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 injection 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
Main Outcome Measure : Wrinkle severity was graded by 4 independent experts blinded to the treatment received using digital photographs and a standardized 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 botulinum toxin A vs 37 receiving placebo) received 3 injections; 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 (PϽ.001 for both). No major adverse effects were observed. Conclusions: The 3 central injection sites are essential
3–injection site pattern (3 injections of 10 U of botulinum 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.
for the treatment of glabellar wrinkles. The 2 additional injection sites in the forehead region, targeting the frontalis muscle, did not significantly improve efficacy. Arch Dermatol. 2006;142:320-326 studies, with a minimum of 3 injection sites covering the corrugator and procerus 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.
Author Affiliations: Division of Evidence Based Medicine, Klinik fu ¨ r Dermatologie, Venerologie und Allergologie, Charite ´ Universita ¨ tsmedizin, 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 Sa ˜ o Paulo, Sa ˜ o Paulo, Brazil (Dr Talarico). Group Information: A list of the members of the GLADYS Study Group appears on page 325.
used successfully for esthetic 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 series. Dysport (Ipsen Pharma, Ettlingen, Germany), 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 dermatology,4-8 a field in which there is considerable practical experience with its cosmetic 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 injection sites, as well as the dose, vary among
OTULINUM TOXIN A HAS BEEN
For editorial comment see page 362
To our knowledge, this study represents the largest multicenter trial of Dysport for an esthetic indication to date. The objective of this study was to evaluate the efficacy and safety of 2 injection site patterns for botulinum toxin A in the treat-
(REPRINTED) ARCH DERMATOL/ VOL 142, MAR 2006 320
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. Ipsen Pharma. 16week trial.archdermatol. 4. Placebo was also injected into these sites.com on January 14. The key evaluations were performed.ARCHDERMATOL. by a committee of 4 of us (B.
. and S. moderate wrinkles. In study arm 2. using standardized digital photographs.
Each vial of 500 U of botulinum toxin A (Dysport) was diluted with 2. there were 2 additional cranial sites covering part of the frontalis muscle (Figure 1). and another injection site pattern included 2 other more cranial sites (5 injections of 10 U of botulinum toxin A or placebo). All rights reserved.M.
(REPRINTED) ARCH DERMATOL/ VOL 142. only 1 scale was used to grade the wrinkles at maximum frown and at rest in this study. Germany]. mild wrinkles.5 mL of saline. 2. (The units of the 2 botulinum toxin A preparations on the market. An injection volume of 0. In dermatologic practice.
Patients included in the study were aged 18 to 75 years. 3 U of Dysport is generally accepted as being equal to 1 U of Botox. no wrinkles. and centers in study arm 2 treated wrinkles via 5 injection sites. 3 injection sites covered the medial parts of the corrugator muscles and parts of the procerus muscle. 2. G. Centers were allocated randomly to 1 of 2 study arms: centers in study arm 1 treated wrinkles via 3 injection sites.COM
Downloaded from www. Ettlingen. one injection site pattern was limited to these 3 sites (3 injections of 10 U of botulinum toxin A or placebo). The method used has been described elsewhere. An injection volume of 0. Ettlingen. giving a total botulinum toxin A dose per patient of 30 U or 50 U.
ASSESSMENTS AND CLINICAL OUTCOME MEASURES
Assessments were performed at weeks 0. All patients gave written informed consent. placebo-controlled. depending on study arm enrollment. The main efficacy assessments were based on a 4-point standardized clinical scale (0.11 Unlike other studies1-3 that have used 2 separate scales.05 mL containing 10 U of botulinum toxin A was used at each injection point.D. are not equivalent.F. or 3) vertical or diagonal glabellar wrinkles at rest. Within each center. Germany).05 mL of saline was used for placebo injections. randomized. and had mild. 2. or severe (scores of 1.. and 3.A
Figure 1. Injection sites (shown here on a cadaver) for 3-injection (A) and 5-injection (B) patterns of botulinum toxin A (Dysport. It was conducted in 23 dermatologic centers in Germany.T. A. MAR 2006 321
ment of wrinkles of the glabella and the central forehead area. and this ratio has recently been confirmed for use in the treatment of dystonia by a Cochrane systematic review. severe wrinkles) that has been shown to have good to excellent reproducibility. 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. patients were randomized 2:1 to receive botulinum toxin A or placebo. Both injection site patterns covered 3 central sites. 1. and 16. Dysport and Botox [Pharm Allergan.) who had not been involved in the daily protocol of the study.A. Women of childbearing potential with a negative pregnancy test result before enrollment in the study were included. moderate.10) In both study arms. 12.11
This was a double-blind.. 2008 ©2006 American Medical Association.
001) (Table 1. 2008 ©2006 American Medical Association. and 37 patients received 3 injections of placebo) were included in study arm 1. This difference was statistically significant (PϽ.9% (7 of 37 patients) for 3 injections of placebo.archdermatol.3) 27 (73. There were no differences at baseline between the botulinum toxin A–treated and the placebo groups (data not shown). There were also no large differences in the mean wrinkle severity scores recorded by the committee vs those recorded by the investigator (data not shown).0) 2. and 16 (data not shown).9) 9 (25. 4.1%) of 73 patients in the botulinum toxin
*Data are given as number (percentage) unless otherwise indicated.70 Visit 2 at Week 2 (n = 70) 8 (11.8) 52 (72. 2.9% (98/109) of the patients in study arm 1 and 90. 42 (61.6) 2.69 Visit 3 at Week 4 (n = 72) 10 (13. At week 16.7) 25 (71.8) 17 (25. †0 Indicates no wrinkles. and 3.ARCHDERMATOL.9) 37 (51.3% (63 of 73 patients) for 5 injections of botulinum toxin A and 7.6±9.0) 24 (64. 2. 2.0) 2.29 (n = 37) 0 3 (8. Ettlingen. and 16 (data not shown).2) 13 (18. RESULTS
PATIENT CHARACTERISTICS All 221 patients who were randomized into the study received study medication.1) 25 (36.com on January 14.4±8. 49 (67.1) 6 (8.
SECONDARY EFFICACY CRITERIA
The secondary efficacy criteria were the following: (1) the scores at maximum frown (evaluated by the committee) at weeks 0. The mean±SD ages were 46.9) 19 (27.
A validated system was established to prevent tampering of the digital images before their transfer to the database and was monitored throughout the study. and 16 (data not shown). Table 2. 12. 12. Table 5.8) 27 (39.1 years in study arm 2.12 (n = 35) 0 1 (2.2) 2.7) 25 (71.4) 2. The difference between groups was statistically significant (PϽ. and Figure 2). 4. 4. was not white.2 years in study arm 1 and 46.9% (3 of 38 patients) for 5 injections of placebo. severe wrinkles. the Fisher exact test or Cochran-Mantel-Haenszel test with table scores was used. Study Arm 2 The responder rates at maximum frown at week 4 based on the evaluation by the committee were 86.8%) of 68 patients in the botulinum toxin A–treated group were at least moderately satisfied with the treatment.3) 1.Table 1. and Figure 3).2) 42 (61.1) 10 (27. moderate wrinkles. Germany) 0 1 2 3 Mean score 3 Injections of placebo 0 1 2 3 Mean score Visit 1 at Week 0 (n = 72) 0 0 20 (27.4) 2.68 (n = 33) 0 1 (3. EFFICACY Study Arm 1 The responder rates at maximum frown at week 4 (primary efficacy criterion) based on the evaluation by the committee were 86. and (5) the assessment of patients’ global satisfaction with the treatment at week 16. mild wrinkles.
toxin A.33 (n = 35) 0 1 (2. All patients were evaluated by another investigator among us during study visits. Only 1 patient.4) 19 (26. Women composed 89.9) 2.001) (Table 4. At week 16. Based on the data set. 1.72 (n = 37) 0 1 (2. (3) the scores at maximum frown and at rest (evaluated by the investigator) at weeks 0.9) 9 (25.58 Visit 5 at Week 16 (n = 68) 0 9 (13.6) 1.7) 9 (24. in study arm 2. (4) the subjective assessment of improvement since the first visit (evaluated by the patient) at weeks 2. (2) the scores at rest (evaluated by the committee) at weeks 0.4) 37 (52.2%) in the botulinum toxin A–treated group and all patients in the placebo group were dissatisfied (PϽ. 2.8) 1.
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 classified as being a responder).4) 6 (8. Fisher exact test) (Table 3). All rights reserved. All but 1 patient (in study arm 1) were included in the intention-to-treat analysis. 4. Evaluation of Glabellar Wrinkles at Maximum Frown by the Committee in Study Arm 1*
Rating† 3 Injections of 10 U of botulinum toxin A (Dysport.57 Visit 4 at Week 12 (n = 69) 4 (5. and 16.1% (100/111) in study arm 2.
.001. Differences between treatment groups for the primary efficacy criterion were tested using the Fisher exact test (2-sided) with ␣ = . Ipsen Pharma.0) 12 (36. 12.1% (62 of 72 patients) for 3 injections of botulinum toxin A and 18. One hundred ten patients (73 patients received 3 injections of 10 U of botulinum
(REPRINTED) ARCH DERMATOL/ VOL 142. The number (rate) of responders was considered the primary efficacy criterion.4) 20 (60.05 in each study arm. Differences between treatment groups for the secondary efficacy criteria were tested on an exploratory basis. and 111 patients (73 patients received 5 injections of 10 U of botulinum toxin A.COM
The primary analysis was based on the intention-to-treat data set. The remaining 26 patients (38. MAR 2006 322
Downloaded from www. 12. and 38 patients received 5 injections of placebo) were included in study arm 2.
Ptosis of the right eyelid started 13 days after the injections.9) 47 (68.94 (n = 37) 1 (2.4) 0. All rights reserved.4) 11 (15.
WWW. and Spock eyebrow). and in 4 patients receiving placebo in this study arm (headache. MAR 2006 323
0 1 2 3 Mean score
*Data are given as number (percentage) unless otherwise indicated. and 4 other patients experienced Spock eyebrow.7) 18 (48.7) 0 1. Ettlingen.8) 1.6) 16 (45. injection site discomfort.0) 0 0 0 0.00
Only 1 serious adverse event occurred in the trial (acute depression after a bereavement in a patient in study arm 2). blepharochalasis. Only 1 case of eyelid ptosis was reported (in the group receiving 5 injections of botulinum toxin A).6) 0 1. The remaining 24 patients (32.7) 1. had improved by week 4.
erate.4) 17 (51.ARCHDERMATOL. Except for the case of Spock eyebrow in study arm 2.1) 9 (12. Fisher exact test) (Table 6). subjectively heavy eyelids. Ipsen Pharma. severe wrinkles. †0 Indicates no wrinkles.7) 16 (45.4) 51 (70.97 (n = 35) 3 (8.46 Visit 4 at Week 12 (n = 69) 11 (15. and eyelid ptosis). and 3. Germany).5) 1 (1.4) 12 (17.09
3 Injections of Placebo (n = 35) 35 (100.001.6) 44 (64.6) 0 1. SAFETY
Table 3.7) 1 (1.9%) in the botulinum toxin A–treated group and all but 2 patients in the placebo group were dissatisfied (PϽ.1) 12 (36. Ipsen Pharma. dizziness. Ettlingen. 1.4) 1.6) 0 1.4) 1.4) 15 (40.5) 0 1.1) 10 (14.29 (n = 37) 1 (2. hoarseness.
Figure 2. was considered to be mild.7) 12 (17. moderate wrinkles.43
*Data are given as number (percentage) unless otherwise indicated.00 (n = 35) 2 (5. in 2 patients receiving placebo in the same study arm (headache and pyrexia). mild wrinkles. in 8 patients treated with 5 injections of botulinum toxin A (4 patients experienced headache. 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. and this was not considered to be related to the study medication.2) 20 (29. No treatment was required. Ettlingen. Ipsen Pharma. Adverse events in which a causal relationship to the study drug could not be excluded occurred in 3 patients treated with 3 injections of botulinum toxin A (hypoesthesia. 2008 ©2006 American Medical Association.01 (n = 33) 4 (12. and swollen face).archdermatol.6) 44 (61. very satisfied.5) 2 (5.
A–treated group were at least moderately satisfied with the treatment. all adverse events were considered to be mild.49 Visit 2 at Week 2 (n = 70) 15 (21. which was rated as mod(REPRINTED) ARCH DERMATOL/ VOL 142.37 Visit 3 at Week 4 (n = 72) 17 (23. Germany) 0 1 2 3 Mean score 3 Injections of placebo 0 1 2 3 Mean score Visit 1 at Week 0 (n = 72) 1 (1. satisfied. †0 Indicates not satisfied.0) 2 (2. Germany) (n = 68) 26 (38. moderately satisfied. Evaluation of Glabellar Wrinkles at Rest by the Committee in Study Arm 1*
Rating† 3 Injections of 10 U of botulinum toxin A (Dysport. and 3. and was not visible by week 12.8) 18 (25. 2.8) 0.6) 18 (48.39 Visit 5 at Week 16 (n = 68) 12 (17.4) 43 (61.
.Table 2. Assessment of Patients’ Global Satisfaction With the Treatment at Week 16 in Study Arm 1*
3 Injections of 10 U of Botulinum Toxin A (Dysport.6) 10 (14.7) 17 (48.com on January 14.7) 16 (45.COM
Downloaded from www.5) 2 (2. dizziness. 1.7) 19 (51. 2.
This was not a simple dose-ranging trial to evaluate different doses.2) 2.5) 20 (27. Ipsen Pharma.6) 29 (76. severe wrinkles.7) 9 (23.29 Visit 2 at Week 2 (n = 72) 12 (16.7) 26 (70. MAR 2006 324
but rather a study of the number and distribution of injection sites.3) 24 (63.29 Visit 4 at Week 12 (n = 73) 11 (15. as in the study performed by Ascher et al.1) 13 (17.07 (n = 38) 0 28 (73.archdermatol.9) 11 (29.4) 3 (4.4) 21 (29.4) 0 1.61 Visit 2 at Week 2 (n = 72) 9 (12. Germany) 0 1 2 3 Mean score 5 Injections of placebo 0 1 2 3 Mean score Visit 1 at Week 0 (n = 73) 0 50 (68. moderate wrinkles.7) 46 (63.ARCHDERMATOL.9) 14 (19.2) 5 (6. 1.6) 15 (39.3) 7 (18.55 (n = 38) 0 0 15 (39. severe wrinkles.
Figure 3.7) 1.34 (n = 38) 0 1 (2.99 (n = 38) 0 1 (2. One injection site pattern (3 injections of 10 U of botulinum toxin A) involved only the glabella.4) 1 (2.5) 2.61
*Data are given as number (percentage) unless otherwise indicated.73 (n = 38) 0 1 (2.55 Visit 5 at Week 16 (n = 73) 1 (1.2) 11 (28.36 (n = 38) 1 (2.0) 33 (45.03 (n = 37) 1 (2.2) 20 (27. 2008 ©2006 American Medical Association.1) 49 (67.66 Visit 4 at Week 12 (n = 73) 2 (2.7) 26 (35. Ipsen Pharma.7) 2 (2.8) 15 (20.6) 27 (71.29
*Data are given as number (percentage) unless otherwise indicated.8) 0 1.2) 2. Evaluation of Glabellar Wrinkles at Rest by the Committee in Study Arm 2*
Rating† 5 Injections of 10 U of botulinum toxin A (Dysport.3) 2.00 (n = 38) 2 (5.9) 26 (68. 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.6) 1.31 (n = 37) 0 0 11 (29.2) 47 (64.9) 1 (2.
. All rights reserved.6) 1.4) 19 (26.1) 1.1) 2 (5.4) 31 (42.6) 1.32 Visit 3 at Week 4 (n = 73) 14 (19.6) 41 (56.7) 1. †0 Indicates no wrinkles.70 Visit 3 at Week 4 (n = 73) 7 (9. Ettlingen. and 3.7) 1 (2.1
(REPRINTED) ARCH DERMATOL/ VOL 142.7) 1 (2.5) 41 (56.6) 1. Germany) 0 1 2 3 Mean score 5 Injections of placebo 0 1 2 3 Mean score Visit 1 at Week 0 (n = 73) 0 1 (1.7) 24 (64. †0 Indicates no wrinkles.
Table 5. Germany).9) 10 (13.COM
Downloaded from www. 2. Ettlingen. 2.4) 2.2) 18 (24.7) 1.Table 4. and 3.5) 0 1.03 (n = 38) 1 (2.9) 1.4) 1.6) 13 (34.6) 11 (28.7) 7 (9. Ettlingen.7) 48 (65. the other injection site pattern (5 injections of 10 U of
WWW.2) 24 (63.5) 23 (60.6) 35 (47. Evaluation of Glabellar Wrinkles at Maximum Frown by the Committee in Study Arm 2*
Rating† 5 Injections of 10 U of botulinum toxin A (Dysport. moderate wrinkles.com on January 14. mild wrinkles. Ipsen Pharma.4) 10 (13.21 Visit 5 at Week 16 (n = 73) 10 (13.3) 1.5) 22 (57.1) 8 (21. 1.9) 2.5) 37 (51. mild wrinkles.
4% (13 of 203 patients) in a pilot study. MAR 2006 325
Table 6. the eyelid ptosis was mild and did not require treatment. rigorous clinical trials are needed to evaluate its efficacy and safety. Given
(REPRINTED) ARCH DERMATOL/ VOL 142.2. Study supervision: Rzany and Sterry. MD. the advantage of using only 1 scale may be better reproducibility: the clinical scale used herein has good to excellent interinvestigator and intrainvestigator reproducibility. Rostock. both botulinum toxin A dosages proved to be safe.com on January 14. However. this level of satisfaction might not be acceptable for this esthetic procedure.
. MD. with the results that the mean scores at rest are.2 Ascher et al1 meanwhile reported no eyelid ptosis in 102 patients treated with 25. Ba ¨ rbel Ehlers. and Talarico. Ascher. Although patients’ satisfaction was generally good.2) 1. Monheit. 2008 ©2006 American Medical Association. MD. 50. Schumannstrasse 20/23. for the treatment of glabellar and central forehead wrinkles. the use of photographs is more likely to ensure that the investigators are completely blinded and are less biased about treatment efficacy. Drafting of the manuscript: Rzany. which may bias the maximum range of possible scores toward the mean. However. Klinik fu ¨ r Dermatologie. Mu ¨ nster. Even for the group receiving 5 injections of botulinum toxin A. Mannheim. Previously. Therefore. as shown by Ascher et al1 for 25. MD. 50. Randolf Brehler. Group Members: The GLADYS Study Group includes the following investigators (all in Germany): Ju ¨ rgen Bauerschmitz. 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. Accepted for Publication: July 28. 1. declining to 1. and such trials are crucial to a full examination of safety.3) 0 0. All rights reserved. satisfied.3 Larger studies. Mannheim. In our study. Venerologie und Allergologie. MD. 2. of course. Author Contributions: Study concept and design: Rzany and Sterry. Marburg.7) 0 2 (5. and 75 U total of botulinum toxin A. most clinical trials studying the efficacy of botulinum toxin A have involved only a few centers2. very satisfied. Obtained funding: Sterry. a high rate of adverse events such as eyelid ptosis would be unacceptable. such as the present trial involving 23 centers and 42 investigators. only wrinkles in the glabellar area were evaluated in this trial. Erlangen. Increasing the dosage to the 3 central sites or adding 2 sites targeting the medial portion of the corrugator muscles might increase overall satisfaction.
that the treatment of glabellar wrinkles is a cosmetic procedure. This trial demonstrates the efficacy and safety of the European brand of botulinum toxin A. In this context. the position of the 2 extra injection sites may be important: the sites were distinctly more lateral in the studies conducted by Carruthers et al. MD. Monheit. and Talarico. Ettlingen. MD. Critical revision of the manuscript for important intellectual content: Ascher.ARCHDERMATOL. Jens Gille. Fratila. Correspondence: Berthold Rzany. ScM. Homburg. and 3. which showed a smaller proportion of moderately satisfied patients. Germany (berthold. MD.11 In a clinical trial studying mimic wrinkles.botulinum toxin A) involved the glabella and 2 additional cranial sites in the central forehead.13 compared with those in the present study and in the study by Ascher et al.archdermatol. better reflect clinical practice than those carried out in a few expert centers.7) 14 (19. Ascher. only 1 scale was used. Rostock. On the other hand. †0 Indicates not satisfied. 2005.0% (2 of 202 patients) in a subsequent study. Frankfurt a Main. Campus Charite ´ Mitte. Carruthers et al13 reported an eyelid ptosis rate of 6. Other more lateral sites or an increased dosage might further improve the efficacy.3) 18 (24. Talarico.rzany@charite. However.30
Rating† 0 1 2 3 Mean score
5 Injections of Placebo (n = 38) 36 (94. Division of Evidence Based Medicine. these would be the subjects of further study. a score of 2 (moderate wrinkles) does not represent the same depth of wrinkles in each case. effective blinding of the assessment of wrinkles is often difficult because it may be clear from patients’ muscle movements that botulinum toxin A has been used.1 Although botulinum toxin A has been used for esthetic indications for a long time.1-3 most have in fact used one scale for the assessment of wrinkles at rest and another for the assessment of wrinkles at maximum frown. Consequently.4% (in the group receiving 3 injections of botulinum toxin A) and 23. Rostock. However. Katharina Friebe. Gita Gharari.COM
Downloaded from www.3% (in the group receiving 5 injections of botulinum toxin A) of patients reported only moderate satisfaction. D-10117 Berlin. What are the right outcome criteria for studies evaluating the efficacy of botulinum toxin A? Although a 4-point clinical scale ranging from 0 (no wrinkles) to 3 (severe wrinkles) has been used in almost all previous studies. Gabriele Feller. a score of 2 represents the same depth of wrinkles at rest and at maximum frown. lower than those at maximum frown and that changes between the botulinum toxin A and placebo study arms at rest are harder to measure. Fratila.12 The addition of these 2 sites targeting the frontalis muscle did not increase the efficacy. Monheit. only 1 trial has included more than 10 centers.de). HildeWWW. Andrea Garbea. Acquisition of data: Rzany. moderately satisfied. Fratila. This trial also raised some methodological issues.13. MD. MD. Dysport. Using Botox in the glabellar area. Charite ´ Universita ¨ tsmedizin. in fact. 29. Anne-Kathrin Bomke.11
*Data are given as number (percentage) unless otherwise indicated. Only 1 case of eyelid ptosis was reported among our patients. and 75 U total of Dysport. and Sterry. Germany) (n = 73) 24 (32. MD. 3 injections of 10 U of botulinum toxin A might be a sufficient dosage for the glabellar region for most patients. a committee relying on photographs gets only a glimpse of the possible magnitude of wrinkles. Dorothee DillMu ¨ ller. Based on our results. Analysis and interpretation of data: Rzany. In this study. Ipsen Pharma.9) 17 (23. and we cannot rule out the possibility that evaluation of central forehead wrinkles would have shown the 5-injection site pattern to be more effective.
Ettlingen. MD. MD. dose-ranging study of botulinum toxin type A in female subjects with horizontal forehead rhytides. Ascher B. MD. Ludwigshafen. Botulinum toxin A for axillary hyperhidrosis (excessive sweating).46:840-849. Korrektur der dynamischen Gesichtsfalten ® mit Botulinum toxin A (Dysport ): eine Pilotstudie [Correction of mimic wrinkles with botulinum toxin A (Dysport)]. Lowe JN. 12. Germany: Urban und Vogel.344:488-493. 2000. double-blind. N Engl J Med. randomized. MD. Schnider P. Franca Noack-Wiemers. Gesina Hansel. Wiest. Frankfurt a Main. Dresden. 4. Helga Konrad. 2003. Leipzig. Ettlingen. double-blind. Mu ¨ nchen. J Am Acad Dermatol. and Wolf-Ingo Worret. Akt Dermatol. 9. MD. Ludwigshafen. Berlin. 2002. MD. Mov Disord.
. 2004. Role of the Sponsor: Ipsen Pharma supported the design and conduct of the study. Santini J. Lars Ko ¨ hler. MD. Heckmann M. Dermatol Surg. placebo-controlled study of efficacy and safety of three doses of botulinum toxin A in the treatment of glabellar lines. Ferreira JJ. MD. Costa J. Bericht zum 1: Expertentreffen zur Anwendung von Botulinumtoxin A ¨ sthetischen Dermatologie [First meeting of experts: botulinum toxin A in in der A aesthetic dermatology]. Ludwigshafen. MD. Robert Kasten. MD. Berlin. 2008 ©2006 American Medical Association. Feller G. MD.136:548-552. Mu ¨ nster. MD. Kerstin Tru ¨ mper. Heckmann M. Martina Hund. Menter MA. Lucie Rauch. Schnider P. MD. Andrea Misic.ARCHDERMATOL. Bougara A. Baspeyras M. Hamburg. Carruthers JA. Mu ¨ nchen. Carruthers J. 7. Dresden. Markus Krause. Menter MA. Innsbruck. 13. Carruthers JD. Plewig G. Martin Jung. Sterry W. Facial Plast Surg Clin North Am.11:439-443. 2001. Honeck P. Double-blind trial of botulinum A toxin for the treatment of focal hyperhidrosis of the palms. 5. Rzany B. Funding/Support: This study was supported by a grant from Ipsen Pharma. 2003. Constanze Voigtla ¨ nder. Sabine Werfel. Binder M. Zakine B. Auff E. 3.
(REPRINTED) ARCH DERMATOL/ VOL 142. Treatment of focal hyperhidrosis with botulinum toxin type A: long-term follow-up in 61 patients. 11. MD. Luitgard G.29:461-467. and analysis of the data. Marburg. Bayerl C. 2001. et al. placebo-controlled study of the safety and efficacy of botulinum toxin type A for patients with glabellar lines. Br J Derm. Relevant anatomy for botulinum toxin facial rejuvenation. Kittler H. Rzany B.24:2-8. Magdeburg. Erlangen. Botox Glabellar Lines II Study Group.gard Gundel-Leiter. Regensburg. Financial Disclosure: Dr Rzany has received grants from Ipsen Pharma. 2. Jo ¨ rg Tittelbach. Loos BM. Konstanze Spieth. Dortmund. Carruthers A. Gibson J. Marc Heckmann. randomized. Claudia Pirker. All rights reserved. for other clinical trials not related to this study. Plast Reconstr Surg. Annette Stein. Double-blind.19(suppl 8):S129-S136.26:65-69. GLADYS Study Group. 8. randomized. MAR 2006 326
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