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Research Letter |

A Randomized Double-Blind Study of the Effect of Botox and Dysport/Reloxin on Forehead Wrinkles and Electromyographic Activity FREE

Syrus Karsai, MD; Robert Adrian, MD; Stefan Hammes, MD; Jürgen Thimm, MD; Christian Raulin, MD, PhD
Arch Dermatol. 2007;143(11):1447-1462. doi:10.1001/archderm.143.11.1447-b.
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Published online

The difference between the potency units of the 2 main botulinum toxin A products, Botox (Allergan, Irvine, California) and Dysport/Reloxin (Ipsen Ltd, Slough, England), is still a subject of discussion even after 15 years of clinical use. The manufacturer of Botox recommends higher ratios than does the manufacturer of Dysport/Reloxin. Herein, we report the findings of a randomized, double-blind, split-face study of forehead wrinkles and electromyographic (EMG) activity following application of the 2 products at a 3:1 dose ratio, independent of the support of either manufacturer.

Patients included in the study were aged 30 to 70 years, had moderate to severe hyperfunctional forehead wrinkles at rest and maximum contraction, and gave written informed consent. The study was approved by the institution's human research review committee.

Twenty-six patients were enrolled, 2 of whom were lost to follow-up and thus excluded from the study. Of the 24 remaining patients, 20 were women (83%), with a mean ± SEM age of 41.9 ± 1.4 years.

Patients were randomly assigned to receive the 2 different formulations in each side of the frontalis muscle in a 3-injection site pattern: 12 U of Botox and 36 U of Dysport/Reloxin were diluted in 0.3 mL of isotonic sodium chloride solution, and the syringes were prepared according to a computerized randomization by an assistant, who passed the unmarked syringes to the treating physician. The EMG electrode was placed 3 cm above the upper medial eyebrow, and the baseline frontalis muscle voltage was measured. All measurements of electric muscle activity were performed during maximum voluntary contraction of the frontalis muscle using the MyoSystem 1200 and the MyoResearch XP software package for analysis (Noraxon, Scottsdale, Arizona). The injections were placed 0, 1, and 2 cm lateral to the position of the electrode.

Study end points were assessed at baseline and 0.5, 1.0, 2.0, 4.0, 8.0, and 10.0 weeks after injection, followed by weekly examinations for a total observation period of 20 weeks. Photographs taken during maximum contraction at each follow-up visit were presented randomly to a panel of 3 experts who were blind to the treatment and duration of time since the treatment. Wrinkle severity was assessed by the panel using the photographs and directly at each visit by the investigator and the patient using a simple 3-item rating scale: “more wrinkles on the right side,” “no difference between sides,” and “more wrinkles on the left side.”

After completion of the study, the blind was broken and all scores recorded according to the side of treatment (0, more wrinkles on the Botox side; 1, no difference; and 2, more wrinkles on the Dysport/Reloxin side).

For statistical analysis, a paired t test was used (GraphPad Prism 3.0 and GraphPad Instat 3.05; GraphPad Software, San Diego, California, and SPSS 13.0; SPSS, Chicago, Illinois).

Muscle EMG activity was depressed by both products, reaching a minimum 2 weeks after injection. The effect of Dysport/Reloxin was longer lasting, and the difference from the effect caused by Botox was statistically significant beginning 10 weeks after injection and lasting until the end of observation (P < .001) (Figure 1). Wrinkle severity, as assessed by the panel (P < .001 at week 10), investigator (P < .001 at week 10), and patients (P = .03 at week 10), increased accordingly in the Botox-treated sides.

Place holder to copy figure label and caption
Figure 1.

Electromyography (EMG) results from the frontalis muscle prior to injection and during the 20-week follow-up period. Displayed are the mean ± SEM microvoltage readings in each group. Botox and Dysport/Reloxin are proprietary names for botulinum A toxin products manufactured by Allergan (Irvine, California) and Ipsen Ltd (Slough, England), respectively. *Statistically significant difference between groups.

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After the difference in unit potency between Botox and Dysport/Reloxin was recognized, a conversion factor of 4:1 to 5:1 was hypothesized.1 This conversion factor remains widely used despite evidence from the manufacturers' assay methods2 and comparative clinical trials carried out according to Cochrane standards of evidence-based medicine3 showing that 3:1 is a more appropriate conversion ratio than 4:1. More recent data suggest that the best dose conversion ratio may in fact be less than 3:1.46 The recommended ratio for the treatment of glabella lines in Germany is 2.5:1.0 (50 U of Dysport/Reloxin to 20 U of Botox).

Lowe et al7 published a study in which the effect of Dysport/Reloxin was less sustained than that of Botox in a 2.5:1.0 regimen, which contradicts the results of our study. In addition, the effect of Botox increased 16 weeks after injection, which was not seen in any other study. These results need independent confirmation.

The results of the present study show that Dysport/Reloxin has a longer duration of effect on EMG activity and forehead wrinkles than does Botox at a unit dose conversion ratio of 3:1 (Figure 2). This suggests that the conversion ratio for bioequivalence may be less than 3:1. We recommend this model as a relatively simple and accessible way of obtaining quantitative comparative data in a clinical treatment situation.

Place holder to copy figure label and caption
Figure 2.

Forehead area of a 41-year-old woman at maximum frown before (A) and 10 weeks after (B) injection of 36 U of Dysport/Reloxin (right side of the forehead) and 12 U of Botox (left side of the forehead). The dots in panel A indicate the sites of injection. Botox and Dysport/Reloxin are proprietary names for botulinum A toxin products manufactured by Allergan (Irvine, California) and Ipsen Ltd (Slough, England), respectively.

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ARTICLE INFORMATION

Correspondence: Dr Karsai, Laserklinik Karlsruhe, Kaiserstrasse 104, Karlsruhe 76133, Germany (info@raulin.de).

Financial Disclosure: None reported.

Additional Contributions: Jochen Hirsch, MD, PhD, provided expert statistical assistance.

Brin  MFBlitzer  A Botulinum toxin: dangerous terminology errors. J R Soc Med 1993;86 (8) 493- 494
PubMed
Hambleton  PPickett  AM Potency equivalence of botulinum toxin preparations. J R Soc Med 1994;87 (11) 719
PubMed
Sampaio  CCosta  JFerreira  JJ Clinical comparability of marketed formulations of botulinum toxin. Mov Disord 2004;19 ((suppl 8)) S129- S136
PubMed Link to Article
Ranoux  DGury  CFondarai  JMas  JLZuber  M Respective potencies of Botox and Dysport: a double-blind, randomised, crossover study in cervical dystonia. J Neurol Neurosurg Psychiatry 2002;72 (4) 459- 462
PubMed
Poewe  W Respective potencies of Botox and Dysport: a double-blind, randomised, crossover study in cervical dystonia. J Neurol Neurosurg Psychiatry 2002;72 (4) 430
PubMed
Rosales  RLBigalke  HDressler  D Pharmacology of botulinum toxin: differences between type A preparations. Eur J Neurol 2006;13 ((suppl 1)) 2- 10
Link to Article
Lowe  PPatnaik  RLowe  N Comparison of two formulations of botulinum toxin type A for the treatment of glabellar lines: a double-blind, randomized study. J Am Acad Dermatol 2006;55 (6) 975- 980
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Electromyography (EMG) results from the frontalis muscle prior to injection and during the 20-week follow-up period. Displayed are the mean ± SEM microvoltage readings in each group. Botox and Dysport/Reloxin are proprietary names for botulinum A toxin products manufactured by Allergan (Irvine, California) and Ipsen Ltd (Slough, England), respectively. *Statistically significant difference between groups.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Forehead area of a 41-year-old woman at maximum frown before (A) and 10 weeks after (B) injection of 36 U of Dysport/Reloxin (right side of the forehead) and 12 U of Botox (left side of the forehead). The dots in panel A indicate the sites of injection. Botox and Dysport/Reloxin are proprietary names for botulinum A toxin products manufactured by Allergan (Irvine, California) and Ipsen Ltd (Slough, England), respectively.

Graphic Jump Location

Tables

References

Brin  MFBlitzer  A Botulinum toxin: dangerous terminology errors. J R Soc Med 1993;86 (8) 493- 494
PubMed
Hambleton  PPickett  AM Potency equivalence of botulinum toxin preparations. J R Soc Med 1994;87 (11) 719
PubMed
Sampaio  CCosta  JFerreira  JJ Clinical comparability of marketed formulations of botulinum toxin. Mov Disord 2004;19 ((suppl 8)) S129- S136
PubMed Link to Article
Ranoux  DGury  CFondarai  JMas  JLZuber  M Respective potencies of Botox and Dysport: a double-blind, randomised, crossover study in cervical dystonia. J Neurol Neurosurg Psychiatry 2002;72 (4) 459- 462
PubMed
Poewe  W Respective potencies of Botox and Dysport: a double-blind, randomised, crossover study in cervical dystonia. J Neurol Neurosurg Psychiatry 2002;72 (4) 430
PubMed
Rosales  RLBigalke  HDressler  D Pharmacology of botulinum toxin: differences between type A preparations. Eur J Neurol 2006;13 ((suppl 1)) 2- 10
Link to Article
Lowe  PPatnaik  RLowe  N Comparison of two formulations of botulinum toxin type A for the treatment of glabellar lines: a double-blind, randomized study. J Am Acad Dermatol 2006;55 (6) 975- 980
PubMed Link to Article

Correspondence

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