Interim results from a five-year study of Artefill (polymethylmethacrylate/PMMA, Suneva) required by the Food and Drug Administration show that the product appears to be as safe as existing fillers for the nasolabial folds, a lead investigator says.
Artefill earned FDA approval in October 2006. In late 2007, though, the FDA launched a review of dermal filler safety, partly in response to purported Artefill-related safety concerns raised by a group of eight dermatologists led by Arnold W. Klein, M.D.
This review uncovered 191 reported adverse events associated with NLF injections, but in most cases could not pinpoint which products caused them, according to a Nov. 18, 2008, FDA executive summary.
However, he says these misperceptions stem from experience abroad with early-generation PMMA products that do not meet the same standards for manufacturing that Artefill does. Less than 1 percent of its particles measure less than 20µ, he explains, and microspheres smaller than this are likely to cause inflammation and granuloma formation.
"There is also a misperception that Artefill does not have a long-term follow-up data," Dr. Werschler says. However, he says that an already-completed five-year follow-up study involving 60 percent of pivotal study patients revealed favorable safety and efficacy data up to five years after Artefill treatment (Cohen SR, Berner CF, Busso M, et al. Dermatol Surg. 2007 Dec;33 Suppl 2:S222-230).
"Additionally," Dr. Werschler says, "the five-year prospective safety study on which I am an investigator is further establishing the product's long-term safety." This study - the largest and longest-lasting U.S. safety surveillance study of any dermal filler - enrolled 1,008 patients (with no history of recent NLF correction) at 23 centers starting in September 2007. Nearly 90 percent of patients enrolled are female; average patient age is 54 years.
Investigators performed bilateral NLF treatment on each patient, plus up to two touch-up procedures, until patients achieved full correction. Post-injection, researchers are using a forced-choice questionnaire to monitor potential adverse events (AEs).
More specifically, at six, 12, 18, 24, 36, 48 and 60 months post-treatment, patients must complete a detailed questionnaire which inquires about the presence or absence of any potential AEs and about any changes in health or concurrent therapies, including other cosmetic treatments. The questionnaire also tracks patient satisfaction using a five-point scale.
Researchers are following up all AE reports by phone and requiring any patients with potentially device-related AEs to schedule an office visit for evaluation and perhaps treatment. If a lump or bump is reported, researchers use biopsy and histology to rule out possible granulomas. The study protocol does not require typical injection-site reactions such as swelling, minor redness or bruising lasting less than 30 days postinjection to be recorded as AEs.
At the 18-month time point, investigators had lost only 17 patients to follow-up out of the 1,008 enrolled. However, Dr. Werschler says that all of the remaining 991 patients have reached or passed six months post-initial injection. In fact, 973 patients have completed at least 12 months follow-up, and 310 have completed at least 18 months. To date, incidence of device-related AEs is approximately 7 percent.
Dr. Werschler says it is difficult to compare this study to studies of existing fillers because their methodologies differ. However, he says that other FDA-approved fillers' AE rates are approximately equal to that of the PMMA filler.