Difamilast Ointment Safe, Efficacious for Pediatric Atopic Dermatitis

The selective topical PDE4 inhibitor demonstrated rapid improvements in IGA and EASI scores and high tolerability in pediatric populations.

New findings support the efficacy of difamilast 0.3% and 1% ointments in managing pediatric atopic dermatitis.

The phase 3, randomized, double-blind study was conducted by Hidesha Saeki, MD, of Nippon Medical School, and colleagues in Japan. The investigators compared the selective topical PDE4 inhibitor against a vehicle in terms of improvements in Investigator’s Global Assessment (IGA) score.

“In Japan, topical corticosteroids (TCSs) and the topical calcineurin inhibitor (TCI), tacrolimus ointment, are mainly used to shorten and suppress inflammation caused by AD,” they wrote. 

“Although effective, both TCSs and TCIs are limited by several issues including safety concerns and local side effects. As a result, there is a need for new topical therapies for AD which can overcome the limitations of existing therapies.”

In previous Phase 2 trials from both the Unites States and Japan, difamilast demonstrated a highly promising efficacy and safety profile in pediatric and adult patients.

The Study

Saeki and colleagues screened patients between the ages of 2 – 14 years old, thus enrolling a total of 251 participants.

Following assessment at baseline, enrollees were then randomized 1:1:1 to difamilast 0.3%, difamilast 1%, or vehicle for a total of 4 weeks. Treatment was self-administered twice daily, with roughly 12 hours between applications. 

All patients presented with atopic dermatitis, as diagnosed according to the Japanese Dermatological Association’s criteria, affecting ≥5% to ≤ 40% of body surface area (BSA), excluding the scalp. As many as 67.7% had moderate severity, 10.0% had mild severity, and 22.3% had high severity.

Further, 15.5% of patients had an IGA score of 2, while 84.5% had a score of 3.

The Results

“For the primary endpoint, success rates in IGA score at week 4 were 44.6%, 47.1%, and 18.1% in the difamilast 0.3%, the difamilast 1%, and the vehicle groups, respectively,” Saeki’s team reported

“Significant differences at week 4 were observed between difamilast 0.3% and vehicle (24.7%; 95% CI, 11.3– 38.0; P = .0005), and between difamilast 1% and vehicle (28.7%; 95% CI, 15.0–42·5; P<.0001).”

Both difamilast groups demonstrated highly significant rates of improvements in IGA compared to vehicle as early as weeks 1 and 2.

The investigators also reported that 43.4% of difamilast 0.3% patients, 57.7% of difamilast 1% patients, and 18.1% of vehicle patients achieved EASI 75 at week 4, a secondary endpoint sought by the investigators.

The difference in success rate between difamilast 0.3% and vehicle was considered significant (23.9%; 95% CI, 10.6–37.3; P = .0007)—as was the difference between difamilast 1% and vehicle (38.9%; 95% CI, 25.5–52.3; P<.0001).

Significant reductions in EASI score were observed as early as week 1 and maintained through week 4, with differences between the difamilast and vehicle cohorts similarly maintained through the study period.

As for safety profile, most of the treatment-emergent adverse events—which had an occurrence rate of 32.5% and 34.1% in the difamilast 0.3% and 1% groups, respectively, and 33.7% in the vehicle group—were considered mild or moderate. There were no observed serious events or deaths.

The most common events were nasopharyngitis, followed by impetigo and dermatitis atopic.

“Although the results of ongoing and additional studies are anticipated, difamilast appears to show potential as a new treatment option for paediatric patients with AD with high and rapid efficacy, and a favourable tolerability profile,” the investigators wrote.

The study, “Difamilast ointment, a selective phosphodiesterase 4 inhibitor, in paediatric patients with atopic dermatitis: A phase 3 randomised double-blind, vehicle-controlled trial,” was published online in British Journal of Dermatology.