Cosmetic medicine — and you thought it was for your health

This week, Johnson & Johnson filed its Securities and Exchange (SEC) tender offer to acquire Mentor Corporation, with a reported $1.07 Billion bid.

Mentor [website Loveyourlook.com] is a leading supplier of silicon gel breast implants and liposuction, and is awaiting FDA approval for its new dermal filler and a botox type product for frown lines. Its cosmetic surgery products will join J&J’s Ethicon division, strengthening its worldwide presence in the aesthetic medicine market, according to financial news reports. J&J, the 6^th largest pharmaceutical company in the world, and its Ethicon Endo-Surgery is also the world’s supplier for the bariatric surgery gastric band, Realize.

Alex Gorsky, a Chairman at Johnson & Johnson over Ethicon worldwide said in a press release: “The addition of Mentor, a market-leader and one of the most respected companies in the aesthetic space, expands our capacity to provide physicians with products that can restore patients’ appearance, self-esteem and quality of life.” Mentor shares Ethicon’s commitment to science, health and wellness, he said.

Cosmetic marketing primarily to women, raising insecurities about having an ideally thin, youthful body, has led to mostly women seeking weight loss through gastric banding. It makes good business sense to capitalize on those body insecurities by offering other cosmetic surgeries. The public is finally realizing that gastric banding isn’t really about health, and it’s not likely that liposuction and breast implants will be marketed as being for our health. Why, they’d have to begin a campaign to convince us that instead of BMI, we should be worried about our waist circumferences or hourglass figures. Oh…

In 2004, that idea was nipped in the bud when researchers at Washington University School of Medicine in St. Louis and the Istituto Superiore di Sanità Rome in Rome published their findings in the Journal of the American Medical Association. They evaluated the insulin sensitivity and metabolic syndrome risk factors among women with abdominal obesity, half of whom had type 2 diabetes. They did extensive liposuction, reducing the women’s’ abdominal fat by a massive 28-44% (a whopping 22 pounds of fat). Liposuction made no improvement in any metabolic lab measure (insulin sensitivity of muscle, liver or adipose tissue; glucose; C-reactive protein; interleukin-6; tumor necrosis factor {alpha}; and adiponectin). Nor did liposuction change any other heart disease or diabetes risk factor (blood pressure, plasma glucose, insulin, and lipids). Of course, significantly larger clinical trials have already found BMI and metabolic syndrome unrelated to cardiovascular disease or diabetes.

J&J added another cosmetic surgery product to its lines in July, when another J&J company, OrthoNeutrogena-Aesthetics Group, got FDA approval for Evolence. It’s a pig collagen dermal filler injected into facial wrinkles and folds that lasts about a year. It will join the competitive market of injectable dermal fillers by makers of Botox, Juvederm and Restylane. According to the American Society for Aesthetic Plastic Surgery, more than 1.6 million injectable fillers were sold last year in the United States at a cost of $500+ apiece — meaning it’s more than a $800 million a year market.

A small clinical trial, financed by ColBar Life Sciences Ltd (now J&J Israel), found Evolence worked comparably to its competitor Restylane. This study of 145 people (9 out of 10 were women), published in the June issue of Dermatologic Surgery, also reported more local adverse events in the Evolence arm compared to the Restylane at the 12-month evaluation (19% versus 4.6%).

Cosmetic injections — consumer warnings of risks

While, clearly, injecting fillers into your face isn’t for your health, it can affect your health. Last month, the FDA’s General and Plastic Surgery Devices Panel held two days of safety hearings on dermal fillers. With consumer demand for dermal fillers growing, so were safety concerns. An FDA survey had found that many uses are going beyond the temporary filling of facial wrinkles — laugh lines, crow’s feet and frown furrows — and that dermal fillers are even being used to contour lips, chins, nose, cheeks and breasts; and being implanted into bones, joints and blood vessels.

The FDA had issued a consumer update in June, warning the public that cosmetic fillers should not be used for unapproved uses. It also listed the risks and side effects being reported from cosmetic wrinkle fillers and cautioned that these products appear especially risky for certain people. Consumers were also provided a guide for reporting problems here.

At the FDA Committee safety meetings in November, Dr. Jiyoung Dang, Ph.D., an FDA reviewer in the Plastic and Reconstructive Surgery Branch of the Office of Device Evaluation, reported that dermal filler use doubled between 2000 and 2006 and that about five new dermal fillers were approved just in 2006. This meeting was to evaluate post-market experiences and determine if improvements could be made to the design of pre-market studies being done for FDA approval, with product labeling, and in communicating to the public how to report adverse events to enable more complete information to be learned and shared to protect consumers.

The FDA Committee reviewed the safety data from its Medical Devise Reporting System, a national passive surveillance system that gets about 175,000 reports of adverse reactions a year. According to Nasrin Mirsaidi, a Medical Device Report Reviewer in the FDA’s Office of Postmarket Surveillance, most of their reports come from manufacturers who are required to report adverse incidences, and only 5% came from voluntary reports of users and facilities. As she noted, they know there is a serious problem of underreporting of after-market problems with this voluntary system, as they only hear about a fraction of the millions of procedures done, making precise incident rates impossible for them to obtain. Relying on manufacturers, they said, “the information is biased” and incomplete. Voluntary reports from the public are less frequent - few people even know they can and should report problems from drugs and devices to the FDA in order for problems to be known and addressed. But when they do, the voluntarily reported information from consumers is “a totally different narrative than what the manufacturers are telling us.”

The FDA Manufacturer and User Facility Device Experience (MAUDE) database was searched for the reports of adverse effects from dermal fillers it had received from January 2003 through September 2008. They found a total of 930 reports of complications: 823 injuries (88%), 93 malfunctions (10%), and 14 reports identified as “Other” (2%).

Of the 823 injury reports, 94% required surgery to treat. There were 19 reports of patients admitted to emergency rooms for anaphylactic shock and severe hypersensitivity reactions. Twelve people had required hospitalization for extended IV antibiotic therapy and monitoring.

Since 2003, the FDA approved nine dermal fillers under the condition that the company conduct a post-market study to assess the safety of their products, among people with Fitzpatrick skin types IV-VI who were under represented in the clinical studies yet can experience keloid formation, pigmentation changers, hypertrophic scaring and hypersensitivity. In evaluating the design of these studies, the FDA found serious methodological problems with systematic errors and bias. Incredibly, not one study had included a control group, none were large enough to be sufficiently powered to detect low-incidence complications, none were double blinded, and they were all short-term and lasted only up to 6 months. The FDA concluded that reliable information on keloid formation, pigmentation changes and scarring in darker skin people isn’t available, there are case reports and a random sampling of African populations suggesting up to 16% experience keloids.

The FDA raised expectations for clinical study designs to evaluate new uses of dermal fillers, with stricter parameters to address those identified shortfalls, including determinations of risk to benefit ratio for a given indication. The Committee also said product labels need to include stronger warnings of side effects. Now, if the FDA will follow the very same scientific process for weight loss surgeries, it can protect the health of millions more women and men.

© 2008 Sandy Szwarc