RES E A R C H A R T I C L E Open Access
The impact of onabotulinumtoxinA on
severe headache days: PREEMPT 56-week
, Rashmi Halker
, Patricia Pozo-Rosich
, Ronald DeGryse
, Aubrey Manack Adams
and Sheena K. Aurora
Background: OnabotulinumtoxinA has been shown to reduce headache-days among patients with chronic
migraine (CM). The objective of this analysis was to determine whether onabotulinumtoxinA has an impact on
headache-day severity in patients with CM among those patients who were deemed non-responders based on
reduction in the frequency of headache days alone.
Methods: Data from the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical trial program (a
24-week, 2-treatment cycle, double-blind, randomized, placebo-controlled, parallel-group phase, followed by a 32-week,
3-treatment cycle, open-label phase) were pooled for analysis. Patients kept a daily diary to record headache severity on
a 4-point scale (from none to severe), and a 6-domain Headache Impact Test (HIT-6) was used to determine the clinical
impact of headaches. Analysis was undertaken to assess whether the subset of patients that were headache-day
frequency non-responders at week 24 (patients with <50% reduction in headache-day frequency) experienced a
reduction in headache severity whilst receiving onabotulinumtoxinA.
Results: For headache-day frequency non-responders, significant reductions in the number of severe headache days,
average daily headache severity, pooled percentage of severe headache days and headache severity score were
observed at week 24 for patients who had received onabotulinumtoxinA compared with those who had received
placebo. The between-group differences were reduced and non-significant at week 56. Similarly, headache-day
frequency non-responders receiving onabotulinumtoxinA were found to have an improvement in the clinical impact
of headaches using results from the HIT-6.
Conclusions: These results suggest that even those patients with CM who are deemed non-responders based on
analysis of headache frequency alone experience clinically meaningful relief from headache intensity following
treatment with onabotulinumtoxinA.
Keywords: Chronic migraine, OnabotulinumtoxinA, Headache severity, Hit-6, PREEMPT
Chronic migraine (CM; ≥15 headache days per month
for ≥3 consecutive months and with ≥8 days/month of
migraine-type headaches)  is associated with signifi-
cant personal, societal, and economic burdens [2–5].
Compared with people with episodic migraine (EM; <15
headache days per month), those with CM experience
greater headache intensity, increased pain severity and
disability,  higher rates of comorbid medical condi-
tions, [2, 4] reduced health-related quality of life, 
greater economic burden,  and reduced productivity.
The Phase 3 REsearch Evaluating Migraine Prophylaxis
Therapy (PREEMPT) clinical trial program established
the safety and efficacy of onabotulinumtoxinA for CM
[7–10]. In PREEMPT 1 and 2, patients were randomized
to double-blind treatment with onabotulinumtoxinA or
* Correspondence: email@example.com
University College London (UCL) Institute of Neurology and The National
Hospital for Neurology and Neurosurgery, Queen Square, London WC1N3BG,
Full list of author information is available at the end of the article
The Journal of Headache
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made.
Matharu et al. The Journal of Headache and Pain (2017) 18:78