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Aesthetic Plastic Surgery

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23-01-2022 | Injectable Filler | Review

Monophasic and Biphasic Hyaluronic Acid Fillers for Esthetic Correction of Nasolabial Folds: A Meta-Analysis of Randomized Controlled Trials

Authors: Yiwen Huang, Yibin Zhang, Xiaojing Fei, Qi Fan, Jie Mao

Published in: Aesthetic Plastic Surgery | Issue 3/2022

Abstract

Background

Hyaluronic acid (HA) fillers have become the most popular dermal fillers for esthetic nasolabial folds (NLFs) correction. Based on the cross-linking method, they can be classified as monophasic or biphasic types.

Objectives

The aim of this meta-analysis is to compare the efficacy and safety of monophasic HA fillers with that of biphasic HA fillers for treatment of NLFs. PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and Chinese databases were searched from inception to January 2021.

Methods

Randomized controlled trials (RCTs) that compared treatment outcomes of a monophasic HA filler with a biphasic HA filler for esthetic NLF correction were selected. Twenty-two RCTs with totally 1848 subjects were included to this meta-analysis. A significantly higher improvement of NLF severity score was seen for monophasic fillers than biphasic fillers at 2 (p = 0.005), 8 (p <0.0001), 12 (p = 0.03), 16 (p = 0.005), 24 (p <0.00001), 36 (p = 0.007), and 52 week (p <0.0001) after treatment.

Results

The effect was retained regardless of ethnicity, total injection volume, and baseline NLF severity. More subjects preferred monophasic fillers over biphasic ones (≤7 months: RR = 3.45, 95% CI 1.17 to 10.11; >7 months: RR = 2.37, 95% CI 1.45 to 3.86). Rate of post-injection pain was significantly lower for monophasic fillers (RR = 0.85, 95% CI 0.78 to 0.92, p <0.0001), but no statistical difference was observed for other post-injection adverse events. Compared to biphasic HA fillers, monophasic HA fillers were associated with a greater and more durable esthetic NLFs improvement, a lower rate of post-injection pain, and were favored by more patients.

Level of Evidence II

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.

Bukhari SNA, Roswandi NL, Waqas M, Habib H, Hussain F, Khan S et al (2018) Hyaluronic acid, a promising skin rejuvenating biomedicine: a review of recent updates and pre-clinical and clinical investigations on cosmetic and nutricosmetic effects. Int J of Biol Macromol 120(Pt B):1682–1695CrossRef

Grablowitz D, Sulovsky M, Höller S, Ivezic-Schoenfeld Z, Chang-Rodriguez S, Prinz M (2019) Safety and efficacy of princess® filler lidocaine in the correction of nasolabial folds. Clin Cosmet Investig Dermatol 12:857–864PubMedPubMedCentralCrossRef

Kühne U, Esmann J, Von Heimburg D, Imhof M, Weissenberger P, Sattler G (2016) Safety and performance of cohesive polydensified matrix hyaluronic acid fillers with lidocaine in the clinical setting-an open-label, multicenter study. Clin Cosmet Investig Dermatol 9:373–381PubMedPubMedCentralCrossRef

Levy PM, Boulle KD, Raspaldo H (2009) A split-face comparison of a new hyaluronic acid facial filler containing pre-incorporated lidocaine versus a standard hyaluronic acid facial filler in the treatment of naso-labial folds. J Cosmet Laser Ther 11(3):169–173PubMedCrossRef

Lee JH, Kim S, Park ES (2017) The efficacy and safety of HA IDF plus (with lidocaine) versus HA IDF (without lidocaine) in nasolabial folds injection: a randomized, multicenter, double-blind, split-face study. Aesth Plast Surg 41:422–428CrossRef

Kopera D, Palatin M, Bartsch R, Bartsch K, O'Rourke M, Höller S, et al (2015) An open-label uncontrolled, multicenter study for the evaluation of the efficacy and safety of the dermal filler princess VOLUME in the treatment of nasolabial folds. Biomed Res Int, 195328

Choi WJ, Han SW, Kim JE, Kim HW, Kim MB, Kang H (2015) The efficacy and safety of lidocaine-containing hyaluronic acid dermal filler for treatment of nasolabial folds: a multicenter, randomized clinical study. Aesth Plast Surg 39(6):953–962CrossRef

Kim MJ, Moon WJ, Hur MS, Han SH, Lee YW, Choe YB et al (2018) Ex vivo magnetic resonance imaging using hyaluronic acid fillers: differences between monophasic and biphasic fillers. Skin Res Technol 24(1):16–19PubMedCrossRef

Kwon HJ, Ko EJ, Choi SY, Choi EJ, Jang YJ, Kim BJ et al (2018) The efficacy and safety of a monophasic hyaluronic acid filler in the correction of nasolabial folds: a randomized, multicenter, single blinded, split-face study. J Cosmet Dermatol 17(4):584–589PubMedCrossRef

10.

Huang X, Liang Y, Li Q (2013) Safety and efficacy of hyaluronic acid for the correction of nasolabial folds: a meta-analysis. Eur J Dermatol 23(5):592–599PubMedCrossRef

11.

Moher D, Liberati A, Tetzlaff Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Plos Med 6(7):e1000097PubMedPubMedCentralCrossRef

12.

Hou M, Xing H, Cai Y, Wang X, Xie Z, Zhang Q et al (2019) Short-term effect and safety of a new generation of monoclonal antibodies targeting interleukin-23p19 for treatment of psoriasis: a systematic review and meta-analysis. Eur J Dermatol 29(3):302–314PubMed

13.

Cao HR, Long X, Liu ZF, Zeng A, Bai M, Wang XJ (2016) Safety and efficacy of cross-linked hyaluronic acid revanesse ultra for treatment of nasolabial folds. Med J Peking Union Med Coll Hosp 2(2):88–92 (Chinese)

14.

Dai X, Li L, Peterson W, Baumgartner RR, Huang J, Baer-Zwick A et al (2019) Safety and effectiveness of hyaluronic acid dermal filler in correction of moderate-to-severe nasolabial folds in Chinese subjects. Clin Cosmet Investig Dermatol 12:57–62PubMedPubMedCentralCrossRef

15.

Li D, Xie Y, Li Q, Sun J, Jiang P, Jia Y et al (2017) Safety and effectiveness of juvéderm ultra plus injectable gel in correcting severe nasolabial folds in chinese subjects. Plast Reconstr Surg Glob Open 5(1):e1133PubMedPubMedCentralCrossRef

16.

Qiao J, Li F, Jin HZ et al (2020) The efficacy and safety of dermalaxTM deep in the correction of moderate to severe nasolabial folds: a multicenter, randomized, double-blind clinical study. J Dermatolog Treat 32(5):1–8

17.

Zhang YW (2012) A randomized, controlled study to evaluate the efficacy and safety of Revanesse® Ultra for the correction of nasolabial folds [master’s thesis]. Chinese PLA general hospital & postgraduate medical school, Haidian (BJ)

18.

Zhou SB, Xie Y, Chiang CA, Liu K, Li QF (2016) A randomized clinical trial of comparing monophasic monodensified and biphasic nonanimal stabilized hyaluronic acid dermal fillers in treatment of Asian nasolabial folds. Dermatol Surg 42(9):1061–1068PubMedCrossRef

19.

Joo HJ, Woo YJ, Kim JE, Kim BJ, Kang H (2016) A randomized clinical trial to evaluate the efficacy and safety of lidocaine-containing monophasic hyaluronic acid filler for nasolabial folds. Plast Reconstr Surg 137(3):799–808PubMedCrossRef

20.

Kim BW, Moon IJ, Yun WJ, Chung BY, Kim SD, Lee GY et al (2016) A randomized, evaluator-blinded, split-face comparison study of the efficacy and safety of a novel mannitol containing monophasic hyaluronic acid dermal filler for the treatment of moderate to severe nasolabial folds. Ann Dermatol 28(3):297–303PubMedPubMedCentralCrossRef

21.

Pak C, Park J, Hong J, Jeong J, Bang S, Heo CY (2015) A phase III, randomized, multi-center, double-masked, matched-pairs, active-controlled trial to compare the efficacy and safety between neuramis deep and restylane in the correction of nasolabial folds. Arch Plast Surg 42(6):721–728PubMedPubMedCentralCrossRef

22.

Rhee DY, Won CH, Chang SE, Noh TK, Kim MS, Kim BJ et al (2014) Efficacy and safety of a new monophasic hyaluronic acid filler in the correction of nasolabial folds: a randomized, evaluator-blinded, split-face study. J Dermatolog Treat 25(5):448–452CrossRef

23.

Suh JH, Oh CT, Im SI, Lim JS, Kim BJ, Lee JH (2017) A multicenter, randomized, double-blind clinical study to evaluate the efficacy and safety of a new monophasic hyaluronic acid filler with lidocaine 0.3% in the correction of nasolabial fold. J Cosmet Dermatol 16(3):327–332PubMedCrossRef

24.

Gold MH, Baumann LS, Clark CP III, Schlessinger J (2018) A multicenter, double-blinded, randomized, split-face study of the safety and efficacy of a novel hyaluronic acid gel for the correction of nasolabial folds. J Drugs Dermatol 17(1):66–73PubMed

25.

Janette JK, Taylor SC, Cox SE, Weinkle SH, Smith S, Kinney BM (2019) Efficacy and safety of a new resilient hyaluronic acid dermal filler, in the correction of moderate-to-severe nasolabial folds: a 64-week, prospective, multicenter, controlled, randomized, double-blind and within subject study. J Cosmet Dermatol 18(5):1244–1253CrossRef

26.

ClinicalTrails. Gov [Internet]. U.S.: National Library of Medicine; c2021 [Updated 2019 Jan 9; cited 2021 Mar 09]. Available from: https://clinicaltrials.gov/ct2/show/NCT00850889?term=00850889&draw=2&rank=1

27.

Ascher B, Bayerl C, Kestemont P, Rzany B, Edwartz C, Podda M (2017) A 12-month follow-up, randomized comparison of effectiveness and safety of two hyaluronic acid fillers for treatment of severe nasolabial folds. Dermatol Surg 43(3):389–395PubMedCrossRef

28.

Buntrock H, Reuther T, Prager W, Kerscher M (2013) Efficacy, safety, and patient satisfaction of a monophasic cohesive polydensified matrix versus a biphasic nonanimal stabilized hyaluronic acid filler after single injection in nasolabial folds. Dermatol Surg 39(7):1097–1105PubMedCrossRef

29.

Nast A, Reytan N, Hartmann V, Pathirana D, Bachmann F, Erdmann R et al (2011) Efficacy and durability of two hyaluronic acid-based fillers in the correction of nasolabial folds: results of a prospective, randomized, double-blind, actively controlled clinical pilot study. Dermatol Surg 37(6):768–775PubMed

30.

Prager W, Steinkraus V (2010) A prospective, rater-blind, randomized comparison of the effectiveness and tolerability of belotero (®) basic versus restylane (®) for correction of nasolabial folds. Eur J Dermatol 20(6):748–752PubMed

31.

Rzany B, Bayerl C, Bodokh I, Boineau D, Dirschka T, Roussel CQ et al (2017) An 18-month follow-up, randomized comparison of effectiveness and safety of two hyaluronic acid fillers for treatment of moderate nasolabial folds. Dermatol Surg 43(1):58–65PubMedCrossRef

32.

Goodman GJ, Bekhor P, Rich M, Rosen RH, Halstead MB, Rogers JD (2011) A comparison of the efficacy, safety, and longevity of two different hyaluronic acid dermal fillers in the treatment of severe nasolabial folds: a multicenter, prospective, randomized, controlled, single-blind, within-subject study. Clin Cosmet Investig Dermatol 4:197–205PubMedPubMedCentralCrossRef

33.

Nasrollahi SA, Yazdanparast T, Ameri S, Zonouz SM, Kashani NM (2017) Firooz A (2017) Comparative clinical assessment of two nasolabial hyaluronic acid fillers: a double-blind, randomized controlled trial. Iranian J Dermatol 20(1):1–5

34.

Cochrane handbook for systematic reviews of interventions [Internet] (2019) The Cochrane Collaboration; c2021. Chapter 6: Choosing effect measures and computing estimates of effect Hul [cited 2021 Mar 09]. Available from: https://training.cochrane.org/handbook/current/chapter-06

35.

Jeong KH, Gwak MJ, Moon SK, Lee SJ, Shin MK (2018) Efficacy and durability of hyaluronic acid fillers for malar enhancement: a prospective, randomized, split-face clinical controlled trial. J Cosmet Laser Ther 20(3):184–188PubMedCrossRef

36.

Sundaram H, Cassuto D (2013) Biophysical characteristics of hyaluronic acid soft-tissue fillers and their relevance to aesthetic applications. Plast Reconstr Surg 132(4S–2):5S-21SPubMedCrossRef

37.

Sundaram H, Fagien S (2015) Cohesive polydensified matrix hyaluronic acid for fine lines. Plast Reconstr Surg 136(5S):149S-163SPubMedCrossRef

38.

Flynn TC, Sarazin D, Bezzola A, Terrani C, Micheels P (2011) Comparative histology of intradermal implantation of mono and biphasic hyaluronic acid fillers. Dermatol Surg 37(5):637–643PubMedCrossRef

39.

Micheels P, Sarazin D, Besse S, Sundaram H, Flynn TC (2013) A blanching technique for intradermal injection of the hyaluronic acid Belotero. Plast Reconstr Surg 132(4S–2):59S-68SPubMedCrossRef

40.

Signorini M, Liew S, Sundaram H, De Boulle KL, Goodman GJ, Monheit G et al (2016) Global aesthetics consensus: avoidance and management of complications from hyaluronic acid fillers-evidence- and opinion-based review and consensus recommendations. Plast Reconstr Surg 137(6):961e–971ePubMedCrossRef

41.

Vedamurthy M, Vedamurthy A, Kc N (2010) Dermal fillers: do’s and don’t’s. J Cutan Aesthet Surg 3(1):11–15PubMedPubMedCentralCrossRef

42.

Urdiales-Galvez F, Delgado NE, Figueiredo V, Lajo-Plaza JV, Mira M, Ortiz-Marti F et al (2017) Preventing the complications associated with the use of dermal fillers in facial aesthetic procedures: an expert group consensus report. Aesthetic Plast Surg 41(3):667–677PubMedPubMedCentralCrossRef

43.

Lee W, Oh W, Moon HJ, Koh IS, Yang EJ (2020) Soft tissue filler properties can be altered by a small-diameter needle. Dermatol Surg 46(9):1155–1162PubMedCrossRef

44.

Flynn TC, Thompson DH, Hyun SH, Howell DJ (2015) Ultrastructural analysis of 3 hyaluronic acid soft-tissue fillers using scanning electron microscopy. Dermatol Surg 41(4S):S143-152PubMedCrossRef

45.

Chan IL, Cohen S, Cunha MG, Maluf LC (2019) Characteristics and management of Asian skin. Int J Dermatol 58(2):131–143PubMedCrossRef

46.

Oranges CM, Gohritz A, Haug M, Harder Y, Schaefer DJ (2016) Universal and ethnic-specific considerations on facial rejuvenation: Where do you inject your fillers? Plast Reconstr Surg Glob Open 4(8):e842PubMedPubMedCentralCrossRef

47.

Davis EC, Callender VD (2011) Aesthetic dermatology for aging ethnic skin. Dermatol Surg 37(7):901–917PubMedCrossRef

48.

Hong JY, Choi EJ, Choi SY, Li K, Kim BJ (2018) Randomized, patient/evaluator-blinded, intraindividual comparison study to evaluate the efficacy and safety of a novel hyaluronic acid dermal filler in the treatment of nasolabial folds. Dermatol Surg 44(4):542–548PubMedCrossRef

49.

Windhager S, Mitteroecker P, Rupić I, Lauc T, Polašek O, Schaefer K (2019) Facial aging trajectories: a common shape pattern in male and female faces is disrupted after menopause. Am J Phys Anthropol 169(1):678–688PubMedPubMedCentralCrossRef

50.

Fang RY, Zhang HC, Liu YG, Sun QN (2021) Quantitative evaluation of rejuvenation treatment of nasolabial fold wrinkles by regression model and 3D photography. J Cosmet Dermatol 20(1):338–345PubMedCrossRef

51.

Fagien S, Bertucci V, von Grote E, Mashburn JH (2019) Rheologic and physicochemical properties used to differentiate injectable hyaluronic acid filler products. Plast Reconstr Surg 143(4):707e–720ePubMedCrossRef

52.

Greene JJ, Sidle DM (2015) The hyaluronic acid fillers: current understanding of the tissue device interface. Facial Plast Surg Clin North Am 23(4):423–432PubMedCrossRef

53.

Wang C, Sun T, Li H, Li Z, Wang X (2021) Hypersensitivity caused by cosmetic injection: systematic review and case report. Aesthetic Plast Surg 45(1):263–272PubMedCrossRef

54.

Mikkilineni R, Wipf A, Farah R, Sadick N (2020) New classification schemata of hypersensitivity adverse effects after hyaluronic acid injections: pathophysiology, treatment algorithm, and prevention. Dermatol Surg 46(11):1404–1409PubMedCrossRef

55.

Prasetyo AD, Prager W, Rubin MG, Moretti EA, Nikolis A (2016) Hyaluronic acid fillers with cohesive polydensified matrix for soft-tissue augmentation and rejuvenation: a literature review. Clin Cosmet Investig Dermatol 9:257–280PubMedPubMedCentralCrossRef

56.

Lima RA, Moura ICG, Pitoni JBG, Ramos ESM, da Costa A (2021) Physicians’ and patients’ self-perceptions of hyaluronic acid-based facial volumization: Are they compatible? J Cosmet Dermatol 20(5):1486–1494PubMedCrossRef

57.

Wang C, Luan S, Panayi AC, Xin M, Mi B, Luan J (2018) Effectiveness and safety of hyaluronic acid gel with lidocaine for the treatment of nasolabial folds: a systematic review and meta-analysis. Aesthetic Plast Surg 42(4):1104–1110PubMedCrossRef

Title: Monophasic and Biphasic Hyaluronic Acid Fillers for Esthetic Correction of Nasolabial Folds: A Meta-Analysis of Randomized Controlled Trials
Authors: Yiwen Huang
Yibin Zhang
Xiaojing Fei
Qi Fan
Jie Mao
Publication date: 23-01-2022
Publisher: Springer US
Keyword: Injectable Filler
Published in: Aesthetic Plastic Surgery / Issue 3/2022
Print ISSN: 0364-216X
Electronic ISSN: 1432-5241
DOI: https://doi.org/10.1007/s00266-021-02729-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Monophasic and Biphasic Hyaluronic Acid Fillers for Esthetic Correction of Nasolabial Folds: A Meta-Analysis of Randomized Controlled Trials

Abstract

Background

Objectives

Methods

Results

Level of Evidence II

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Objectives

Methods

Results

Level of Evidence II

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