New Drugs and Therapies for 2016: Cosmetics

Drs. Neal Bhatia and Ted Rosen

Part 7 of an 8-part series on the large number of new topical and systemic medications that have become available or moved closer to approval in the last 12 months.

Injectable Deoxycholic Acid

In April, 2015 the FDA approved deoxycholic acid (Kybella®), a treatment for adults with moderate-to-severe fat below the chin, known as submental fat. Kybella, a cytolytic drug, is identical to the deoxycholic acid that is produced in the body and which helps absorb fats. When properly injected into submental fat, the drug destroys fat cells. It is the only approved for the treatment of fat occurring below the chin (Figure 4). The safety and effectiveness of Kybella for treatment of submental fat were established in two clinical trials that enrolled 1,022 adult patients with moderate or severe submental fat. Results showed that reductions in submental fat were observed more frequently in participants who received deoxycholic acid vs placebo.

It is important to note that Kybella can cause serious side effects, including nerve injury in the jaw that can cause an uneven smile or facial muscle weakness, and trouble swallowing. The most common side effects seen with this new treatment are swelling, bruising, pain, numbness, redness and areas of hardness in the treatment area.

Integrating Cosmeceuticals into a Procedural Practice

Zoe Diana Draelos, MD

How can we integrate cosmeceuticals into procedural practices? Dr Draelos provides us with some important clinical pearls:

  • Cosmeceuticals that are relevant post-procedure are: barrier repair moisturizers, growth factors, antioxidants, and skin lighteners
  • Procedure induced barrier repair can be accomplished with:
    • Occlusive substances that reduce TEWL: Petrolatum=99%, Mineral oil=50%, vegetable oils=40%
    • Humectant substances that hold water: Hyaluronic acid, glycerin, proteins, vitamins, sodium PCA, lactic acid, urea
  • Growth factors, found in some post procedure cosmeceuticals, function as humectants to hold water and proteins can form a protective film over wounded skin
  • Growth factors are multifunctional peptides active in the picogram rang; they act as signaling molecules between cells by binding to cell surface receptors
  • Antioxidants are able to donate an electron to reactive oxygen species (ROS)
  • Wounding induces ROS, but antioxidants have never been shown to reduce post-procedural inflammation
  • Antioxidant vitamins A, D, and E used in healing products; but function as vitamin humectants or product preservatives
  •  Skin lightening ingredients include: kojic acid, licorice extract, arbutin, soy, lignin peroxidase, ellagic acid, hydroxyphenoxy propionic acid, niacinamide, and resorcinol

 

Debunking the Myths of Sunscreen

Curtis Cole, PhD

Curtis Cole, PhD, from Johnson & Johnson Consumer Products, is a leading expert on sunscreens and has spent his life’s work on sunscreen technology and formulation. In this presentation, Dr Cole leads a discussion on what every dermatologist needs to know about the current status of sunscreens.

If sunscreens are so good for you, why is there so much noise about it?

Dr Cole mentions the fact that the press and media tend to comment on sunscreen use prior to sunscreen season(s). Many of these comments are read and misinterpreted by consumers and provoke questions around the safety of sunscreens. So what is the truth about sunscreens? Dr Cole states that fundamentally, ultraviolet radiation from sunlight is the major cause of skin cancer. Sunscreens can diminish the amount of ultraviolet radiation entering the skin; therefore, protecting and helping to prevent skin cancer.

Over the last ten years, several papers have been published demonstrating the proof that sunscreen does prevent and reduce skin cancer risk in humans if they are used on a regular basis. (Green A, et al. Lancet. 1999;354:723-729., Heather, L et al. Pigment Cell Melanoma Res. 2010;23:835-837., Adele C, et al. J Clin Oncol. 2011;29:257-263.)

What about estrogenicity and sunscreens?

The SCCNFP is a European “watchdog” group that oversees the safety of UV filters. In a 2001 meeting, the SCCNFP states that “it is of the opinion that the organic UV filters used in cosmetic sunscreen products, allowed in the EU market today, have no estrogenic effects that could potentially affect human health.” There really is no significant estrogenic effect from these UV filters. Studies have shown that estrogenic activity detected in in vitro binding assays did not correlate with in vivo activity. In addition, in vitro binding activity of UV filters are on the order of 1 to 3 million times less potent than estradiol, the standard estrogen compound. Research has also found that UV filters are several hundred times less potent than nutritional sources of estrogen, such as soy or natural supplements.

Does Retinyl Palmitate (RP) in sunscreens increase susceptibility to skin cancer?

The National Toxicology Program (NTP) conducted a nine-year study of RP in albino hairless mouse model. They utilized four concentrations of RP and two of Retinoic Acid and were evaluated against vehicle and untreated controls-solar simulator V source as well as BL and FS lamps. The endpoints were latency period to tumor appearance and tumor yield. Unfortunately this study was flawed; therefore, making the ability to draw a conclusion difficult if not impossible. The study was flawed for several reasons including:

  • Vehicle utilized 15% isopropyl adipate, a potent penetration enhancer
  • The top two concentrations of RP were toxic and had to be eliminated from the study
  • The “enhancing effect” of the vehicle over the untreated but irradiated mice was equivalent to 200% increase in the UV dose
  • The effect of RP was only evident in one gender of the mouse model and not the other

The results are contrary to human evidence that retinoids are chemoprotective to skin cancers. The NTP is considering redoing this study in order to achieve results that are more accurate.

Nano Materials in Cosmetic Materials

Nano materials are much more efficient in blocking UV and they are much more cosmetically acceptable. There are hundreds of papers that are published looking at the “nano sizes” questioning the penetration of TiO2 and ZnO particles. A recent paper by the FDA demonstrated that they could not find penetration from these nano-sized particles. A paper from Sayre R, et al. looked at whether “physical blockers” really act differently than “chemical” UV filters. They found that ZnO and TiO2 actually have a semiconductor energy band gap and absorb UV with the same mechanism as “chemical” UV filters. The “transparent” micronized inorganic filters have little scattering effect, if they did, they would be very visible on the skin. (Sayre R, Kollias N, Roberts R.  Physical sunscreens.  J. Soc. Cosmet Chem; 41:103-109)

What about inorganic (mineral filters)?

Are they better than organic (chemical) filter-based sunscreen? Dr Cole states that there is a much higher level of absorbance among the organic filters because the chemical filters are much more potent. Dr Cole is not saying that the physical filters are not useful, they do; however, have a place for patients who cannot tolerate the organic filters. Also of note, the organic filters are much more aesthetically pleasing.

Sunscreen

 

Do you really have to wait 15-20 minutes for sunscreen protection?

Sunscreen testing protocols mandate drying times of 15-20 minutes before SPF testing can begin; the mandatory labeling reflects this instruction. Actually, UV protection is instantaneous. However, it is important to remember that water resistance may require more drying time. All of the sunscreens that claim water resistance have a type of polymer that is set up to be a barrier against the water. Reapplication (every two hours) of sunscreen is another key component of preventing/reducing sunburns, in fact this is mandatory labeling by the FDA.  A paper in 2001 surveyed 57 people on a beach in Texas. Out of these subjects, there were at least 50 people who got sunburned on the beach; those who do not get sunburned re-applied their sunscreen every two hours. (1Wright M, Wright S, Wagner F.  Mechanisms of sunscreen failure.  J Amer Acad Dermatol. 2001;44:781-784)

Current Misconceptions on High SPF

Dr Cole asks the question of whether SPF 100 is really better than SPF 50. Here are the facts: SPF 100 blocks 99% of damaging UVR and SPF 50 blocks 98% of damaging UVR. Therefore, 1% of SPF 100 is getting through the filter and 2% of SPF 50 is getting through the filter. This means that it is the amount getting through the filter that matters. It’s not so much what you block, it is how much gets through. It would take twice as long to get the damage with SPF 100 than what you get with SPF 50.

Numerous studies have demonstrated that consumers typically under apply sunscreens. Higher SPFs can help compensate for under-application as SPF protection is directly proportional to the amount applied.

How does all of this information affect the products and labeling?
  • Most sunscreen products were unchanged
    • High SPF products (>SPF 50) still allowed
  • What did change?
    • All products now labeled with drug facts box
    • Test method for broad spectrum claims final – CW
      • Broad spectrum claims not allowed for products with SPF<15
  • Statement recognizing use of sunscreens for skin cancer prevention and skin aging is permitted (with an SPF of at least 15 and/or Broad Spectrum)
Broad Spectrum

Broad Spectrum is determined based on “critical wavelength” in vitro absorbance calculation, i.e., wavelength below which 90% of the absorbance is present. 370nm is the “pass/fail” critical wavelength for “Broad Spectrum Protection.” It is important to remember that critical wavelength measures the breadth of protection, yet it does not measure the magnitude; therefore, critical wavelength does not always correlate with UVA protection. The ability to achieve a critical wavelength of 370 becomes more and more difficult as SPFs increase above 30. Dr Cole recommends looking for products with an SPF:UVA-PF ratio of less than 3:1 (which is a requirement for European sunscreen products).

Individuals Particularly Sensitive

Patients/Consumers who are need of the best available protection are those who are highly sensitive (Phototypes I and II, photosensitive conditions and patients on immune suppressive drugs and those who have skin cancers. Others who are also in need of good protection are those who want to limit further photodamge, fine lines, wrinkling and pigmentation.

Why use a high SPF?

Extreme conditions of exposure warrant a higher SPF. These are conditions such as high altitude and those of high reflectivity such as ocean surface, sand and snow. In a controlled consumer trial (split-face, double-blind design) of 56 people at 8500 feet with all day sun exposure demonstrated that more individuals had sunburn using an SPF 50 versus an SPF 85 product. (Rigel et al. 2009. J Am Acad Dermatol;62, I:2:348-349)

Testing of high SPF products has been validated up to SPF 90. A controlled, randomized, multi-center trial was conducted using SPFs 16, 70 and 90 and four test laboratories using multiport and singleport solar stimulators. The results showed that all of the SPF levels could be distinguished from each other in the four labs; yet, no significant differences in SPF values of each product between laboratories. The testing demonstrated the ability of the laboratories to determine high SPF values with accuracy and reproducibility. (Stanfield,  Ou-Yang,  Chen, Cole, & Appa. 2011. Photodermatology, Photoimmunology & Photomedicine ;27:1,30-35)

Sunscreens and Squamous Cell Carcinoma and Malignant Melanoma

A randomized controlled study in Australia looked at sunscreen use (daily versus discretionary), risk of BCC and SCC (and melanoma). Use of an SPF 16 product and weight of the product brought in was measured every three months. The researchers found a significant reduction in the risk of SCC (RR 0.61; 95% CI 0.46 to 0.81). This suggests that melanoma may be preventable in adults with the regular use of sunscreen. (Green AC, et al. J Clin Oncol. 2011;29(3):257-263.)

Conclusions

Skin protection from damaging sunlight requires a multi-layer defense. Sunscreen should be part of the overall plan for protecting from sun damage. It is important to avoid unnecessary sunlight and you should avoid highest UVB intensities of sunlight (10am-4pm). Skin should be covered with clothing and a hat and high SPF should be used for skin that remains exposed.

 

 

 

 

 

 

 

 

The Science of Aging Skin

Michael Gold, MD

How do we look at all of the skincare products available? What does it mean to our patients? It is important that clinicians recognize what drugs and therapies work for dermal aging. Sunscreens, i.e., those with UVA and UVB protection, can prevent melanin production and collagen and elastin degradation. Dermatologists need to be aware of what ingredients are in these various sunscreens. Retinoids have also changed the management paradigm of aging skin showing a clinical improvement in skin texture, wrinkles, and pigmentation. Hydroquinone is probably the most effective inhibitor of melanogenesis. It exerts its depigmenting effect by selective action on melanocyte metabolism which results in more even skin tone and reversal of abnormal pigmentation. Hydroquinone helps prevent/reduce PIH and has been proven safe and effective by the FDA for over forty-five years. Many clinicians use hydroquinone in conjunction with retinoids.

Because of the increasing aging population, there as been a consumer demand for anti-aging products. The average patient is 30 to 55 years old and well educated. Because of the number of products available, there is also a lot of confusion around choosing what products would be the most efficacious and safe.

What is a Cosmeceutical?

According to Dr Al Kligman, the physician who termed this word, it is “something between a cosmetic and pharmaceutical”. They are topical cosmetic products that exert a pharmaceutical, but not necessarily a biologic, therapeutic benefit. Their use is mainly for anti-aging purposes, designed to improve the appearance of lines and wrinkles, skin discoloration and other defects.

How do we evaluate these various compounds? Healthcare providers know that a biologically sound rationale exists for their cutaneous effect. The therapeutic concentration range of the ingredient is known, the formulation science stabilizes the ingredient in the product, and the trans-stratum corneum delivery science for the ingredient is incorporated into the formulation. However, we need more clinical blinded trials conducted by third-party companies in order to better represent the data, as clinicians want to see patient satisfaction.

What Cosmeceuticals Exist?

Pierre Fabre

Pierre Fabre has a water-based dermocosmeceutical that hydrates the skin and has many uses as a moisturizer and anti-inflammatory agent. One of the company’s products, Retrinal™, comes in three doses for hypersensitive skin and the eye area, all skin types, and intensive skin rejuvenation. Clinical studies show that these retinoid products, which can be purchased OTC, are as effective as prescription retinoids. Another one of their products, Gel d’eau Thermale, is a water-based gel that can be used in post-laser procedures such as laser hair removal and has an immediate cooling effect, and analgesic effect, and a soothing, anti-inflammatory effect. Pierre Fabre also has positive data around its product Avene Thermal Spray Water. Glytone, a vitaceutical facial serum, provides all day anti-oxident protection through its continuous release of free Detla-Tocopheryl. Six month studies on photodamaged skin showed efficacy.

Recently, the European Journal of Dermatology published a series of peer-reviewed papers showing the clinical efficacy of these water-based products in in photoaged skin as well as disease states such as eczema and psoriasis.

Neocutis

Neocutis has many products using multiple fetal fibroblast cell lysates. Several papers have been published discussing how this novel human growth factor and cytokine skin cream and improve skin surface topography of aged facial skin.

Blanche

Blanche Skin Lightening Cream with Melaplex represents a novel and first time approach to target the pathway of melanin formation at multiple levels. Blanche contains a prescription strength Hydroquinone (4%) for effective skin lightening when used with Melaplex, which is a unique skin-brightening complex that is used to restore the youthful appearance of even skin tone. In a head to head study Blanche produced equivalent results to Triluma in the treatment of dyspigmentation.

Perle

Perle is a Skin Brightening Cream with Melaplex. Many clinicians do not like to utilize hydroquinone, and some of these newer products, such as Perle, are well-tolerated and hydroquinone-free. A 45% reduction in pigment was found after a 12 week study protocol. Many clinicians have used hydroquinone products for 12 weeks and then switch to hydroquinone-free products. The advantage of this product is that there is no restriction on how long you can use this product and it can be used safely in pregnancy.

Both of these products have enabled clinicians to help block the pathway of melanin formation.

Syneron

Elure, which is a skin-lightening product, is based on Melanozyme containing lignin peroxidase (LIP). LIP is a naturally occurring enzyme deriving from a tree fungus. For many years, LIP has been identified as the enzyme that breaks down lignin in decaying trees, causing rapid decolorization. Because the molecular structure of lignin is similar to that of melanin, recent research confirmed that LIP also has the potential to improve the appearance of skin by reducing eumelanin. Data suggest that Elure is significantly more efficient that 2% hydroquinone.

Looking ahead, Dr Gold stated: “In 2011 pigment will be the new wrinkle.”

Biopele Growth Factors (GFs)

GFs work as chemical messengers between cells to turn on or off specific cellular activities. They can be derived from a number of sources, including epidermal cells, placental cells, colostrum and plants. GFs promote fibroblast and keratinocyte proliferation and induce extracellular matrix formation. SCA Biorepair technology (Tensage) is a novel fibroblast growth factor. Secretion of the snail Cryptomphalus aspersa (SCA) is an active, glycosaminoglycan secretion generated by the snail during times of stress such as exposure to radiation, burns, etc. SCA is shown to repair the snail’s skin in as little as 48 hours and eliminates concern expressed over VEGFs. Data suggest that this product shows marked improvement in skin texture and moisture, enhanced collagen deposition, increased hyaluronic acid content and a reduction in solar elastosis.

Biopele also makes non-prescription retinoids to counteract the effects of photoaging.

It is important that dermatologists realize that we now have the opportunity to change the function of skin. Cosmeceuticals are showing a great improvement in this ability.

Obagi

ELASTIderm is a topical eye treatment that is clinically proven to show increased elasticity and a reduction in visible wrinkles.

Obagi’s Nu-Derm System is an OTC product designed to be used in conjunction with a prescription retinoid to transform damaged skin cell functions in order to reverse photoaging. The data suggest that Nu-Derm System demonstrates a superior efficacy at 2 weeks as compared to other therapies.

The 4-step Obagi hydroquinone/tretinoin-based skin care system helps to correct premature skin damage, reduce future skin damage. Care in customizing the system to the individual is important. The sequence of application of component products is:

  1. Skin preparation (cleanser + toner)
  2. Skin correction (4% hydroquinone + exfoliant)
  3. Skin stimulation (4% hydroquinone + 0.05% or 0.1% tretinoin)
  4. Skin protection (sunscreen)

The published data suggests that there are benefits of using a hydroquinone/tretinoin skin care system for patients particularly when used in conjunction with light based devices such as IPL.

Coffeeberry

CoffeeBerry® is the fruit from the coffee plant (Coffea arabica), from which the commonly known coffee bean is derived. When harvested at a sub-ripe growth stage, the flesh of the CoffeeBerry® fruit is at peak antioxidant concentration. RevaleSkin utilizes coffeeberry and has shown a decrease in the appearance of fine lines and wrinkles.

Priori Skincare

Priori now has their own coffeeberry line, the Priori Coffeeberry Natureceutials with all of their products designed to improve skin renewal and decrease fine lines and wrinkles. Idebenone is another product of Priori’s, again showing a reduction in pigmentation and rosacea.

Allergan

Allergan’s product, Vivite, which combines glycolics and antioxidants, has shown improvement in the appearance of fine lines/wrinkles, skin roughness and hyperpigmentation after 8 weeks of treatment.

LATISSE®

LATISSE® is the first and only FDA approved therapy for the treatment of hypotrichosis of the eyelashes. LATISSE works by increasing eyelash growth including length, thickness, and darkness. The exact mechanism of action for LASTISSE® is unknown. LATISSE® solution is a structural prostaglandin analog that exerts its action by selectively mimicking the effects of naturally occurring prostamides. The physiochemical properties of LATISSE® solution favor its effective skin absorption into the dermis where the hair follicles reside.

LATISSE® is associated with enhanced eyelash growth and most subjects in clinical trials noticed favorable changes in their eyelashes.

NIA24

The NIA company uses a Pro-drug system that turns into an active within the skin. The company utilizes iacin in order to improve skin function. Pro-Niacin has shown to dramatically strengthen the skin barrier, improve cell turnover/differentiation, improve moisture retention and increase sun protection. Its visible improvements include increased smoothness and firmness, improved texture and tone, reductions in the appearance of fine lines and wrinkles and improvements in chin and jaw firmness.

Skin Medica

TNS is another Growth Factor. Its work has been verified time and time again, by seeing improvement in fine lines and skin elasticity. TNS is unique for several reasons: patented advanced manufacturing process; physiologically balanced growth factor mixture; stability of a high concentration of growth factors; proven safety of growth factors over time.

Clinical studies have demonstrated the efficacy of TNS and it has an excellent safety profile with over 7 years of use.

Recently, SkinMedica has come out with TNS Essential Serum that is both a Recovery Complex (same TNS) and a Corrective Complex. It is an interesting synergy of the products and several independent studies have verified its effectiveness in skin texture roughness, peri-ocular wrinkles, smoothness and skin tone.

SkinMedica also makes a variety of antioxidants and retinoids. In comparator studies the Tri-Retinol performed as well as tretinoin .025% in the treatment of photoaging but with less irritation.

Anti-redness Products

According to Dr. Gold, in addition to pigment disorders, another “huge” area being targeted by the cosmeceutical companies is redness. There are lots of reasons that patients become red in their skin. Some of the most common reasons are blushing, acute redness/flushing, which can be due to sun exposure, cosmetic procedures or drug-induced as well as chronic redness associated with skin disorders such as acne, rosacea or atopic dermatitis. Most of the products being developed in this space target prostaglandin E2 (PGE2) that is a bioactive molecule in the prostanoid family of lipids responsible for vasodilation. It is elevated by a number of stimuli including UV exposure, chemical exposure, neuronal and hormonal stimuli and inflammatory skin conditions such as rosacea.

CalmPlex is a novel product containing patented ingredients and has shown its effect on skin redness. Most cosmetic products hide redness or temporarily reduce blood flow to the skin using vasoconstrictors. However, CalmPlex prevents UV and chemical induced release of inflammatory mediators, especially PGE2. Several studies have shown its effectiveness in reducing skin redness.

Summary

It is important to know what products your patients are already using at home to avoid patient confusion. Patient education and staff education are keys to the success of these products and patient satisfaction. Aestheticians must spend a lot of time with patients going over their regimens in order to achieve success. Taking lots of before/after photographs can help your patients, build confidence and trust and it serves as a nice cross-referral.