Log in

Efficacy and Safety of Botulinum Toxin Type A for Treatment of Glabellar Lines: A Network Meta-Analysis of Randomized Controlled Trials

  • Review
  • Non-Surgical Aesthetic
  • Published:
Aesthetic Plastic Surgery Aims and scope Submit manuscript

Abstract

Background

Botulinum toxin type A (BoNT/A) has been used in aesthetic applications worldwide, including glabellar lines. Currently, four BoNT/A preparations were approved for the improvement of moderate-to-severe glabellar lines: onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and prabotulinumtoxinA. DaxibotulinumtoxinA is a new form of BoNT/A drug that is developed in clinical application. We performed this network meta-analysis (NMA) to assess the efficacy and safety of all these different BoNT/A formulations for treating glabellar lines.

Methods

The investigators searched randomized controlled trials (RCTs) using the Medical Subject Headings (MeSH) terms “botulinum toxin” and “glabellar lines.” We searched the relevant studies in electronic databases as following: PubMed, Elsevier, EMBASE and the Cochrane Library. The end points included the percentage of subjects with a glabellar line severity (GLS) score of none (0) or mild (1), and the percentage of subjects achieving ≥ 1-point and 2-point improvement in glabellar line severity at maximum frown at approximately month 1 by the investigators’ assessment.

Results

All formulations of BoNT/A were far superior to placebo in efficacy. DaxibotulinumtoxinA was the only treatment that significantly increased the proportion of subjects achieving ≥ 1 point improvement in GLS score compared with other BoNT/A formulations. Moreover, daxibotulinumtoxinA was ranked the highest for the proportion of subjects achieving ≥ 2-point improvement in GLS score. No significant differences were revealed for the incidence of any adverse events (AEs) that related to treatment or drug among all BoNT/A preparations.

Conclusion

The overall results of this NMA suggested that daxibotulinumtoxinA is a new BoNT/A preparation that may be not only more effective but also well-tolerated for the treatment of glabellar lines.

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 online Instructions to Authors www.springer.com/00266.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Kim BJ, Kwon HH, Park SY et al (2014) Double-blind, randomized non-inferiority trial of a novel botulinum toxin A processed from the strain CBFC26, compared with onabotulinumtoxin A in the treatment of glabellar lines. J Eur Acad Dermatol Venereol 28(12):1761–1767

    Article  CAS  PubMed  Google Scholar 

  2. Kawashima M, Harii K, Horiuchi Y et al (2020) Safety, efficacy, and patient satisfaction with onabotulinumtoxin A for the treatment of upper facial lines in Japanese subjects. Dermatol Surg 46(4):483–490

    Article  CAS  PubMed  Google Scholar 

  3. William Hanke C, Narins RS, Brandt F et al (2013) A randomized, placebo-controlled, double-blind phase iii trial investigating the efficacy and safety of incobotulinumtoxin A in the treatment of glabellar frown lines using a stringent composite endpoint. Dermatol Surg 39(6):891–899

    Article  PubMed  Google Scholar 

  4. Yoo KH, Lee YW, Lee JS et al (2021) Efficacy and safety of a new botulinum toxin (HU-014) versus existing onabotulinumtoxin A in subjects with moderate to severe glabellar lines. Dermatol Surg 47(3):e91–e96

    CAS  PubMed  Google Scholar 

  5. Gubanova E, Haddad TM, Bergerova Y et al (2018) Assessment of subject and physician satisfaction after long-term treatment of glabellar lines with AbobotulinumtoxinA (Dysport((R))/Azzalure((R))): primary results of the APPEAL noninterventional study. Aesthetic Plast Surg 42(6):1672–1680

    Article  PubMed  PubMed Central  Google Scholar 

  6. Yoelin SG, Dhawan SS, Vitarella D et al (2018) Safety and efficacy of EB-001, a novel type E botulinum toxin, in subjects with glabellar frown lines: results of a phase 2, randomized, placebo-controlled, ascending-dose study. Plast Reconstr Surg 142(6):847e–855e

    Article  CAS  PubMed  Google Scholar 

  7. Ascher B, Rzany B, Kestemont P et al (2020) Liquid formulation of AbobotulinumtoxinA: A 6-month, phase 3, double-blind, randomized, placebo-controlled study of a single treatment, ready-to-use toxin for moderate-to-severe glabellar lines. Aesthetic Surg J 40(1):93–104

    Article  Google Scholar 

  8. Polacco MA, Singleton AE, Barnes CH et al (2021) A double-blind, randomized clinical trial to determine effects of increasing doses and dose-response relationship of incobotulinumtoxin A in the treatment of glabellar rhytids. Aesthetic Surg J 41(6):500–511

    Article  Google Scholar 

  9. Ogilvie P, Rivkin AZ, Dayan S et al (2019) Onabotulinumtoxin A for treatment of forehead and glabellar lines: subject-reported satisfaction and impact from a phase 3 double-blind study. Dermatol Surg 45(5):689–699

    Article  CAS  PubMed  Google Scholar 

  10. Kane MA, Gold MH, Coleman WR et al (2015) A randomized, double-blind trial to investigate the equivalence of incobotulinumtoxin A and onabotulinumtoxin A for glabellar frown lines. Dermatol Surg 41(11):1310–1319

    Article  CAS  PubMed  Google Scholar 

  11. Moers-Carpi M, Dirschka T, Feller-Heppt G et al (2012) A randomised, double-blind comparison of 20 units of onabotulinumtoxin A with 30 units of incobotulinumtoxin A for glabellar lines. J Cosmet Laser Ther 14(6):296–303

    Article  PubMed  Google Scholar 

  12. Schlessinger J, Cohen JL, Shamban A et al (2021) A multicenter study to evaluate subject satisfaction with two treatments of abobotulinumtoxin A a year in the glabellar lines. Dermatol Surg 47(4):504–509

    Article  CAS  PubMed  Google Scholar 

  13. Kaufman J, Cohen JL, Peredo MI et al (2019) Clinical assessment of 2 licensed abobotulinumtoxin A injection volumes for the treatment of glabellar lines. Dermatol Surg 45(10):1274–1284

    Article  CAS  PubMed  Google Scholar 

  14. Schlessinger J, Friedmann DP, Mayoral F et al (2021) Abobotulinumtoxin A treatment of glabellar lines using a new reconstitution and injection volume: randomized, Placebo-controlled data. J Drugs Dermatol 20(9):988–995

    Article  PubMed  Google Scholar 

  15. Kestemont P, Hilton S, Andriopoulos B et al (2022) Long-term efficacy and safety of liquid abobotulinumtoxina formulation for moderate-to-severe glabellar lines: a phase III, double-blind, randomized, placebo-controlled and open-label study. Aesthetic Surg J 42(3):301–313

    Article  Google Scholar 

  16. Jones D, Carruthers J, Narins RS et al (2014) Efficacy of incobotulinumtoxin A for treatment of glabellar frown lines: a post hoc pooled analysis of 2 randomized, placebo-controlled, phase 3 trials. Dermatol Surg 40(7):776–785

    CAS  PubMed  Google Scholar 

  17. Carruthers A, Carruthers J, Coleman WR et al (2013) Multicenter, randomized, phase III study of a single dose of incobotulinumtoxin A, free from complexing proteins, in the treatment of glabellar frown lines. Dermatol Surg 39(4):551–558

    Article  CAS  PubMed  Google Scholar 

  18. Sattler G, Callander MJ, Grablowitz D et al (2010) Noninferiority of incobotulinumtoxin A, free from complexing proteins, compared with another botulinum toxin type A in the treatment of glabellar frown lines. Dermatol Surg 36(Suppl 4):2146–2154

    Article  CAS  PubMed  Google Scholar 

  19. Beer KR, Shamban AT, Avelar RL et al (2019) Efficacy and safety of prabotulinumtoxin A for the treatment of glabellar lines in adult subjects: results from 2 identical phase III studies. Dermatol Surg 45(11):1381–1393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rzany BJ, Ascher B, Avelar RL et al (2020) A multicenter, randomized, double-blind, placebo-controlled, single-dose, phase III, non-inferiority study comparing prabotulinumtoxin A and onabotulinumtoxin A for the treatment of moderate to severe glabellar lines in adult patients. Aesthet Surg J 40(4):413–429

    PubMed  Google Scholar 

  21. Won CH, Kim HK, Kim BJ et al (2015) Comparative trial of a novel botulinum neurotoxin type A versus onabotulinumtoxin A in the treatment of glabellar lines: a multicenter, randomized, double-blind, active-controlled study. Int J Dermatol 54(2):227–234

    Article  CAS  PubMed  Google Scholar 

  22. Bertucci V, Humphrey S, Carruthers J et al (2017) Comparing injectable daxibotulinumtoxin A and onabotulinumtoxin A in moderate and severe glabellar lines: additional analyses from a phase 2, randomized, dose-ranging, double-blind, multicenter study. Dermatol Surg 43(Suppl 3):S262–S273

    Article  PubMed  Google Scholar 

  23. Guo Y, Lu Y, Liu T 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(3):310e–318e

    Article  CAS  PubMed  Google Scholar 

  24. Hutton B, Salanti G, Caldwell DM et al (2015) The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med 162(11):777–784

    Article  PubMed  Google Scholar 

  25. Higgins JPT (2020) Cochrane handbook for systematic reviews of interventions, 2nd edn. Springer, Berlin

    Google Scholar 

  26. Bai F, Li GG, Liu Q et al (2019) Short-term efficacy and safety of IL-17, IL-12/23, and IL-23 inhibitors brodalumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tildrakizumab, and risankizumab for the treatment of moderate to severe plaque psoriasis: a systematic review and network meta-analysis of randomized controlled trials. J Immunol Res 2019:2546161

    Article  PubMed  PubMed Central  Google Scholar 

  27. Joseph J, Moradi A, Lorenc ZP et al (2021) Abobotulinumtoxin A for the treatment of moderate-to-severe glabellar lines: a randomized, dose-escalating, double-blind study. J Drugs Dermatol 20(9):980–987

    Article  PubMed  Google Scholar 

  28. Monheit GD, Baumann L, Maas C et al (2020) Efficacy, safety, and subject satisfaction after abobotulinumtoxin A treatment for moderate to severe glabellar lines. Dermatol Surg 46(1):61–69

    Article  CAS  PubMed  Google Scholar 

  29. Brandt F, Swanson N, Baumann L et al (2009) Randomized, placebo-controlled study of a new botulinum toxin type a for treatment of glabellar lines: efficacy and safety. Dermatol Surg 35(12):1893–1901

    Article  CAS  PubMed  Google Scholar 

  30. Ascher B, Kestemont P, Boineau D et al (2018) Liquid formulation of Abobotulinumtoxin A exhibits a favorable efficacy and safety profile in moderate to severe glabellar lines: a randomized, double-blind, placebo- and active comparator-controlled trial. Aesthetic Surg J 38(2):183–191

    Article  Google Scholar 

  31. Hanke CW, Narins RS, Brandt F et al (2013) A randomized, placebo-controlled, double-blind phase III trial investigating the efficacy and safety of incobotulinumtoxin A in the treatment of glabellar frown lines using a stringent composite endpoint. Dermatol Surg 39(6):891–899

    Article  CAS  PubMed  Google Scholar 

  32. Rzany BJ, Ascher B, Avelar RL et al (2020) A multicenter, randomized, double-blind, placebo-controlled, single-dose, phase III, non-inferiority study comparing prabotulinumtoxin A and onabotulinumtoxin A for the treatment of moderate to severe glabellar lines in adult patients. Aesthetic Surg J 40(4):413–429

    Google Scholar 

  33. Carruthers JD, Fagien S, Joseph JH et al (2017) Injectable daxibotulinumtoxina for the treatment of glabellar lines: a phase 2, randomized, dose-ranging, double-blind, multicenter comparison with onabotulinumtoxina and placebo. Dermatol Surg 43(11):1321–1331

    Article  CAS  PubMed  Google Scholar 

  34. Carruthers JD, Fagien S, Joseph JH et al (2020) Daxibotulinumtoxin A for injection for the treatment of glabellar lines: results from each of two multicenter, randomized, double-blind, placebo-controlled, phase 3 studies (SAKURA 1 and SAKURA 2). Plast Reconstr Surg 145(1):45–58

    Article  CAS  PubMed  Google Scholar 

  35. Kerscher M, Fabi S, Fischer T et al (2021) Incobotulinumtoxin A demonstrates safety and prolonged duration of effect in a dose-ranging study for glabellar lines. J Drugs Dermatol JDD 20(10):1052–1060

    PubMed  Google Scholar 

  36. Fabi SG, Cohen JL, Green LJ et al (2021) Daxibotulinumtoxin A for injection for the treatment of glabellar lines: efficacy results from SAKURA 3, a large, open-label, phase 3 safety study. Dermatol Surg 47(1):48–54

    Article  CAS  PubMed  Google Scholar 

  37. Glogau R, Kontis TC, Liu Y et al (2021) Progressive improvement in static glabellar lines after repeated treatment with daxibotulinumtoxina for injection. Dermatol Surg 47(12):1579–1584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bertucci V, Solish N, Kaufman-Janette J et al (2020) DaxibotulinumtoxinA for Injection has a prolonged duration of response in the treatment of glabellar lines: pooled data from two multicenter, randomized, double-blind, placebo-controlled, phase 3 studies (SAKURA 1 and SAKURA 2). J Am Acad Dermatol 82(4):838–845

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work is supported by the Medical Health Science and Technology Project of Shandong Provincial Health Commission (Grant Number 202104120294).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to **ujuan **a or **an** Chen.

Ethics declarations

Conflict of interest

No potential conflict of interest was reported by the authors.

Human and Animal Rights

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent

For this type of study, informed consent is not required.For this type of study, informed consent is not required.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, X., Sui, C., **a, X. et al. Efficacy and Safety of Botulinum Toxin Type A for Treatment of Glabellar Lines: A Network Meta-Analysis of Randomized Controlled Trials. Aesth Plast Surg 47, 365–377 (2023). https://doi.org/10.1007/s00266-022-03018-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00266-022-03018-y

Keywords

Navigation