What’s New and Hot in Atopic Dermatitis
VIDEO Highlight: What's New and Hot in Atopic Dermatitis - YouTube
In this session, Emma Guttman-Yassky, M.D., Ph.D. explored new therapies in the pipeline for atopic dermatitis (AD) beginning with dupilumab, an IL-4Ra inhibitor that was recently approved for ages 6 months to 5 years. In phase 3 trials, 53% of children treated with dupilumab achieved EASI75 at week 16 compared with just 11% of those treated with placebo. The safety profile of dupilumab in children appears similar to that in adults with no new safety signals. Interleukin-13 inhibition alone has also been shown to be effective in the treatment of AD. Two IL-13 inhibitors, lebrikizumab (currently in development) and tralokinumab (recently FDA approved), have been shown to be safe and efficacious in long term clinical studies.
Dr. Guttman-Yassky introduced a new target in atopic dermatitis, OX40—a molecule expressed by activated T cells. KHK4083 is a fully human anti-OX40 monoclonal antibody currently under investigation for the treatment of AD. Phase 2 trials of KHK4083 showed significantly higher proportions of EASI75 responders at week 16 in all dosage cohorts versus placebo with durable response for another 20 weeks after discontinuation, suggesting the potential for disease modification with KHK4083.
To conclude this session, Dr. Guttman-Yassky highlighted the efficacy and safety data of upadacitinib and abrocitinib, two oral janus kinase (JAK)-1 inhibitors recently approved for the treatment of atopic dermatitis. Both medications demonstrated higher efficacy in clinical trials than currently approved biologic medications, but their use may be limited in some groups due to the riskier side effect profile. It is an exciting time to be treating atopic dermatitis as the therapeutic drought in AD is finally ending!
Validating Genomics for Melanoma Prognosis: Critical New Studies
VIDEO Highlight: (1) Validating Genomics for Melanoma Prognosis: Critical New Studies - YouTube
The annual number of Americans who die from melanoma has been increasing over the last few years, highlighting the need for improved prognostic information for patients diagnosed with melanoma. In this session, Clay Cockerell, M.D., MBA and Darrell S. Rigel, M.D., MS reviewed the latest data on using genomics to aid in melanoma prognostication. Current guidelines utilize the AJCC version 8 staging system to determine which patients are high risk, needing sentinel lymph node biopsy (SLNB), imaging, and/or systemic therapies. However, most melanoma deaths occur in patients initially diagnosed with localized disease and AJCC staging often does not identify high risk patients with stage I-II melanoma.
Dr. Cockerell reviewed the 31-gene expression profile test, which quantifies expression of 31 genes and uses a validated algorithm to more accurately predict the individual risk of recurrence or metastasis for patients with stage I-III cutaneous melanoma. A recent meta-analysis of 1,479 patients showed that the 31-GEP test yields excellent risk stratification, consistent with previously published studies. Dr. Cockerell concluded his portion of the talk by reviewing a large, prospective cohort study using the SEER database to compare prognosis and survival for patients with melanoma tested with 31-GEP to those not tested. This cohort study also confirmed the ability of 31-GEP to risk stratify patients and revealed that patients tested with 31-GEP had a 21% benefit in overall survival at 3 years over those not tested.
Dr. Rigel continued highlighting the ability of the 31-GEP test to aid in determining which patients should receive a SLNBx. Retrospective studies have shown that clinicopathologic predictors of SLNBx positivity include younger age, Breslow depth > 0.8mm, mitoses, and ulceration. Guidelines currently recommend that SLNBx be considered for patients with greater than 5% risk of positivity. The 31-GEP test has been integrated with the above clinicopathologic risk factors in a validated AI-driven algorithm to provide individual SLNBx positivity risk (i31-GEP). Compared to other online models, the integrated 31-GEP test was shown to be more precise and accurate in determining positivity risk. In one study of T1a-high risk melanoma patients, for whom SLNBx guidelines are not definitive, the i31-GEP test re-classified 49.6% of patients into the <5% positivity risk group, highlighting the ability of this test to reduce the number of avoidable SLNBxs performed.
Dr. Rigel concluded this important session with a few words on how the 31-GEP score can also be integrated with clinicopathologic characteristics to determine individual risk of recurrence, helping guide management decisions after SLNBx. The 31-GEP suite of testing has proven to be reliable for risk stratification and provide added benefit for management decisions in patients with cutaneous melanoma.
What’s New and Hot in Topical Therapy
VIDEO Highlight: What's New and Hot in Topical Therapy - YouTube
Topical medications are the backbone of therapy in dermatologic disease, and in this exciting session, Linda Stein Gold, M.D. discussed best practices for topical treatments. When treating psoriasis, combination therapy is generally better than one single therapy alone. Phase 3 studies of halobetasol propionate + tazarotene lotion show significantly higher rates of clear or almost clear skin at week 8 versus vehicle with good tolerability. Dr. Stein Gold transitioned to discuss a new formulation of calcipotriene and betamethasone which utilizes PAD™ technology to suspend both active ingredients in oil droplets and deliver both to the skin in an elegant vehicle. This new formulation demonstrates superior efficacy for treatment of psoriasis over traditional calcipotriene-betamethasone suspensions. Dr. Stein Gold also emphasized the importance of proactive treatment to prevent the number and severity of flares. One study showed that proactive twice weekly calcipotriene 0.005%-betamethasone dipropionate 0.064% foam led to a 43% reduction in the risk of psoriasis relapse and provided 41 extra days in remission compared to reactive treatment.
Dr. Stein Gold moved on to discuss new topicals recently FDA approved including ruxolitinib and tapinarof. Ruxolitinib, a topical JAK-1/JAK-2 inhibitor, was recently approved for the treatment of atopic dermatitis. Phase 3 studies of ruxolitinib 2.5% cream BID show roughly 50% IGA success rates with minimal side effects and rapid reduction in itch as early as week 1. Dr. Stein Gold reminded listeners not to use ruxolitinib on more than 20% BSA or continuously for extended periods of time. Tapinarof is a first-in-class topical aryl hydrocarbon receptor modulator recently FDA approved for the treatment of psoriasis. Up to 40% of patients achieved clear or almost clear skin at week 12 compared to 6% of vehicle treated patients in the phase 3 clinical trials. Tapinarof cream was well-tolerated, with application site folliculitis being the most common side effect. Long term maintenance studies indicate that tapinarof may have a remittive effect, with patients being able to maintain clear or almost clear skin for a median of 115 days off-treatment. Tapinarof is also being studied for the treatment of atopic dermatitis.
Dr. Stein Gold concluded with a discussion of roflumilast cream 0.3%, a potent topical PDE-4 inhibitor recently approved for the treatment of plaque psoriasis. In phase 3 studies, 37-42% achieved clear or almost clear skin at week 8 compared to 6% of those treated with vehicle. Roflumilast also showed high rates of clearance for intertriginous psoriasis plaques as well as rapid itch response starting at week 2. Roflumilast was well-tolerated in studies with low rates of application site reactions. Roflumilast is also being studied in a 0.3% foam formulation for scalp and body psoriasis as well as seborrheic dermatitis.
What’s New and Hot in Pediatric Dermatology
VIDEO Highlight: (1) What's New and Hot in Pediatric Dermatology - YouTube
Lisa Swanson, M.D. kicked off this session with new pearls for one of the most common pediatric dermatologic conditions—atopic dermatitis. A decades-old topical regimen of compounded betamethasone valerate, mupirocin, and vanicream was recently brought back into relevance and can work well for persistent facial eczema in babies and toddlers. One hot button issue in the atopic dermatitis world is the potential association between AD and increased neuropsychiatric co-morbidities. Dr. Swanson discussed how elevated IL-4 levels have been linked to developmental delay in mouse-models and the possible preventative role of dupilumab (an IL-4Ra inhibitor) in this setting.
Dr. Swanson continued the discussion by highlighting which biologic agents are approved for pediatric psoriasis and how to screen for irritable bowel disease when considering the use of IL-17 inhibitors in children. Moving on to common lumps and bumps in children, Dr. Swanson gave great tips on using WartPeel™ for warts on and off the face and discussed new treatments on the horizon for molluscum. Hair loss was the next topic of focus, with Dr. Swanson discussing low-dose oral minoxidil, pulse prednisone, and baricitinib for alopecia areata as well as mentioning a recent consensus opinion that routine blood tests and screening labs are not needed in otherwise healthy children with AA.
This session concluded with some quick tips on common pediatric disorders including how to distinguish between yeast and irritant contact diaper dermatitis, topical timolol for pyogenic granulomas, dermoscopic features of spitz nevi, and how to appropriately manage tinea facei. Audience members left this talk with many excellent additions to their pediatric dermatology toolbox from Dr. Swanson!
Friday AM POTD: Efficacy and Safety of Ruxolitinib Cream in Adolescent Patients With Vitiligo: Pooled Analysis of the 52-Week TRuE-V Phase 3 Studies
Ruxolitinib 1.5% is a topical janus kinase (JAK)1/JAK2 inhibitor in a cream formulation that was recently approved for nonsegmental vitiligo in adults and adolescents 12 years of age and older. This poster presents pooled efficacy and safety data for adolescent patients aged 12-17 years from the pivotal phase 3 trials of ruxolitinib cream. Seventy-two adolescent patients were included in the analysis (ruxolitinib cream, n=55; vehicle, n=17). At week 24, 32.1% of patients treated with ruxolitinib cream achieved a 75% improvement in facial VASI scores compared with 0% of vehicle treated patients, with efficacy rates improving through week 52. Overall, efficacy results in adolescents were similar to those in the adult population. Ruxolitinib cream was well-tolerated in the adolescent population with no serious adverse events related to treatment.
What’s New and Hot in Melanoma
VIDEO Highlight: (1) What's New and Hot in Melanoma - YouTube
Melanoma is always a hot topic, and in this highly anticipated session, Laura K. Ferris, M.D., Ph.D. provided the audience with and overview of the latest developments in melanoma treatment. Immune checkpoint therapy has become a cornerstone of melanoma treatmenpet, and Dr. Ferris began the discussion by highlighting a new therapeutic target: lymphocyte activation gene 3 (LAG-3). LAG-3, found on the surface of T cells, normally binds to MHC II on tumor cells to inhibit downstream signaling of the T-cell receptor. Relatlimab is a human anti-LAG-3 antibody which blocks the interaction of LAG-3 and MHC II. Combination relatlimab + nivolumab therapy led to a median progression-free survival of 10.12 months, compared with just 4.63 months in the nivolumab monotherapy group in patients with unresectable or metastatic melanoma.
Pembrolizumab is now FDA approved for the adjuvant treatment of adult and adolescent patients with stage IIB or IIC melanoma following complete resection after phase 3 clinical trials showed improved recurrence free survival versus placebo. For patients with resectable stage IIIB or stage IV melanoma, neoadjuvant pembrolizumab led to a statistically significant improvement in event-free survival compared to resection followed by adjuvant pembrolizumab. Pivoting to intralesional therapy, Dr. Ferris highlighted results from a phase 2 study of talimogene laherparepvec (T-VEC) neoadjuvant treatment plus surgery versus immediate surgery in patients with resectable stage IIIB or IV melanoma. Statistically significant improvements in 5 year overall survival, recurrence-free survival, and event-free survival were seen in the neoadjuvant T-VEC group compared to the surgery alone group.
Finally, Dr. Ferris presented data from two studies which showed that for BRAF mutation-positive metastatic melanoma, initial treatment with immunotherapy until disease progression followed by MEK/BRAF targeted therapy leads to statistically significant improvement in overall survival and progression-free survival when compared to initial MEK/BRAF targeted therapy followed by immunotherapy.
What’s New and Hot in Aesthetics
VIDEO Highlight: (1) What's New and Hot in Aesthetics - YouTube
In this session, Dee Anna Glaser, M.D. provided the audience with the latest updates from the field of aesthetics. Exosomes are a class of small, cell-derived extracellular vesicles containing cell contents such as proteins, lipids, mRNA, or DNA. Our bodies contain thousands of exosomes, which are thought to have a potential therapeutic role in fighting cellular senescence. Exosomes can be derived from plants, stem cells, and platelets. A recent study found that 6 weeks of topical platelet exosomes for facial rejuvenation led to a statistically significant increase in skin health score, a decrease in redness and brown spot fractional area, and an increase in luminosity and color evenness.
Moving on from exosomes, Dr. Glaser continued the discussion with a review of the FDA-approved botulinum toxins, including the newly approved daxibotulinumtoxin. DaxibotulinumtoxinA is a 150 kilodalton protein supplied at a concentration of 40u/0.18 ng that is stored at room temperature. Numerous other botulinum toxins are currently in development, such as letibotulinumtoxinA. In phase 3 trials, letibotulinumtoxinA met its primary endpoint and was well-tolerated with no treatment related severe adverse events. RelabotulinumtoxinA is another novel toxin in development. It is being developed in a complex-free, liquid formulation to eliminate errors of and time for reconstitution. To conclude this session, Dr. Glaser briefly reviewed a new, recently approved resilient hyaluronic acid filler for the correction of moderate-to-severe dynamic perioral rhytides.
Friday PM POTD: Non-Invasive Genomic Profiling of Pigmented Lesions – an Interim Registry Analysis
The DermTech Melanoma Test is a non-invasive gene-expression test designed to rule-out melanoma, with greater than 99% negative predictive value in previous studies, using detection of two genomic markers associated with melanoma plus one promoter mutation. This poster presents results from a registry study examining the real-world correlation of genomically atypical lesions with histopathologic diagnoses. Of the 997 lesions with genomic atypia (positive test) that had histopathologic diagnoses, 134 (13.4%) were diagnosed as melanoma and 73 (7.3%) exhibited severe cytologic atypia, indicating that the DermTech Melanoma Test guides appropriate biopsy decisions in real-world settings.