Purpose: Poly-L-lactic acid (PLLA) is a biodegradable, biocompatible synthetic polymer currently approved in the United States as an injectable device for the treatment of facial fat loss (lipoatrophy) in people with human immunodeficiency virus. A cosmetic indication for the treatment of nasolabial fold wrinkles with PLLA is currently under review by the US Food and Drug Administration (FDA). The aim of this study was to investigate the efficacy of PLLA compared with that of commercially available human collagen implant (Cosmoplast^™) in the treatment of dermal nasolabial fold wrinkles for 13 months. Efficacy was assessed by investigator evaluations of improvement following treatment.
Methodology: The treatment phase in this randomized, parallel-group, multicenter clinical study consisted of one to four visits at 3-week intervals, during which eligible subjects received bilateral injections of either PLLA or human collagen in the left and right nasolabial fold wrinkles. Standardized photographs were taken at screening, at all treatment phase visits, and at all follow-up phase visits. Investigator evaluations of efficacy were collected at all visits beginning 3 weeks after the last injection of study treatment. Assessments were made by comparison to baseline (pretreatment) values, using the photograph at visit 1 (screening) as a reference. The treating investigator rated the subject’s nasolabial folds for global aesthetic improvement based on the following scale (one composite score for both the left and right nasolabial folds): 0 = worse; 1 = no change; 2 = improved; 3 = much improved; 4 = excellent improvement. The follow-up phase consisted of visits at week 3 and months 3, 6, 9 and 13 after the last treatment.
Results: A total of 233 subjects comprising the intent-to-treat population were randomized to treatment with PLLA (n=116) or human collagen (n=117). Statistically significant differences (p<0.001) in the total investigator global evaluation assessments (including excellent improvement, much improved, improved, no change, and worse)  were observed between the PLLA and human collagen treatment groups at the week 3, and month 3, 6, 9, and 13 visits after the final treatment. There was a consistently high level of investigator global evaluation scores for “overall improved” (excellent improvement, much improved, and improved) attributed to the PLLA group. In the PLLA group, the proportion of  investigator global evaluation scores for “overall improved” remained above 88% during the entire 13-month follow-up period, whereas in the human collagen group the proportion of investigator global evaluation scores for “overall improved”  decreased steadily from 95.7% at week 3 to 6.3% at month 13. For the human collagen group, the investigators initially gave a rating of much improved (49.6%) or excellent improvement (28.7%) at week 3; however, at the month 3 follow-up visit, nearly 83% of the investigators gave a rating of improved or no change. At month 6, most investigators (72.6%) scored the subjects receiving human collagen as showing no change from baseline. Overall, postinjection AEs were similar in both treatment groups; the majority of AEs were mild or moderate in intensity. Fewer subjects receiving PLLA had ≥1 AE (53.4% vs 63.2%; p=0.002). Fewer PLLA-treated subjects reported product-related (20.7% vs 35.9%; p<0.05) or injection-related AEs (20.7% vs 29.1%; p=0.005).The incidence of product-related application site papules (PLLA, 8.6%; human collagen, 3.4%) or nodules (6.9% and 6.0%, respectively) was low for both groups.
Conclusions: Treatment with PLLA resulted in significantly higher investigators global evaluation scores of improvement from baseline at all follow-up visits through month 13, compared with treatment using human collagen. Investigators global evaluation of improvement following PLLA treatment remained consistently high, whereas investigators global evaluations of human collagen treatment were high at week 3 following the final treatment, but quickly declined at the month 3 follow-up visit. Treatment with PLLA or human collagen was well tolerated. In summary, injectable PLLA provided greater and sustained improvement in nasolabial fold wrinkles during the 13-month period than did human collagen.