Long-Term Safety and Effectiveness of Cold-Crosslinked Hyaluronic Acid Fillers: Multicenter, Randomized, Controlled, Double-Blind Study.

Abstract

Background: EVOLYSSE FORM (EVLF) and EVOLYSSE SMOOTH (EVLS) are new hyaluronic acid fillers created using an innovative cold crosslinking process.

Objectives: To collect safety and effectiveness data on new cold-crosslinked fillers to support US approval for the correction of moderate to severe dynamic facial wrinkles and folds.

Methods: In this randomized, controlled, split-face study, 140 subjects with moderate to severe nasolabial folds received a cold-crosslinked filler in 1 nasolabial fold (EVLF = 70, EVLS = 70) and a traditionally-crosslinked filler, Restylane-L (RESL), in the contralateral fold and were followed through 12 months with an optional retreatment at that timepoint and subsequent 3 months of safety follow-up.

Results: The primary endpoint of mean Wrinkle Severity Rating Scale change from baseline to Month 6 as rated by photographic review panel demonstrated non-inferiority and statistical superiority for the cold-crosslinked fillers. Blinded evaluator Wrinkle Severity Rating Scale assessments showed a mean change from baseline that was statistically significantly better than RESL for EVLF at all visits through 12 months and for EVLS at 6 and 9 months. Most subjects were responders on the Global Aesthetic Improvement Scale throughout the study according to ratings by blinded evaluators, treating investigators, and subjects. The FACE-Q Appraisal of Nasolabial Folds overall mean score showed significant improvement from baseline (p < 0.0001) at all timepoints through Month 12 for all treatment groups. All treatments were well tolerated.

Conclusions: The new cold-crosslinked fillers were shown to be safe and effective for correction of nasolabial folds, with results lasting for 1 year.