AbobotulinumtoxinA for the Treatment of Moderate-to-Severe Glabellar Lines: A Randomized, Dose-Escalating, Double-Blind Study

Abstract

Objective: To evaluate the efficacy and safety of AbobotulinumtoxinA (ABO) dose escalation in the correction of moderate-to-severe glabellar lines. Design: Phase 2, 36-week, multicenter, randomized, dose-ranging, double-blind, placebo-controlled study. Methods: Adults with moderate-to-severe glabellar lines received a single ABO treatment, dosed at 50, 75, 100, or 125 U, or placebo. Primary endpoint was week 4 composite ≥2-grade responder rate among those achieving a severity score of 0 (none) or 1 (mild) at maximum frown, evaluated using concurrent investigator and subject assessments. Secondary endpoints included ≥1-grade severity improvement, duration of effect, and reporting of treatment-emergent adverse events (TEAEs). Results: Overall, 399 subjects were included (88.2% were female). Week 4 composite ≥2-grade ABO responder rate was 80.0% (50 U), 88.8% (75 U), 90.0% (100 U) and 95.1% (125 U), versus 2.6% with placebo (P<0.001). Responder rate (≥1-grade) ranged between 53% (50 U) and 69% (125 U) at week 24 and between 18% (50 U) and 31% (125 U) at week 36. Median time (weeks) to return to baseline severity/worse, among those scoring 0 (none) or 1 (mild), was 32.3 (50 U), 34.3 (75 U), 36.0 (100 U) and 36.6 (125 U), versus 23.7 (placebo). ABO-related TEAEs were reported in 4% of subjects (80% were mild). No seroconversion to ABO neutralizing antibodies was seen. Conclusion:A single ABO treatment provided rapid and effective improvements in glabellar line severity at all doses. Higher doses tended to demonstrate elevated response rates and longer duration of effect. All ABO doses were well-tolerated with low TEAE incidence.

Subject satisfaction and psychological well‐being with escalating abobotulinumtoxinA injection dose for the treatment of moderate to severe glabellar lines

“…The main results of the study, reported by Joseph et al, revealed a tendency toward higher response rates, with subjects achieving ≥2‐grade improvements alongside severity scores of 0 (none) or 1 (mild), and longer duration of aesthetic effect with increasing ABO dosage when assessed over a 9‐month period 21 . Incidence of adverse events was consistently low across all ABO doses and comparable with the literature regarding safety with the licensed dose 3‐13,21 . Here, we report subject self‐assessment of efficacy, as well as satisfaction and FACE‐Q data from the same ABO dose‐ranging study with the aim of advancing understanding regarding the relationship between treatment efficacy, satisfaction, and psychological well‐being with escalating ABO dose 21 .…”

“…The primary endpoint was composite ≥2‐grade responder rate at Week 4 in those achieving a severity score of 0 (none) or 1 (mild) at maximum frown, evaluated using concurrent ILA and SSA scales (reported in Joseph et al) 21 …”

“…The present study was a Phase 2, 9‐month, multicenter, randomized, dose‐ranging, double‐blind, placebo‐controlled study in which individuals with moderate to severe glabellar lines received a single treatment at doses ranging between 50 and 125 U. The main results of the study, reported by Joseph et al, revealed a tendency toward higher response rates, with subjects achieving ≥2‐grade improvements alongside severity scores of 0 (none) or 1 (mild), and longer duration of aesthetic effect with increasing ABO dosage when assessed over a 9‐month period 21 . Incidence of adverse events was consistently low across all ABO doses and comparable with the literature regarding safety with the licensed dose 3‐13,21 .…”

“…A single treatment provides significant improvements in glabellar line severity, typically lasting 4–5 months 3‐11 . However, emerging data indicate that higher ABO doses may prolong aesthetic effect for up to 6–9 months without impacting safety or tolerability 5,20,21 …”

Important Considerations in the High-Dose Toxins Discussion

“…Further, the reported duration for time to loss of none or mild of ABO 50U for GL in the pivotal studies ranged from 85 to 119 days compared to the ≈168 days reported for the same dose and reconstitution scheme for the 50U dose in the ABO HD study. 5 , 6 , 10 Given these large discrepancies from the pivotal data, we find it hard to accept the findings from the ABO HD study. While this was not addressed in the article, we feel it is worthy of discussion.…”