A Decade of Experience with Injectable Poly-L-Lactic Acid A Focus on Safety

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A Decade of Experience with Injectable Poly-L-Lactic Acid: A Focus on Safety CYNTHIA BARTUS, MD,* C. WILLIAM HANKE, MD,†

AND

ELIZABETH DARO-KAFTAN, PHD‡

BACKGROUND Injectable poly-L-lactic acid (PLLA) is a biodegradable synthetic polymer device that stimulates collagen production, leading to gradual volume restoration. It has been used worldwide for more than a decade to treat the lines and wrinkles of the aging face and in individuals with the human immunodeficiency virus for treatment of facial lipoatrophy. OBJECTIVE To provide an overview of the experience with injectable PLLA in Europe and the United States and the practices that have improved product use. MATERIALS AND METHODS A review of the literature was conducted, and the authors’ clinical experience was included detailing the evolution of the use of injectable PLLA for facial restoration. RESULTS Although relatively high rates of nodule and papule formation were reported during early use of injectable PLLA, updated methods have led to better safety and efficacy, including patient selection, preparation, and instruction; product preparation; timing of injections and avoidance of overcorrection; an updated understanding of the anatomy of the aging face; and site-specific injection techniques. CONCLUSION Important lessons have been learned that have enhanced the safety and efficacy of injectable PLLA and have made it a desirable product for restoring facial volume. Elizabeth Daro-Kaftan, PhD, of Peloton Advantage, LLC, provided editorial support for this article, which was funded by Medicis, a division of Valeant Pharmaceuticals.The authors were fully responsible for the content, editorial decisions,and opinions expressed in the current article. No author received an honorarium related to the development of this manuscript.

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njectable poly-L-lactic acid (PLLA) has been used for soft tissue augmentation for more than a decade in Europe and nearly a decade in the United States. Injectable PLLA is a biodegradable synthetic polymer device that stimulates collagen production, leading to gradual volume restoration.1,2 The effects of injectable PLLA volume augmentation may last up to 2 years and possibly longer.3,4 Poly-L-lactic acid has been widely used for many years in a variety of medical applications, such as in absorbable suture material, bone implants, and medication vectors for subcutaneous and intramuscular injections.5 As an injectable soft tissue volume

augmentation device, injectable PLLA is approved for use in the United States for restoration and/or correction of lipoatrophy in patients with the human immunodeficiency virus (HIV) and for correction of nasolabial folds and other facial wrinkles in immunocompetent patients.6,7 Although injectable PLLA creates the appearance of immediate volumization because of the mechanical effects of the injected suspension, this is transient and disappears within a few days as the suspension fluid is absorbed.6 The longer-lasting effects of injectable PLLA are realized over the next few months. As the PLLA microparticles degrade, the inflammatory reaction responsible for degradation

*Advanced Dermatology Associates, Allentown, Pennsylvania; †Laser and Skin Surgery Center of Indiana, Carmel, Indiana; ‡Peloton Advantage, LLC, Parsippany, New Jersey © 2013 by the American Society for Dermatologic Surgery, Inc.  Published by Wiley Periodicals, Inc.  ISSN: 1076-0512  Dermatol Surg 2013;39:698–705  DOI: 10.1111/dsu.12128 698

BARTUS ET AL

of the particles results in the formation of fibrous connective tissue and neocollagenesis1,7–9 and leads to gradual correction of the underlying lipoatrophy or age-related changes in the face.

Evolution of Injectable PLLA Use The safety of injectable PLLA has been well documented in numerous studies.3–6,10–28 Early use revealed a relatively high frequency of papule and nodule formation.10,12,17 As its use has expanded, and injection techniques have evolved, the frequency of adverse events has decreased.3–5,11,13–16,18–28 In 1999, injectable PLLA was approved for use in Europe (New-Fill; Biotech Industry SA, Luxembourg, Luxembourg) for soft tissue augmentation of scars and wrinkles.10 In its early use, injectable PLLA was reconstituted with 3 mL of sterile water and allowed to stand for 2–12 hours before injection. The senior author’s early experience with injectable PLLA was included in a report by Woerle and colleagues11 of 300 patients who underwent 819 treatments over a 5-year period. Injectable PLLA was found to be effective for the treatment of lower face wrinkles and folds with long-lasting results. Frequent side effects were bruising, redness, and edema. During the first 3 years of treatment, 10% of patients experienced subcutaneous papules. In mid-2002, the authors modified a number of parameters, which led to a reduction in subcutaneous papule formation from 10% to