National report - Dermatologists who had safety concerns about the permanent filler ArteFill (polymethylmethacrylate, bovine collagen; Artes Medical) say the manufacturer?s recent failure is good for the dermatology community.
- Dermatologists who had safety concerns about the permanent filler ArteFill (polymethylmethacrylate, bovine collagen; Artes Medical) say the manufacturer’s recent failure is good for the dermatology community.
But others say the December 2008 bankruptcy filing ultimately will be bad for the industry.
And opinions are divided about the risks of permanent fillers, whose longevity and relative efficiency can be both a blessing and a curse, dermatologists say.
"The loss of ArteFill is a good thing for the entire dermatology community," says Joel Schlessinger, M.D., an Omaha, Neb., board-certified dermatologist and general cosmetic surgeon, and a past president of the American Society of Cosmetic Dermatology and Aesthetic Surgery.
"This product was approved without adequate safety data, as can be seen from the recent FDA panel reports that led to an investigation of all fillers, but mainly surrounded issues from this one," he says,The FDA review uncovered 930 reports of adverse events associated with dermal fillers of all types that had been reported to the agency’s Manufacturer and User Facility Device Experience database from January 2003 to Sept. 20, 2008, according to a November 2008 FDA executive summary.
However, the report doesn’t specify how many were associated with ArteFill, whose manufacturer, California-based Artes Medical, filed bankruptcy in December.
To provide postmarketing safety data, Artes had begun a five-year prospective study involving ArteFill.
Since the company declared bankruptcy, says Rhoda S. Narins, M.D., "We don’t know what’s going to happen with the study. But all the patients have already been injected." She is clinical professor of dermatology, New York University Medical School, and director, Dermatology Surgery and Laser Center, New York.
Dr. Narins says the 30 study patients she treated (of 1,000 total at various U.S. sites) loved the easy-to-inject product.
"It would have been nice to see (Artes) go on for the duration of the study, so we could see how big, if any, an improvement ArteFill was over ArteColl," the formulation used in FDA trials, she says.
Dr. Narins says a communiqué from the study’s director indicates that all sites will continue monitoring their patients. Regarding her patients, many of whom have reached six months post-treatment, Dr. Narins says, "I haven’t seen a single problem yet."
She says Artes’ bankruptcy is "bad for the industry. ArteFill wasn’t shown in any way to be unsafe.&3#34;
The company’s failure leaves patients with no FDA-approved permanent filler, says Dr. Narins, "and there are patients who like permanent fillers."
For these patients, Dr. Narins says, "The idea of doing something again and again bothers them. They don’t realize that many other fillers last a very long time. I just published an article showing that if you use Restylane (hyaluronic acid, Medicis) to optimal cosmetic improvement, then do a minor touchup between 4.5 and nine months, it will last at least 18 months (Narins RS et al. Dermatol Surg. 2008 Jun;34 Suppl 1:S2-8)."
Furthermore, Dr. Narins says many patients from ArteFill’s original FDA approval studies looked better five years post-treatment than shortly after treatment.
But Amy E. Newburger, M.D., says that while many observers might rejoice in ArteFill’s demise, "The jury’s still out regarding its safety and efficacy." She is director, Dermatology Consultants of Westchester, N.Y.
She also served on the FDA advisory panel that in October 2003 voted to approve ArteFill, with the stipulation that it should not be used outside of nasolabial folds.
Part of the product’s bad rap came from misuse, she says. U.S. physicians were injecting ArteFill in the mouth area, she says, although Canadian colleagues already had reported many "disasters" with such injections.
However, she says FDA reviewers couldn’t consider evidence outside of studies submitted with Artes’ application. Nor could they consider a report of a granuloma that occurred in an Israeli patient when ArteFill beads implanted in his forehead ruptured (Reisberger EM et al. Arch Dermatol. 2003 Jan;139(1):17-20).
"People will always use (fillers) off-label. And unfortunately, the nature of the material is that when it’s used off-label, there is a higher likelihood that you’ll run into trouble," Dr. Newburger says. But if physicians limit injections to the nasolabial fold and an adverse event occurs, she says, "It’s not as difficult to excise, because there’s a natural fold there."
As for other permanent fillers, liquid injectable silicone earned FDA approval for treating retinal detachment in 1998.
"Depending on whom you ask, permanent fillers are a blessing or a millstone around your neck. I believe the answer is in the middle," says David M. Duffy, M.D., a Torrance, Calif., board-certified dermatologist who has been injecting liquid silicone for 26 years.
For starters, "The long term is different from the short term." Rarely, he explains, "You can see problems later on. But predicting them is not always easy, and they’re sometimes hard to treat."
Nevertheless, Dr. Duffy says that in his practice, "Silicone and permanent fillers in general are a wonderful modality." He doesn’t want any of them eliminated, he says, "but the criteria for using them should be tightened."
Standard contraindications for permanent fillers include the presence of inflammatory disease, a tendency toward keloids, or - in the case of ArteFill - thick, sebaceous skin, Dr. Duffy notes.
However, he says, "My criteria are much stricter." For example, he says he rarely uses permanent fillers in lips because bacteria from the mouth can trigger complications, possibly through biofilm, in the long term.
He also avoids permanent fillers in patients who have had permanent fillers injected by anyone else.
"Since complications can be delayed," he says, "I’m going to be blamed" if any occur. Dr. Duffy also considers a history of dental infections, sinus infections or other chronic inflammatory processes a relative contraindication.
Most authoritative publications refute a causal role associating implants with collagen vascular disease (CVD), he adds. However, Dr. Duffy speculates that commensal bacteria interacting with long-term implants may permit the insertion of bacterial DNA into the host genome in a genetically susceptible individual, leading to discrepancies in self/non-self recognition.
Accordingly, he suggests that a personal or family history of CVD or sarcoidosis should be considered a contraindication of permanent implants.
Dr. Duffy says appropriate indications for permanent fillers include HIV lipoatrophy and patients who require small-volume corrections, such as those with dog-bite scars. With such patients, he explains, "The notion of spending $20,000 on fillers over the years is intolerable for me."
However, Dr. Duffy cautions that with permanent fillers, "Patient selection is everything."
Permanent fillers create lifetime patient relationships, he explains, "and you must decide if the person is stable or litigious." For such reasons, he says, "I always start with a temporary filler." DT
Disclosures: Jefferies & Co. co-managed IPOs for Cynosure and BioForm Medical. Dr. Duffy has received speaking fees from Contura. Ms. Lewis and Dr. Newburger report no relevant financial interests. Dr. Narins is an investigator in the ArteFill post-market study.
For more information:www.FDA.gov