New Study Demonstrates Significant Differences In Migration Characteristics Between Botulinum Toxin Type A Formulations: (Botox(R) And Dysport(R)

Main Category: Headache / Migraine
Article Date: 29 Jul 2006 - 0:00 PDT

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A pilot study designed to compare the migration characteristics of different formulations of botulinum toxin type A has demonstrated that Botox(R) (Allergan, Inc.) has a significantly smaller area of migration beyond the targeted area of injection compared to Dysport(R) (Ipsen, Ltd.), a brand of botulinum toxin type A that is available in Europe but not yet approved for use in the U.S.(1) Different migration characteristics among botulinum toxin type A formulations may result in different tolerability profiles, according to the researchers, who are presenting their results today at the American Academy of Dermatology '06 meeting in San Diego, CA.

"Our study reinforces the important fact that no two botulinum toxins are alike. Each behaves differently, physiologically and clinically, and each has a unique structure, formulation, efficacy and safety profile. Therefore results obtained with one formulation cannot be extrapolated to another," said Sandeep H. Cliff, BSc, FRCP, consulting dermatologist with the St. Helier NHS Trust, Carshalton, Surrey, UK and an investigator for this study. "Our findings suggest that the extent of migration post-injection with botulinum toxin type A appears to be influenced not only by the dose and volume of injection but also by the distinct formulation itself."

For instance, Botox(R) has the largest molecule of all neurotoxins with a uniform weight of 900kD whereas the Dysport(R) molecule ranges from 500kD to 900kD. Pre-clinical studies suggest that migration within muscle is dependent on molecular size and that smaller proteins diffuse more;(2) thus, the larger Botox(R) molecule may minimize migration outside of targeted tissue. "This is an important issue because adverse events can result if the neurotoxin migrates or leaks to untreated muscles near the injection site," explained Dr. Cliff. Some clinical studies have noted a higher incidence of adverse effects after Dysport(R) treatment than after Botox(R) treatment.(3,4,5,6,7)

"To minimize the potential for adverse events, it is important to ensure that clinical effects following botulinum toxin type A injection are precise and localized," said Dr. Cliff. "A high degree of control is particularly important anywhere that other muscles are close to the target muscles, such in the face and hands, where migration could expose adjacent muscles to undesired weakness."

The study being presented at AAD was a single-center, double-blind, placebo-controlled randomized pilot study of 12 healthy volunteers. Each patient received one injection of Botox(R) (4 U) on one side of their forehead, one injection of Dysport(R) (12 U) on the other side of their forehead (reflecting the currently recommended dose ratio of 1:3 Botox(R) to Dysport(R)), and one injection of preservative-free saline (placebo) in the center of their forehead. All injections were of identical volume (0.1 mL). Two weeks following injection, the participants foreheads were stained with an iodine and starch solution (Minor's starch iodine test) and then, to induce forehead sweating, they engaged in 30 minutes of physical exercise in a hot room. The area of any forehead anhydrosis (no sweating) was assessed using Canfield photography. The anhydrotic "halos" visible in the resulting photographs enabled investigators to directly compare areas of migration surrounding each injection site.

Overall, in 11 of 12 study participants the area of anhydrosis was significantly larger (an average of 77 percent larger) with Dysport(R) than with Botox(R) (p=.005). The area of anhydrosis ranged from 0.76-2.76 cm2 with Botox(R) and 1.90-4.26 cm2 with Dysport(R). No anhydrosis was apparent as a result of the control injections with saline alone.

This study was funded by an unrestricted grant from Allergan, Inc.

(1) Cliff SH, Judodihardjo H. Different formulations of botulinum toxin type A have different migration characteristics. Poster presented at the Academy '06 meeting of the American Academy of Dermatology, July 26-30, 2006, San Diego, CA. [Poster #410]

(2) Papadopoulos et al. Biophys J 2000;79:2084-94.

(3) Lew H, Yun YS, Lee SY, Kim SJ. Effect of botulinum toxin A on facial wrinkle lines in Koreans. Ophthalmologica 2002:216:50-4.

(4) Nussgens Z, Roggenkamper P. Comparison of two botulinum toxin preparations in the treatment of essential blepharospasm. Graefes Arch Clin Exo Ophthalmol 1997;235:197-9.

(5) Ranous D. Gury C, Fonderal J, Mas JL, Zuber M. Respective potencies of Botox and Dysport: a double blind, randomized, crossover study in cervical dystonia. J Neurol Neurosurg Psychiatry 2002;72:459-62.

(6) Dodel RC, Kirchner A, Koehne-Volland R, et al. Costs of treating dystonias and hemifacial spasm with botulinum toxin A. Pharmacoeconomics 1997;12:695-706.

(7) Simonetta Moreau M, Cauhepe C, Magues JP, Senard JM. A double-blind, randomized, comparative study of Dysport(R) vs. Botox(R) in primary palmar hyperhidrosis.

Sandeep H. Cliff FRCP

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