American Society of Regional Anesthesia and Pain Medicine November 2017 - 25

2016 Winner of the ASRA Chronic Pain Grant: Effectiveness of OnabotulinumtoxinA (Botox®) in Pediatric Patients
Experiencing Migraines: A Randomized, Double-Blinded, Placebo Crossover Study in the Pediatric Pain Population

W

hile many chronic pain conditions are manageable,
migraine pain can be devastating. Migraine episodes
are unpredictable in onset and duration and profoundly
debilitating for sufferers. Recently, onabotulinumtoxinA (OBTA)
was approved for the prophylaxis of adult migraine symptoms by
the United States Food and Drug Administration (FDA), which has
dramatically altered the way pain physicians approach migraine pain.
Most adults who suffer with migraines have their first headache
during childhood or adolescence.1 Although many preventative
agents appear to be safe for use in children, none are currently
FDA approved for that age group (apart from topiramate, which
achieved on-label status in 2014). As a result, despite experiencing
significant disability, the vast majority of children who present to
their physician with migraine headaches do not receive prophylactic
therapy.2 A 2003 study published in JAMA found that health care
costs, work-related disability for parents, and lost educational
opportunities for children lead to an annual economic impact in the
United States of approximately $36 billion, because of both direct
medical costs and lost productivity into adulthood.3
Thus, treatment for pediatric head pain is an extrapolation from
all that we have learned about adult headaches combined with
what we have learned from working with children in pain. Pediatric
pain medicine historically has its own challenges, largely suffering
from underassessment and treatment paradigms extrapolated
from adult literature that may not work as well in the pediatric
population. Current clinical
studies, when able to
demonstrate efficacy, may not
demonstrate safety, or vice
versa. In the case of pediatric
migraines, the best current
treatment recommends
involves nonsteroidal
anti-inflammatory drugs,
acetaminophen, and
antiemetics.

Principle Investigator:
Shalini Shah, MD
Assistant Clinical Professor

Faculty Mentor:
Joseph Rinehart, MD
Associate Clinical Professor

Department of Anesthesiology and Perioperative Care
University of California
Irvine, California

practice saw a substantial reduction in migraine days and migraine
duration. In some cases, this meant a significant improvement in
school attendance and daily functional status, and the effect seemed
to persist over longitudinal treatments. In preparation for proposal
of the prospective study, we went back and more formally assessed
the treatment effect of OBTA for refractory pediatric migraine and
found strong evidence in support of its use; the manuscript based on
this work is currently under review for publication.
Looking at our historical
off-label data, we realized
we had an ideal candidate
to investigate for ASRA's
goal of identification of
novel applications of
existing therapeutics.
Moreover, the findings
from this trial may benefit
an understudied pain
population with the longterm aim of obtaining a new FDA indication to "on-label" status.
The proposal also carries policy and legislative impact by fulfilling
the federal initiative to design and conduct trials in the pediatric
pain population within the confines of the Best Pharmaceuticals for
Children Act (BPCA) of 2002. The goal of the BPCA program is to
improve pediatric therapeutics through preclinical and clinical drug
trials that lead to drug labeling changes.

"Treatment for pediatric head pain is
an extrapolation from all that we have
learned about adult headaches combined
with what we have learned from working
with children in pain."

The significance of this study is to evaluate the efficacy of OBTA
(sold commercially as Botox®) for the treatment and prophylaxis
of pediatric migraine in a randomized, double-blinded, placebo
crossover study. No trials currently exist in literature studying
OBTA for efficacy and/or safety for indication of pediatric migraine,
although significant contributions have been made by retrospective
case series over the past 10 years.2,7-10 Additional historical and
longitudinal interest for the design of this study comes from the
principal investigator's (PI) extensive use of off-label OBTA to treat
refractory pediatric migraine over the past five years.
We had impressive anecdotal evidence: Patients who presented with
refractory migraines who were treated with OBTA in the PI's clinical

Because we intended to formally study an off-label use of OBTA,
we had to submit an Investigational New Drug (IND) application
to the FDA prior to institutional review board (IRB) approval. The
FDA was very responsive to our application and, after some minor
revisions, approved our application. However, we then discovered

American Society of Regional Anesthesia and Pain Medicine
2017

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Table of Contents for the Digital Edition of American Society of Regional Anesthesia and Pain Medicine November 2017

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http://www.brightcopy.net/allen/asra/18-04
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http://www.brightcopy.net/allen/asra/15-3
https://www.nxtbook.com/allen/asra/15-2
https://www.nxtbook.com/allen/asra/15-1
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