LAUSR

BACKGROUND Onabotulinumtoxin A (Onabot A) has already marked its name in history as the first to be approved for aesthetic indications, namely glabellar (GL), crow's feet (CFL) and forehead lines (FHL), with 64 units of cumulative dose. OBJECTIVE As more real-world evidence and robust randomised clinical studies exist, the authors sought to conduct a meta-analysis with trial sequential analysis to combine the available data with approved doses for GL, CFL and FHL to explore the effect and duration of simultaneous treatment with Onabot A. METHODS PubMed/MEDLINE, EMBASE and other national clinical trial registries were searched for randomized controlled trials (RCTs) from January 2010 to July 2022. The meta-analysis, trial sequential analysis and the investigator-assessed time to return to the non-responder status in GL, CFL and FHL following Onabot A were plotted to elicit a cumulative dose-adjusted response curve using the Kaplan-Meier analysis with the log-rank test. RESULTS Fourteen RCTs were eligible for quantitative analysis. A total of 8369 subjects were recruited across the trials. The meta-analysis results show that Onabotulinum toxin a is very effective in reducing moderate to severe GL, CFL and FHL. The cumulative Z-curve for GL, CFL and FHL t also exceeds the information size. Kaplan-Meier analysis with the log-rank test demonstrated that simultaneous treatment of GL, CFL and FHL requires 182 days (95% CI 179, 215) (p < 0.00002) to return to the non-responder status. CONCLUSIONS Treatment of the upper facial expression lines with Onabot A has proven effective with a longer duration of effects with the approved doses of 64 units. Until future trials explore the dose titration in males, neuromuscular junction mapping, and pharmaco-epigenetic profiling to explore the role and effect of messenger ribonucleic acid (mRNA) on sprouting, clinicians should adhere to the most substantial scientific evidence available.