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Aesthetic Surgery Journal
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Prospective Randomized Comparison of OnabotulinumtoxinA (Botox) and AbobotulinumtoxinA (Dysport) in the
Treatment of Forehead, Glabellar, and Periorbital Wrinkles
Basil M. Michaels, George A. Csank, Gabriel E. Ryb, Frederick N. Eko and Abigail Rubin
Aesthetic Surgery Journal 2012 32: 96
DOI: 10.1177/1090820X11430685
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Cosmetic Medicine
Prospective Randomized Comparison
of OnabotulinumtoxinA (Botox) and
AbobotulinumtoxinA (Dysport) in the
Treatment of Forehead, Glabellar, and
Periorbital Wrinkles
Aesthetic Surgery Journal
32(1) 96­–102
© 2012 The American Society for
Aesthetic Plastic Surgery, Inc.
Reprints and permission:
http://www.​ sagepub.com/
journalsPermissions.nav
DOI: 10.1177/1090820X11430685
www.aestheticsurgeryjournal.com
Basil M. Michaels, MD; George A. Csank, MD;
Gabriel E. Ryb, MD, MPH; Frederick N. Eko, MD;
and Abigail Rubin, DO
Abstract
Background: There are several commercially available neurotoxins to improve facial aesthetics, but few prospective, randomized trials have been
conducted without commercial support to compare these agents.
Objectives: The authors present the results of a study examining and comparing the effects of onabotulinumtoxinA (BoNT-ONA; Botox,
Allergan, Inc., Irvine, California) and abobotulinumtoxinA (BoNT-ABO; Dysport, Ipsen Ltd, Slough, UK).
Methods: The authors enrolled 53 patients in a prospective, randomized trial in which each patient received a dose of BoNT-ONA on one side of
the upper face and BoNT-ABO on the other. The effects of each agent were monitored and recorded over 150 days according to each patient’s ability to
elevate the brow, wrinkle count (as measured by the Visia system; Canfield Imaging Systems, Fairfield, New Jersey), and assessment of Fitzpatrick wrinkle
scale rankings by blinded graders.
Results: Results showed no statistically significant differences between the two agents. Both agents yielded measurable improvements on wrinkles of
the upper face at 150 days.
Conclusions: At the current pricing of the agents, BoNT-ABO offers a significant cost savings over BoNT-ONA, with a comparable efficacy. The effect
of both drugs appears to be more prolonged than indicated in the current manufacturer guidelines.
Level of Evidence: 2
Keywords
Botox, cosmetic medicine, Dysport, noninvasive plastic surgery
Accepted for publication June 23, 2011.
Botulinum toxin A, a neurotoxic protein produced by
Clostridium botulinum, is being utilized by clinicians to
decrease muscle hyperactivity for a multitude of therapeutic and cosmetic symptoms ranging from cervical dystonia
to glabellar rhytids. Its use accounted for more than 25%
of nonsurgical aesthetic procedures in the United States in
2008.1 There are eight serotypes of the toxin, synthesized
as a single-chain polypeptide protoxin and “nicked” by
proteases to activate binding at nerve terminal receptors.
Once bound to synaptic receptor SNAP-25, the toxin inhibits release of acetylcholine, thus causing muscle paralysis.
Dr. Michaels and Dr. Csank are Assistant Professors of Clinical
Surgery at the University of Massachusetts, Pittsfield, Massachusetts.
Dr. Ryb is Assistant Professor in the Department of Surgery, Trauma
Program at the University of Maryland School of Medicine, Baltimore,
Maryland. Dr. Eko is a plastic surgery resident at Tulane University,
New Orleans, Louisiana. Dr. Rubin is a third-year postgraduate surgical
resident at Berkshire Medical Center, Pittsfield, Massachusetts.
Corresponding Author:
Dr. Basil M. Michaels, 426 South Street, Pittsfield, MA, 01201 USA.
E-mail: [email protected]
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97
At the time of this study, two commercial preparations
of botulinum toxin A had been approved by the US Food
and Drug Administration (FDA) for cosmetic use. Initially
studied for therapeutic uses in animals, BoNTA-A was the
first FDA–approved neurotoxin. It was originally named
Oculinum, but this was later changed to onabotulinumtoxinA
(BoNT-ONA; Botox, Allergan, Inc., Irvine, California). It
found applications in the treatment of strabismus, blepharospasm, and facial spasm. BoNT-ONA is currently FDAapproved for the treatment of cervical dystonia, severe
primary axillary hyperhidrosis, strabismus, and blepharospasm as well as for the temporary improvement in the
appearance of glabellar wrinkles.2 The second compound,
abobotulinumtoxinA (BoNT-ABO; Dysport, Ipsen Ltd,
Slough, UK), has been approved for the treatment of cervical dystonia and glabellar wrinkles. Several randomized,
placebo-controlled, double-blind studies showed its effectiveness prior to approval.3-7
BoNT-ONA and BoNT-ABO differ in the carrier protein
attached to the 150-kDa botulinum toxin A protein molecule. Although BoNT-ONA contains a 900-kDa carrier
protein attached to the toxin, a 750-kDa carrier exists in
BoNT-ABO.3 Despite the differences in molecular weights,
no differences in diffusion times or efficacy have been
shown in vivo between the two formulations.5
We found few studies comparing the onset of action,
duration of action, or efficacy of these two formulations of
botulinum toxin A in the literature.3,4,6 We sought to compare the characteristics of the two formulations through
side-by-side comparison in the same subject—in effect,
using each patient as his or her own control. In this report,
we present the results of a randomized, controlled comparison of the onset of action, duration of action, and
efficacy of BoNT-ONA and BoNT-ABO in the treatment of
forehead, glabellar, and periorbital wrinkles.
Methods
Study Design and Protocol
This double-blinded, randomized, controlled clinical trial
was conducted in a private plastic surgery clinical office
setting in Pittsfield, Massachusetts. A multidisciplinary
Institutional Review Board at Berkshire Medical Center
approved the protocol. Fifty-three subjects were enrolled
in the study. Eight were smokers, and 26 had undergone
treatment with BoNT-ONA in the past. Both men and
women between the ages of 20 and 90 with glabellar and/
or periorbital wrinkles (crow’s feet) were eligible to participate in this study. Pregnancy or plans to become pregnant were considered exclusion criteria. Other excluded
patients included those with known cardiovascular or
neuromuscular disorders, dysphasia, history of recent
facial infections, allergies to milk proteins or albumin, or
current aminoglycoside therapy. Patients who had undergone BoNT-ONA or BoNT-ABO treatments within the previous six months were also excluded. In addition, patients
on any blood-thinning medications were excluded to
minimize injection site bleeding complications.
Figure 1. The areas treated were marked on a facial
diagram, along with which treatment had been injected into
each side of the face (not shown).
Each study participant attended an initial informational session. At this session, an overview of the study,
along with the inclusion and exclusion criteria and other
pertinent information, was provided. Each participant
was required to have read and understood detailed study
consent prior to participation in the study. The patients
understood that injections outside of the glabellar region
were considered an off-label use. After reviewing and
signing the consent, study participants underwent a treatment session, followed by nine subsequent evaluation
sessions. The treatment session was considered Day 0 of
the study.
At the treatment session, Day 0, pretreatment photos
were taken of each patient, and an initial wrinkle analysis
was conducted with the Visia complexion analysis system
(Canfield Imaging Systems, Fairfield, New Jersey). Digital
photos were taken in a studio setting against a standard
blue background with uniform flash shots on a Nikon D80
camera (Tokyo, Japan) with a Nikkor lens (Tokyo, Japan)
set at a lens angle of 135 mm, exposure of 1/25 of a second, and F-stop of 16. For the Visia analysis, each patient
was placed with the chin resting on the bottom of the
machine (as opposed to the chin rest, as recommended by
the manufacturer) in order to focus on the upper half of
the face. Each patient’s head was also slightly angled so as
to perform analysis on each half of the face separately.
The two botulinum preparations were diluted with sterile
saline so that 1 mL of solution contained either 25 units of
BoNT-ONA or 62.5 units of BoNT-ABO. This ratio of 1:2.5
BoNT-ONA:BoNT-ABO was based the manufacturer’s insert
provided with both products; BoNT-ONA instructions recommended 20 units to treat the glabella, and BoNT-ABO recommended 50 units. Therefore, again, a total of 25 units of
BoNT-ONA were injected into one side and 62.5 units of
BoNT-ABO on the opposite side in standard predetermined
areas (Figure 1) in an equal volume of 0.6 mL. This 1:2.5
BoNT-ONA:BoNT-ABO ratio was chosen based on previously
published effective doses of these medications.2 We used
equal volumes to negate volume dispersal differences.
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Aesthetic Surgery Journal 32(1)
Figure 2. Modified Fitzpatrick wrinkle grading scale. Grade
0: absence of wrinkles; Grade 0.5: very shallow yet visible
wrinkle; Grade 1: visible wrinkle with slight indentation;
Grade 1.5: visible wrinkle and clear indentation less than
1 mm in depth; Grade 2: clearly visible wrinkle 1 to 2 mm
in depth; Grade 2.5: prominent and visible wrinkle more
than 2 mm and up to 3 mm in depth; Grade 3: deep furrow
appearing to measure more than 3 mm in depth.
Injections were performed after EtOH prep, with BoNTONA injected into half of the upper face and BoNT-ABO into
the other half. Although in a clinical setting, variable dosing
regimens based on muscle mass and depth of wrinkles are
most appropriate, for the purpose of this study, we chose a
fixed-dosage regimen to eliminate injector variability. All
treatments were administered by a board-certified plastic
surgeon, with patients randomly assigned to each of two
plastic surgeons (BMM, GAC). A coin toss was used to randomly assign the side of the face to receive BoNT-ONA as
follows: “heads” meant that BoNT-ONA was injected on the
right side, whereas “tails” meant that BoNT-ONA was
injected on the left. Patients were blinded to the laterality of
treatments. Areas treated on each patient included forehead
frown lines, the glabellar area, and crow’s feet. Areas treated
were marked on a facial diagram, along with which treatment had been injected into each side of the face (Figure 1).
Each patient was required to return for nine subsequent
sessions on posttreatment Days 2, 3, 4, 7, 90, 105, 120, 135,
and 150. Digital photographs and wrinkle evaluations were
also performed at each session. Each patient was required
to complete an evaluation form beginning on Day 7 and
every subsequent session thereafter, detailing his or her
opinions on observed differences in facial appearance.
Data Collection
Digital photos were uploaded to the Mirror photo analysis
software system (Version 7.2; Canfield Imaging Systems).
The photos were then graded on the Mirrorphoto system
using the modified Fitzpatrick wrinkle scale originally
developed for nasolabial wrinkles (Figure 2).8 We modified
the Fitzpatrick wrinkle classification system to grade the
appearance of wrinkles on a subjective scale as follows:
Grade 0 was assigned to the absence of wrinkles, Grade 0.5
described a very shallow yet visible wrinkle, Grade 1 was a
visible wrinkle with slight indentation, Grade 1.5 was
assigned to a visible wrinkle and clear indentation less than
1 mm in depth, Grade 2 was a clearly visible wrinkle 1 to 2
mm in depth, Grade 2.5 was a prominent and visible wrinkle more than 2 mm and up to 3 mm in depth, and Grade
3 described a deep furrow appearing to measure more than
3 mm in depth (Figure 2). Photo grading was performed by
two plastic surgeons and two general surgery residents
(BMM, GAC, FNE, AR). All graders were blinded to the
laterality of treatments during grading, and grading data
were collected separately from treatment data. Patients were
randomly assigned to one of the four graders, with each
grader scoring all photo sessions for a particular patient.
Each grader scored a total of 13 to 14 sets of photos.
Eyebrow height in the frontal view was measured with
the Mirrormeasuring tool, with pictures taken when the
patient was asked to look surprised or frown for facial animation. Forehead wrinkles were graded on the previouslydescribed scale in the frontal view with the face at rest and
when the patient was asked to look surprised. Glabellar
wrinkles were also graded on the frontal view with the face
at rest and after asking the patient to frown. Finally, periorbital wrinkles were graded on a 30-degree lateral view with
the face at rest and frowning/squinting. Scores for each
photo session were collated into a Microsoft Access database (Redmond, Washington) for subsequent analysis with
Microsoft Excel. All patients also underwent Visia facial
analysis at each session, and wrinkles detected by the Visia
system were recorded as a single score for each half of the
upper face. These scores were recorded for each session and
also collected in a Microsoft Access database.
Clinical results are shown in Figures 3 to 5.
Results
The 53 patients (one male and 52 females) treated in this
study ranged in age from 34 to 65 years (average, 50).
Outcomes were measured according to three different
methods of assessment with results analyzed in Excel
using the XL STAT program.
The eyebrow height for each subject’s right and left
facial half was measured in centimeters by blinded evaluators. The change in height over time from Day 1 through
Day 150 was not significantly different for BoNT-ABO versus BoNT-ONA, as confirmed by t-test and Wilcoxon
signed t-test. There was no difference in the overall height
between Day 1 (average, 2.5 cm) and Day 150 (average,
2.5 cm) with maximum effect seen at Day 7 (average, 1.7
cm), illustrating a return to baseline muscle action (Figures
6 and 7). We detected no difference in onset of action or
duration between the agents affecting eyebrow motion.
The Fitzpatrick wrinkle grading scale was used to
evaluate wrinkles through time in the forehead, glabellar,
and periorbital regions. There was no significant difference found between BoNT-ABO and BoNT-ONA in terms
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99
Figure 3. This 55-year-old woman is shown (A) with her face at rest on Day 0 (prior to treatment) and (B) at Day 150, when
she demonstrates continued effects of treatment with both BoNT-ABO and BoNT-ONA.
Figure 4. The same patient shown in Figure 3 is shown with maximum brow elevation at (A) Day 0, (B) Day 2, (C) Day 3, (D)
Day 7, (E) Day 120, and (F) Day 150.
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Aesthetic Surgery Journal 32(1)
Figure 5. This 56-year-old woman is shown (A) with her face at rest on Day 0 (prior to treatment) and (B) at Day 150, when
she demonstrates continued effects of treatment with both BoNT-ABO and BoNT-ONA.
Figure 6. Change in eyebrow height (cm) over time (days)
for BoNT-ABO (Dysport) and BoNT-ONA (Botox).
Figure 7. Average eyebrow height (cm) by day for BoNTABO (Dysport) and BoNT-ONA (Botox).
of wrinkle grade (Figures 8-10). A Mann-Whitney twotailed test was used in place of analysis of variance
(ANOVA) to assess significance. There was no difference
from Day 2 through Day 150 (P < .05) for BoNT-ONA and
BoNT-ABO in the forehead and glabellar regions. No difference was seen in the periorbital region through Day
135, with equivocal results at Day 150. Of note, the overall
wrinkle grade was less (average, 0.5) than the initial score
on Day 1 (average, 0.8-0.9). This indicates a continued
effect of BoNT-ONA and BoNT-ABO beyond the 150-day
time course expected (Table 1).
The Visia computerized wrinkle grading system measured total wrinkles for the forehead, glabellar, and periorbital regions over time (Figures 11 and 12). There was no
statistically significant difference seen in a change from
baseline between BoNT-ONA and BoNT-ABO (P < .05)
from Days 2 through 150, with the average number of
wrinkles being 15 and 13 for BoNT-ONA on the respective
days and 14 and 15 for BoNT-ABO on the same days. An
overall decrease in the number of wrinkles on Day 150
compared to Day 1 also demonstrates the continued effect
of BoNT-ONA and BoNT-ABO on wrinkle appearance at
Day 150.
Patients were interviewed regarding adverse events.
Specifically, patients were asked at each session if they
experienced any of the following: flu-like symptoms, headache, pain at injection site, eyelid ptosis, visual field
change, or allergic response. No patients reported any
adverse events.
Discussion
We found no statistically significant difference in the efficacy of BoNT-ONA versus BoNT-ABO in muscle function
or wrinkle appearance using multiple methods of observation and measurement through 150 posttreatment days.
The same efficacy was demonstrated for BoNT-ONA and
BoNT-ABO using the dose ratio of 1:2.5 BoNT-ONA to
BoNT-ABO recommended by the manufacturers. With current pricing of BoNT-ONA at $525 per 100 U and BoNTABO at $475 per 300 U, BoNT-ABO costs $1.58 per unit,
whereas BoNT-ONA is $5.25 per unit. With equal efficacy,
there is a clear cost benefit to BoNT-ABO over BoNT-ONA.
The action of BoNT-ONA and BoNT-ABO on muscle
function was shown to be statistically similar, with an
overall return of muscle height to near-baseline values at
the end of the 150-day time course. Both the Fitzpatrick
scale and Visia wrinkle grading tools showed no statistical
significance between the efficacy of BoNT-ONA and
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Michaels et al
101
Table 1. Percentage of Patients With Continued Aesthetic Effect
Forehead: Dysport 15 U, Botox 6 U
Days
Glabella: Dysport 20 U, Botox 8 U
Periorbital: Dysport 27 U, Botox 11 U
90
120
150
90
120
150
90
120
150
Improvement
75
74
64
60
54
43
49
32
28
Worsening
2
0
4
8
8
2
8
11
13
No change
23
26
28
32
38
51
43
57
55
Improvement
72
68
60
56
41
45
43
26
34
Worsening
2
0
2
6
6
2
6
17
9
No change
26
32
34
38
53
49
51
57
53
Dysport, %
Botox, %
Not measured
4
4
4
Figure 8. Average forehead Fitzpatrick score over time
(days) for BoNT-ABO (Dysport) and BoNT-ONA (Botox).
Figure 9. Average glabellar Fitzpatrick score over time
(days) for BoNT-ABO (Dysport) and BoNT-ONA (Botox).
Figure 10. Average periorbital Fitzpatrick score over time
(days) for BoNT-ABO (Dysport) and BoNT-ONA (Botox).
Figure 11. Visia (Canfield Imaging Systems, Fairfield, New
Jersey) average overall number of wrinkles over time (days)
for BoNT-ABO (Dysport) and BoNT-ONA (Botox).
BoNT-ABO. In fact, a continued measurable muscle weakness and aesthetic effect was demonstrated at Day 150.
This indicates that the effects of both BoNT-ABO and
BoNT-ONA last longer than the manufacturer-reported
duration. Further analysis beyond our chosen end point
(which was based on the recommended drug action)
could reveal a longer duration of efficacy than previously
reported.
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Aesthetic Surgery Journal 32(1)
Funding
The authors received no financial support for the research,
authorship, and publication of this article.
References
Figure 12. Visia (Canfield Imaging Systems, Fairfield, New
Jersey) change in wrinkles (number) over time (days) for
BoNT-ABO (Dysport) and BoNT-ONA (Botox).
The visual grading systems did demonstrate a continued
efficacy beyond Day 150. The difference in the effect on muscle function and wrinkle visibility indicates that the aesthetic
effect of each drug outlasts the paralytic effect. The paralytic
effects of each drug are demonstrated in many of our eyebrow elevation images, as subjects compensate for their glabellar muscle paralysis by directing their gaze upward. There
is potentially a delay between muscle contraction and wrinkle appearance on the skin. This could also be explained by
edema from the injection in the skin. Like other authors, we
found no differences in diffusion characteristics between the
two agents.9
Other authors have noted a persistent aesthetic effect of
botulinum toxin in 25% of patients.10 With a similar dosage,
we found a much higher rate of persistent effect of both
agents in the forehead and glabellar regions. Interestingly,
over the same time period, we noted that a number of
patients demonstrated worsening of the appearance of wrinkles in the periorbital region. This implies that weakening of
the elevators of the forehead leads to some degree of ptosis
and consequently compression of the periorbial tissues, causing worsening of wrinkles in some patients.
Conclusions
BoNT-ABO (abobotulinumtoxinA; Dysport) exhibits the
same efficacy as BoNT-ONA (onabotulinumtoxinA; Botox)
in reducing the appearance of wrinkles in forehead, glabellar, and periorbital regions at a lower cost to the consumer. Additionally, both drugs exhibit continued efficacy
beyond 150 days.
Disclosures
The authors declared no potential conflicts of interest with
respect to the research, authorship, and publication of this
article.
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OnabotulinumA (Botox, Allergan Inc., Irvine CA, USA)/
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rimabotulinumtoxinB (marketed as Myobloc). Available
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on forehead wrinkles and electromyographic activity.
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in facial aesthetic applications. Am J Clin Dermatol
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8. Shoshani D, Markovoitz E, Monstrey SJ, Narins DJ. The
modified Fitzpatrick wrinkle scale: a clinical validated
measurement tool for nasolabial wrinkle severity assessment. Dermatol Surg 2008;34:S85-S91.
9. Kranz G, Haubenberger D, Voller B, et al. Respective
potencies of Botox and Dysport in a human skin model: a
randomized, double-blind study. Mov Disord 2009;24:231236.
10.Matarasso A, Shafer D. Botulinum neurotoxin type
A-ABO (Dysport): clinical indications and practice guide.
Aesthetic Surg J 2009;29(suppl):S72-S79.
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