Botulinum Toxin Type A for Glabellar Frown Lines: What Impact of Higher Doses on Outcomes?

Botulinum toxin serotype-A (BoNT-A) preparations are widely used to improve the appearance of wrinkles. While effective and well tolerated, patients require retreatment over time to re-establish the effects. There is growing interest from patients as to whether higher doses can prolong response without significantly increasing side effects. We reviewed the efficacy and safety evidence for high-dose BoNT-A treatment of glabellar lines, by evaluating high-dose studies published since 2015. Toxins approved for glabellar line treatment in the US or Europe were considered. “High-dose” indicated doses above the licensed dose for each BoNT-A preparation. Five studies met the inclusion criteria and most were randomized, double-blind trials; designs and population sizes varied. Findings suggested that higher-dose BoNT-A treatment is feasible and may improve response duration without increased safety issues. Around 9 months’ median duration was achieved with a 2–2.5-fold increase of the abobotulinumtoxinA on-label dose, or with a 5-fold increase in incobotulinumtoxinA dose. A 2–4-fold increase of the onabotulinumtoxinA on-label dose yielded a median duration of around 6 months. Importantly, patient satisfaction and natural look remained with increasing abobotulinumtoxinA doses. While more data are needed, these findings may lead to more effective, individually tailored treatment plans to meet patient expectations

The Second of Two One-Year, Multicenter, Open-Label, Repeat-Dose, Phase II Safety Studies of PrabotulinumtoxinA for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients

Abstract Background PrabotulinumtoxinA is a 900-kDa botulinum toxin type A produced by Clostridium botulinum. Objectives The authors sought to investigate the safety of prabotulinumtoxinA for treatment of glabellar lines. Methods This was a multicenter, open-label, repeat-dose, 1-year phase II safety study. Adults with moderate to severe glabellar lines at maximum frown, as independently assessed by both investigator and patient on the validated 4-point photonumeric Glabellar Line Scale (0 = no lines, 1 = mild, 2 = moderate, 3 = severe), were enrolled. On day 0, patients received an initial treatment (IT) of 20 U prabotulinumtoxinA (4 U/0.1 mL final vacuum-dried formulation injected into 5 glabellar sites). On and after day 90, patients received a repeat treatment (RT) if their Glabellar Line Scale score was ≥2 at maximum frown by investigator assessment. Safety outcomes were evaluated throughout the study. Results The 570 study patients received a median total dose of 60 U, that is, 3 treatments. Sixty-one patients (10.7%) experienced adverse events (AEs) assessed as possibly study drug related; 6.5% experienced study drug–related AEs after the IT. With each RT, progressively lower percentages of patients experienced study drug–related AEs. Eight patients (1.4%) experienced study drug–related AEs of special interest: 5 experienced eyelid ptosis (0.9%), 3 eyebrow ptosis (0.5%), 1 blepharospasm (0.2%), and 1 blurred vision (0.2%). Seven patients (1.2%) experienced serious AEs, but none were study drug related. A total of 4060 serum samples were tested for antibotulinum toxin antibodies; no seroconversion was observed. Conclusions The safety of RTs of 20 U of prabotulinumtoxinA for moderate to severe glabellar lines was confirmed in this second phase II study based on a broad range of outcomes