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

Stephen D. Silberstein, Hans Christoph Diener, David W. Dodick, Aubrey Manack Adams, Ronald E. DeGryse, Richard B. Lipton

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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: identifiers, NCT00156910 (PREEMPT 1) and NCT00168428 (PREEMPT 2).

Original languageEnglish (US)
Pages (from-to)695-707
Number of pages13
JournalPain and Therapy
Issue number2
StatePublished - Dec 1 2020


  • Botulinum toxin type A
  • Chronic migraine
  • Headache
  • Quality of life

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine


Dive into the research topics of 'The Impact of OnabotulinumtoxinA vs. Placebo on Efficacy Outcomes in Headache Day Responder and Nonresponder Patients with Chronic Migraine'. Together they form a unique fingerprint.

Cite this