Onset and duration of effect of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA in the treatment of glabellar frown lines: a randomized, double-blind study

Thomas Rappl, Daryousch Parvizi, Herwig Friedl, Maria Wiedner, Simone May, Bettina Kranzelbinder, Paul Wurzer, Bengt Hellbom, Thomas Rappl, Daryousch Parvizi, Herwig Friedl, Maria Wiedner, Simone May, Bettina Kranzelbinder, Paul Wurzer, Bengt Hellbom

Abstract

Background: Three botulinum neurotoxin type A preparations (incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA) are widely approved in Europe and in the US for the treatment of glabellar frown lines. The purpose of this study was to determine and compare the time to onset and duration of treatment effect of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA for the treatment of glabellar frown lines.

Subjects and methods: Subjects aged 20-60 years with moderate to severe glabellar frown lines received one treatment of either 21 units (U) incobotulinumtoxinA, 21 U onabotulinumtoxinA, or 63 U abobotulinumtoxinA. Assessments were made over a period of 180 days. Onset of treatment effect was defined as the day that the observer noted a decrease in glabellar muscle activity compared with baseline photographs and videos. Duration of treatment effect was defined as the time until glabellar muscle action returned to the baseline level. Analyses were performed using a Weibull log(T) regression model.

Results: The study enrolled 180 subjects; 60 per group. For all three products, onset of treatment effect occurred earlier in female subjects compared to male subjects. For both sexes, a significantly earlier time to onset of treatment effect was seen for incobotulinumtoxinA compared to onabotulinumtoxinA and abobotulinumtoxinA; in female subjects these times were 3.02 days, 5.29 days, and 5.32 days, respectively. The duration of treatment effect was longer for incobotulinumtoxinA compared to onabotulinumtoxinA and abobotulinumtoxinA; for all products, treatment effect duration was longer in females than in males. Time to onset was not a predictor of treatment duration.

Conclusion: IncobotulinumtoxinA demonstrated a more rapid onset and a longer duration of treatment effect than onabotulinumtoxinA (1:1 dose ratio) and abobotulinumtoxinA (1:3 dose ratio). Onset of effect was faster and duration of effect was longer in female subjects compared to male subjects.

Keywords: botulinum neurotoxin type A; glabellar frown lines; incobotulinumtoxinA; regression analysis.

Figures

Figure 1
Figure 1
The validated Merz 5-point scale for glabellar frown lines at maximum frown. Note: Reproduced with permission from Flynn TC, Carruthers A, Carruthers J, et al. Validated assessment scales for the upper face, Dermatologic Surgery, Wiley Periodicals, Inc.
Figure 2
Figure 2
Syringes lacking numbered graduations used in order to maintain blinding of injecting physician. Notes: (A) syringe containing onabotulinumtoxinA or incobotulinumtoxinA; (B) syringe containing abobotulinumtoxinA.
Figure 3
Figure 3
Injection sites. Notes: (a) Procerus muscle; (b) right medial corrugator muscle; (c) left medial corrugator muscle; (d) right lateral corrugator muscle; (e) left lateral corrugator muscle. When subjects were injected with incobotulinumtoxinA or onabotulinumtoxinA, injection sites a, b, and c received 5 U each, while d and e received 3 U each. AbobotulinumtoxinA treatment consisted of 15 U injections at sites a, b, and c, and 9 U at sites d and e.
Figure 4
Figure 4
Kaplan–Meier curves for time to onset of treatment effect for (A) female and (B) male subjects.
Figure 5
Figure 5
Kaplan–Meier curves for duration of treatment effect for (A) female and (B) male subjects.

References

    1. The American Society for Aesthetic Plastic Surgery statistics Available from: Accessed April 4, 2012
    1. Cox SE, Finn JC. Social implications of hyperdynamic facial lines and patient satisfaction outcomes. Int Ophthalmol Clin. 2005;45(3):13–24.
    1. Fedok FG. Advances in minimally invasive facial rejuvenation. Curr Opin Otolaryngol Head Neck Surg. 2008;16(4):359–368.
    1. Eisele KH, Fink K, Vey M, Taylor HV. Studies on the dissociation of botulinum neurotoxin type A complexes. Toxicon. 2011;57(4):555–565.
    1. Frevert J, Dressler D. Complexing proteins in botulinum toxin type A drugs: a help or a hindrance? Biologics. 2010;4:325–332.
    1. Frevert J. Content of botulinum neurotoxin in Botox®/Vistabel®, Dysport®/Azzalure®, and Xeomin®/Bocouture®. Drugs R D. 2010;10(2):67–73.
    1. Dressler D, Adib Saberi F. New formulation of Botox: complete antibody-induced treatment failure in cervical dystonia. J Neurol Neurosurg Psychiatry. 2007;78(1):108–109.
    1. Dressler D, Wohlfahrt K, Meyer-Rogge E, Wiest L, Bigalke H. Antibody-induced failure of botulinum toxin a therapy in cosmetic indications. Dermatol Surg. 2010;36(Suppl 4):2182–2187.
    1. Jankovic J, Vuong KD, Ahsan J. Comparison of efficacy and immunogenicity of original versus current botulinum toxin in cervical dystonia. Neurology. 2003;60(7):1186–1188.
    1. Stengel G, Bee EK. Antibody-induced secondary treatment failure in a patient treated with botulinum toxin type A for glabellar frown lines. Clin Interv Aging. 2011;6:281–284.
    1. Carruthers A, Carruthers J, Lowe NJ, et al. One-year, randomised, multicenter, two-period study of the safety and efficacy of repeated treatments with botulinum toxin type A in patients with glabellar lines. J Clin Res. 2004;7:1–20.
    1. Carruthers JA, Lowe NJ, Menter MA, et al. A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines. J Am Acad Dermatol. 2002;46(6):840–849.
    1. Carruthers JD, Lowe NJ, Menter MA, Gibson J, Eadie N, Botox Glabellar, Lines II, Study Group Double-blind, placebo-controlled study of the safety and efficacy of botulinum toxin type A for patients with glabellar lines. Plast Reconstr Surg. 2003;112(4):1089–1098.
    1. Ascher B, Zakine B, Kestemont P, Baspeyras M, Bougara A, Santini J. A multicenter, randomized, double-blind, placebo-controlled study of efficacy and safety of 3 doses of botulinum toxin A in the treatment of glabellar lines. J Am Acad Dermatol. 2004;51(2):223–233.
    1. Monheit G, Carruthers A, Brandt F, Rand R. A randomized, double-blind, placebo-controlled study of botulinum toxin type A for the treatment of glabellar lines: determination of optimal dose. Dermatol Surg. 2007;33(1 Spec):S51–S59.
    1. Imhof M, Kühne U. A Phase III study of incobotulinumtoxinA in the treatment of glabellar frown lines. J Clin Aesthet Dermatol. 2011;4(10):28–34.
    1. Sattler G, Callander M, Grablowitz D, et al. Noninferiority of incobotulinumtoxinA, free from complexing proteins, compared with another botulinum toxin type A in the treatment of glabellar frown lines. Dermatol Surg. 2010;36(Suppl 4):2146–2154.
    1. Beer KR, Boyd C, Patel RK, Bowen B, James SP, Brin MF. Rapid onset of response and patient-reported outcomes after onabotulinumtoxinA treatment of moderate-to-severe glabellar lines. J Drugs Dermatol. 2011;10(1):39–44.
    1. Schlessinger J, Monheit G, Kane MA, Mendelsohn N. Time to onset of response of abobotulinumtoxinA in the treatment of glabellar lines: a subset analysis of phase 3 clinical trials of a new botulinum toxin type A. Dermatol Surg. 2011;37(10):1434–1442.
    1. Prager W, Bee EK, Havermann I, Zschocke I. Onset, longevity and subject satisfaction with incobotulinumtoxinA for the treatment of glabellar frown lines: a single-arm, prospective clinical study. Clin Interv Aging. 2013
    1. Carruthers A, Carruthers J, Said S. Dose-ranging study of botulinum toxin type A in the treatment of glabellar rhytids in females. Dermatol Surg. 2005;31(4):414–422.
    1. Carruthers A, Carruthers J. Prospective, double-blind, randomized, parallel-group, dose-ranging study of botulinum toxin type A in men with glabellar rhytids. Dermatol Surg. 2005;31(10):1297–1303.
    1. Blitzer A, Binder WJ, Aviv JE, Keen MS, Brin MF. The management of hyperfunctional facial lines with botulinum toxin. A collaborative study of 210 injection sites in 162 patients. Arch Otolaryngol Head Neck Surg. 1997;123(4):389–392.
    1. Bocouture® Summary of Product Characteristics Merz Pharmaceuticals GmbH; 2013Available from: Accessed February 10, 2013
    1. Hanke CW, Narins RS, Brandt F, et al. A randomized, placebo-controlled, double-blind Phase III trial investigating the efficacy and safety of incobotulinumtoxinA in the treatment of glabellar frown lines using a stringent composite endpoint. Dermatol Surg. 2013
    1. Carruthers A, Carruthers J, Coleman WP, 3rd, et al. Multicenter, randomized, Phase III study of a single dose of incobotulinumtoxinA, free from complexing proteins, in the treatment of glabellar frown lines. Dermatol Surg. 2013 Feb 4; Epub.
    1. Rzany B, Flynn T, Schlöbe A, Heinz M, Harrington L. Long-term results for incobotulinumtoxinA in the treatment of glabellar frown lines. Dermatol Surg. 2013;39(1 Pt 1):95–103.
    1. Flynn TC, Carruthers A, Carruthers J, et al. Validated assessment scales for the upper face. Dermatol Surg. 2012;38(2 Spec):309–319.
    1. Prager W, Rappl T. Phase IV study comparing incobotulinumtoxinA and onabotulinumtoxinA using a 1:1.5 dose-conversion ratio for the treatment of glabellar frown lines. J Cosmet Dermatol. 2012;11(4):267–271.
    1. Ranoux D, Gury C, Fondarai J, Mas JL, Zuber 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.
    1. Carruthers A, Carruthers J. Botulinum toxin products overview. Skin Therapy Lett. 2008;13(6):1–4.
    1. Azzalure® Summary of Product Characteristics Galderma (UK) Ltd; 2013Available from: Accessed February 13, 2013
    1. Karsai S, Raulin C. Current evidence on the unit equivalence of different botulinum neurotoxin A formulations and recommendations for clinical practice in dermatology. Dermatol Surg. 2009;35(1):1–8.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner