Topical Therapies for Adult Atopic Dermatitis

“Medical Journeys” is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. “Medical Journeys” chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

In spite of advances in the systemic treatment of atopic dermatitis, topical therapies “remain one of the most popular options due to their effective track record and overall safety,” according to Robert Sidbury, MD, MPH.

Sidbury is professor of Pediatrics and chief of the Division of Dermatology in the Department of Pediatrics at the University of Washington School of Medicine and Seattle Children’s Hospital. He is also co-chair of the expert working group that is updating the 2014 American Academy of Dermatology (AAD) guidelines on atopic dermatitis in a series of four separate guidelines.

The second guideline was recently published in the Journal of the American Academy of Dermatology, providing 12 evidence-based recommendations for the use of prescription and non-prescription topical treatments in adults with atopic dermatitis. “Topical treatments have come a long way,” said Sidbury.

The new guideline makes strong recommendations for use of prescription corticosteroids, topical calcineurin inhibitors (TCIs), Janus kinase (JAK) inhibitors, and phosphodiesterase-4 (PDE-4) inhibitors. The document also makes conditional recommendations for the use of nonprescription topical agents such as moisturizers, bathing, and wet wraps, and against the use of topical antimicrobials, antiseptics, and antihistamines.

“These recommended treatments can be used individually or in combination with other treatments,” said the other co-chair of the AAD expert working group, Dawn M.R. Davis, MD, professor of Dermatology and Pediatrics at the Mayo Clinic in Rochester, Minnesota.

Since the 2014 guidelines, several non-steroidal options have been added to the topical therapy toolbox, and more are under investigation. The two most important additions include the PDE-4 inhibitor crisaborole 2% ointment and ruxolitinib 1.5% cream, a topical selective JAK inhibitor.

“Having more options that don’t come with a topical steroid side effect are always welcome,” said Jonathan Silverberg, MD, PhD, MPH, director of Clinical Research and Contact Dermatitis at George Washington University School of Medicine and Health Sciences in Washington, D.C., and another member of the expert working group.

While each non-steroidal option has the potential for safe long-term use without the risk of skin atrophy associated with chronic steroid use, each class of medication has a novel mechanism of action, Silverberg told MedPage Today. “That comes with theoretical concerns about adverse events that need to be addressed. In certain respects, this has added to the considerations around side effects. We have to think about each drug separately.”

Strong Recommendation: Crisaborole 2% Ointment

The guideline strongly recommends the use of crisaborole 2% ointment, which was approved in 2016 for the treatment of atopic dermatitis in infants as young as 3 months. The recommendation is based on high-certainty evidence showing a small but significant improvement in dermatitis and pruritus compared with vehicle, and a favorable safety profile compared with placebo.

A small percentage of patients reported burning, stinging, and/or pain with application, but the discontinuation rate was comparable to that of placebo. Silverberg said crisaborole provides a safe, effective non-steroidal option, particularly in younger patients who are often more vulnerable to the adverse events associated with topical steroids.

Strong Recommendation: Ruxolitinib 1.5% Cream

The use of ruxolitinib 1.5% cream, which was approved in 2021 for short-term and noncontinuous chronic treatment of mild-to-moderate atopic dermatitis in patients age 12 and older, is strongly recommended. This is based on moderate-certainty evidence of short-term efficacy and safety that will likely be updated as long-term data become available.

The phase II efficacy data suggest that topical ruxolitinib may be “the most effective of the non-steroidal topical therapies out there,” Silverberg said. Ruxolitinib also has similar or greater efficacy than a mid-potency topical corticosteroid cream, and a rapid onset of action. However, the label carries a black box warning that lists lymphoma, major adverse cardiovascular events, thrombosis, and death as potential risks.

Physicians must discuss this warning with patients, he emphasized. “In general, we don’t think that these concerns are particularly common in most patients, but the black box warning should not be ignored. It is part of the shared decision-making conversation with patients and needs to be discussed.”

“In my experience, ruxolitinib is really very well tolerated,” said Amy S. Paller, the Walter J. Hamlin Professor of Dermatology and professor of Pediatrics (Dermatology) at Northwestern University Feinberg School of Medicine in Chicago and another member of the AAD expert working group.

Strong Recommendation: Topical Calcineurin Inhibitors (TCIs)

Two TCIs were approved more than 20 years ago and represent the “oldies and goodies that remain important options for managing atopic dermatitis,” Silverberg said. The working group found high-certainty evidence to strongly recommend the use of both topical tacrolimus 0.1% and 0.03% ointments and pimecrolimus 1% cream for the treatment of mild-to-moderate disease.

The guideline authors said that although data from three randomized trials indicated that tacrolimus 0.1% was significantly more effective than pimecrolimus 1%, “pimecrolimus may be more appropriate for patients who prefer a cream vehicle, have milder disease, or may be more sensitive to local reactions.” The group also determined from safety studies showing a low absolute risk of lymphoma with TCIs that the cancer risk was “likely not clinically meaningful.”

Strong Recommendation: Topical Corticosteroids

Topical corticosteroids remain the most commonly used FDA-approved first-line treatment for mild-to-severe atopic dermatitis in all skin regions, and the new guideline strongly recommends their use based on high-certainty evidence.

“They are predictably effective,” Silverberg said. “In dermatology we have an understanding, relatively speaking, of the comparative effectiveness of different classes of topical corticosteroids.”

Despite the need for large studies to determine optimal treatment regimens with the seven potency-based classes of topical steroids, the guideline authors found overwhelming clinical evidence demonstrating their efficacy in active atopic dermatitis, whether acute or chronic.

Topical steroids are also highly effective in reducing pruritus associated with atopic dermatitis, and in preventing disease relapse.

Randomized studies of the very high potency steroids used in the treatment of severe disease and flares demonstrated that cutaneous side effects were minimal and the rates of adverse events such as skin atrophy were low. In fact, the working group reported that the prolonged and inappropriate use of potent topical steroids was the most consistent risk factor associated with topical steroid addiction and topical steroid withdrawal.

“There’s nothing wrong with topical steroids,” said Paller, adding, “There’s a lot of phobia out there that limits their use and reduces adherence.”

Topical steroids are relatively inexpensive and available in generic formulations, making them more accessible to patients. “For that reason, whether we like them or not, they’re going to a part of how we are going to be managing patients for the foreseeable future,” Silverberg said.

Conditional Recommendations Against Three Groups of Agents

The guideline conditionally recommends against the use of topical antimicrobials, topical antihistamines, and topical antiseptics for atopic dermatitis, based on low-certainty evidence.

Non-Prescription Treatments With Strong Recommendations

Among the non-prescription therapies, moisturizers — including emollients, occlusive agents, and humectants — are strongly recommended based on moderate-certainty evidence.

An analysis of five studies showed that moisturizers improved the signs, symptoms, and inflammation associated with atopic dermatitis, reduced disease severity, and increased the time between flares.

The use of moisturizers also appeared to help reduce symptoms of itch. However, there was only limited evidence to support recommendations for the use of any particular moisturizer or active ingredient, and the data were sparse on atopic dermatitis in patients of color, and on the costs associated with the use of moisturizers.

“While moisturizing is generally superior to lack of moisturizing, the vehicle in emollient studies is often as effective as the vehicle plus active ingredient,” the guideline authors noted, adding that most studies of emollients did not examine the use of moisturizers in patients with actively inflamed skin.

The guideline conditionally recommends the use of bathing, followed by moisturization. Since most studies have been conducted in children, however, a standard for the frequency and duration of bathing, water temperature, or the use of bleach in adults with atopic dermatitis could not be established.

Conversely, there was evidence that wet wrap therapy is an effective option to control flares and reduce recalcitrant disease. “In addition to providing a physical barrier against scratching, wet wrap therapy exerts its effects via occlusion of the topical agent, resulting in greater penetration and reduced water loss/greater hydration,” the guideline explained.

Read previous installments in this series:

Part 1: Atopic Dermatitis: Reasons for Optimism

Part 2: Atopic Dermatitis: The Latest on Diagnosis and Assessment

Part 3: The Many Ways to Measure the Severity of Atopic Dermatitis

Part 4: Case Study: Why Is This Young Boy’s Atopic Dermatitis So Resistant to Treatment?

Part 5: Atopic Dermatitis Has Myriad Life-Altering Comorbidities