Safety and Efficacy of Hyaluronic Acid-Based Filler for Neck Wrinkles: A Prospective, Multicenter, Randomized, Parallel-Controlled Non-Inferiority Trial

Background: Horizontal neck lines are an early and conspicuous marker of cutaneous aging. Intradermal hyaluronic acid (HA) injections have become a standard minimally invasive countermeasure, yet comparative data for composite HA solutions in Asian populations remain scarce. Purpose: To evaluate the efficacy and safety of injectable sodium hyaluronate composite solution (NCTF ® 135 HA) compared with injectable sodium hyaluronate composite solution (HEARTY ® ) for the correction of moderate-to-severe neck wrinkles. Methods: In this prospective, multicenter, randomized, evaluator-blinded, active-controlled, non-inferiority trial, 188 subjects with moderate-to-severe neck wrinkles were randomly assigned (1:1) to the experimental group or the control group, with both groups receiving three sessions of non-cross-linked injectable sodium hyaluronate composite solution at 4-week intervals. Improvement of Allergan Transverse Neck Lines Scale (ATNLS), subject-assessed Global Aesthetic Improvement Scale (GAIS) and adverse events (AEs) were evaluated and compared before the 3 injection sessions and at 4, 12, and 24 weeks post-final injection. Results: At week 4 post-final injection, the ATNLS response rates were 88.30% in the experimental group and 85.11% in the control group, respectively, with a between-group difference of 3.19% (95% confidence interval (CI): [− 0.0723, 0.0987], p = 0.5410), demonstrating non-inferiority of the experimental treatment to the active control. Among the secondary endpoints, neither ATNLS response rates at additional time points nor subject-assessed GAIS responder rates showed statistically significant differences between groups. A total of 128 adverse events were reported, with no statistically significant difference between groups: 26 (27.66%) in the experimental group and 38 (40.43%) in the control group. No device- or procedure-related serious adverse events occurred. Conclusion: Injectable sodium hyaluronate composite solution (non-cross-linked) provides safe, effective, and non-inferior correction of moderate-to-severe neck wrinkles compared with active control, expanding minimally invasive therapeutic options for cervical rejuvenation. Keywords: multicenter, neck wrinkles, hyaluronic acid, mesotherapy, neck rejuvenation