinA on clinically meaningful changes in headache severity, headache-related impact, and quality of life.

Methods: Pooled, 24-week data were used to determine percentages of patients meeting responder criteria for the change in headache days (≥ 50% reduction in headache-day frequency), Headache Impact Test (HIT-6; ≥ 5-point improvement), MSQ Role Function-Restrictive (MSQ-RFR; ≥ 10.9-point improvement), and Average Daily Headache Severity (ADHS; ≥ 1-point improvement on a 4-point ordinal scale [0 = no pain, 3 = severe pain]).

Results: In the pooled analysis population (N = 1384; onabotulinumtoxinA, n = 688; placebo, n = 696), significantly more patients treated with onabotulinumtoxinA compared with placebo were responders on HIT-6 (40.8 vs. 25.3%), MSQ-RFR (59.0 vs. 40.2%), and ADHS (35.5 vs. 22.4%) measures, and achieved traditional ≥ 50% reduction in headache days (44.8 vs. 34.2%; all P < 0.001). At least one responder criterion was met by 72.1% and 56.6% of onabotulinumtoxinA- and placebo-treated patients, respectively; all four were met by 20.4% and 8.6%, respectively (P < 0.001). Linear regression analysis showed that approximately 20% of the variance in HIT-6 and MSQ-RFR improvement was explained by improvement in headache days.

Conclusions: Treatment with onabotulinumtoxinA for 24 weeks was associated with clinically meaningful benefits beyond reduction in headache days; including reductions in headache severity and headache-related impact, and improved quality of life. While 45% of patients met responder criteria for monthly headache days, over 70% had clinically meaningful improvements on at least one outcome measure.

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

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

Fig. 1

Responder rates for various outcome measures (mLOCF) for weeks 21–24 relative to the pretreatment baseline. ^a Includes any patient who achieved at least one of these four criteria: at least a 50% reduction in headache days, clinically meaningful change in the HIT-6 total score, MSQ-RFR domain score, or headache severity at week 24. ADHS Average Daily Headache Severity, HIT-6 6-item Headache Impact Test, MSQ-RFR Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive

Fig. 2

Percentage of patients who were responders on ≥ 1, ≥ 2, ≥ 3, and 4 outcome measures. Any patient who achieved at least one of these four outcome measures—50% reduction in headache days, or clinically meaningful change in HIT-6, MSQ-RFR, or headache severity at week 24—was counted as a responder. HIT-6 6-item Headache Impact Test, MSQ-RFR Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive

Fig. 3

Number of patients who met all possible responder criteria combinations. Areas defined by the intersections are not proportional. ADHS Average Daily Headache Severity, HA headache, HIT-6 6-item Headache Impact Test, MSQ-RFR Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive