Nonsteroidal Topical Treatments for Eczema: A Product Snapshot with Mona Shahriari, MD

The well-known limitations of topical corticosteroids for treatment of atopic dermatitis (AD), or eczema, include skin atrophy, skin barrier disruption, rebound flares, and tachyphylaxis, the last of which may require an increase in potency or switching to an alternative treatment. While the topical steroids can be effective for short-term management of acute eczema flares, they may not provide adequate long-term control for the chronic relapsing skin disease.

In addition, it is not uncommon for patients, and particularly those with children, to be hesitant about using topical steroids based on the potential for adverse events. This “corticosteroid phobia” is associated with poor treatment adherence and poor disease outcomes.

In a recent interview with Patient Care, dermatologist and clinical researcher Mona Shahriari, MD, described the drawbacks mentioned here and then spoke in detail about the new and rapidly evolving group of nonsteroidal topical treatments that she says need to be in every primary care clinician’s dermatologic toolbox.

Shahriari is assistant clinical professor of dermatology at Yale University School of Medicine in New Haven, Connecticut and co-founder of Central Connecticut Dermatology in Cromwell, Connecticut.

The following transcript of the interview has been lightly edited for clarity and length.

Patient Care. Would you talk about the evolving group of nonsteroidal topical treatments for eczema including how their mechanism of action differs from the topical corticosteroids?

Mona Shahriari, MD. The first FDA-approved topical nonsteroidal is ruxolitinib, a twice-daily topical Janus kinase (JAK) inhibitor indicated for mild to moderate AD in patients aged 12 years and older. In clinical trials, ruxolitinib demonstrated rapid itch control, and in some studies participants had improvement as quickly as 15 minutes after application. When we compared it with the mid-potency topical steroid triamcinolone, ruxolitinib was noninferior for skin clearance, and numerically more patients experienced itch improvement at 4 weeks. That was a very good outcome given the comparison with the gold standard topical steroid, too. From a safety standpoint, ruxolitinib does carry boxed warnings for mortality, malignancy, serious infections, blood clots, and major adverse cardiovascular events, and I always discuss these with patients because I don’t want them to search online and be frightened into stopping the treatment. Also, these safety signals have not been borne out in clinical trials. We also have maximal use studies that found no additional safety concerns when more than 20% body surface area was treated with a JAK inhibitor. But, that is also not likely going to happen in clinical practice because if a patient has eczema over 20% of the body, a topical treatment alone is not going to help that patient and it’s time to consider a systemic agent.

The next novel topical is the phosphodiesterase-4 (PDE4) inhibitor roflumilast, recently FDA-approved for mild to severe AD in patients 6 years and older. I like to say this is not your grandmother’s PDE4 inhibitor. It has 300 times the binding affinity for PDE4 compared to previous formulations. Roflumilast is the first once-daily, steroid-free topical cream for AD and is formulated with unique hydro-arc technology and a proprietary emulsifier that is actually used in popular cosmetic products. The combination creates a highly moisturizing, elegant, non-greasy cream. It spreads easily on the skin and is absorbed quickly. It has none of the irritants that can disrupt the patient’s skin barrier. I do counsel my patients on the adverse effects like headache, diarrhea, and vomiting that were observed in less than 3% of clinical trial participants, but the discontinuation rate in those trials due to adverse events was less than 2%. We also have safety data from roflumilast's use in different strengths and formulations for plaque psoriasis and seborrheic dermatitis that is similar to what we have seen in atopic dermatitis, so that is helpful to share with patients, too.

And, finally, the topical aryl hydrocarbon receptor agonist tapinarof, 1% cream is awaiting FDA approval for mild to severe AD in patients 2 years and older. And that is something I am looking forward to because I struggle with my youngest patients to use something other than a topical corticosteroid. Tapinarof has a really unique mechanism of action. The aryl hydrocarbon receptor is a ligand-dependent receptor so depending on what it is bound to, different cytokines will be signaling. When tapinarof binds the hydrocarbon receptor, we see a reduction in the cytokines that drive the type 2 inflammatory response and an enhancement of skin barrier proteins. In the clinical trials tapinarof demonstrated effective control of AD signs and symptoms, including itch. In terms of the safety profile, most of the adverse events were deemed mild-to-moderate and they included folliculitis, acne, and headache. Again, the discontinuation rates due to the adverse events drug were low. As with roflumilast, we have safety data on tapinarof in another disease state since it was approved with an indication for plaque psoriasis 2 years ago. No new safety signals have been reported.

PC. Is there still a place for topical corticosteroids in the dermatologic toolbox?

Shariari: Yes. Remember that AD is highly heterogenous and so there may be individuals for whom the new nonsteroidal topical agents are not effective or who can’t tolerate them. We still need steroids n our dermatologic armamentarium. In my own practice, though, they are a second- or third-line option for many of the reasons we have discussed. I strongly believe that the risks that we are now aware of with topical corticosteroids outweigh the benefits as a first line agent; We have better options that we can shift into that first line position.