analysis showed that nasolabial fold improvement from baseline by WAS score was statistically significant in the treatment group and with the CIs between the groups overlapping, resulting in the primary objective being successfully met.
Additional measurements of effectiveness further confirmed a comparable treatment effect between the groups; aesthetic improvement was high during the whole study for both groups from GAIS assessments by subjects and investigators. FACE-Q appraisal of nasolabial folds showed that subjects in both groups were more satisfied with how their nasolabial folds looked following treatment through week 48. Subject satisfaction with treatment was also high and lasted across week 48 for both groups. The decrease by session in median injection volume that was observed for the reference group did not affect the total amount injected across the entire treatment regimen, which was similar between the groups. However, the larger amount of PLLA that was injected for the reference group at the first and second session could explain the slightly higher WAS responder rates observed for the reference group early in the study.
Overall, both treatments were well tolerated; all related adverse events reported in the treatment group and most in the reference group were mild in intensity, and the majority resolved within 1 week after treatment for both groups. As expected, Sculptra Aesthetic reconstituted with the addition of 1 mL lidocaine was associated with less pain on injection, and safety was not complicated with the addition of lidocaine.
Nodules, papules, and induration are known non-immediate side effects of PLLA injections. Possible causes include using a too concentrated product (<5 mL dilution); injecting too much product in the same area; interval between sessions being too short; and injecting in hyperkinetic regions and/or too superficial.9 The safety profile of Sculptra Aesthetic has improved over the years, resulting from increased knowledge in selection of treatment areas, and injection technique. Also, a decreased risk of adverse events and nodules in particular, has been noted with a larger reconstitution volume.12,13 In the current study, two events of injection site nodule/papule that was experienced in the reference group, as well as the nodule and induration from the treatment group, were mild in severity and no intervention was required. In order to allow a sufficient depth of injection, both groups received subdermal (subcutaneous and supraperiosteal) injections, which is different from the current US label, where deep dermal injections are stated.
In a retrospective chart review,7 information about the safety associated with reconstitution volumes of 7–10 mL including anesthetics was collected. Data from more than 4000 facial treatments performed in 1000 subjects was analyzed, and the results showed very few adverse events related to study product or injection procedure being reported (3.6% of subjects; nodules 0.4% of subjects). This could be reflective of well-functioning patient education of expected events by health care professionals, potentially leading to under-reporting in a retrospective chart review compared to a clinical trial. Still these results suggest that the rate of adverse events may be lower using a higher reconstitution volume than 5 mL.
Hydration of the product has historically been considered important with standing times of 2 to 168 hours implemented,13 also in consensus manuscripts hydration with long reconstitution times has been recommended.8,9 It is now known that the suspending agents included in the formulation will instantly start to swell (hydrate) when dispersed in water and shaken vigorously. PLLA particles themselves are insoluble in water but are uniformly distributed in the suspension from the viscosity achieved by the suspending agents. Indeed, physicochemical properties and PLLA particle shape and size distribution of Sculptra product suspension have been similar when comparing different standing times, including vigorous shaking after adding SWFI.10 This unique immediate use protocol can be considered a paradigm shift in how injectors have been taught to reconstitute the product during a long period of time.
This study has shown that both procedures for reconstitution of Sculptra Aesthetic are effective and safe as a single treatment regimen for correction of nasolabial fold contour deficiencies. Evaluations were performed by blinded evaluators, as well as by treating investigators and subjects themselves, all assessments showing similar high effectiveness.
The effectiveness was not impacted when used in nasolabial folds of an ethnically diverse population. The results from this study support a change to the current US Sculptra Aesthetic label, which hopefully will benefit both patients and injectors.
Additional measurements of effectiveness further confirmed a comparable treatment effect between the groups; aesthetic improvement was high during the whole study for both groups from GAIS assessments by subjects and investigators. FACE-Q appraisal of nasolabial folds showed that subjects in both groups were more satisfied with how their nasolabial folds looked following treatment through week 48. Subject satisfaction with treatment was also high and lasted across week 48 for both groups. The decrease by session in median injection volume that was observed for the reference group did not affect the total amount injected across the entire treatment regimen, which was similar between the groups. However, the larger amount of PLLA that was injected for the reference group at the first and second session could explain the slightly higher WAS responder rates observed for the reference group early in the study.
Overall, both treatments were well tolerated; all related adverse events reported in the treatment group and most in the reference group were mild in intensity, and the majority resolved within 1 week after treatment for both groups. As expected, Sculptra Aesthetic reconstituted with the addition of 1 mL lidocaine was associated with less pain on injection, and safety was not complicated with the addition of lidocaine.
Nodules, papules, and induration are known non-immediate side effects of PLLA injections. Possible causes include using a too concentrated product (<5 mL dilution); injecting too much product in the same area; interval between sessions being too short; and injecting in hyperkinetic regions and/or too superficial.9 The safety profile of Sculptra Aesthetic has improved over the years, resulting from increased knowledge in selection of treatment areas, and injection technique. Also, a decreased risk of adverse events and nodules in particular, has been noted with a larger reconstitution volume.12,13 In the current study, two events of injection site nodule/papule that was experienced in the reference group, as well as the nodule and induration from the treatment group, were mild in severity and no intervention was required. In order to allow a sufficient depth of injection, both groups received subdermal (subcutaneous and supraperiosteal) injections, which is different from the current US label, where deep dermal injections are stated.
In a retrospective chart review,7 information about the safety associated with reconstitution volumes of 7–10 mL including anesthetics was collected. Data from more than 4000 facial treatments performed in 1000 subjects was analyzed, and the results showed very few adverse events related to study product or injection procedure being reported (3.6% of subjects; nodules 0.4% of subjects). This could be reflective of well-functioning patient education of expected events by health care professionals, potentially leading to under-reporting in a retrospective chart review compared to a clinical trial. Still these results suggest that the rate of adverse events may be lower using a higher reconstitution volume than 5 mL.
Hydration of the product has historically been considered important with standing times of 2 to 168 hours implemented,13 also in consensus manuscripts hydration with long reconstitution times has been recommended.8,9 It is now known that the suspending agents included in the formulation will instantly start to swell (hydrate) when dispersed in water and shaken vigorously. PLLA particles themselves are insoluble in water but are uniformly distributed in the suspension from the viscosity achieved by the suspending agents. Indeed, physicochemical properties and PLLA particle shape and size distribution of Sculptra product suspension have been similar when comparing different standing times, including vigorous shaking after adding SWFI.10 This unique immediate use protocol can be considered a paradigm shift in how injectors have been taught to reconstitute the product during a long period of time.
This study has shown that both procedures for reconstitution of Sculptra Aesthetic are effective and safe as a single treatment regimen for correction of nasolabial fold contour deficiencies. Evaluations were performed by blinded evaluators, as well as by treating investigators and subjects themselves, all assessments showing similar high effectiveness.
The effectiveness was not impacted when used in nasolabial folds of an ethnically diverse population. The results from this study support a change to the current US Sculptra Aesthetic label, which hopefully will benefit both patients and injectors.
CONCLUSION
Sculptra Aesthetic reconstituted with 8 mL SWFI + 1 mL 2%
lidocaine injected in subdermal regions immediately after
reconstitution, demonstrated a comparable treatment effect,
high satisfaction and aesthetic improvement to that of the
reference group in reducing nasolabial fold wrinkle severity at
week 48. The new reconstitution and injection procedures were
associated with a satisfactory safety profile.
DISCLOSURES
Dr Palm is an investigator, speaker, paid advisory board
member, and consultant for Galderma. Dr Weinkle is an
investigator for Galderma, Allergan, Revance, Teoxane, and
Merz; a consultant for Galderma, Allergan, Merz, Teoxane, and
Revance; a speaker for Galderma, Allergan, and Merz; and an
advisory board member for Allergan and Merz. Dr Cho
is an investigator for Galderma and FirstString Research;
a consultant for Galderma, Allergan, and Merz; and a
