Treating glabellar lines with botulinum toxin type A-hemagglutinin complex: a review of the science, the clinical data, and patient satisfaction

Koenraad De Boulle, Steven Fagien, Boris Sommer, Richard Glogau, Koenraad De Boulle, Steven Fagien, Boris Sommer, Richard Glogau

Abstract

Botulinum toxin type A treatment is the foundation of minimally invasive aesthetic facial procedures. Clinicians and their patients recognize the important role, both negative and positive, that facial expression, particularly the glabellar frown lines, plays in self-perception, emotional well-being, and perception by others. This article provides up-to-date information on fundamental properties and mechanisms of action of the major approved formulations of botulinum toxin type A, summarizes recent changes in naming conventions (nonproprietary names) mandated by the United States Food and Drug Administration, and describes the reasons for these changes. The request for these changes provides recognition that formulations of botulinum toxins (eg, onabotulinumtoxinA and abobotulinumtoxinA) are not interchangeable and that dosing recommendations cannot be based on any one single conversion ratio. The extensive safety, tolerability, and efficacy data are summarized in detail, including the patient-reported outcomes that contribute to overall patient satisfaction and probability treatment continuation. Based on this in-depth review, the authors conclude that botulinum toxin type A treatment remains a cornerstone of facial aesthetic treatments, and clinicians must realize that techniques and dosing from one formulation cannot be applied to others, that each patient should undergo a full aesthetic evaluation, and that products and procedures must be selected in the context of individual needs and goals.

Keywords: botulinum toxin type A; cosmetic; glabellar; onabotulinumtoxinA; patient satisfaction.

Figures

Figure 1
Figure 1
Responder rates at each follow-up visit after treatment with onabotulinumtoxinA during the double-blind period of the study. A) Physician’s ratings of glabellar line severity at maximum frown. Responder rates were the percentage of subjects with ratings of none or mild. B) Subject’s assessment of changes in the appearance of glabellar lines. Responder rates were the percentages of subjects with a least moderate improvement.
Figure 2
Figure 2
Responder rates (percentage of subjects with ratings of none or mild) following each of 3 treatments with onabotulinumtoxinA: based on physician’s assessment of glabellar line severity at maximum frown (n = 258; subjects receiving all 3 treatments). Carruthers A, Carruthers J, Lowe NJ, et al; for the BOTOX® Glabellar Lines I and II Study Groups. 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. © 2004 Informa Healthcare. Reproduced with permission. aIndicates that the value is significantly greater than the value at the same time point after one or both previous botulinum toxin treatments (P < 0.028). Arrow indicates time of botulinum toxin treatment.
Figure 3
Figure 3
Percentage of subjects with glabellar severity of none or mild post treatment. Investigator and subject assessments – Study GL-1; abobotulinumtoxinA, n = 105; placebo, n = 53.
Figure 4
Figure 4
Mean FLO scores after onabotulinumtoxinA or placebo treatment in subjects with moderate to severe glabellar lines. The double-blind phase of the study was 4 weeks in duration, but subjects were followed for 12 weeks. Reprinted with permission from Fagien S, Cox SE, Finn JC, Werschler WP, Kowalski JW. Patient-reported outcomes with botulinum toxin type A treatment of glabellar rhytids: a double-blind, randomized, placebo-controlled study. Dermatol Surg. 2007;33(1 Spec No):S2–S9. © John Wiley & Sons Inc; 2007. Abbreviation: FLD, Facial Lines Outcomes Questionnaire.
Figure 5
Figure 5
Patients’ reactions to treatment with onabotulinumtoxinA (N = 30). Reprinted with permission from Sommer B, Zschocke I, Bergfeld D, Sattler G, Augustin M. Satisfaction of patients after treatment with botulinum toxin for dynamic facial lines. Dermatol Surg. 2003;29(5):456–460. © John Wiley & Sons Inc, 2003.
Figure 6
Figure 6
Improvements in FLO scores in 2 studies following treatment with onabotulinumtoxinA. A) Reprinted with permission from Carruthers J, Carruthers A. Botulinum toxin type A treatment of multiple upper facial sites: patient-reported outcomes. Dermatol Surg. 2007;33(1 Spec No):S10–S17. © John Wiley & Sons Inc; 2007. B) Reprinted with permission from Fagien S, Cox SE, Finn JC, Werschler WP, Kowalski JW. Patient-reported outcomes with botulinum toxin type A treatment of glabellar rhytids: a double-blind, randomized, placebo-controlled study. Dermatol Surg. 2007;33(1 Spec No):S2–S9. © John Wiley & Sons Inc; 2007.

References

    1. Shakespeare W.The Tragedy of MacbethAct 1, scene 4, line 13.
    1. Lewis MB, Bowler PJ. Botulinum toxin cosmetic therapy correlates with a more positive mood. J Cosmet Dermatol. 2009;8(1):24–26.
    1. Ekman P. Facial expression and emotion. Am Psychol. 1993;48(4):384–392.
    1. Heckmann M, Teichmann B, Schroder U, Sprengelmeyer R, Ceballos-Baumann AO. Pharmacologic denervation of frown muscles enhances baseline expression of happiness and decreases baseline expression of anger, sadness, and fear. J Am Acad Dermatol. 2003;49(2):213–216.
    1. Strack F, Neumann R. Furrowing the brow may undermine perceived fame: the role of facial feedback in judgments of celebrity. Pers Soc Psychol Bull. 2000;26(7):762–768.
    1. Dimberg U. Facial reactions to fear-relevant and fear-irrelevant stimuli. Biol Psychol. 1986;23(2):153–161.
    1. Hoffmann K, Hahn C, Leising D, Bechara FG, Georgas D, Tomi NS. “Emotional expressivity” after botulinumtoxin anti-wrinkle treatment. [poster]. 21st Annual World Congress of Dermatology; September 30–October 5, 2007; Buenos Aires, Argentina.
    1. Hoffmann K, Hahn C, Leising D, Bechara FG, Georgas D, Tomi NS. “Interpersonal attraction” and “well-being” after botulinumtoxin anti-wrinkle treatment. [poster]. 21st Annual World Congress of Dermatology; September 30–October 5, 2007; Buenos Aires, Argentina.
    1. Mac Pherson S. Self-esteem and cosmetic enhancement. Plast Surg Nurs. 2005;25(1):5–20.
    1. Strack F, Martin LL, Stepper S. Inhibiting and facilitating conditions of the human smile: a nonobtrusive test of the facial feedback hypothesis. J Pers Soc Psychol. 1988;54(5):768–777.
    1. VanSwearingen JM, Cohn JF, Bajaj-Luthra A. Specific impairment of smiling increases the severity of depressive symptoms in patients with facial neuromuscular disorders. Aesthetic Plast Surg. 1999;23(6):416–423.
    1. Finzi E, Wasserman E. Treatment of depression with botulinum toxin A: a case series. Dermatol Surg. 2006;32(5):645–649.
    1. Leffell DJ. Foreword. In: Kaminer MS, Dover JS, Arndt KA, editors. Atlas of Cosmetic Surgery. 1st ed. Philadelphia, Pa: W. B. Saunders Company; 2001. pp. ix–x.
    1. Carruthers JDA, Carruthers JA. Treatment of glabellar frown lines with C. botulinum-A exotoxin. J Dermatol Surg Oncol. 1992;18(1):17–21.
    1. Allergan Inc Botox Cosmetic: About Safety Accessed September 1, 2009.
    1. US Food and Drug Administration FDA Requires Boxed Warning for All Botulinum Toxin Products Accessed August 25, 2009.
    1. Flynn TC, Clark RE. Botulinum toxin type B (Myobloc) versus botulinum toxin type A (Botox) frontalis study: rate of onset and radius of diffusion. Dermatol Surg. 2003;29(5):519–522.
    1. Baumann L, Slezinger A, Vujevich J, et al. A double-blinded, randomized, placebo-controlled pilot study of the safety and efficacy of Myobloc (botulinum toxin type B)-purified neurotoxin complex for the treatment of crow’s feet: a double-blinded, placebo-controlled trial. Dermatol Surg. 2003;29(5):508–515.
    1. Glogau RG. Topically applied botulinum toxin type a for the treatment of primary axillary hyperhidrosis: results of a randomized, blinded, vehicle-controlled study. Dermatol Surg. 2007;33(1 Spec No):S76–S80.
    1. Aoki KR, Guyer B. Botulinum toxin type A and other botulinum toxin serotypes: a comparative review of biochemical and pharmacological actions. Eur J Neurol. 2001;8(Suppl 5):21–29.
    1. Aoki KR. Botulinum toxin: a successful therapeutic protein. Curr Med Chem. 2004;11(23):3085–3092.
    1. Carruthers A, Carruthers J. Botulinum toxin products overview. Skin Therapy Lett. 2008;13(6):1–4.
    1. Baumann L, Black L. Botulinum toxin type B (Myobloc) Dermatol Surg. 2003;29(5):496–500.
    1. Sadick NS. Prospective open-label study of botulinum toxin type B (Myobloc) at doses of 2,400 and 3,000 U for the treatment of glabellar wrinkles. Dermatol Surg. 2003;29(5):501–507.
    1. Ramirez AL, Reeck J, Maas CS. Botulinum toxin type B (MyoBloc) in the management of hyperkinetic facial lines. Otolaryngol Head Neck Surg. 2002;126(5):459–467.
    1. Klein AW, Carruthers A, Fagien S, Lowe NJ. Comparisons among botulinum toxins: an evidence-based review. Plast Reconstr Surg. 2008;121(6):413e–422e.
    1. Aoki KR. Pharmacology and immunology of botulinum neurotoxins. Int Ophthalmol Clin. 2005;45(3):25–37.
    1. Flynn TC. Botulinum toxin: examining duration of effect in facial aesthetic. Am J Clin Dermatol. 2009
    1. Fagien S, Carruthers JDA. A comprehensive review of patient-reported satisfaction with botulinum toxin type A for aesthetic procedures. Plast Reconstr Surg. 2008;122(6):1915–1925.
    1. De Boulle KLV. Botulinum neurotoxin type A in facial aesthetics. Expert Opin Pharmacother. 2007;8(8):1059–1072.
    1. Dolly JO, Aoki KR. The structure and mode of action of different botulinum toxins. Eur J Neurol. 2006;13(Suppl 4):1–9.
    1. Frevert J. Xeomin is free from complexing proteins. Toxicon. 2009:1–5.
    1. Hunt T, Clarke K. Potency evaluation of a formulated drug product containing 150-kd botulinum neurotoxin type A. Clin Neuropharmacol. 2009;32(1):28–31.
    1. Jost WH, Kohl A, Brinkmann S, Comes G. Efficacy and tolerability of a botulinum toxin type A free of complexing proteins (NT 201) compared with commercially available botulinum toxin type A (BOTOX) in healthy volunteers. J Neural Transm. 2005;112(7):905–913.
    1. Rosales RL, Bigalke H, Dressler D. Pharmacology of botulinum toxin: differences between type A preparations. Eur J Neurol. 2006;13(Suppl 1):2–10.
    1. Aoki KR, Satorius A, Ardila C, Brown M, Nicholson G, Francis J. Pharmacology of BOTOX, Dysport, Myobloc and BTX-A in animal models of efficacy and safety. [abstract] International Conference on Basic and Therapeutic Aspects of Botulinum and Tetanus Toxins; June 23–25, 2005; Denver, CO, USA.
    1. Trindade De Almeida A, de Boulle K. Diffusion characteristics of botulinum neurotoxin products and their clinical significance in cosmetic applications. J Cosmet Laser Ther. 2007;9(Suppl 1):17–22.
    1. Hexsel D, Dal’Forno T, Hexsel C, do Prado DZ, Lima MM. A randomized pilot study comparing the action halos of two commercial preparations of botulinum toxin type A. Dermatol Surg. 2008;34(1):52–59.
    1. Cliff SH, Judodihardjo H, Eltringham E. Different formulations of botulinum toxin type A have different migration characteristics: a double-blind, randomized study. J Cosmet Dermatol. 2008;7(1):50–54.
    1. Hexsel D, Rodrigues TC, Soirefmann M, et al. Efficacy and field of effectiveness of two commercial preparations of botulinum toxin type A in the frontalis muscles – a double-blind, randomized and controlled study. [abstract] European Masters of Anti Aging Annual Conference; October 2–3, 2009; Paris, France.
    1. Carruthers A, Carruthers J, Lowe NJ, et al. for the BOTOX® Glabellar Lines I and II Study Groups 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. Dysport [package insert] Brisbane, CA: Medicis Aesthetics Inc.; 2009.
    1. US Food and Drug Administration Information for Healthcare Professionals: OnabotulinumtoxinA (marketed as Botox/Botox Cosmetic), AbobotulinumtoxinA (marketed as Dysport) and RimabotulinumtoxinB (marketed as Myobloc) Accessed August 25, 2009.
    1. US Food and Drug Administration Follow-up to the February 8, 2008, Early Communication about an Ongoing Safety Review of Botox and Botox Cosmetic (Botulinum toxin Type A) and Myobloc (Botulinum toxin Type B) Accessed September 14, 2009.
    1. Botox Cosmetic [package insert] Irvine, CA: Allergan, Inc.; 2009.
    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. Wiest LG. An overview of the cosmetic treatment of facial muscles with a new botulinum toxin. Acta Dermatovenerol Croat. 2009;17(1):48–53.
    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 No):S51–S59.
    1. Carruthers A, Carruthers J. Long-term safety review of subjects treated with botulinum toxin type A for cosmetic use. [poster]. Proceedings of the 13th Congress of the European Academy of Dermatology and Venereology; November 17–21, 2004; Florence, Italy.
    1. Kawashima M, Harii K. An open-label, randomized, 64-week study repeating 10- and 20-U doses of botulinum toxin type A for treatment of glabellar lines in Japanese subjects. Int J Dermatol. 2009;48(7):768–776.
    1. Rzany B, Dill-Müller D, Grablowitz D, Heckmann M, Caird D. Repeated botulinum toxin a injections for the treatment of lines in the upper face: a retrospective study of 4,103 treatments in 945 patients. Dermatol Surg. 2007;33(1 Spec No):S18–S25.
    1. Monheit GD, Cohen JL. Reloxin Investigational Group. Long-term safety of repeated administrations of a new formulation of botulinum toxin type A in the treatment of glabellar lines: Interim analysis from an open-label extension study. J Am Acad Dermatol. 2009;61(3):421–425.
    1. Moy R, Maas C, Monheit G, Huber B, for the Reloxin Investigational Group Long-term safety and efficacy of a new botulinum toxin type A in treating glabellar lines. Arch Facial Plast Surg. 2009;11(2):77–83.
    1. Brin MF, Boodhoo TI, Pogoda JM, et al. Safety and tolerability of onabotulinumtoxinA in the treatment of facial lines: A meta-analysis of individual patient data from global clinical registration studies in 1678 participants. J Am Acad Dermatol. 2009;61(6):961–970.
    1. Brandt F, Swanson N, Baumann L, Huber B. Randomized, placebo-controlled study of a new botulinum toxin type A for treatment of glabellar lines: efficacy and safety. Dermatol Surg. 2009;35:1893–1901.
    1. Harii K, Kawashima M. A double-blind, randomized, placebo-controlled, two-dose comparative study of botulinum toxin type A for treating glabellar lines in Japanese subjects. Aesthetic Plast Surg. 2008;32(5):724–730.
    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. 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, Cohen J. Dilution volume of botulinum toxin type A for the treatment of glabellar rhytides: does it matter? Dermatol Surg. 2007;33(1 Spec No):S97–S104.
    1. Grimes PE, Shabazz D. A four-month randomized, double-blind evaluation of the efficacy of botulinum toxin type A for the treatment of glabellar lines in women with skin types V and VI. Dermatol Surg. 2009;35(3):429–435.
    1. Rzany B, Ascher B, Fratila A, Monheit GD, Talarico S, Sterry W, for the GLADYS Study Group 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. Arch Dermatol. 2006;142(3):320–326.
    1. Kane MA, Brandt F, Rohrich RJ, Narins RS, Monheit GD, Huber MB. Relovin Investigational Group. Evaluation of variable-dose treatment with a new US botulinum toxin type A (Dysport) for correction of moderate to severe glabellar lines: results from a phase III, randomized, double-blind, placebo-controlled study. Plast Reconstr Surg. 2009;124(5):1619–1629.
    1. Lowe P, Patnaik R, Lowe 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.
    1. Ascher B, Zakine B, Kestemont P, et al. Botulinum toxin A in the treatment of glabellar lines: scheduling the next injection. Aesth Surg J. 2005;25:365–375.
    1. Cox SE, Finn JC, Stetler L, Mackowiak J, Kowalski JW. Development of the Facial Lines Treatment Satisfaction Questionnaire and initial results for botulinum toxin type A-treated patients. Dermatol Surg. 2003;29(5):444–449.
    1. Stotland MA, Kowalski JW, Ray BB. Patient-reported benefit and satisfaction with botulinum toxin type A treatment of moderate to severe glabellar rhytides: results from a prospective open-label study. Plast Reconstr Surg. 2007;120(5):1386–1393.
    1. Beer KR. Comparative evaluation of the safety and efficacy of botulinum toxin type A and topical creams for treating moderate-to-severe glabellar rhytids. Dermatol Surg. 2006;32(2):184–192.
    1. Grimes PE. A four-month randomized, double-masked evaluation of the efficacy of botulinum toxin type A for the treatment of glabellar lines in women with skin types V and VI. Poster presented at: the 62nd Annual Meeting of the American Academy of Dermatology; February 6–11, 2004; Washington, DC:
    1. Ellis DAF, Chi PL, Tan AKW. Facial rejuvenation with botulinum. Dermatol Nurs. 1997;9(5):329–333. 365.
    1. Edwards CR, Teelucksingh S. Glycyrrhetinic acid and potentiation of hydrocortisone activity in skin. Lancet. 1990;336(8710):322–323.
    1. De Boulle K. Patient satisfaction with different botulinum toxin type A formulations in the treatment of moderate to severe upper facial rhytids. J Cosmet Laser Ther. 2008;10(2):87–92.
    1. Draycott S, Dabbs A. Cognitive dissonance 1: An overview of the literature and its integration into theory and practice in clinical psychology. Br J Clin Psychol. 1998;37(Pt 3):341–353.
    1. Kowalski J, Kozma C, Reese PR, Slaton T, Lee J. Initial development of a patient-completed questionnaire to assess outcomes of aesthetic treatment for hyperfunctional facial lines of the upper face. [poster] American Academy of Dermatology Academy’s 2005 Annual Meeting; July 20–24, 2005; Chicago, Ill, USA.
    1. Carruthers J, Carruthers A. Botulinum toxin type A treatment of multiple upper facial sites: patient-reported outcomes. Dermatol Surg. 2007;33(1 Spec No):S10–S17.
    1. Fagien S, Cox SE, Finn JC, Werschler WP, Kowalski JW. Patient-reported outcomes with botulinum toxin type A treatment of glabellar rhytids: a double-blind, randomized, placebo-controlled study. Dermatol Surg. 2007;33(1 Spec No):S2–S9.
    1. Sommer B, Zschocke I, Bergfeld D, Sattler G, Augustin M. Satisfaction of patients after treatment with botulinum toxin for dynamic facial lines. Dermatol Surg. 2003;29(5):456–460.
    1. Carruthers J, Fagien S, Matarasso SL, the Botox Consensus Group Consensus recommendations on the use of botulinum toxin type A in facial aesthetics. Plast Reconstr Surg. 2004;114(Suppl 6):1S–22S.
    1. Carruthers JDA, Glogau RG, Blitzer A, the Facial Aesthetics Consensus Group Faculty Advances in facial rejuvenation: botulinum toxin type A, hyaluronic acid dermal fillers, and combination therapies – consensus recommendations. Plast Reconstr Surg. 2008;121(Suppl 5):5S–30S.
    1. Carruthers J, Carruthers A. A prospective, randomized, parallel group study analyzing the effect of BTX-A (Botox) and nonanimal sourced hyaluronic acid (NASHA, Restylane) in combination compared with NASHA (Restylane) alone in severe glabellar rhytides in adult female subjects: treatment of severe glabellar rhytides with a hyaluronic acid derivative compared with the derivative and BTX-A. Dermatol Surg. 2003;29(8):802–809.
    1. Patel MP, Talmor M, Nolan WB. Botox and collagen for glabellar furrows: advantages of combination therapy. Ann Plast Surg. 2004;52(5):442–447.
    1. Khoury JG, Saluja R, Goldman MP. The effect of botulinum toxin type A on full-face intense pulsed light treatment: a randomized, double-blind, split-face study. Dermatol Surg. 2008:1–8.
    1. West TB, Alster TS. Effect of botulinum toxin type A on movement-associated rhytides following CO2 laser resurfacing. Dermatol Surg. 1999;25(4):259–261.
    1. Yamauchi PS, Lask G, Lowe NJ. Botulinum toxin type A gives adjunctive benefit to periorbital laser resurfacing. J Cosmet Laser Ther. 2004;6(3):145–148.
    1. Zimbler MS, Holds JB, Kokoska MS, et al. Effect of botulinum toxin pretreatment on laser resurfacing results: a prospective, randomized, blinded trial. Arch Facial Plast Surg. 2001;3(3):165–169.
    1. Carruthers J, Carruthers A. The effect of full-face broadband light treatments alone and in combination with bilateral crow’s feet botulinum toxin type A chemodenervation. Dermatol Surg. 2004;30(3):355–366.
    1. Carruthers J, Carruthers A. Complications of botulinum toxin type A. Facial Plast Surg Clin North Am. 2007;15(1):51–54. vi.
    1. Krishtul A, Waldorf HA, Blitzer A. Complications of cosmetic botulinum toxin therapy. In: Carruthers A, Carruthers J, editors. Procedures in Cosmetic Dermatology Series: Botulinum Toxin. Philadelphia, PA: WB Saunders Company; 2005.
    1. American Society for Aesthetic Plastic Surgery Cosmetic Surgery National Data Bank: 2008 Statistics. . Accessed March17, 2009.
    1. Tierney EP, Hanke CW. Recent trends in cosmetic and surgical procedure volumes in dermatologic surgery. Dermatol Surg. 2009;35(9):1324–1333.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj