STUDY

Efficacy and Safety of 3- and 5-Injection Patterns

(30 and 50 U) of Botulinum Toxin A (Dysport)
for the Treatment of Wrinkles in the Glabella
and the Central Forehead Region
Berthold Rzany, MD, ScM; Benjamin Ascher, MD; Alina Fratila, MD; Gary D. Monheit, MD;
Sergio Talarico, MD; Wolfram Sterry, MD; for the GLADYS Study Group

Objective: To investigate the efficacy and safety of 2 in-
jection site patterns (3- and 5-injection patterns [30 and
50 U]) of botulinum toxin A (Dysport; Ipsen Pharma,
Ettlingen, Germany), in the treatment of glabellar and
central forehead wrinkles.
Design: Multicenter, double-blind, placebo-controlled,
randomized, 16-week trial.
Setting: Twenty-three German dermatologic centers.
Patients: Two hundred twenty-one patients with
moderate or severe glabellar wrinkles when frowning
maximally.
Intervention: Centers were randomly assigned to the
3–injection site pattern (3 injections of 10 U of botuli-
num toxin A or placebo) or 5–injection site pattern
(5 injections of 10 U of botulinum toxin A or placebo).
All centers used 3 sites in the procerus and corrugator
muscles; the 2 additional sites were approximately
1-cm cranial from the corrugator sites.
Main Outcome Measure: Wrinkle severity was
graded by 4 independent experts blinded to the treat-
ment received using digital photographs and a stan-
dardized clinical scale (range, 0 [no wrinkles] to 3
[severe wrinkles]). A reduction of at least 1 point
between weeks 0 and 4 was considered a therapeutic
success (responder).
Result: One hundred ten patients (73 receiving botuli-
num toxin A vs 37 receiving placebo) received 3 injec-
tions; 111 patients (73 receiving botulinum toxin A vs
38 receiving placebo) received 5 injections. After 4 weeks,
the proportions of responders were 86.1% vs 18.9% and
86.3% vs 7.9%, respectively (P⬍.001 for both). No ma-
jor adverse effects were observed.
Conclusions: The 3 central injection sites are essential
for the treatment of glabellar wrinkles. The 2 additional
injection sites in the forehead region, targeting the fron-
talis muscle, did not significantly improve efficacy.
Arch Dermatol. 2006;142:320-326

Author Affiliations: Division of
Evidence Based Medicine,
Klinik für Dermatologie,
Venerologie und Allergologie,
Charité Universitätsmedizin,
Berlin (Drs Rzany and Sterry),
and Jungbrunnen-Klinik
Dr Fratila GmbH, Bonn
(Dr Fratila), Germany; Clinique
Iena, Paris, France (Dr Ascher);
Dermatology Associates,
Birmingham, Ala (Dr Monheit);
and Department of
Dermatology, Federal University
of São Paulo, São Paulo, Brazil
(Dr Talarico).
Group Information: A list of
the members of the GLADYS
Study Group appears on
page 325.
B
OTULINUM TOXIN A HAS BEEN
used successfully for es-
thetic purposes for almost 2
decades, although only a few
clinical trials supporting its
use have been published so far,1-3 and most
of the evidence is in the form of case se-
ries. Dysport (Ipsen Pharma, Ettlingen, Ger-
many), the brand of botulinum toxin A used
in this study, has been available for more
than a decade in Europe and is registered
for various neurological indications. The
product has been used “off label” in der-
matology,4-8 a field in which there is con-
siderable practical experience with its cos-
metic use but few controlled trials reporting
its efficacy and safety to date.
Botulinum toxin A is injected into the
glabellar area, targeting the corrugator,
procerus, and part of the frontalis muscles.8
The number and distribution of the injec-
tion sites, as well as the dose, vary among
studies, with a minimum of 3 injection
sites covering the corrugator and proce-
rus muscles.8 An additional 2 sites may be
injected laterally in the medial part of the
corrugator muscles (shaped like a flying
bird)2,3 or cranially in part of the frontalis
muscle (shaped like an upside-down
house),9 as in the present study. Because
the muscles in this area are interwoven,
1 injection point might target several
muscles.
For editorial comment
see page 362
To our knowledge, this study repre-
sents the largest multicenter trial of Dys-
port for an esthetic indication to date. The
objective of this study was to evaluate the
efficacy and safety of 2 injection site pat-
terns for botulinum toxin A in the treat-

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 A B
Figure 1. Injection sites (shown here on a cadaver) for 3-injection (A) and 5-injection (B) patterns of botulinum toxin A (Dysport; Ipsen Pharma, Ettlingen,
Germany). Placebo was also injected into these sites.
ment of wrinkles of the glabella and the central fore-
head area. Both injection site patterns covered 3 central
sites; one injection site pattern was limited to these 3 sites
(3 injections of 10 U of botulinum toxin A or placebo),
and another injection site pattern included 2 other more
cranial sites (5 injections of 10 U of botulinum toxin A
or placebo).
METHODS
PATIENTS
Patients included in the study were aged 18 to 75 years; had
moderate or severe vertical or diagonal glabellar wrinkles (scores
of 2 or 3 on a standardized 4-point clinical scale ranging from
0 [no wrinkles] to 3 [severe wrinkles]) at maximum frown; and
had mild, moderate, or severe (scores of 1, 2, or 3) vertical or
diagonal glabellar wrinkles at rest. Women of childbearing po-
tential with a negative pregnancy test result before enrollment
in the study were included. All patients gave written informed
consent.
STUDY DESIGN
This was a double-blind, placebo-controlled, randomized, 16-
week trial. It was conducted in 23 dermatologic centers in
Germany.
Centers were allocated randomly to 1 of 2 study arms: cen-
ters in study arm 1 treated wrinkles via 3 injection sites, and
centers in study arm 2 treated wrinkles via 5 injection sites.
Within each center, patients were randomized 2:1 to receive
botulinum toxin A or placebo.
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INTERVENTIONS
Each vial of 500 U of botulinum toxin A (Dysport) was di-
luted with 2.5 mL of saline. An injection volume of 0.05 mL
containing 10 U of botulinum toxin A was used at each injec-
tion point, giving a total botulinum toxin A dose per patient of
30 U or 50 U, depending on study arm enrollment. An injec-
tion volume of 0.05 mL of saline was used for placebo injec-
tions. (The units of the 2 botulinum toxin A preparations on
the market, Dysport and Botox [Pharm Allergan, Ettlingen, Ger-
many], are not equivalent. In dermatologic practice, 3 U of Dys-
port is generally accepted as being equal to 1 U of Botox, and
this ratio has recently been confirmed for use in the treatment
of dystonia by a Cochrane systematic review.10)
In both study arms, 3 injection sites covered the medial parts
of the corrugator muscles and parts of the procerus muscle. In
study arm 2, there were 2 additional cranial sites covering part
of the frontalis muscle (Figure 1).
ASSESSMENTS AND CLINICAL
OUTCOME MEASURES
Assessments were performed at weeks 0, 2, 4, 12, and 16. The
main efficacy assessments were based on a 4-point standard-
ized clinical scale (0, no wrinkles; 1, mild wrinkles; 2, moder-
ate wrinkles; and 3, severe wrinkles) that has been shown to
have good to excellent reproducibility.11 Unlike other stud-
ies1-3 that have used 2 separate scales, only 1 scale was used to
grade the wrinkles at maximum frown and at rest in this study.
The key evaluations were performed, using standardized digi-
tal photographs, by a committee of 4 of us (B.A., A.F., G.D.M.,
and S.T.) who had not been involved in the daily protocol of
the study. The method used has been described elsewhere.11
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 Table 1. Evaluation of Glabellar Wrinkles at Maximum Frown by the Committee in Study Arm 1*

Rating† Visit 1 at Week 0 Visit 2 at Week 2 Visit 3 at Week 4 Visit 4 at Week 12 Visit 5 at Week 16
3 Injections of 10 U of botulinum toxin A (n = 72) (n = 70) (n = 72) (n = 69) (n = 68)
(Dysport; Ipsen Pharma, Ettlingen, Germany)
0 0 8 (11.4) 10 (13.9) 4 (5.8) 0
1 0 37 (52.9) 37 (51.4) 27 (39.1) 9 (13.2)
2 20 (27.8) 19 (27.1) 19 (26.4) 25 (36.2) 42 (61.8)
3 52 (72.2) 6 (8.6) 6 (8.3) 13 (18.8) 17 (25.0)
Mean score 2.72 1.33 1.29 1.68 2.12
3 Injections of placebo (n = 37) (n = 35) (n = 37) (n = 33) (n = 35)
0 0 0 0 0 0
1 1 (2.7) 1 (2.9) 3 (8.1) 1 (3.0) 1 (2.9)
2 9 (24.3) 9 (25.7) 10 (27.0) 12 (36.4) 9 (25.7)
3 27 (73.0) 25 (71.4) 24 (64.9) 20 (60.6) 25 (71.4)
Mean score 2.70 2.69 2.57 2.58 2.69

*Data are given as number (percentage) unless otherwise indicated.

†0 Indicates no wrinkles; 1, mild wrinkles; 2, moderate wrinkles; and 3, severe wrinkles.

A validated system was established to prevent tampering of the
digital images before their transfer to the database and was moni-
tored throughout the study. All patients were evaluated by an-
other investigator among us during study visits.
PRIMARY EFFICACY CRITERION
A reduction of at least 1 point (as assessed by the committee)
between weeks 0 and 4 for glabellar wrinkles at maximum frown
was considered a therapeutic success (the patient was classi-
fied as being a responder). The number (rate) of responders
was considered the primary efficacy criterion.
SECONDARY EFFICACY CRITERIA
The secondary efficacy criteria were the following: (1) the scores
at maximum frown (evaluated by the committee) at weeks 0,
2, 4, 12, and 16 (data not shown); (2) the scores at rest (evalu-
ated by the committee) at weeks 0, 2, 4, 12, and 16; (3) the
scores at maximum frown and at rest (evaluated by the inves-
tigator) at weeks 0, 2, 4, 12, and 16 (data not shown); (4) the
subjective assessment of improvement since the first visit (evalu-
ated by the patient) at weeks 2, 4, 12, and 16 (data not shown);
and (5) the assessment of patients’ global satisfaction with the
treatment at week 16.
STATISTICAL ANALYSIS
The primary analysis was based on the intention-to-treat data
set. Differences between treatment groups for the primary
efficacy criterion were tested using the Fisher exact test
(2-sided) with ␣=.05 in each study arm. Differences between
treatment groups for the secondary efficacy criteria were
tested on an exploratory basis. Based on the data set, the
Fisher exact test or Cochran-Mantel-Haenszel test with table
scores was used.
RESULTS
PATIENT CHARACTERISTICS
All 221 patients who were randomized into the study
received study medication. One hundred ten patients
(73 patients received 3 injections of 10 U of botulinum
toxin A, and 37 patients received 3 injections of placebo)
were included in study arm 1, and 111 patients (73 pa-
tients received 5 injections of 10 U of botulinum toxin A,
and 38 patients received 5 injections of placebo) were in-
cluded in study arm 2. All but 1 patient (in study arm 1)
were included in the intention-to-treat analysis.
Women composed 89.9% (98/109) of the patients in
study arm 1 and 90.1% (100/111) in study arm 2. The
mean±SD ages were 46.6±9.2 years in study arm 1 and
46.4±8.1 years in study arm 2. Only 1 patient, in study
arm 2, was not white. There were no differences at base-
line between the botulinum toxin A–treated and the pla-
cebo groups (data not shown). There were also no large
differences in the mean wrinkle severity scores re-
corded by the committee vs those recorded by the inves-
tigator (data not shown).
EFFICACY
Study Arm 1
The responder rates at maximum frown at week 4 (pri-
mary efficacy criterion) based on the evaluation by the
committee were 86.1% (62 of 72 patients) for 3 injec-
tions of botulinum toxin A and 18.9% (7 of 37 patients)
for 3 injections of placebo. This difference was statisti-
cally significant (P⬍.001) (Table 1, Table 2, and
Figure 2). At week 16, 42 (61.8%) of 68 patients in the
botulinum toxin A–treated group were at least moder-
ately satisfied with the treatment. The remaining 26 pa-
tients (38.2%) in the botulinum toxin A–treated group
and all patients in the placebo group were dissatisfied
(P⬍.001, Fisher exact test) (Table 3).
Study Arm 2
The responder rates at maximum frown at week 4 based
on the evaluation by the committee were 86.3% (63 of
73 patients) for 5 injections of botulinum toxin A and
7.9% (3 of 38 patients) for 5 injections of placebo. The
difference between groups was statistically significant
(P⬍.001) (Table 4, Table 5, and Figure 3). At week
16, 49 (67.1%) of 73 patients in the botulinum toxin

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 Table 2. Evaluation of Glabellar Wrinkles at Rest by the Committee in Study Arm 1*

Rating† Visit 1 at Week 0 Visit 2 at Week 2 Visit 3 at Week 4 Visit 4 at Week 12 Visit 5 at Week 16
3 Injections of 10 U of botulinum toxin A (n = 72) (n = 70) (n = 72) (n = 69) (n = 68)
(Dysport; Ipsen Pharma, Ettlingen, Germany)
0 1 (1.4) 15 (21.4) 17 (23.6) 11 (15.9) 12 (17.6)
1 51 (70.8) 43 (61.4) 44 (61.1) 47 (68.1) 44 (64.7)
2 18 (25.0) 11 (15.7) 9 (12.5) 10 (14.5) 12 (17.6)
3 2 (2.8) 1 (1.4) 2 (2.8) 1 (1.4) 0
Mean score 1.29 0.97 0.94 1.01 1.00
3 Injections of placebo (n = 37) (n = 35) (n = 37) (n = 33) (n = 35)
0 1 (2.7) 3 (8.6) 1 (2.7) 4 (12.1) 2 (5.7)
1 19 (51.4) 16 (45.7) 18 (48.6) 12 (36.4) 16 (45.7)
2 15 (40.5) 16 (45.7) 18 (48.6) 17 (51.5) 17 (48.6)
3 2 (5.4) 0 0 0 0
Mean score 1.49 1.37 1.46 1.39 1.43

*Data are given as number (percentage) unless otherwise indicated.

†0 Indicates no wrinkles; 1, mild wrinkles; 2, moderate wrinkles; and 3, severe wrinkles.

A B

Figure 2. Glabellar area of a 51-year-old woman at maximum frown before (A) and 4 weeks after (B) 3 injections of 10 U of botulinum toxin A (Dysport; Ipsen
Pharma, Ettlingen, Germany).

A–treated group were at least moderately satisfied with

the treatment. The remaining 24 patients (32.9%) in the Table 3. Assessment of Patients’ Global Satisfaction
botulinum toxin A–treated group and all but 2 patients With the Treatment at Week 16 in Study Arm 1*
in the placebo group were dissatisfied (P⬍.001, Fisher
3 Injections of 10 U
exact test) (Table 6). of Botulinum Toxin A
(Dysport; Ipsen Pharma, 3 Injections
SAFETY Ettlingen, Germany) of Placebo
Rating† (n = 68) (n = 35)
Only 1 serious adverse event occurred in the trial (acute de- 0 26 (38.2) 35 (100.0)
pression after a bereavement in a patient in study arm 2), 1 20 (29.4) 0
and this was not considered to be related to the study medi- 2 12 (17.6) 0
cation. Adverse events in which a causal relationship to the 3 10 (14.7) 0
Mean score 1.09 0.00
study drug could not be excluded occurred in 3 patients
treated with 3 injections of botulinum toxin A (hypoesthe- *Data are given as number (percentage) unless otherwise indicated.
sia, injection site discomfort, subjectively heavy eyelids, and †0 Indicates not satisfied; 1, moderately satisfied; 2, satisfied; and 3, very
Spock eyebrow), in 2 patients receiving placebo in the same satisfied.
study arm (headache and pyrexia), in 8 patients treated with
5 injections of botulinum toxin A (4 patients experienced erate, all adverse events were considered to be mild. Only
headache, and 4 other patients experienced Spock eyebrow, 1 case of eyelid ptosis was reported (in the group receiv-
hoarseness, dizziness, and eyelid ptosis), and in 4 patients ing 5 injections of botulinum toxin A). Ptosis of the right
receiving placebo in this study arm (headache, dizziness, eyelid started 13 days after the injections, was considered
blepharochalasis, and swollen face). Except for the case of to be mild, had improved by week 4, and was not visible
Spock eyebrow in study arm 2, which was rated as mod- by week 12. No treatment was required.

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 Table 4. Evaluation of Glabellar Wrinkles at Maximum Frown by the Committee in Study Arm 2*

Rating† Visit 1 at Week 0 Visit 2 at Week 2 Visit 3 at Week 4 Visit 4 at Week 12 Visit 5 at Week 16
5 Injections of 10 U of botulinum toxin A (n = 73) (n = 72) (n = 73) (n = 73) (n = 73)
(Dysport; Ipsen Pharma, Ettlingen, Germany)
0 0 9 (12.5) 7 (9.6) 2 (2.7) 1 (1.4)
1 1 (1.4) 37 (51.4) 41 (56.2) 26 (35.6) 19 (26.0)
2 31 (42.5) 21 (29.2) 18 (24.7) 35 (47.9) 33 (45.2)
3 41 (56.2) 5 (6.9) 7 (9.6) 10 (13.7) 20 (27.4)
Mean score 2.55 1.31 1.34 1.73 1.99
5 Injections of placebo (n = 38) (n = 37) (n = 38) (n = 38) (n = 38)
0 0 0 0 0 0
1 0 0 1 (2.6) 1 (2.6) 1 (2.6)
2 15 (39.5) 11 (29.7) 11 (28.9) 15 (39.5) 13 (34.2)
3 23 (60.5) 26 (70.3) 26 (68.4) 22 (57.9) 24 (63.2)
Mean score 2.61 2.70 2.66 2.55 2.61

*Data are given as number (percentage) unless otherwise indicated.

†0 Indicates no wrinkles; 1, mild wrinkles; 2, moderate wrinkles; and 3, severe wrinkles.

Table 5. Evaluation of Glabellar Wrinkles at Rest by the Committee in Study Arm 2*

Rating† Visit 1 at Week 0 Visit 2 at Week 2 Visit 3 at Week 4 Visit 4 at Week 12 Visit 5 at Week 16
5 Injections of 10 U of botulinum toxin A (n = 73) (n = 72) (n = 73) (n = 73) (n = 73)
(Dysport; Ipsen Pharma, Ettlingen, Germany)
0 0 12 (16.7) 14 (19.2) 11 (15.1) 10 (13.7)
1 50 (68.5) 46 (63.9) 47 (64.4) 49 (67.1) 48 (65.8)
2 20 (27.4) 14 (19.4) 10 (13.7) 13 (17.8) 15 (20.5)
3 3 (4.1) 0 2 (2.7) 0 0
Mean score 1.36 1.03 1.00 1.03 1.07
5 Injections of placebo (n = 38) (n = 37) (n = 38) (n = 38) (n = 38)
0 1 (2.6) 1 (2.7) 2 (5.3) 1 (2.6) 0
1 27 (71.1) 24 (64.9) 24 (63.2) 29 (76.3) 28 (73.7)
2 8 (21.1) 11 (29.7) 11 (28.9) 7 (18.4) 9 (23.7)
3 2 (5.3) 1 (2.7) 1 (2.6) 1 (2.6) 1 (2.6)
Mean score 1.29 1.32 1.29 1.21 1.29

*Data are given as number (percentage) unless otherwise indicated.

†0 Indicates no wrinkles; 1, mild wrinkles; 2, moderate wrinkles; and 3, severe wrinkles.

A B

Figure 3. Glabellar area of a 28-year-old woman at maximum frown before (A) and 4 weeks after (B) 5 injections of 10 U of botulinum toxin A (Dysport; Ipsen
Pharma, Ettlingen, Germany).

COMMENT but rather a study of the number and distribution of in-

jection sites. One injection site pattern (3 injections of
This was not a simple dose-ranging trial to evaluate dif- 10 U of botulinum toxin A) involved only the glabella;
ferent doses, as in the study performed by Ascher et al,1 the other injection site pattern (5 injections of 10 U of

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 botulinum toxin A) involved the glabella and 2 addi-
tional cranial sites in the central forehead.12 The addi-
tion of these 2 sites targeting the frontalis muscle did
not increase the efficacy. However, only wrinkles in the
glabellar area were evaluated in this trial, and we cannot
rule out the possibility that evaluation of central fore-
head wrinkles would have shown the 5-injection site pat-
tern to be more effective.
Based on our results, 3 injections of 10 U of botuli-
num toxin A might be a sufficient dosage for the glabel-
lar region for most patients. Other more lateral sites or
an increased dosage might further improve the efficacy,
as shown by Ascher et al1 for 25, 50, and 75 U total of
botulinum toxin A.
Although patients’ satisfaction was generally good,
29.4% (in the group receiving 3 injections of botulinum
toxin A) and 23.3% (in the group receiving 5 injections
of botulinum toxin A) of patients reported only moder-
ate satisfaction. Even for the group receiving 5 injec-
tions of botulinum toxin A, which showed a smaller pro-
portion of moderately satisfied patients, this level of
satisfaction might not be acceptable for this esthetic pro-
cedure. Increasing the dosage to the 3 central sites or add-
ing 2 sites targeting the medial portion of the corrugator
muscles might increase overall satisfaction. However, these
would be the subjects of further study.
This trial also raised some methodological issues. What
are the right outcome criteria for studies evaluating the
efficacy of botulinum toxin A? Although a 4-point clini-
cal scale ranging from 0 (no wrinkles) to 3 (severe
wrinkles) has been used in almost all previous stud-
ies,1-3 most have in fact used one scale for the assess-
ment of wrinkles at rest and another for the assessment
of wrinkles at maximum frown. Consequently, a score
of 2 (moderate wrinkles) does not represent the same
depth of wrinkles in each case. In our study, only 1 scale
was used. Therefore, a score of 2 represents the same depth
of wrinkles at rest and at maximum frown, with the re-
sults that the mean scores at rest are, of course, lower
than those at maximum frown and that changes be-
tween the botulinum toxin A and placebo study arms at
rest are harder to measure. However, the advantage of
using only 1 scale may be better reproducibility: the clini-
cal scale used herein has good to excellent interinvesti-
gator and intrainvestigator reproducibility.11
In a clinical trial studying mimic wrinkles, effective
blinding of the assessment of wrinkles is often difficult
because it may be clear from patients’ muscle move-
ments that botulinum toxin A has been used. On the other
hand, a committee relying on photographs gets only a
glimpse of the possible magnitude of wrinkles, which may
bias the maximum range of possible scores toward the
mean. However, the use of photographs is more likely
to ensure that the investigators are completely blinded
and are less biased about treatment efficacy.
Previously, most clinical trials studying the efficacy
of botulinum toxin A have involved only a few cen-
ters2,13; in fact, only 1 trial has included more than 10 cen-
ters.3 Larger studies, such as the present trial involving
23 centers and 42 investigators, better reflect clinical prac-
tice than those carried out in a few expert centers, and
such trials are crucial to a full examination of safety. Given
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Table 6. Assessment of Patients’ Global Satisfaction
With the Treatment at Week 16 in Study Arm 2*
5 Injections of 10 U
of Botulinum Toxin A
(Dysport; Ipsen Pharma, 5 Injections
Ettlingen, Germany) of Placebo
Rating† (n = 73) (n = 38)
0 24 (32.9) 36 (94.7)
1 17 (23.3) 0
2 18 (24.7) 2 (5.3)
3 14 (19.2) 0
Mean score 1.30 0.11
*Data are given as number (percentage) unless otherwise indicated.
†0 Indicates not satisfied; 1, moderately satisfied; 2, satisfied; and
3, very satisfied.
that the treatment of glabellar wrinkles is a cosmetic pro-
cedure, a high rate of adverse events such as eyelid pto-
sis would be unacceptable. In this study, both botuli-
num toxin A dosages proved to be safe. Only 1 case of
eyelid ptosis was reported among our patients; the eye-
lid ptosis was mild and did not require treatment. Using
Botox in the glabellar area, Carruthers et al13 reported an
eyelid ptosis rate of 6.4% (13 of 203 patients) in a pilot
study, declining to 1.0% (2 of 202 patients) in a subse-
quent study.2 Ascher et al1 meanwhile reported no eye-
lid ptosis in 102 patients treated with 25, 50, and 75 U
total of Dysport. In this context, the position of the 2 ex-
tra injection sites may be important: the sites were dis-
tinctly more lateral in the studies conducted by Car-
ruthers et al,2,13 compared with those in the present study
and in the study by Ascher et al.1
Although botulinum toxin A has been used for es-
thetic indications for a long time, rigorous clinical trials
are needed to evaluate its efficacy and safety. This trial
demonstrates the efficacy and safety of the European brand
of botulinum toxin A, Dysport, for the treatment of gla-
bellar and central forehead wrinkles.
Accepted for Publication: July 28, 2005.
Correspondence: Berthold Rzany, MD, ScM, Division of
Evidence Based Medicine, Klinik für Dermatologie, Ven-
erologie und Allergologie, Charité Universitätsmedizin,
Campus Charité Mitte, Schumannstrasse 20/23, D-10117
Berlin, Germany (berthold.rzany@charite.de).
Author Contributions: Study concept and design: Rzany
and Sterry. Acquisition of data: Rzany, Ascher, Fratila, Mon-
heit, and Talarico. Analysis and interpretation of data:
Rzany, Ascher, Fratila, Monheit, and Talarico. Drafting
of the manuscript: Rzany. Critical revision of the manu-
script for important intellectual content: Ascher, Fratila,
Monheit, Talarico, and Sterry. Obtained funding: Sterry.
Study supervision: Rzany and Sterry.
Group Members: The GLADYS Study Group includes the
following investigators (all in Germany): Jürgen Bauer-
schmitz, MD, Erlangen; Anne-Kathrin Bomke, MD, Ros-
tock; Randolf Brehler, MD, Münster; Dorothee Dill-
Müller, MD, Homburg; Bärbel Ehlers, MD, Rostock;
Gabriele Feller, MD, Mannheim; Katharina Friebe, MD,
Marburg; Andrea Garbea, MD, Mannheim; Gita Gharari,
MD, Rostock; Jens Gille, MD, Frankfurt a Main; Hilde-
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 gard Gundel-Leiter, MD, Innsbruck; Stefan Hammes, MD,
Ludwigshafen; Gesina Hansel, MD, Dresden; Marc Heck-
mann, MD, Starnberg and Percha; Martina Hund, MD,
Berlin; Susanne Jockenhöfer, MD, Berlin; Martin Jung,
MD, Berlin; Sigrid Karrer, MD, Regensburg; Robert Kas-
ten, MD, Ludwigshafen; Lars Köhler, MD, Ludwig-
shafen; Helga Konrad, MD, Dresden; Markus Krause, MD,
Magdeburg; Tina Küster, MD, Marburg; Andrea Misic,
MD, Dortmund; Marion Moers-Carpi, MD, Hamburg;
Franca Noack-Wiemers, MD, Leipzig; Ulrike Ortner, MD,
Innsbruck; Claudia Pirker, MD, Dortmund; Lucie Rauch,
MD, Düsseldorf; Anita Rütter, MD, Münster; Konstanze
Spieth, MD, Frankfurt a Main; Annette Stein, MD,
Dresden; Rolf-Markus Szeimies, MD, Regensburg; Jörg
Tittelbach, MD, Jena; Kerstin Trümper, MD, Dresden;
Constanze Voigtländer, MD, Erlangen; Sabine Werfel, MD,
München; Luitgard G. Wiest, MD, München; Ulrike
Wilsch, MD, Magdeburg; Petra Wörl, MD, Erlangen; and
Wolf-Ingo Worret, MD, München.
Financial Disclosure: Dr Rzany has received grants from
Ipsen Pharma, Ettlingen, as well as from Pharma Aller-
gan, Ettlingen, for other clinical trials not related to this
study. Dr Rzany also has received honoraria from Ipsen
Pharma for consulting and for conducting educational
workshops.
Funding/Support: This study was supported by a grant
from Ipsen Pharma.
Role of the Sponsor: Ipsen Pharma supported the de-
sign and conduct of the study; the collection, manage-
ment, and analysis of the data; and the final report.
(REPRINTED) ARCH DERMATOL/ VOL 142, MAR 2006
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