Developments in management for atopic dermatitis

Wailea, HI -- The investigational pipeline is flowing with new treatments for atopic dermatitis (AD). However, because topical corticosteroids remain the therapeutic mainstay, clinicians should be mindful that steroid phobia is a prominent problem undermining treatment success, says Lawrence F. Eichenfield, M.D., rofessor of pediatrics and dermatology, University of California, San Diego and Rady Children’s Hospital.

Dr. Eichenfield discussed these topics and other new information relevant to the management of AD during a presentation earlier this year at the MauiDerm 2014 meeting.

“Since the FDA implemented the boxed warning for topical calcineurin inhibitors (TCIs), we have been waiting for new topical therapies for AD. Several nonsteroidal agents are now in development,” Dr. Eichenfield says.

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“In addition, it is an exciting time because we can anticipate new systemic medications to help manage patients with moderate to severe disease.”

AN2728 (Anacor) is being developed as a topical treatment of AD. It is a boron-based, phosphodiesterase inhibitor that inhibits a variety of pro-inflammatory cytokines implicated in AD pathogenesis. Phase 2 studies have been completed, including one open-label pharmacokinetic study in pediatric patients.

The data from the AN2728 studies have not yet been published in the peer-reviewed literature, but as reported in presentations at scientific meetings, the safety, tolerability, and efficacy results are favorable. The pediatric study enrolled children ages 2 to 11 years old with at least 35 percent body surface area (BSA) involvement and 12 to 17 year olds with a minimum BSA involvement of 25 percent. After 28 days of BID application, about 60 percent of patients achieved clear to almost clear status in the investigator’s global assessment.

“This is a pretty successful outcome, although the data must be considered in the context that they have not been subjected to peer-review and are from an open-label trial,” Dr. Eichenfield says.

The therapeutic pipeline for dermatology also holds some biologic agents that are being specifically developed for AD, albeit the studies conducted so far have been in adults only.

Dupilumab (Regeneron) is one of these biologic agents. It is a monoclonal antibody targeting interleukin-4 receptorα (IL-4Rα) that inhibits both IL-4 and IL-13.

Results from dupilumab studies have also been presented at scientific meetings only. Data from a Phase 1B dose-ranging study supported its biological activity. The highest dose tested was paired with topical corticosteroid treatment in a second trial in which controls received topical treatment and placebo injection. All patients receiving combination therapy were EASI-50 responders, and they achieved that outcome using less topical corticosteroid than the controls.

“Safety data for dupilumab are very limited to date, but so far showed nasopharyngitis and headache were the most common adverse events. Phase 3 studies are now underway,” Dr. Eichenfield says.

Next: Confronting steroid phobia

Confronting steroid phobia

Fear of potential side effects with use of topical corticosteroids is a common cause of non-adherence, thus hampering treatment success. Currently, Dr. Eichenfield and colleagues are undertaking a blinded study evaluating the potential value of an educational intervention targeting steroid phobia. In the meantime, clinicians should consider that it is important to address this issue early on. To minimize problems with underuse, he recommended estimating the amount of topical agent that will need to be used until the next visit, prescribing that quantity, and instructing the family to use the entire amount.

“Information seen online or supplied by the pharmacy may recommend that topical steroids be applied sparingly. We need to circumvent underuse that will not be effective and prevent families from understanding that with proper treatment, AD can be controlled,” Dr. Eichenfield says.

Families are also advised that once the AD is under control, the frequency of topical corticosteroid use can be reduced to just twice a week. This regimen for a midpotency or lower corticosteroid greatly minimizes the risk of adrenal axis suppression.

Scheduling frequent follow-up visits can also be helpful for achieving compliance based on data showing that patients are most likely to use their medications as directed for short periods immediately after and before a scheduled visit.

Other developments

The multiyear process of developing new American Academy of Dermatology guidelines of care for the management of AD is nearly complete. The information is being published in four installments, the first paper of which focused on diagnosis and assessment and was published last year [J Am Acad Dermatol. 2014;70(2):338-351]. The next three papers will be related to the use of topical therapies, systemic therapies, and the prevention of flares/use of adjunctive therapies.

“Various guideline statements on the use of topical corticosteroids and TCIs should be particularly helpful for getting patient access to medications that has sometimes been difficult because of restrictions from managed care,” Dr. Eichenfield says.

Looking ahead, Dr. Eichenfield noted that data will be forthcoming from ongoing research investigating whether early skin care intervention to enhance the skin barrier might prevent AD development. There is also interest in the potential effects of climate and the microflora of the skin and gut on AD development, although the answers are still pending. In addition, there are a number of trials underway investigating hypochlorite-based products for management of patients with AD along with some interesting new information from preclinical research indicating that hypochlorite may have anti-inflammatory activity and affect skin aging via effects on nuclear factor-κB.

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