Top

Aesthetic Plastic Surgery

Published in:

01-10-2016 | Review

Adverse Events of Botulinum Toxin Type A in Facial Rejuvenation: A Systematic Review and Meta-Analysis

Authors: Zhenhua Jia, Haibin Lu, Xiaonan Yang, Xiaolei Jin, Rongwei Wu, Jingyi Zhao, Lulu Chen, Zuoliang Qi

Published in: Aesthetic Plastic Surgery | Issue 5/2016

Abstract

Background

Botulinum toxin A (BTX-A) is a medical product that is used widely in cosmetics, and concern over the safety profile has increased among injectors and patients.

Objective

The purpose was to enhance the statistical effect size using a meta-analysis to detect the incidence rate of adverse events (AEs) in the treatment of facial wrinkles.

Methods

A systematic search was performed for randomized, double-blind, placebo-controlled trials published through July 2015.

Results

We searched 16 trials, including 42,405 individual participants, and found that in all enrolled facial rejuvenation studies, patients in the BTX-A group had significantly more AEs than those patients in the placebo group (RR = 1.24; 95 % CI 1.07–1.43; p = 0.003). For crow’s feet lines injection analysis, the BTX-A group did not exhibit any significant increase in AEs compared with the control group (RR = 1.19; 95 % CI 0.96–1.48; p = 0.12), except in injection site hematoma (RR = 2.14; 95 % CI 1.13–4.07; p = 0.02) in the treatment group. For frown wrinkle injection analysis, AEs were significantly observed in the BTX-A group (RR = 1.47; 95 % CI 1.23–1.77; p < 0.0001), particularly headaches (RR = 1.53; 95 % CI 1.15–2.03; p = 0.003), eyelid ptosis (RR = 5.56; 95 % CI 1.68–18.38; p = 0.005), and heavy eyelids (RR = 6.94; 95 % CI 1.27–37.93; p = 0.03).

Conclusion

This meta-analysis confirmed the safety profile of BTX-A for glabellar and crow’s feet lines, and BTX-A usage for the removal of upper facial wrinkles, which have some significant mild-to-moderate adverse profiles, including headache, eye disorder, eyelid ptosis, and heavy eyelids. Facial injectors should abide by the technical standards of neurotoxic drugs and be familiar with the local pharmacological effects to lessen the severe side effects.

Level of Evidence I

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the A5 online Instructions to Authors www.springer.com/00266.

Charles FJ, Cox SE, Earl ML (2003) Social implications of hyperfunctional facial lines. Dermatol Surg 29:450–455CrossRef

Mac PS (2005) Self-esteem and cosmetic enhancement. Plast Surg Nurs 25:5–20CrossRef

Leffell DJ, Arndt KA (2000) The dermatologic surgery issue: a new face for the ARCHIVES. Arch Dermatol 136:1404CrossRefPubMed

Fagien S (1999) Botox for the treatment of dynamic and hyperkinetic facial lines and furrows: adjunctive use in facial aesthetic surgery. Plast Reconstr Surg 103:701–713CrossRefPubMed

Carruthers J, Carruthers A (2007) The evolution of botulinum neurotoxin type A for cosmetic applications. J Cosmet Laser Ther 9:186–192CrossRefPubMed

Hotta TA (2014) ASAPS (American Society of Aesthetic Plastic Surgery)–2013 annual statistics. Plast Surg Nurs 34:47–48CrossRefPubMed

Fagien S, Cox SE, Finn JC, Werschler WP, Kowalski JW (2007) Patient-reported outcomes with botulinum toxin type A treatment of glabellar rhytids: a double-blind, randomized, placebo-controlled study. Dermatol Surg 33:S2–S9CrossRefPubMed

Glogau R, Kane M, Beddingfield F, Somogyi C, Lei X, Caulkins C et al (2012) OnabotulinumtoxinA: a meta-analysis of duration of effect in the treatment of glabellar lines. Dermatol Surg 38:1794–1803CrossRefPubMed

de Boulle K (2008) Patient satisfaction with different botulinum toxin type A formulations in the treatment of moderate to severe upper facial rhytides. J Cosmet Laser Ther 10:87–92CrossRefPubMed

10.

Carruthers JA, Lowe NJ, Menter MA, Gibson J, Nordquist M, Mordaunt J et al (2002) 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 46:840–849CrossRefPubMed

11.

Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary. Control Clin Trials 17:1–12CrossRefPubMed

12.

Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M et al (1998) Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses. Lancet 352:609–613CrossRefPubMed

13.

Sweeting MJ, Sutton AJ, Lambert PC (2004) What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data. Stat Med 23:1351–1375CrossRefPubMed

14.

Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129CrossRef

15.

Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558CrossRefPubMed

16.

Carruthers JD, Lowe NJ, Menter MA, Gibson J, Eadie N (2003) Double-blind, placebo-controlled study of the safety and efficacy of botulinum toxin type A for patients with glabellar lines. Plast Reconstr Surg 112:1089–1098CrossRefPubMed

17.

Harii K, Kawashima M (2008) 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 32:724–730CrossRefPubMedPubMedCentral

18.

Rubin MG, Dover J, Glogau RG, Goldberg DJ, Goldman MP, Schlessinger J (2009) The efficacy and safety of a new U.S. Botulinum toxin type A in the retreatment of glabellar lines following open-label treatment. J Drugs Dermatol 8:439–444PubMed

19.

Brandt F, Swanson N, Baumann L, Huber B (2009) Randomized, placebo-controlled study of a new botulinum toxin type a for treatment of glabellar lines: efficacy and safety. Dermatol Surg 35:1893–1901CrossRefPubMed

20.

Wu Y, Zhao G, Li H, Zheng Z, Zhong S, Yang Z et al (2010) Botulinum toxin type A for the treatment of glabellar lines in Chinese: a double-blind, randomized, placebo-controlled study. Dermatol Surg 36:102–108CrossRefPubMed

21.

Carruthers A, Carruthers J, Coleman WP 3rd, Donofrio L, Flynn T, Gold M et al (2013) Multicenter, randomized, phase III study of a single dose of incobotulinumtoxinA, free from complexing proteins, in the treatment of glabellar frown lines. Dermatol Surg 39:551–558CrossRefPubMed

22.

Hanke CW, Narins RS, Brandt F, Cohen JL, Donofrio LM, Downie J et al (2013) 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 39:891–899CrossRefPubMed

23.

Moers-Carpi M, Carruthers J, Fagien S, Lupo M, Delmar H, Jones D et al (2015) Efficacy and safety of onabotulinumtoxinA for treating crow’s feet lines alone or in combination with glabellar lines: a multicenter, randomized, controlled trial. Dermatol Surg 41:102–112CrossRefPubMed

24.

Lowe NJ, Ascher B, Heckmann M, Kumar C, Fraczek S, Eadie N (2005) Double-blind, randomized, placebo-controlled, dose-response study of the safety and efficacy of botulinum toxin type A in subjects with crow’s feet. Dermatol Surg 31:257–262CrossRefPubMed

25.

Monheit G, Carruthers A, Brandt F, Rand R (2007) A randomized, double-blind, placebo-controlled study of botulinum toxin type A for the treatment of glabellar lines: determination of optimal dose. Dermatol Surg 33:S51–S59CrossRefPubMed

26.

Kane MA, Brandt F, Rohrich RJ, Narins RS, Monheit GD, Huber MB (2009) Evaluation of variable-dose treatment with a new U.S. 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 124:1619–1629CrossRefPubMed

27.

Wollmer MA, de Boer C, Kalak N, Beck J, Gotz T, Schmidt T et al (2012) Facing depression with botulinum toxin: a randomized controlled trial. J Psychiatr Res 46:574–581CrossRefPubMed

28.

Carruthers A, Bruce S, de Coninck A, Connolly S, Cox SE, Davis PG et al (2014) Efficacy and safety of onabotulinumtoxinA for the treatment of crows feet lines: a multicenter, randomized, controlled trial. Dermatol Surg 40:1181–1190CrossRefPubMed

29.

Feng Z, Sun Q, He L, Wu Y, Xie H, Zhao G et al (2015) Optimal dosage of botulinum toxin type A for treatment of glabellar frown lines: efficacy and safety in a clinical trial. Dermatol Surg 41:S56–S63CrossRefPubMed

30.

de Almeida AT, Carruthers J, Cox SE, Goldman MP, Wheeler S, Gallagher CJ (2015) Patient satisfaction and safety with aesthetic onabotulinumtoxinA after at least 5 years: a retrospective cross-sectional analysis of 4402 glabellar treatments. Dermatol Surg 41:S19–S28CrossRef

31.

Ahn BK, Kim YS, Kim HJ, Rho NK, Kim HS (2013) Consensus recommendations on the aesthetic usage of botulinum toxin type A in Asians. Dermatol Surg 39:1843–1860CrossRefPubMed

32.

Guo Y, Lu Y, Liu T, Zhou Y, Yang P, Zhu J et al (2015) Efficacy and safety of botulinum toxin type A in the treatment of glabellar lines: a meta-analysis of randomized, placebo-controlled, double-blind trials. Plast Reconstr Surg. 136:310e–318eCrossRefPubMed

33.

Bonaparte JP, Ellis D, Quinn JG, Ansari MT, Rabski J, Kilty SJ (2013) A comparative assessment of three formulations of botulinum toxin A for facial rhytides: a systematic review and meta-analyses. Syst Rev 2:40CrossRefPubMedPubMedCentral

34.

Zagui RM, Matayoshi S, Moura FC (2008) Adverse effects associated with facial application of botulinum toxin: a systematic review with meta-analysis. Arq Bras Oftalmol 71:894–901CrossRefPubMed

35.

Ascher B, Zakine B, Kestemont P, Baspeyras M, Bougara A, Niforos F et al (2005) Botulinum toxin A in the treatment of glabellar lines: scheduling the next injection. Aesthet Surg J 25:365–375CrossRefPubMed

36.

Aguggia M (2008) Treating headaches with botulinum toxin. Neurol Sci 29(Suppl 1):S137–S139CrossRefPubMed

37.

Brin MF, Boodhoo TI, Pogoda JM, James LM, Demos G, Terashima Y et al (2009) 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 61:961–970CrossRefPubMed

38.

Ascher B, Rzany BJ, Grover R (2009) Efficacy and safety of botulinum toxin type A in the treatment of lateral crow’s feet: double-blind, placebo-controlled, dose-ranging study. Dermatol Surg 35:1478–1486CrossRefPubMed

39.

Rzany B, Dill-Muller D, Grablowitz D, Heckmann M, Caird D (2007) Repeated botulinum toxin A injections for the treatment of lines in the upper face: a retrospective study of 4103 treatments in 945 patients. Dermatol Surg 33:S18–S25CrossRefPubMed

40.

Brin MF, Blitzer A (1993) Botulinum toxin: dangerous terminology errors. J R Soc Med 86:493–494PubMedPubMedCentral

41.

Harper L (2009) Botulinum toxin A-when is a unit not a unit? J Urol 181:414–415CrossRefPubMed

Title: Adverse Events of Botulinum Toxin Type A in Facial Rejuvenation: A Systematic Review and Meta-Analysis
Authors: Zhenhua Jia
Haibin Lu
Xiaonan Yang
Xiaolei Jin
Rongwei Wu
Jingyi Zhao
Lulu Chen
Zuoliang Qi
Publication date: 01-10-2016
Publisher: Springer US
Published in: Aesthetic Plastic Surgery / Issue 5/2016
Print ISSN: 0364-216X
Electronic ISSN: 1432-5241
DOI: https://doi.org/10.1007/s00266-016-0682-1

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Adverse Events of Botulinum Toxin Type A in Facial Rejuvenation: A Systematic Review and Meta-Analysis

Abstract

Background

Objective

Methods

Results

Conclusion

Level of Evidence I

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Objective

Methods

Results

Conclusion

Level of Evidence I

Please log in to get access to this content

Other articles of this Issue 5/2016

Aesthetic Plastic Surgery Checklist: A Safety Tool

Erratum to: Current Trends in the Oncologic and Surgical Managements of Breast Cancer in Women with Implants: Incidence, Diagnosis, and Treatment

Analysis of Lower Breast Pole Length and Nipple–Areola Complex Position Following Superior Pedicle, Short Horizontal Scar Breast Reduction

Thumb Tip Defect Reconstruction Using Neurovascular Island Pedicle Flap Obtained From Long Finger

A New Method of Salvaging Breast Reconstruction After Breast Implant Using Negative Pressure Wound Therapy and Instillation

Analysis of 109 Consecutive Explanted Breast Implants: Correlation Between Suspected Implant Rupture and Surgical Findings