OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study

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• 作者：Jon M. Hanifin ; MD^a ; Charles N. Ellis ; MD^b ; Ilona J. Frieden ; MD^c ; Regina Fö ; lster-Holst ; MD^d ; Linda F. Stein Gold ; MD^e ; Angelo Secci ; MD^f ; Angela J. Smith ; PA^f ; Cathy Zhao ; PhD^f ; Elena Kornyeyeva ; MD ; PhD^f ; ^{elena.kornyeyeva@otsuka-us.com" class="auth_mail" title="E-mail the corresponding author} ; Lawrence F. Eichenfield ; MD^g
• 关键词：atopic dermatitis ; atopic eczema ; OPA-15406 ; phosphodiesterase type 4 inhibitor ; topical agents ; topical calcineurin inhibitor
• 刊名：Journal of the American Academy of Dermatology
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：75
• 期：2
• 页码：297-305
• 全文大小：1004 K

文摘

Peripheral leukocytes in patients with atopic dermatitis (AD) have elevated phosphodiesterase-4 activity, which is associated with production of proinflammatory mediators. OPA-15406 is a phosphodiesterase-4 inhibitor with high selectivity for phosphodiesterase-4-B.

Objectives

We sought to assess effectiveness and tolerability of topical OPA-15406 in patients with AD.

Methods

This was a randomized, double-blind, vehicle-controlled, phase-II study. Patients 10 to 70 years of age with mild or moderate AD received topical OPA-15406 0.3% (n = 41), OPA-15406 1% (n = 43), or vehicle (n = 37) twice daily for 8 weeks.

Results

The primary end point, Investigator Global Assessment of Disease Severity score of 0 or 1 with greater than or equal to 2-grade reduction, was met at week 4 in the OPA-15406 1% group (P = .0165 vs vehicle). Mean percentage improvement from baseline Eczema Area and Severity Index score for OPA-15406 1% was notable in week 1 (31.4% vs 6.0% for vehicle; P = .0005), even larger in week 2 (39.0% vs 3.0%; P = .0001), and persisted for 8 weeks. Visual analog scale pruritus scores improved from moderate to mild within the first week in the OPA-15406 1% group (36.4% mean change; P = .0011). OPA-15406 levels in blood were negligible. Incidence of adverse events was low, with most events mild in intensity.

Limitations

Further confirmatory phase-III studies are required.

Conclusion

OPA-15406 ointment may provide an effective therapeutic modality for patients with mild to moderate AD.