Controversies about botulinum toxin type A duration effect
Keywords:
Botulinum toxin, botulinum toxin A, duration of toxin effect, immunogenic response, toxin reconstitution, toxin injection techniqueAbstract
Botulinum toxin is a commonly used treatment in aesthetic medicine. However, physicians have expressed concerns about the brief duration of the toxin's effect on patients. Nonetheless, the manufacturers and distributors of the toxin deny any manufacturer-dependent cause for the shortened efficacy of the toxin.
The aim of this paper is to analyse the possible causes that may influence the duration of action of botulinum toxin through an extensive review of published articles on the subject.
The causes of the condition may be linked to the patients’ immune response or non-immune factors. These factors include the association of toxins with accompanying proteins, which can affect the neuromuscular receptors, as well as the patient's emotional expression through gesticulation, toxin reconstitution, or the injection technique performed.
In conclusion, to achieve positive outcomes, it is essential to consider potential factors that may adversely affect the duration of the effect, conduct a thorough patient assessment, administer treatments at safe intervals, and avoid using questionable toxins.
References
1. ISAPS. Aesthetic/Cosmetic procedures performed in 2020. https://www.isaps.org
2. Aesthetic Plastic Surgery National Databank. STATISTICS 2020–2021. The Aesthetic Society Web site. http://www.surgery.org
3. Dong M, Yeh F, Tepp WH, et al. SV2 is the protein receptor for botulinum neurotoxin A. Science. 2006; 312(5773):592-6.
4. Rossi R, Arjmand S, Bærentzen SL, Gjedde A, Landau AM. Synaptic Vesicle Glycoprotein 2A: Features and Functions. Front Neurosci. 2022; 16:864514.
5. Colasante C, Rossetto O, Morbiato L, Pirazzini M, Molgó J, Montecucco C. Botulinum neurotoxin type A is internalized and translocated from small synaptic vesicles at the neuromuscular junction. Mol Neurobiol. 2013; 48(1):120-7.
6. Rummel A. Double receptor anchorage of botulinum neurotoxins accounts for their exquisite neurospecificity. Curr Top Microbiol Immunol. 2013; 364:61-90.
7. Yao G, Zhang S, Mahrhold S, et al. N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A. Nat Struct Mol Biol. 2016; 23(7):656-62.
8. Bellows S, Jankovic J. Immunogenicity Associated with Botulinum Toxin Treatment. Toxins (Basel). 2019; 11(9):491.
9. Eisele KH, Fink K, Vey M, Taylor HV. Studies on the dissociation of botulinum neurotoxin type A complexes. Toxicon. 2011; 57(4):555-65.
10. Frevert J. Pharmaceutical, biological, and clinical properties of botulinum neurotoxin type A products. Drugs R D. 2015; 15(1):1-9.
11. Gardner AP, Barbieri JT, Pellett S. How Botulinum Neurotoxin Light Chain A1 Maintains Stable Association with the Intracellular Neuronal Plasma Membrane. Toxins (Basel). 2022; 14(12):814.
12. Alcolea JM. Actualización sobre aplicaciones de la toxina botulínica en estética facial. Cir.plást.iberolatinoam. 2011; 37(1):81-90.
13. Eleopra R, Rinaldo S, Montecucco C, Rossetto O, Devigili G. Clinical duration of action of different botulinum toxin types in humans. Toxicon. 2020; 179:84-91.
14. Field M, Splevins A, Picaut P, et al. AbobotulinumtoxinA (Dysport®), OnabotulinumtoxinA (Botox®), and IncobotulinumtoxinA (Xeomin®) Neurotoxin Content and Potential Implications for Duration of Response in Patients. Toxins (Basel). 2018; 10(12):535.
15. Brin MF, James C, Maltman J. Botulinum toxin type A products are not interchangeable: a review of the evidence. Biologics. 2014; 8:227-41.
16. Dover JS, Monheit G, Greener M, Pickett A. Botulinum Toxin in Aesthetic Medicine: Myths and Realities. Dermatol Surg. 2018; 44(2):249-260.
17. Lacroix-Desmazes S, Mouly S, Popoff MR, Colosimo C. Systematic analysis of botulinum neurotoxin type A immunogenicity in clinical studies. Basal Ganglia. 2017; 9(4):12–17.
18. Wanitphakdeedecha R, Yan C, Apinuntham C, et al. Intradermal Micro-Dosing of AbobotulinumtoxinA for Face-Lifting: How Long Does It Last? Dermatol Ther (Heidelb). 2020; 10(4):779-789.
19. Sharma SK, Singh BR. Enhancement of the endopeptidase activity of purified botulinum neurotoxins A and E by an isolated component of the native neurotoxin associated proteins. Biochemistry. 2004; 43(16):4791-8.
20. Malissen B, Tamoutounour S, Henri S. The origins and functions of dendritic cells and macrophages in the skin. Nat Rev Immunol. 2014; 14(6):417-28.
21. Pirazzini M, Montecucco C, Rossetto O. Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update. Arch Toxicol. 2022; 96(6):1521-1539.
22. Dressler D, Bigalke H. Reconstituting botulinum toxin drugs: shaking, stirring or what? J Neural Transm (Vienna). 2016; 123(5):523-5.
23. Ramirez-Castaneda J, Jankovic J. Long-term efficacy and safety of botulinum toxin injections in dystonia. Toxins (Basel). 2013; 5(2):249-66.
24. Jankovic J, Carruthers J, Naumann M, et al. Neutralizing Antibody Formation with OnabotulinumtoxinA (BOTOX®) Treatment from Global Registration Studies across Multiple Indications: A Meta-Analysis. Toxins (Basel). 2023; 15(5):342.
25. Fabbri M, Leodori G, Fernandes RM, et al. Neutralizing Antibody and Botulinum Toxin Therapy: A Systematic Review and Meta-analysis. Neurotox Res. 2016; 29(1):105-17.
26. Hanna PA, Jankovic J, Vincent A. Comparison of mouse bioassay and immunoprecipitation assay for botulinum toxin antibodies. J Neurol Neurosurg Psychiatry. 1999; 66(5):612-6.
27. Lange O, Bigalke H, Dengler R, Wegner F, deGroot M, Wohlfarth K. Neutralizing antibodies and secondary therapy failure after treatment with botulinum toxin type A: much ado about nothing? Clin Neuropharmacol. 2009; 32(4):213-8.
28. Srinoulprasert Y, Kantaviro W, Nokdhes YN, et al. Development of inhibition ELISA to detect antibody-induced failure of botulinum toxin a therapy in cosmetic indications. J Immunol Methods. 2019; 473:112635.
29. Naumann M, Jankovic J. Safety of botulinum toxin type A: a systematic review and meta-analysis. Curr Med Res Opin. 2004; 20(7):981-90.
30. Glaser DA, Pariser DM, Hebert AA, et al. A Prospective, Nonrandomized, Open-Label Study of the Efficacy and Safety of OnabotulinumtoxinA in Adolescents with Primary Axillary Hyperhidrosis. Pediatr Dermatol. 2015; 32(5):609-17.
31. Hanna E, Pon K. Updates on Botulinum Neurotoxins in Dermatology. Am J Clin Dermatol. 2020; 21(2):157-162.
32. Kerscher M, Roll S, Becker A, Wigger-Alberti W. Comparison of the spread of three botulinum toxin type A preparations. Arch Dermatol Res. 2012; 304(2):155-61.
33. Park JY, Corduff N, Frevert J, Wanitphakdeedecha R, Chao YYY. Immunogenicity Associated with Aesthetic Botulinumtoxin A: A Survey of Asia-Pacific Physicians' Experiences and Recommendations. Plast Reconstr Surg Glob Open. 2022; 10(4):e4217.
34. Frevert J, Ahn KY, Park MY, Sunga O. Comparison of botulinum neurotoxin type A formulations in Asia. Clin Cosmet Investig Dermatol. 2018; 11:327-331.
35. Nestor M, Ablon G, Pickett A. Key Parameters for the Use of AbobotulinumtoxinA in Aesthetics: Onset and Duration. Aesthet Surg J. 2017; 37(suppl_1):S20-S31.
36. Nestor MS, Kleinfelder RE, Pickett A. The Use of Botulinum Neurotoxin Type A in Aesthetics: Key Clinical Postulates. Dermatol Surg. 2017; 43 Suppl 3:S344-S362.
37. Nestor MS, Arnold D, Fischer DL. The mechanisms of action and use of botulinum neurotoxin type A in aesthetics: Key Clinical Postulates II. J Cosmet Dermatol. 2020; 19(11):2785-2804.
38. Ho WWS, Albrecht P, Calderon PE, et al. Emerging Trends in Botulinum Neurotoxin A Resistance: An International Multidisciplinary Review and Consensus. Plast Reconstr Surg Glob Open. 2022; 10(6):e4407.
39. Hsu TS, Dover JS, Arndt KA. Effect of volume and concentration on the diffusion of botulinum exotoxin A. Arch Dermatol. 2004; 140(11):1351-4.
40. Dressler D, Pan L, Adib Saberi F. Antibody-induced failure of botulinum toxin therapy: re-start with low-antigenicity drugs offers a new treatment opportunity. J Neural Transm (Vienna). 2018; 125(10):1481-1486.
41. Shome D, Kapoor R, Khare S. Two different types of botulinum toxins: Is there a difference in efficacy and longevity? J Cosmet Dermatol. 2019; 18(6):1635-1641.
42. De Maio M, Ofenböck I, Narvaes C. Toxina botulínica: relación entre tipo de paciente y duración del efecto. Cir.plást.iberolatinoam. 2008; 34(1):19-26.
43. Shtefan V, Fletcher J, Duclos OA. Causes of Botulinum Toxin Treatment Failure. Clin Cosmet Investig Dermatol. 2022; 15:1045-1049.
44. Lewandowski M, Świerczewska Z, Barańska-Rybak W. Off-Label Use of Botulinum Toxin in Dermatology-Current State of the Art. Molecules. 2022; 27(10):3143.
45. Naik PP. Utilities of Botulinum Toxins in Dermatology and Cosmetology. Clin Cosmet Investig Dermatol. 2021; 14:1319-1330.
46. Du W, Zhou M, Zhang C, Sun Q. The efficacy of botulinum toxin A in the treatment of Raynaud's phenomenon in systemic sclerosis: A randomized self-controlled trial. Dermatol Ther. 2022; 35(7):e15529.
47. Prager W. Differential characteristics of incobotulinumtoxinA and its use in the management of glabellar frown lines. Clin Pharmacol. 2013; 5:39-52.
48. Kazim NA, Black EH. Botox: shaken, not stirred. Ophthalmic Plast Reconstr Surg. 2008; 24(1):10-2.
49. Beer K, Cohen J, Carruthers A. Cosmetic uses of botulinum toxin A. In: Ward A, Barnes M, editors. Clinical Uses of Botulinum Toxins. Cambridge, United Kingdom: Cambridge University Press; 2007; pp. 328–48.
50. Hallett M. Explanation of timing of botulinum neurotoxin effects, onset and duration, and clinical ways of influencing them. Toxicon. 2015; 107(Pt A):64-7.
51. Irkoren S, Ozkan HS, Karaca H. A Clinical Comparison of EMLA Cream and Ethyl Chloride Spray Application for Pain Relief of Forehead Botulinum Toxin Injection. Ann Plast Surg. 2015; 75(3):272-4.
52. Sami MS, Soparkar CN, Patrinely JR, Hollier LM, Hollier LH. Efficacy of botulinum toxin type a after topical anesthesia. Ophthalmic Plast Reconstr Surg. 2006; 22(6):448-52.
53. García-Monforte F, Castaño P. Toxina botulínica tipo A. Uso en medicina estética. En: Tresguerres JAF. Medicina Estética y Antienvejecimiento. Editorial Panamericana. 2ª edición. 2018. Madrid. págs. 303-318.
54. de Sanctis Pecora C, Pinheiro MVB, Ventura Ferreira K, Jacobino de Barros Nunes G, Miot HA. The One21 Technique: An Individualized Treatment for Glabellar Lines Based on Clinical and Anatomical Landmarks. Clin Cosmet Investig Dermatol. 2021; 14:97-105.
55. Abbasi NR, Durfee MA, Petrell K, Dover JS, Arndt KA. A small study of the relationship between abobotulinum toxin A concentration and forehead wrinkle reduction. Arch Dermatol. 2012; 148(1):119-21.
56. García-Monforte F. Marcación de los puntos de inyección con toxina botulínica en el tercio superior de la cara. Medicina Estética. 2020;65(4):29-33.
57. Alcolea JM, Trelles MA. Actualización sobre aplicaciones en estética de la toxina botulínica en el tercio inferior de la cara. Alcolea JM. Cir.plást.iberolatinoam. 2011;37(2):179-190.
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