The second day of the 2018 South Beach Symposium focused on clinical dermatology sessions covering acne, psoriasis, atopic dermatitis as well as a Futures Symposium on Innovations in Dermatology.
Pharmaceutical Breakthroughs and Clinical Trials Update
Leon Kircik, MD
Dr. Kircik started the session on innovations in clinical therapeutics with an excellent update on what is new in clinical trials. First, Dr. Kircik discussed olumacostat glasaretil (OMG), which is a novel therapeutic designed to reduce sebum production. For acne vulgaris, a study showed significant reduction in acne vulgaris lesions after 12 weeks of use. Also, Dr. Kircik shared that topical cortexolone, a 17-a propionate antiandrogen was better than both placebo and tretinoin 0.05% cream for the treatment of acne vulgaris. Another upcoming therapeutic option for acne vulgaris is topical nitric oxide, which is a modulator of inflammation and broad spectrum antimicrobial, and early clinical trial data of the 4% gel applied daily significantly improved acne vulgaris. Also, topical trifarotene is a new retinoid that may be available in the future for the treatment of acne vulgaris. Other new treatments for acne vulgaris on the horizon in include topical minocycline 4% foam, systemic seracycline, and topical bacteriophages to normalize the microbiome of the skin.
Dr. Kircik also shared that another formulation of topical minocycline in a 2% foam is being investigated for the treatment of rosacea. Also for roseacea, omiganan is novel antimicrobial peptide for severe popular pustular rosacea and is currently under investigation in clinical trials. For axillary hyperhidrosis, topical glycopyrrium tosylate is a promising new therapy. In addition, topical combination digoxin and furosemide or topical furosemide alone my be future treatments for verruca. In the cosmetic realm, new topical formulations include retinaldehyde for reduction of rhytids and hydrogen peroxide solution for seborrheic keratosis.
Treatment Options for Melasma
Seemal Desai, MD
There are many treatment options for melasma, and Dr. Dseai began his excellent lecture by reminding us the most important thing to do is educate patients that melasma is a chronic skin disease than can be managed. He went on to recommend the combination use of topical retinoids, azaleic acid, hydroquinone, chemical peels, cosmeceuticals, lasers, dermabration, and most importantly reassurance and time.
In his experience, Dr. Desai finds that triple combination therapy, including a retinoid, hydroquinone, and topical corticosteroid, is the gold standard. Also, he shared that there is no evidence to substantiate claims hydroquinone is carcinogenic. Ochronosis is a real risk with hydroquinone, and is a clinically distinct perifollicular blue discoloration. Dr. Desai recommends that dermatologists not use hydroquinone as monotherapy in the treatment of melasma. In his practice he does not use hydroquinone containing products for longer than 8 weeks, and then he cycles patients to alternative topicals such as 20% topical azelaic acid.
In the future, kojic acid dipalmitate may be available in the United States, It is a topical antibiotic useful that inhibits tyrosinase in the treatment melasma, and the diplamitate formulation more stable to light, heat, and pH stable compared to regular kojic acid.
Dr. Desai went on to recommend soy topical products, which contains fatty acids, isoflavones, serine protease inhibitors (not tyrosinase) to treat melasma. Generall soy products are safe and effective, and skin lightening can be seen after 12 weeks of twice daily use. Next, Dr. Desai shared data regarding methimazole, which is perodidase inhibitor and can be compounded into a 5% cream. Methimazole targets melanogenesis in peroxidase, which is down stream from tyrosinase, and no adverse effects on thyroid function have been reported with topical use.
Dr. Desai also shared with the symposium attendees a new fad treatment in skin lightening called glutathione, which is potent antioxidant with indirect inactivation of tyrosinase. Patients are receiving glutathione infusions off label, however there is no proven benefit to longstanding skin lightening, and serious side effects such as TEN have been reported.
Dr. Desai concluded his discussion of melasma with tranexamic acid, which is fibronolytic agent currently available as the trade name Lysteda. It is FDA approved for menorrhagia, and is an appropriate adjunctive treatment for patients with melasma who have no history of thromboembolic events or oral contraceptive use. Topical formulations of tranexamic acid may be available in the future according to Dr. Desai.
Therapeutic Advancements and the Future of Acne Therapy
James Q. Del Rosso, DO
Dr. Del Rosso began the acne symposium with a review of potential future treatments for acne vulgaris. There are several challenges to develop new acne therapies, including the evaluation of modes of action, antibiotic resistance, clinical efficacy, tolerability, and safety. He shared that topical minocycline, topical nitric oxide, topical olumacostat glasertil and systemic sarecycline are upcoming new agents in the treatment of acne vulgaris.
Then Dr. Del Rosso shared that topical minocycline in foam or gel formulation is both anti-inflammatory and antimicrobial against p. acnes. Early results of clinical trials show significant reduction in acne vulgaris lesions when compared to vehicle. Another new advancement in the treatment of acne vulgaris is topical nitric oxide, which downregulates IL-1b and its down stream inflammatory effects. Dr. Del Rosso also shared a new class of topical medication currently in development. The acetyl-COA carboxylase inhibitor olumacostat glasertil is proposed to improve acne vulgaris by attenuating sebum production. Dr. Del Rosso concluded the therapeutic discussion by mentioning a new tetracycline antibiotic with a better side effect profile called sarecycline that is currently in clinical trials evaluation.
Skincare Advice for the Aging Patient
Doris Day, MD
Dr. Day shared her advice for skincare, which ideally should begin at birth. Historically, the concept of beauty has been associated with fertility and youth. The challenge for the skin care expert today includes factors such as hormones, undoing the damage of youth, and allowing patients to stay relevant in work and social life. The manifestations of skin aging are demonstrated with up to 20% reduction in collagen, Type 3 and type 1 collagen imbalance, and dyspigmentation in the aging patient. Dr. Day explained the mechanisms of photoaging and natural aging which lead to melanocyte activation pigmentary changes, extracellular matrix degeneration.
The first key aspect of skin care in the aging patient according to Dr. Day is antioxidants and sun protection. We should recommend chemical and physical sunscreens to our patients in addition to L-ascorbic acid, blackberry leaf extract, coffee berry, green tea extract, vitamin E, and CoQ10 in topical preparations as a part of their everyday skincare routine. Next, Dr. Day recommended we encourage patients to regulate the pigment production in their skin by using tranexamic acid, hydroquinone, and retinol products. For epidermal strength and renewal, Dr. Day suggests that physicians should consider if patients are appropriate candidates for hormone replacement therapy. Chemical peels, alpha hydroxyl acids, and retinoids are all essential components in the sincare regimen of the aging patient as well. Dr. Day also shared that some of her favorite ingredients in cosmeceutical products are niacinamide, sunflower seed oil, panthenol, hexamidine, n-acetyl glucosamine, allantoin, and growth factors. Dr. Day concluded the discussion on skincare by reminding symposium attendees to make appropriate skincare recommendations in any patient that may undergo an in office procedure to optimize results.
Skincare Regimen Post Procedure
Diane S. Berson, MD
Dr. Berson shared some of her product recommendations during the discussion on skincare regimens and procedures. First, Dr. Berson explained that a pretreatment regimen is essential to minimize complications such as postinflammatory hyperpigmentation, persistent erythema, and infection. A topical antimicrobial before any filler procedure is highly recommended, one example of this is hypochlorous acid gel. Also, skin care regimen should be aimed at the goals of the patient before procedures such as retinoic acid for wrinkles or kojic acid for pigmentation.
Next Dr. Berson explained the variety of products that may be used after a procedure to protect, hydrate, and repair the skin. A post procedure mask may be soothing to the patient and also provide an anti-inflammatory benefit. Ingredients in post procedure gels such as hypochlorous acid and arnica are also important to consider. Dr. Berson recommends that hyaluronic acid be included in the skincare regimen post prodecure, and that a barrier repair cream containing ceramides, cholesterol, and fatty acids should also be used. Recently becoming more frequently used in the United States is a balm that contains panthenol, copper, zinc, manganese, glycerin, and shea butter and is an excellent option for post procedure skin care. Specifically regarding skin care after fractional laser resurfacing Dr. Berson recommends growth factors to aid in repair of the skin. Another product discussed during the skin care symposium is a regenerating skin nectar, which is a hydration lipid gel that can be used both pre and post procedure. The post procedure skin care symposium concluded with recommendations for camouflage and sun protection while the skin is undergoing repair.
Emerging Practice Models
Mark S. Nestor, MD, PhD
We have more ability than ever to care for our patients with new treatments and procedures. However, we are also faced with rising overhead, uninsured patients, policy, and the dreaded acronyms (HIPPA, MACRA, MIPS, EMRs, etc). With the rising costs of owning a small business and other issues practicing in academics, we are seeing a trend toward dermatology group practice as many are considering new practice models.
In the last 3-5 years, consolidation of practices fueled by private equity investments has begun to transform dermatology. Private equity groups are in the business of buying, growing, and selling businesses. Their goal is to provide exceptional returns on investment to their investors and themselves. The draw to dermatology includes high patient demand, skin cancer epidemic, aging population, shortage of dermatologists, cosmetic services, non-physician clinicians, and ancillary lab services.
There is concern that equity investment could lead to the commoditization of the treatment of skin disease, reduction in diversity of practice venues, loss of continued care of patients with complex conditions, a loss of autonomy, unsupervised physician extenders, and referral of dermatopathology and Mohs to the consolidated group.
Dr. Nestor believes that the correct approach is to look for the right practice model and partner that works for an individual dermatologist or group and can advance the practice of dermatology. The optimal, ethical dermatology practice is one that operates effectively and efficiently and where patient care is the primary goal. Dr. Nestor believes that patient care is enhanced when the dermatologist does not have to spend their day being burdened by compliance, regulatory, and administrative concerns.
The advantages to partnering include the monetization of your practice, an improved ability to effectively care for your patients, protection from concerns about the health of the practice, provision of capital, reduced costs of overhead due to pooled purchases, and management of billing, collections, staff, IT, and regulatory compliance.
When choosing a partner, it is important the ensure the dermatologist remains in control of patient care. The dermatologist should remain the head of the practice. Note the size of the company and their track record and research their compliance with medical regulation. Discuss life after the transaction such as services provided and what their involvement with the practice will be. The important numbers to consider are the upfront cash and stock and what you will earn (a percent of collections vs. percent of after cost profits). It is important to have competent and knowledgeable advisors who are able to help you negotiate a fair “market rate” deal. The company will almost certainly sell out; however, this should have negligible impact on day to day operation and there may be more opportunity for capital gain.
Dr. Nestor encourages dermatologists to educate yourself, ask questions, develop trusts, enlist advisors and hire an attorney. The AAD can help you evaluate practice models and learn what is best for you and your practice.
Innovations: Seborrheic Keratoses to Warts
Brian Berman, MD PhD
Recent estimates show that 83.8 million people have seborrheic keratoses. Two-thirds of those are treated with liquid nitrogen. A new topical 40% hydrogen peroxide is now FDA-approved for the treatment of seborrheic keratoses. Phase III trials have shown that targeted lesions will become clear or almost clear in 65% of patients with the most common side effect being mild erythema. Another upcoming treatment involves the use of nanosecond electro-pulses. A 60-nanosecond field can penetrate cells and organelles, creating transient nanopores, allowing calcium to enter cell and causing cellular apoptosis. Within a week, the upper epidermis sloughs off leaving a normal healthy epidermis below.
As we all know, the treatment of warts is challenging and treatments are often not efficacious. Nitric oxide is being explored as a new treatment option. As most skin cells express nitric oxide synthase, they are able to produce nitric oxide. Nitric oxide contributes to the skin protective barrier and antimicrobial defense, amongst numerous other functions. Additionally, NO is an endogenous antiviral that inhibits the replication of HPV-18. There are currently Phase II studies evaluating the safety and efficacy of a nitric oxide gel in the treatment of external genital and perianal warts. 33.3% of patients had complete clearance at week 12. While this number may seem low, it is still higher than a lot of our other current options. Even at highest concentrations, adverse events were rare, with erythema and 2 erosions reported. Lastly, ingenol mebutate was shown to clear all anogenital warts in 16/17 patients with either a 0.05% or 0.015% IM gel. Additionally, the majority cleared with a single application, which is remarkable. Adverse events included local irritation within 24-48 hours and lasting 2-5 days.
Atopic Dermatitis: Most Recent Developments and Emerging Therapeutic Options
Leon Kircik, MD
Dr. Kircik began by remarking over the unbelievable number of developments on the horizon for the treatment of atopic dermatitis, from topicals to orals to biologics.
Dupilumab, an IL-4/IL-13 inhibitor, was the first FDA-approved biologic, but there are several more on the horizon. Nemolizumab, an IL-31 receptor antagonist has shown 60% reduction in skin signs and symptoms after 12 weeks in Phase II trials. Tralokinumab is an IL-14 inhibitor that showed a 2-point reduction in IGA in Phase II studies in 20-26% of patients, depending on dose. Further down the pipeline are Tezepelumab, a human monoclonal antibody, and Lebrikizumab, an IL-13 inhibitor.
JAK Inhibitors are small oral molecules that inhibit JAK1, JAK2, JAK3, or TYK2. Some are selective, others are non-selective. Oclacitinib is selective for JAK1 and is already approved for dog atopic dermatitis, but will soon be available for humans. Baricitinib inhibits JAK1 and JAK2 and has shown 2 grade improvement in IGA in 20-25% of patients, depending on dose. Upadacitinib is a selective JAK1 inhibitor that is also being investigated for use in Crohns, RA, UC, psoriatic arthritis, and axial spondyloarthritis in addition to atopic dermatitis. It has shown improvement between 14 and 50%, depending on dose.
Topically, beyond steroids, we already have crisaborole, a non-steroidal PDE4 inhibitor. On the horizon is OPA-15406, another non-steroidal selective PDE4 inhibitor. VTP-38543 is a Liver X Receptor agonist in very early proof of concept studies. Topical tofacitinib, which did not perform well in psoriasis studies, has shown impressive clearance rates of 60% for atopic dermatitis.
Itching is the most significant symptom of atopic dermatitis. New therapies that address itch include a new antihistamine Bilastine that does not cause somnolence. Serlopitant is small highly potent NK1R antagonist that has been shown to reduce itch up to 39% and is currently entering Phase III studies. Topical doxepin, an old medication that blocks both H1 and H2 receptors, continues to be a very efficacious option to significant reduce itch.
Dr. Kircik closed by emphasizing the importance of the human microbiome. Reduction in bacterial diversity is a major contributing factor in the pathogenesis of atopic dermatitis. Dysbiosis – the imbalance of normal flora and pathogenic microorganisms – must be repaired. Prebiotics are the most promising supplements which contain nondigestable ingredients that selectively stimulate growth and/or activity of indigenous bacteria. Additionally, thermal water has gotten a lot of attention due to the selenium within it. Selenium is anti-inflammatory, anti-neoplastic, keratolytic, and help increase safe levels of gram-negative bacteria Xanthomonas, which helps to balance the high levels of gram-positive bacteria present on the skin. Finally, emollients and moisturization have always been crucial for treatment of atopic dermatitis. Toleriane double repair moisturizer is an excellent therapy that has direct proof of barrier repair by improvement of transepidermal water loss. Non-prescription but emollients are crucial and necessary to repair epidermal barrier.