PMID- 34224576 OWN - NLM STAT- MEDLINE DCOM- 20210812 LR - 20220716 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 7 IP - 7 DP - 2021 Jul 5 TI - Botulinum toxin type A for facial wrinkles. PG - CD011301 LID - 10.1002/14651858.CD011301.pub2 [doi] LID - CD011301 AB - BACKGROUND: Botulinum toxin type A (BontA) is the most frequent treatment for facial wrinkles, but its effectiveness and safety have not previously been assessed in a Cochrane Review. OBJECTIVES: To assess the effects of all commercially available botulinum toxin type A products for the treatment of any type of facial wrinkles. SEARCH METHODS: We searched the following databases up to May 2020: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: We included RCTs with over 50 participants, comparing BontA versus placebo, other types of BontA, or fillers (hyaluronic acid), for treating facial wrinkles in adults. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcomes were participant assessment of success and major adverse events (AEs) (eyelid ptosis, eyelid sensory disorder, strabismus). Secondary outcomes included physician assessment of success; proportion of participants with at least one AE and duration of treatment effect. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included 65 RCTs, involving 14,919 randomised participants. Most participants were female, aged 18 to 65 years. All participants were outpatients (private office or day clinic). Study duration was between one week and one year. No studies were assessed as low risk of bias in all domains; the overall risk of bias was unclear for most studies. The most common comparator was placebo (36 studies). An active control was used in 19 studies. There were eight dose-ranging studies of onabotulinumtoxinA, and a small number of studies compared against fillers. Treatment was given in one cycle (54 studies), two cycles (three studies), or three or more cycles (eight studies). The treated regions were glabella (43 studies), crow's feet (seven studies), forehead (two studies), perioral (two studies), full face (one study), or more than two regions (nine studies). Most studies analysed moderate to severe wrinkles; mean duration of treatment was 20 weeks. The following results summarise the main comparisons, based on studies of one treatment cycle for the glabella. AEs were collected over the duration of these studies (over four to 24 weeks). Compared to placebo, onabotulinumtoxinA-20 U probably has a higher success rate when assessed by participants (risk ratio (RR) 19.45, 95% confidence interval (CI) 8.60 to 43.99; 575 participants; 4 studies; moderate-certainty evidence) or physicians (RR 17.10, 95% CI 10.07 to 29.05; 1339 participants; 7 studies; moderate-certainty evidence) at week four. Major AEs are probably higher with onabotulinumtoxinA-20 U (Peto OR 3.62, 95% CI 1.50 to 8.74; 1390 participants; 8 studies; moderate-certainty evidence), but there may be no difference in any AEs (RR 1.14, 95% CI 0.89 to 1.45; 1388 participants; 8 studies; low-certainty evidence). Compared to placebo, abobotulinumtoxinA-50 U has a higher participant-assessed success rate at week four (RR 21.22, 95% CI 7.40 to 60.56; 915 participants; 6 studies; high-certainty evidence); and probably has a higher physician-assessed success rate (RR 14.93, 95% CI 8.09 to 27.55; 1059 participants; 7 studies; moderate-certainty evidence). There are probably more major AEs with abobotulinumtoxinA-50 U (Peto OR 3.36, 95% CI 0.88 to 12.87; 1294 participants; 7 studies; moderate-certainty evidence). Any AE may be more common with abobotulinumtoxinA-50 U (RR 1.25, 95% CI 1.05 to 1.49; 1471 participants; 8 studies; low-certainty evidence). Compared to placebo, incobotulinumtoxinA-20 U probably has a higher participant-assessed success rate at week four (RR 66.57, 95% CI 13.50 to 328.28; 547 participants; 2 studies; moderate-certainty evidence), and physician-assessed success rate (RR 134.62, 95% CI 19.05 to 951.45; 547 participants; 2 studies; moderate-certainty evidence). Major AEs were not observed (547 participants; 2 studies; moderate-certainty evidence). There may be no difference between groups in any AEs (RR 1.17, 95% CI 0.90 to 1.53; 547 participants; 2 studies; low-certainty evidence). AbobotulinumtoxinA-50 U is no different to onabotulinumtoxinA-20 U in participant-assessed success rate (RR 1.00, 95% CI 0.92 to 1.08, 388 participants, 1 study, high-certainty evidence) and physician-assessed success rate (RR 1.01, 95% CI 0.95 to 1.06; 388 participants; 1 study; high-certainty evidence) at week four. Major AEs are probably more likely in the abobotulinumtoxinA-50 U group than the onabotulinumtoxinA-20 U group (Peto OR 2.65, 95% CI 0.77 to 9.09; 433 participants; 1 study; moderate-certainty evidence). There is probably no difference in any AE (RR 1.02, 95% CI 0.67 to 1.54; 492 participants; 2 studies; moderate-certainty evidence). IncobotulinumtoxinA-24 U may be no different to onabotulinumtoxinA-24 U in physician-assessed success rate at week four (RR 1.01, 95% CI 0.96 to 1.05; 381 participants; 1 study; low-certainty evidence) (participant assessment was not measured). One participant reported ptosis with onabotulinumtoxinA, but we are uncertain of the risk of AEs (Peto OR 0.02, 95% CI 0.00 to 1.77; 381 participants; 1 study; very low-certainty evidence). Compared to placebo, daxibotulinumtoxinA-40 U probably has a higher participant-assessed success rate (RR 21.10, 95% CI 11.31 to 39.34; 683 participants; 2 studies; moderate-certainty evidence) and physician-assessed success rate (RR 23.40, 95% CI 12.56 to 43.61; 683 participants; 2 studies; moderate-certainty evidence) at week four. Major AEs were not observed (716 participants; 2 studies; moderate-certainty evidence). There may be an increase in any AE with daxibotulinumtoxinA compared to placebo (RR 2.23, 95% CI 1.46 to 3.40; 716 participants; 2 studies; moderate-certainty evidence). Major AEs reported were mainly ptosis; BontA is also known to carry a risk of strabismus or eyelid sensory disorders. AUTHORS' CONCLUSIONS: BontA treatment reduces wrinkles within four weeks of treatment, but probably increases risk of ptosis. We found several heterogeneous studies (different types or doses of BontA, number of cycles, and different facial regions) hindering meta-analyses. The certainty of the evidence for effectiveness outcomes was high, low or moderate; for AEs, very low to moderate. Future RCTs should compare the most common BontA (onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, daxibotulinumtoxinA, prabotulinumtoxinA) and evaluate long-term outcomes. There is a lack of evidence about the effects of multiple cycles of BontA, frequency of major AEs, duration of effect, efficacy of recently-approved BontA and comparisons with other treatments. CI - Copyright (c) 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. FAU - Camargo, Cristina Pires AU - Camargo CP AD - Laboratory of Microsurgery and Plastic Surgery (LIM-04), School of Medicine, Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Xia, Jun AU - Xia J AD - Nottingham China Health Institute, The University of Nottingham Ningbo, Ningbo, China. FAU - Costa, Caroline S AU - Costa CS AD - Department of Specialised Medicine, Discipline of Dermatology, Universidade Federal do Piaui, Teresina, Brazil. FAU - Gemperli, Rolf AU - Gemperli R AD - Department of Surgery, Discipline of Plastic Surgery, Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Tatini, Maria Dc AU - Tatini MD AD - c/o Cochrane Skin Group, The University of Nottingham, Nottingham, UK. FAU - Bulsara, Max K AU - Bulsara MK AD - Institute for Health Research, University of Notre Dame Australia, Fremantle, Australia. AD - School of Population and Global Health, The University of Western Australia, Perth, Australia. AD - Division of Surgery and Interventional Science, University College London, London, UK. FAU - Riera, Rachel AU - Riera R AD - Cochrane Brazil Rio de Janeiro, Cochrane, Petropolis, Brazil. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20210705 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 0 (DWP450) RN - 0 (Dermal Fillers) RN - 0 (Placebos) RN - 0 (prabotulinumtoxin A) RN - EC 3.4.24.69 (Botulinum Toxins, Type A) RN - EC 3.4.24.69 (abobotulinumtoxinA) RN - EC 3.4.24.69 (incobotulinumtoxinA) RN - EC 3.4.24.69 (onabotulinum toxin A) SB - IM UOF - doi: 10.1002/14651858.CD011301 MH - Adult MH - Aged MH - Bias MH - Botulinum Toxins, Type A/adverse effects/*therapeutic use MH - Dermal Fillers/therapeutic use MH - Face MH - Female MH - Humans MH - Male MH - Middle Aged MH - Placebos/therapeutic use MH - Randomized Controlled Trials as Topic MH - Skin Aging/*drug effects PMC - PMC8407355 COIS- Cristina Pires Camargo: nothing to declare.
Jun Xia: nothing to declare.
Caroline S Costa: nothing to declare.
Rolf Gemperli: nothing to declare.
Maria DC Tatini: nothing to declare.
Max K Bulsara: nothing to declare.
Rachel Riera: nothing to declare. Professor Berthold Rzany, clinical referee, declared the following: "I am, or have been in the past, a speaker and advisor for IPSEN, Q-Med/Galderma and Merz." BR reports using botulinum toxin in his practice for aesthetic indications for over 20 years, and he is an author of the following included studies: Ascher 2009, Kerscher 2015, Rzany 2006, Rzany 2019, Satler 2010; and excluded study Rzany 2013. EDAT- 2021/07/06 06:00 MHDA- 2021/08/13 06:00 PMCR- 2022/07/05 CRDT- 2021/07/05 17:16 PHST- 2021/07/05 17:16 [entrez] PHST- 2021/07/06 06:00 [pubmed] PHST- 2021/08/13 06:00 [medline] PHST- 2022/07/05 00:00 [pmc-release] AID - CD011301.pub2 [pii] AID - 10.1002/14651858.CD011301.pub2 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2021 Jul 5;7(7):CD011301. doi: 10.1002/14651858.CD011301.pub2.