DISCUSSION
A single ABO treatment provided rapid and high composite responder rates when administered at doses ranging between 50–125 U for moderate-to-severe glabellar lines. Line severity was reduced to grade 0 (none) or 1 (mild) for all responders. Although the study was not powered to examine statistical differences between ABO doses, there was a tendency toward higher response rates and longer duration of aesthetic effect over approximately 6 and 9 months with dose escalation. Incidence of TEAEs was consistently low across all ABO doses and comparable with previous studies examining the safety of the licensed dose.2-6,16-19 Subject satisfaction was high for all ABO doses, with natural looking results reported alongside a desire to receive repeat treatment.
Week 4 composite ≥2-grade responder data showed statistically significant improvements in glabellar line severity versus placebo (P<0.001), irrespective of the ABO dose given. All ABO groups achieved week 4 composite ≥2-grade responder rates ≥80%, with rates reaching 95% with ABO 125 U. These data reflect previous studies examining the safety and efficacy of variable ABO dosing and support the case for further investigations exploring individualization of treatment according to specific client requirements/characteristics (eg, muscle mass, sex).10,14,15,19,20
Median time to onset of treatment effect was 2 days for all ABO doses and most subjects (69–83%) achieved ≥1-grade improvement from baseline at day 2 (ILA scale), comparing favorably with previous data.16-19 As highlighted in other studies, recipients can observe benefits with ABO treatment from 24 hours.16,19 Onset of ABO treatment effect at day 1 ranged between 26% (50 U) and 41% (125 U), suggesting that the higher dose may provide more rapid effect.
Single ABO treatments generally provide visible glabellar line improvements for approximately 4–5 months, but emerging data suggest that elevated doses of botulinum toxin extend the duration of effect.9-12,21 Hypotheses based on non-clinical data infer that efficacy duration is conferred by the neurotoxin light chain, with degradation taking longer where higher quantities are present.11,22 Our results indicate that ABO doses up to 125 U can prolong treatment durability in practice as approximately one-third maintained improvements of ≥1-grade from baseline at week 36 (approximately 9 months). For those achieving a score of 0 (none) or 1 (mild), the median time taken to return to baseline severity ranged between 27 (50 U) and 36 (125 U) weeks for investigator assessments, and 28 (50 U) to 36 (125 U) weeks with subject self-assessments. Although direct comparisons between toxin treatments are not possible, these data suggest that treatment potency and duration may be enhanced with relatively conservative increases in ABO dosing, while greater magnitudes of dose escalation have been required to achieve similar results with other toxins.21 ABO treatment satisfaction remained high through week 36 (approximately 9 months); beyond previously reported expectations for a single treatment (≤6 months post-injection).23 The ability to extend treatment efficacy without impacting safety could influence the frequency of repeat treatments required over time.
All ABO doses were generally well tolerated. Treatment-related TEAEs were mild to moderate in intensity and had resolved at the end of the study period. No serious treatment-related TEAEs were reported and there were no incidences of remote spread of toxin effect recorded during the study.
Week 4 composite ≥2-grade responder data showed statistically significant improvements in glabellar line severity versus placebo (P<0.001), irrespective of the ABO dose given. All ABO groups achieved week 4 composite ≥2-grade responder rates ≥80%, with rates reaching 95% with ABO 125 U. These data reflect previous studies examining the safety and efficacy of variable ABO dosing and support the case for further investigations exploring individualization of treatment according to specific client requirements/characteristics (eg, muscle mass, sex).10,14,15,19,20
Median time to onset of treatment effect was 2 days for all ABO doses and most subjects (69–83%) achieved ≥1-grade improvement from baseline at day 2 (ILA scale), comparing favorably with previous data.16-19 As highlighted in other studies, recipients can observe benefits with ABO treatment from 24 hours.16,19 Onset of ABO treatment effect at day 1 ranged between 26% (50 U) and 41% (125 U), suggesting that the higher dose may provide more rapid effect.
Single ABO treatments generally provide visible glabellar line improvements for approximately 4–5 months, but emerging data suggest that elevated doses of botulinum toxin extend the duration of effect.9-12,21 Hypotheses based on non-clinical data infer that efficacy duration is conferred by the neurotoxin light chain, with degradation taking longer where higher quantities are present.11,22 Our results indicate that ABO doses up to 125 U can prolong treatment durability in practice as approximately one-third maintained improvements of ≥1-grade from baseline at week 36 (approximately 9 months). For those achieving a score of 0 (none) or 1 (mild), the median time taken to return to baseline severity ranged between 27 (50 U) and 36 (125 U) weeks for investigator assessments, and 28 (50 U) to 36 (125 U) weeks with subject self-assessments. Although direct comparisons between toxin treatments are not possible, these data suggest that treatment potency and duration may be enhanced with relatively conservative increases in ABO dosing, while greater magnitudes of dose escalation have been required to achieve similar results with other toxins.21 ABO treatment satisfaction remained high through week 36 (approximately 9 months); beyond previously reported expectations for a single treatment (≤6 months post-injection).23 The ability to extend treatment efficacy without impacting safety could influence the frequency of repeat treatments required over time.
All ABO doses were generally well tolerated. Treatment-related TEAEs were mild to moderate in intensity and had resolved at the end of the study period. No serious treatment-related TEAEs were reported and there were no incidences of remote spread of toxin effect recorded during the study.
CONCLUSION
A single ABO treatment, administered at doses ranging from
50–125 U, provided rapid and effective improvements in
glabellar line severity. Higher ABO doses tended to provide
increased response rates and longer duration of aesthetic effect
over a 36-week period. All ABO doses were well-tolerated with
low incidence of TEAEs and high levels of subject satisfaction.
DISCLOSURES
Dr. Joseph is an investigator and paid speaker for Galderma. Dr. Moradi is a paid consultant and clinical trial investigator for Galderma. Dr. Lorenc is an investigator for Galderma. Dr. Coleman is an investigator for Galderma. Dr. Ablon is an investigator for Galderma. Dr. Kaufman-Janette is a paid advisory board consultant and clinical trial investigator for Galderma. Dr. Cox is an investigator and paid advisory board member for Galderma. Dr. Campbell is an investigator for Galderma. Dr. Dayan is a paid consultant and speaker for Galderma and research support for Galderma. Dr. Berg is an employee of Galderma. Dr. Munavalli is an investigator for Galderma.
This study was funded by Galderma R&D, LLC.
This study was funded by Galderma R&D, LLC.
ACKNOWLEDGMENT
Medical writing support was provided by Rebecca Down at
Copperfox Communications Limited and Zenith Healthcare
Communications Limited and was funded by Galderma.
REFERENCES
1. Aesthetic Society. Aesthetic plastic surgery national databank statistics for 2019. Available at: https://www.surgery.org/sites/default/files/Aesthetic- Society_Stats2019Book_FINAL.pdf accessed May 30 2021
2. De Boulle K, Fagien S, Sommer B, Glogau R. Treating glabellar lines with botulinum toxin type A-hemagglutinin complex: a review of the science, the clinical data, and patient satisfaction. Clin Interv Aging. 2010;5:101-118.
3. Lorenc ZP, Kenkel JM, Fagien S, et al. A review of abobotulinumtoxinA (Dysport). Aesthet Surg J. 2013;33:13S-17S.
4. Monheit GD, Baumann L, Maas C, et al. Efficacy, safety, and subject satisfaction after abobotulinumtoxinA treatment for moderate to severe glabellar lines. Dermatol Surg. 2020;46(1):61-69.
5. Schlessinger J, Cohen JL, Shamban A, et al. A multicenter study to evaluate subject satisfaction with two treatments of abobotulinumtoxinA a year in the glabellar lines. Dermatol Surg. 2021;47(4):504-509.
6. Gubanova E, Haddad Tabet M, Bergerova Y, et al. Assessment of subject and physician satisfaction after long-term treat-ment of glabellar lines with
2. De Boulle K, Fagien S, Sommer B, Glogau R. Treating glabellar lines with botulinum toxin type A-hemagglutinin complex: a review of the science, the clinical data, and patient satisfaction. Clin Interv Aging. 2010;5:101-118.
3. Lorenc ZP, Kenkel JM, Fagien S, et al. A review of abobotulinumtoxinA (Dysport). Aesthet Surg J. 2013;33:13S-17S.
4. Monheit GD, Baumann L, Maas C, et al. Efficacy, safety, and subject satisfaction after abobotulinumtoxinA treatment for moderate to severe glabellar lines. Dermatol Surg. 2020;46(1):61-69.
5. Schlessinger J, Cohen JL, Shamban A, et al. A multicenter study to evaluate subject satisfaction with two treatments of abobotulinumtoxinA a year in the glabellar lines. Dermatol Surg. 2021;47(4):504-509.
6. Gubanova E, Haddad Tabet M, Bergerova Y, et al. Assessment of subject and physician satisfaction after long-term treat-ment of glabellar lines with
