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 < .0001) at all time points 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 NLFs, with results lasting for 1 year.

Figure 1.

Wrinkle Severity Rating Scale difference in mean change at Month 6 by independent photographic review panel for Evolysse Form (EVL_F) arm.

Figure 2.

Wrinkle Severity Rating Scale difference in mean change at Month 6 by independent photographic review panel for Evolysse Smooth (EVL_S) arm.

Figure 3.

Wrinkle Severity Rating Scale mean change by blinded evaluator live assessment for Evolysse Form (EVL_F) arm.

Figure 4.

Wrinkle Severity Rating Scale responder rate by blinded evaluator live assessment for Evolysse Form (EVL_F) arm.

Figure 5.

Wrinkle Severity Rating Scale mean change by blinded evaluator live assessment for Evolysse Smooth (EVL_S) arm.

Figure 6.

Wrinkle Severity Rating Scale responder rate by blinded evaluator live assessment for Evolysse Smooth (EVL_S) arm.

Figure 7.

A 46-year-old White Hispanic female patient treated with 1.0 mL Evolysse Form (EVL_F) in the left nasolabial fold (NLF) and 1.3 mL Restylane-L (RES_L) in the right NLF at baseline (Wrinkle Severity Rating Scale [WSRS] severe), Month 6 (WSRS mild), and Month 12 (WSRS moderate). (A) Right oblique view preoperatively, (B) at Month 6, and (C) at Month 12. (D-F) Anterior view and (G-I) left oblique view at the same time intervals previously stated.

Figure 8.

A 59-year-old White Hispanic female patient treated with 1.3 mL Evolysse Smooth (EVL_S) in the left nasolabial fold (NLF) and 1.3 mL Restylane-L (RES_L) in the right NLF at baseline (Wrinkle Severity Rating Scale [WSRS] severe), Month 6 (WSRS mild on left and moderate on right), and Month 9 (WSRS mild on left and moderate on right). (A) Right oblique view preoperatively, (B) at Month 6, and (C) at Month 9. (D-F) Anterior view and (G-I) left oblique view at the same time intervals previously stated.