Topical PDE4 Inhibitors Suitable for Mild-to-Moderate Atopic Dermatitis

By Marilynn Larkin

April 04, 2019

NEW YORK (Reuters Health) - Topical phosphodiesterase 4 (PDE4) inhibitors are safe and effective for the treatment of mild-to-moderate atopic dermatitis, researchers in China have found.

Dr. Xiao-yan Luo of Chongqing Medical University and colleagues conducted a meta-analysis of double-blind randomized clinical trials with topical PDE4 inhibitors compared to placebo ointments for patients with mild-to-moderate atopic dermatitis.

As reported online March 27 in JAMA Dermatology, seven studies with a total of 1,869 patients were included. Overall, compared with control, topical application of PDE4 inhibitors was associated with a significant decrease in target lesion score (standardized mean difference, −0.40) and a higher response rate according to the investigators' assessment of clear or almost clear skin (relative risk, 1.50).

No differences were seen in treatment-related adverse events or in those that required therapy discontinuation. Subgroup analyses indicated that target lesion scores were significantly decreased after 14 and 28 days of therapy with PDE4 inhibitors, but not at days 7 or 42.

However, the beneficial effects were shown only with crisaborole (at day 14: SMD, −0.59; at day 28: SMD, −0.86) and AN2898 (at day 14: SMD, −0.76; at day 28: SMD, −0.68). There was no significant heterogeneity between studies at these time points.

Overall, the authors conclude, "topical PDE4 inhibitors represent a new option for the management of atopic dermatitis."

US dermatologists commented on crisaborole, the PDE4 inhibitor approved for atopic dermatitis by the Food and Drug Administration. Dr. Holly Kanavy, a dermatologist at Montefiore Medical Center in New York City, told Reuters by email she agrees with the study findings. "In my experience, crisaborole has been best for patients with mild disease, and for use as maintenance therapy between flares, when topical steroids are necessary. It plays a similar role to topical calcineurin inhibitors, but without the black box warning for malignancy that frightens many patients and caregivers."

"I have found it particularly effective in children, and for patients with for types V-VI skin," she noted. "I have seen less irritation and better efficacy in these subgroups."

"Patients and caregivers are motivated to incorporate the treatment into their routines," she said. "(They) are aware of the potential side effects of overuse of topical steroids and love the idea of using a treatment without steroids to control their disease."

"Some patients do experience application site burning and irritation, most frequently if they apply the medication to inflamed skin, so I always advise patients to use a topical steroid for 1-2 weeks during flares and slowly transition to crisaborole for maintenance," she said. "A small number have described worsening of their skin disease with its use."

"I have been pleasantly surprised by the ease with which my patients have been able to obtain the medication," Dr. Kanavy concluded. "Most insurances, as well as managed Medicaid programs, are covering it with a reasonable copay."

Dr. William Huang, associate professor and residency program director in the department of dermatology at Wake Forest School of Medicine in Winston-Salem, North Carolina, said in an email to Reuters Health, "In addition to gentle skin care - e.g., fragrance-free regimens, use of emollients, healthy bathing routines, avoidance of triggers, cool mist vaporizers, etc. - the use of topical medications for atopic dermatitis is a mainstay of treatment."

"These include topical corticosteroids, topical calcineurin inhibitors (pimecrolimus, tacrolimus), and most recently, topical crisaborole," he said. "Depending of the severity of the atopic dermatitis, age of the patient, location of involvement, and preference for vehicle, each of these medications is a reasonable topical option for patients."

"Although the meta-analysis suggests that topical PDE4 inhibitors are safe based on currently available data, we do not have long-term data," he noted. "As a relatively newer class of medication, the overall cost to the patient, insurance company, and medical system may potentially be higher than that of older medications."

Dr. Whitney High, Director of the Dermatology Clinic at UCHealth University of Colorado Hospital in Aurora, also has found that crisaborole is more expensive than most generic topical steroids. In addition, he told Reuters Health by email, "some people like crisaborole, some people don't. It ends up very nearly 50/50. So it makes a strong choice for certain patients and in certain areas of the body."

The authors did not respond to requests for a comment.


JAMA Dermatol 2019.