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) (Symatese, Chaponost, France) are new hyaluronic acid fillers created using an innovative cold-crosslinking process. Objectives The authors of this study aim to collect safety and effectiveness data on new cold-crosslinked fillers to support the US approval for the correction of moderate-to-severe dynamic facial wrinkles and folds. Methods In this randomized, controlled, split-face study, 140 patients with moderate-to-severe nasolabial folds (NLFs) received a cold-crosslinked filler in 1 NLF (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 time point 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 the photographic review panel demonstrated noninferiority 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 patients were responders on the Global Aesthetic Improvement Scale throughout the study, according to ratings by blinded evaluators, treating investigators, and patients. The FACE-Q appraisal of NLFs' overall mean score showed significant improvement from baseline (P