Efficacy and Safety of IncobotulinumtoxinA for the Simultaneous Treatment of Upper Facial Lines: A GRADE Assessed Systematic Review and Meta-Analysis

Abstract Background Upper Facial lines (UFLs), including glabellar frown lines (GFLs), horizontal forehead lines (HFLs), and lateral canthal lines (LCLs) are prevalent aesthetic concerns addressed with botulinum neurotoxin type A (BoNT-A). IncobotulinumtoxinA, a highly purified BoNT-A formulation, is utilized for simultaneous UFLs treatment, yet comprehensive synthesized evidence is limited. Objectives To systematically evaluate the efficacy and safety of IncobotulinumtoxinA compared with placebo for the simultaneous treatment of UFLs in adults, following PRISMA 2020 guidelines. Methods Comprehensive searches of PubMed, Embase, Cochrane CENTRAL, ICTRP and ClinicalTrials.gov were performed to identify RCTs evaluating IncobotulinumtoxinA for combined UFLs treatment. The primary outcome was ≥1-grade improvement on Day 30. Secondary outcomes included ≥2-grade improvement and Global Aesthetic Improvement Scale (GAIS) scores. Safety outcomes included adverse events (AEs), treatment-emergent adverse events (TEAEs) and headaches. Results Three RCTs (n=704) were included. Pooled analysis using random-effects model demonstrated a significant ≥1-grade improvement at Day 30 in IncobotulinumtoxinA compared to placebo across all regions: GFLs (RR 21.49, 95% CI: 9.89–46.73), HFLs (RR 19.17, 95% CI: 9.23–39.80), and LCLs (RR 11.68, 95% CI: 7.49–18.20), all p<0.00001. A ≥2-grade improvement similarly favored treatment across all areas (RRs 76.26-115.04; all p<0.00001). Investigator-assessed GAIS scores also improved significantly (MD 2.29, 95% CI: 2.11–2.46, p<0.00001). Serious AEs were lower with IncobotulinumtoxinA (RR 0.14, p=0.03). There was no significant difference in TEAEs and headaches from placebo. Conclusions IncobotulinumtoxinA demonstrates statistically significant efficacy and a comparable safety profile versus placebo for simultaneous UFLs treatment. These findings support its use in aesthetic practice, warranting further long-term investigation.