Following more than a decade of dormancy, the atopic dermatitis (AD) pipeline is bursting, and Adam J. Friedman, MD, FAAD, Professor and Interim Chair of Dermatology and Residency Program Director at George Washington University (GW) in Washington, DC, talks to Practical Dermatology® about the latest developments.
What’s new in AD treatment?
Adam J. Friedman, MD: A lot. There are so many new things coming out today in terms of topicals and systemics. It was an innovation desert prior to the approval of dupilumab and crisaborole. We had nothing for roughly 12 to 13 years. Now, all of a sudden, there are new, innovative, and exciting treatments for AD, which is one of the most common skin diseases. It’s an exciting time.
What’s new with barrier repair devices?
Dr. Friedman: Barrier dysfunction is inherent in AD, even if inflammation drives a lot of this. No matter what our anti-inflammatory approach, we should always focus on utilizing topicals that in essence teach the skin how to make itself right. OTC and barrier 510k devices promote that they deliver ingredients to stimulate production of things missing in the barrier in AD. Beyond structural elements like filamentous proteins or ceramides, these can also include prebiotics that foster the diversity of the microbiome, although this has not been studied with many of the barrier repair devices. I think we will see a greater focus of products delivering microbiota fostering and stabilizing ingredients (pre- and postbiotics). An issue with some of the available prescription creams is insurance coverage; there is none for the 510Ks. One approach taken by Ortho Dermatologics is to offer cash pricing for Hylatopic Plus at pharmacies. Due to access issues, these prescription barrier products fizzled a bit. OTC moisturizers including those by Aveeno and La Roche-Posay may be just as good if used in the right way.
Let’s talk about JAK inhibitors.
Dr. Friedman: JAK inhibition is a very hot area, and there are topical and systemic JAK inhibitors in the pipeline for the treatment of AD. The data from multiple studies look very promising. They represent a novel mechanism of action and a novel active ingredient.
What about another hot area: CBD?
Dr. Friedman: CBD or cannabidiol may also play a role in treating AD. Animal studies show that CBD binding to both the Type 2-cannabinoid receptor as well as noncanabinoid receptors, like transient receptor potential cation channels (TRPVs), in the skin can both resolve inflammation and normalize epidermal turnover and maturation. Given that AD is the perfect love child of barrier dysfunction and dysregulation of the immune system, manipulation of the endocannabinoid system stands to have tremendous potential. Interestingly, we already have experience augmenting this system with palmitoylethanolamide (PEA) containing creams (think Mimyx), which potentiates the effect of CBD binding to its receptor through activation of peroxisome proliferator-activated receptors.
What else is exciting in the pipeline?
Dr. Friedman: Dermavant’s lead product candidate, tapinarof (DMVT-505), is a novel therapeutic aryl hydrocarbon receptor modulating agent (TAMA) topical cream for the treatment of plaque psoriasis and AD. Tapinarof cream was associated with significant improvement as assessed by Investigator Global Assessment in a cohort of adults and adolescents with atopic dermatitis. There are also some monoclonal antibodies targeting Interleukin (IL)-13 in the pipeline for AD. We are going to see a lot of drugs infiltrate the AD market and get approval given the burden of this disease.
And the $1M question: Will treating AD aggressively prevent comorbidities?
Dr. Friedman: That’s the hope. AD is linked to the development of asthma, allergies, and rhinitis, but it is not a linear march. These can evolve simultaneously. It’s more of an atopic jig. Studies show that in high-risk babies, we can prevent AD if we intervene early and hit them with moisturizer from the moment of birth. Inflammation over time is bad for literally everything. AD is an independent risk factor for bone fractures because these patients are not sleeping and are lethargic from scratching. AD is unique in its ability to disrupt sleep and distract at school, work, or when driving. With time we will see even more connections, even ones we never expected. We will start to see a very similar story to psoriasis. AD is an inflammatory skin disease that goes well beyond skin deep.