WAIKOLOA, HAWAII – Fresh approaches for treating atopic dermatitis are sorely needed, and several intriguing novel therapies are under study, according to Dr. Wynnis Tom.
While topical corticosteroids continue to be the mainstay for control of the inflammation in atopic dermatitis, many patients and families have serious reservations about these medications. Patient concerns persist although, as emphasized in the updated 2014 American Academy of Dermatology guidelines for the management of atopic dermatitis (J. Am. Acad. Dermatol. 2014;70:338-51), these drugs have an excellent risk/benefit ratio when used appropriately.
Dr. Wynnis Tom
It’s because of this widespread "steroid phobia" that AN2728 2% ointment is of particular interest, said Dr. Tom, a pediatric dermatologist at Rady Children’s Hospital and the University of California, San Diego.
AN2728 is a boron-based topical phosphodiesterase-4 inhibitor. The boron, she explained, provides added anti-inflammatory effects.
A recent phase I/II open-label, multicenter study involved 34 patients aged 2-17 years with mild to moderate atopic dermatitis and a 25%-35% body surface area of involvement. In this study, twice-daily application of AN2728 for 28 days resulted in 47% of participants achieving "clear" or "almost clear" on investigators’ global assessment, with at least a two-grade improvement from baseline. The affected body surface area plummeted by an average of 78%, while erythema, excoriations, and other symptoms also improved. Only one patient stopped therapy early.
A phase III trial is now in place. The big question relevant to clinical practice is, how does this agent compare in safety and efficacy to topical steroids and topical calcineurin inhibitors?
"We don’t know yet, but it’s nice to see there may be another class of anti-inflammatory agents we may be able to use, especially for those who are worried about topical steroids," Dr. Tom said at the SDEF Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.
For the minority of cases of atopic dermatitis that are more severe – and refractory to topical therapies – new agents in clinical trials include the oral phosphodiesterase-4 inhibitor apremilast and dupilumab, a monoclonal antibody that binds to the alpha subunit of the interleukin-4 receptor. Dupilumab, the first biologic agent to undergo evaluation for atopic dermatitis in a formal clinical trial, is now in a phase IIb trial involving adults with moderate to severe disease. Dupilumab is also under study for the treatment of other atopic diseases, including asthma.
Apremilast has been investigated in an open-label, prospective pilot study conducted by dermatologists at Oregon Health and Science University, Portland. The study included 16 adults with moderate to severe atopic dermatitis treated with oral apremilast at 20 or 30 mg b.i.d. for up to 6 months. Participants showed significant improvement on the Eczema Area and Severity Index, the Dermatology Life Quality Index, and other measures (Arch. Dermatol. 2012;148:890-7). Apremilast is approved as Otezla for the treatment of adults with psoriatic arthritis and is under study for other chronic inflammatory diseases, including rheumatoid arthritis and ankylosing spondylitis.
Although to date apremilast and dupilumab have been studied only in adults with atopic dermatitis, dermatologists who treat severely affected children are following the results with interest, because at present their main therapeutic options are heavy-hitting immunosuppressants, Dr. Tom noted.
She reported serving without financial compensation as an investigator for studies funded by Amgen and Anacor, which is developing AN2728 2% ointment. Dr. Tom was a member of the working group responsible for the 2014 AAD guidelines on atopic dermatitis.
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