Long-Term (24-Month) Safety Evaluation of Poly-DL-Lactic Acid Filler Injection for the Nasolabial Fold: A Multicenter, Open, Randomized, Evaluator-Blind, Active-Controlled Design.

Abstract

Sir: Many medical devices for antiaging treatment have been introduced into current medical practice. Although hyaluronic acid is the most commonly applied injection device because of its excellent safety and longevity, physicians also prefer to use other fillers such as calcium hydroxyapatite, collagen, and poly-DL-lactic acid.1,2 Concerning hyaluronic acid fillers, there are numerous clinical studies with 1-year or even 2-year long-term safety and efficacy evaluation that have been published in the literature.3 However, regarding other types of fillers, there is a relative paucity of scientific data and clinical evidence for long-term safety. Therefore, we have attempted a 24-month, long-term safety evaluation of poly-DL-lactic acid filler for nasolabial fold correction in Korean patients based on a multicenter, open, randomized, evaluator-blind, active-controlled design. Poly-DL-lactic acid is a U.S. Food and Drug Administration–approved medical material for filler device and can be completely biodegraded into carbon dioxide and water and excreted in the urine. In this study, we have applied poly-DL-lactic acid filler (AestheFill; REGEN Biotech, Seoul, Republic of Korea). The study protocol was approved by the institutional review boards of Chung-Ang University Hospital and Asan Medical Center, Seoul, Republic of Korea. A total of 58 volunteers (seven men and 51 women, aged 37 to 66 years) were enrolled in this study, and 30 patients completed 24-month long-term safety evaluation. Major inclusion criteria were as follows: (1) volunteers older than 20 years (men and women), (2) nasolabial fold with a Wrinkle Severity Rating Scale score of 3 (moderately deep fold; clear facial feature visible at normal appearance but not when stretched; excellent correction expected) or 4 (very long and deep; prominent facial feature; <2 mm visible fold when stretched); and (3) symmetric nasolabial fold scores. For safety evaluation, every side effect such as treatment-emergent adverse events and suspected unexpected serious adverse reactions were also checked. The visiting schedule was a total of five time points (0, 2, 4, 6, and 24 months) and safety check-up parameters were vital signs, physical examination, complete blood count, liver function test, lipid profile, fasting glucose test, electrolytes, blood coagulation test, urinalysis, and urine pregnancy test for female volunteers. Chi-square test and Fisher’s exact test were used for statistical analysis. Clinical trial physical examination revealed four cases of adverse effects at the injection site skin. They were skin discoloration caused by bruising (one case), small transient vesicle formation (one case), and slight mass sensation at the injection site (two cases). They were all mild grade and were restored completely at the 2-month visit. During the 24-month follow-up period, a total of 13 cases of adverse events were identified. However, these were not related to poly-DL-lactic acid filler injection and were without any severe adverse effects, which were arthralgia, gingival pain, musculoskeletal pain, urticaria, and gastrointestinal symptoms. Maximum improvement of nasolabial fold Wrinkle Severity Rating Scale scores was observed at 6-month follow-up, and the scores were normalized at 24-month follow-up (Figs. 1 and 2).Fig. 1: Poly-DL-lactic acid–injected volunteer 1 showing the nasolabial folds at baseline (before treatment).Fig. 2: Poly-DL-lactic acid–injected volunteer 1 showing the nasolabial folds at 6-month follow-up, which was the best improvement time point of the Wrinkle Severity Rating Scale scores.Poly-DL-lactic acid filler was shown to be a safe and effective medical device for nasolabial fold correction. We also believe that complications such as granuloma and vascular occlusion might be potential adverse effects, as with hyaluronic acid filler.4,5 DISCLOSURE The authors have no financial interest to declare in relation to the content of this communication. ACKNOWLEDGMENT This study was supported by a National Research Foundation of Korea grant funded by the Korean government (2011-0008687). Yeon A No, M.D. Joon Seok, M.D. Moo Yeol Hyun, M.D. Tae-Rin Kwon, Ph.D. Chang Taek Oh, M.S. Eun Ja Choi, M.D., Ph.D. Beom Joon Kim, M.D. Department of Dermatology Chung-Ang University College of Medicine Seoul, Republic of Korea