Journal of Cosmetic and Laser Therapy.

2008; 10: 87–92

ORIGINAL ARTICLE

Patient satisfaction with different botulinum toxin type A formulations

in the treatment of moderate to severe upper facial rhytids

KOEN DE BOULLE

Aalst Dermatology Group, Aalst, Belgium

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Abstract
Background: The clinical characteristics of botulinum toxin type A (BoNTA) depend on the formulation used. Objective: To
evaluate whether switching BoNTA formulations affects patient satisfaction. Methods: Forty patients enrolled and all were
satisfied or extremely satisfied with Allergan BoNTA (BoNTA–Allergan) treatment in the glabellar¡crow’s feet¡forehead
area(s) in the preceding 6 months. Once improvement from this previous treatment had started to diminish, treatment was
replicated using Ipsen BoNTA (BoNTA–Ipsen) at a 1:2.5 dose ratio. Results: The incidence of patients rating treatment as
effective or very effective in making them look younger, look rested, and look less stressed was significantly higher with
BoNTA–Allergan than BoNTA–Ipsen – 83% versus 36%, 90% versus 39%, and 83% versus 33%, respectively – even
though evaluations were performed a mean of 20 weeks after BoNTA–Allergan treatment and only 16 weeks after BoNTA–
Ipsen treatment. The incidence of patients who were satisfied or extremely satisfied was 100% (BoNTA–Allergan) versus
31% (BoNTA–Ipsen). BoNTA–Allergan was preferred by 69% of patients. Conclusions: Efficacy, satisfaction, and product
For personal use only.

preference ratings strongly favor the use of BoNTA–Allergan over BoNTA–Ipsen in the treatment of upper facial lines.
Many patients who are satisfied with BoNTA–Allergan treatment become less satisfied if they are switched to BoNTA–
Ipsen.

Key words: Botox, botulinum toxin, Dysport, rhytid

Introduction Allergan) to evaluate any impact of switching to

The electrophysiological and clinical characteristics
of botulinum toxin type A (BoNTA) vary depending
on the formulation used (1–3). Previous reports have
highlighted differences between formulations in the
duration of clinical improvement (2), the degree of
migration from the site of injection (3,4), and the
incidence of adverse effects (5–10). As the duration
of clinical improvement and the incidence of adverse
effects likely influence the degree of patient satisfac-
tion with treatment, it is possible that different
formulations of BoNTA may also be associated with
different levels of patient satisfaction. Currently,
there is only one formulation of BoNTA available in
the US but a second may become available in due
course. As it is possible that some patients previously
treated with the first formulation may subsequently
be switched to a second formulation, it is useful to
understand whether or not patient satisfaction might
be affected by such a change. To evaluate this, a
study has been performed in patients who were
satisfied with their previous treatment using the
currently available BoNTA formulation (from
treatment with a different formulation (from Ipsen).
Materials and methods
Patients
Patients were eligible to enroll in this open-label
crossover study if they had been treated with the
Allergan formulation of BoNTA (BOTOXH) in the
preceding 6 months in the glabellar area, alone or in
conjunction with the crow’s feet and/or forehead
area. Patients were required to have been satisfied or
extremely satisfied with the clinical effects of this
previous treatment (on a scale of extremely satisfied,
satisfied, somewhat satisfied, somewhat dissatisfied,
dissatisfied, and extremely dissatisfied). In addition,
the clinical improvements of the previous treatment
were required to have started to diminish (in the
opinion of the investigator) before patients could be
enrolled in the study. Patients were also required to
be between 18 and 65 years of age and females of
childbearing potential were required to have a

Correspondence: Koen De Boulle, Aalst Dermatology Group, Leopoldlaan 43, Aalst 9300, Belgium. Fax: 32 53 771915. E-mail: koendeboulle@pandora.be

(Received 30 August 2007; accepted 9 December 2007)

ISSN 1476-4172 print/ISSN 1476-4180 online # 2008 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS)
DOI: 10.1080/14764170701854679
 88 K. De Boulle
negative urine pregnancy test result at the baseline
visit.
Key exclusion criteria included: the planning of
any other facial cosmetic procedure during the study
period other than standard facial skin care; a history
of facial nerve palsy or marked facial asymmetry,
ptosis, excessive dermatochalasis, deep dermal scar-
ring, excessively thick sebaceous skin, or an inability
to substantially lessen upper facial rhytids by
physically spreading them apart; a history of eyebrow
or eyelid ptosis before receiving BoNTA (Allergan);
laser resurfacing, professional dermabrasion, or soft
tissue augmentation in the upper facial area in the
preceding 12 months; profound atrophy/excessive
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weakness of muscles in target areas of injection;
systemic or injection site infection; any medical
condition that may increase the risk of exposure to
BoNTA or interfere with neuromuscular function;
current use of aminoglycoside antibiotics, curare-like
agents, or agents that might interfere with neuro-
muscular (skeletal) function; previous exposure to
any serotype of botulinum toxin other than BoNTA
(Allergan); participation in an investigational drug
study within 30 days of the baseline visit; and
pregnancy, planning of a pregnancy during the study
period, breastfeeding, or not using a reliable method
For personal use only.
of contraception.
Treatment
Each patient’s previous treatment with BoNTA
(BOTOXH; Allergan, Irvine, CA, USA) was repli-
cated using BoNTA (DysportH, Ipsen, Slough, UK)
using a 1:2.5 dose conversion ratio. This was
because the dose of BoNTA (Allergan) that is
approved by the Food and Drug Administration
for the treatment of glabellar lines is 20 U (11) and
Table I. Outcome measures assessed through the patient questionnaire.
Question
How satisfied have you been with your Extremely
BoNTA (Allergan) treatments? satisfied
or
How satisfied are you with the
BoNTA (Ipsen) treatment?
How effective was the BoNTA treatment in Very effective
making you look younger?
How effective was the BoNTA treatment in Very effective
making you look rested?
How effective was the BoNTA treatment in Very effective
making you look less stressed?
After your BoNTA (Ipsen) treatment, did Very noticeable
you notice:
a. Eyelid heaviness?
b. Eyebrows feeling heavy or unnatural?
c. Eyebrow asymmetry?
d. Dryness of the eyes?
e. Inability to show facial expressions?
Which product did you prefer? BoNTA
(Allergan)
the optimal dose of BoNTA (Ipsen) for the treat-
ment of glabellar lines is reported to be 50 U
(12,13). Each formulation was injected in the same
muscle areas, at the same injection sites, and using
the same injection volume and the same gauge
needle. (For glabellar lines, the injection sites used
were those that are currently accepted for treatment
with BoNTA (Allergan) (11) and the same as those
used in a recent study with BoNTA (Ipsen) (13).)
The patients were aware that the BoNTA they were
receiving was a different formulation to that used in
their previous treatment and were offered an
additional treatment at the end of the study with
the BoNTA formulation of their choice.
Outcome measures
At baseline and 2, 8, 12, and 16 weeks after BoNTA
(Ipsen) treatment, patients completed a question-
naire (Table I) that evaluated: (A) how satisfied they
were with their most recent BoNTA treatment; (B)
how effective their last treatment was in making
them look younger, rested, and less stressed; and (C)
which BoNTA formulation they preferred.
Adverse events were captured only for BoNTA
(Ipsen) treatment as patients had already received
BoNTA (Allergan) before entering the study.
Adverse events were reported by the investigator
and, in addition, patients were prompted by the
patient questionnaire (Table I) to report if they had
noticed any of the following: eyelid heaviness,
eyebrows feeling heavy or unnatural, eyebrow
asymmetry, dryness of the eyes, or an inability to
show facial expressions.
The study protocol was approved by the appro-
priate institutional review board and all patients gave
informed consent.
Response options
Satisfied Somewhat Somewhat Dissatisfied Extremely
satisfied dissatisfied dissatisfied
Effective Slightly Ineffective – –
effective
Effective Slightly Ineffective – –
effective
Effective Slightly Ineffective – –
effective
Noticeable Slightly None – –
noticeable
BoNTA – – – –
(Ipsen)
 Botulinum toxin satisfaction 89

Statistical analyses
Analyses were on an intent-to-treat basis with an a
of 0.05 considered to be statistically significant.
McNemar’s test was used to evaluate between-
formulation differences in efficacy and a sign test
was used to evaluate between-formulation differ-
ences in product preference.

Results
Patients
Of 40 patients enrolled to receive BoNTA (Ipsen), Figure 2. Compared with BoNTA (Ipsen), a significantly higher
39 (98%) completed. One discontinued after the
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proportion of patients considered BoNTA (Allergan) was effective

week-8 visit due to lack of efficacy. or very effective in making them look younger.
The patients had a mean age of 48 years (range
33–63 years), all were Caucasian, and 90% were
female. Overall, 55% of the patients had been
extremely satisfied, and 45% had been satisfied with
their previous BoNTA (Allergan) treatment. Among
all patients, 98% received BoNTA in the glabellar
area, 48% received BoNTA in the crow’s feet area,
and 33% received BoNTA in the forehead area.
The mean dose injected was: 25.2 U BoNTA
(Allergan) and 63.0 U BoNTA (Ipsen) in the
For personal use only.

glabellar area; 10.5 U BoNTA (Allergan) and

26.3 U BoNTA (Ipsen) in each crow’s feet area;
and 10.5 U BoNTA (Allergan) and 26.2 U BoNTA
(Ipsen) in the forehead. BoNTA (Ipsen) was
injected a mean of 20 weeks after the earlier
BoNTA (Allergan) treatment (Figure 1), as this Figure 3. Compared with BoNTA (Ipsen), a significantly higher
proportion of patients considered BoNTA (Allergan) was effective
was when the investigator considered the effects of or very effective in making them look rested.
the earlier treatment had started to diminish.

effective or very effective in making them look

Efficacy
Patient ratings of efficacy were more favorable for
BoNTA (Allergan) than for BoNTA (Ipsen)
(Figures 2–4). This was the case even though
BoNTA (Allergan) was evaluated at a greater time
post-injection than BoNTA (Ipsen) (a mean of 20
weeks versus 2–16 weeks, respectively) (Figure 1).
Compared with BoNTA (Ipsen) when evaluated
16 weeks after treatment, a higher proportion of
patients rated BoNTA (Allergan) (which was eval-
uated at a mean of 20 weeks after treatment) as
younger (83% vs 36%, p(0.001) (Figure 2), rested
(90% vs 39%, p(0.001) (Figure 3), and less
stressed (83% vs 33%, p(0.001) (Figure 4).
Patient satisfaction
Patient ratings of satisfaction were more favorable
for BoNTA (Allergan) than BoNTA (Ipsen). A
higher proportion of patients were satisfied or
extremely satisfied with BoNTA (Allergan) than
BoNTA (Ipsen): 100% at a mean of 20 weeks after

Figure 1. Study overview.

 90 K. De Boulle
Figure 4. Compared with BoNTA (Ipsen), a significantly higher
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proportion of patients considered BoNTA (Allergan) was effective
or very effective in making them look less stressed.
For personal use only.
Figure 5. A greater proportion of patients were satisfied or
extremely satisfied with their BoNTA (Allergan) treatment than
with their BoNTA (Ipsen) treatment. (Satisfaction with BoNTA
(Allergan) was evaluated a mean of 20 weeks after treatment and
satisfaction with BoNTA (Ipsen) was evaluated 16 weeks after
treatment.)
BoNTA (Allergan) treatment versus 31% at 16
weeks after BoNTA (Ipsen) treatment (Figure 5).
Product preference
A significantly higher proportion of patients pre-
ferred BoNTA (Allergan) to BoNTA (Ipsen): 69%
vs 31% (p(0.05) at the study endpoint (Figure 6).
Figure 6. A significantly higher proportion of patients preferred
BoNTA (Allergan) over BoNTA (Ipsen) at the study endpoint.
Tolerability
Adverse events were captured only for BoNTA
(Ipsen) treatment as patients had already received
BoNTA (Allergan) before entering the study. The
responses to the patient questionnaire revealed that a
sizeable proportion of patients noticed certain effects
after BoNTA (Ipsen) treatment (Figure 7). At 2
weeks after treatment, 33% (13) noticed eyelid
heaviness, 30% (12) noticed their eyebrows were
heavy or unnatural, 18% (seven) noticed eyebrow
asymmetry, 5% (two) noticed dryness of the eyes,
and 25% (10) noticed an inability to show facial
expressions.
Overall, 40% (16) of patients were reported by the
investigator to have adverse events that were at least
probably related to BoNTA (Ipsen). These were a
feeling of heaviness or pressure in the frontal area,
eye area, or side of face (seven), headache (five),
ptosis (two), asymmetry in the glabellar area (one),
vertical line in frontal area (one), swelling above
eyebrow (one), itch in brow and glabellar area (one),
pain after injection (one), periocular hematoma
(one), and dizziness (one).
Discussion
It has previously been shown that the two formula-
tions evaluated in this study differ in terms of their
duration of clinical improvement (2), degree of
migration from the injection site (3,4), and incidence
of adverse effects (5–10). The results of this study
extend these findings and demonstrate that the two
formulations may also result in different levels of
patient satisfaction, with patients demonstrating a
clear preference for BoNTA (Allergan) over BoNTA
(Ipsen). This may not be surprising given that the
duration of clinical improvement and the incidence
of adverse events are likely key determinants of
patient satisfaction and product preference.
In any study that evaluates the effects of switching
treatments, it can be difficult to define the optimal
post-treatment interval at which the switch should
be made. This study aimed to replicate the reality of
clinical practice – where patients seek re-treatment
before the clinical effects of their previous treatment
have completely disappeared – and so the switch was
made when the clinical effects of the initial treatment
had started to diminish. If anything, this may have
biased the results in favor of the Ipsen formulation as
it is likely that the earliest measurements of efficacy
after treatment with the Ipsen formulation would
have included some carryover effect from treatment
with the Allergan formulation.
The effects of switching BoNTA formulations were
evaluated only from the Allergan formulation to the
Ipsen formulation (and not vice versa also) because
the study was designed to reflect clinical reality in the
US where only the Allergan formulation is available

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Figure 7. Proportion of patients reporting that they had noticed the following effects after BoNTA (Ipsen) treatment. (‘Noticed’ includes
responses of slightly noticeable, noticeable, and very noticeable.)
For personal use only.
currently. If the Ipsen formulation subsequently
becomes available (likely marketed by Medicis as
ReloxinH), it is likely that some patients may be
switched to this even though they were previously
satisfied with the Allergan formulation. As the level of
patient satisfaction with the Allergan formulation is
generally very high in North America (14–16),
patients could be enrolled in this study only if they
were representative of this reality by having been
satisfied or extremely satisfied with their previous
treatment with the Allergan formulation.
The dose conversion ratio of 1:2.5 used in this
study was selected because the dose of the Allergan
formulation of BoNTA that is approved by the Food
and Drug Administration for the treatment of
glabellar lines is 20 U (11) and the optimal dose of
BoNTA (Ipsen) for the treatment of glabellar lines is
reported to be 50 U (12,13). Although there have
been comparisons of these formulations using a
higher dose conversion ratio of 1:4, there is some
evidence that this may result in a relatively higher
incidence of adverse effects with BoNTA (Ipsen)
than BoNTA (Allergan) (5,6), and this could
negatively impact patient satisfaction.
A possible limitation of the study was the lack of
adverse event data following treatment with BoNTA
(Allergan). These data were not captured as patients
did not enroll in this study until they were being
switched to the Ipsen formulation. By this time it is
likely that patient recollections of previous adverse
effects would have been incomplete – as any adverse
events are most likely to have occurred very soon
Botulinum toxin satisfaction 91
after treatment and therefore many weeks before
enrollment in the study. However, as one of the
inclusion criteria was that patients had to have been
satisfied or extremely satisfied with their previous
BoNTA (Allergan) treatment, it is likely that they
had experienced few, if any, issues in terms of
adverse effects. Although patient satisfaction, rather
than tolerability, was the primary focus of this study,
it would nevertheless be useful to capture such
information in a prospective manner in any similar
future studies.
Conclusion
Patient ratings of efficacy, satisfaction, and product
preference strongly favor the use of BoNTA
(Allergan) over BoNTA (Ipsen) in the treatment of
upper facial lines. Furthermore, many patients who
are satisfied with BoNTA (Allergan) treatment
become less satisfied if they are switched to
BoNTA (Ipsen) treatment.
Acknowledgements
Supported by Allergan, Inc.
Note
Dosing and results reported in this study are specific
to each formulation. Botulinum toxin products are
not interchangeable and cannot be converted by
using a dose ratio.
 92 K. De Boulle
Financial disclosures
Allergan provided compensation through an honor-
arium for the time spent on preparing and conduct-
ing this study. Vials of Botox provided by Allergan.
Vials of Dysport purchased with funding from
Allergan. Patients were offered a free additional
treatment after the end of the study with the product
of their choice. If patients chose Botox, vials of
Botox provided by Allergan were used. If patients
chose Dysport, vials of Dysport were purchased
using funding from Allergan.
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