Silverberg Jonathan I, Eichenfield Lawrence F, Blauvelt Andrew, Irvine Alan D, Guttman-Yassky Emma, Langley Richard G, Warren Richard B, French Lars E, Felding Jakob, Weiss Anne, Pedersen Claus B, Jensen Morten L, Carlsson Anna, Sommer Morten O A, Kjøller Kim, Simpson Eric L
George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Departments of Dermatology, Pediatric and Adolescent Dermatology, University of California San Diego and Rady Children's Hospital San Diego, San Diego, CA, USA.
Br J Dermatol. 2025 May 19;192(6):995-1006. doi: 10.1093/bjd/ljae507.
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous skin lesions and pruritus. There is an unmet need for effective first-line systemic treatments with good safety profiles, particularly oral medications. Orismilast is a novel first-in-class oral phosphodiesterase 4 (PDE4) B/D inhibitor under investigation for the treatment of moderate-to-severe AD.
To evaluate the optimal dose, efficacy and safety of twice-daily orismilast in patients with moderate-to-severe AD.
This 16-week, multicentre randomized placebo-controlled phase IIb dose-ranging study (NCT05469464) included patients from 48 centres in Europe and the USA. Adults with moderate-to-severe AD were given (1 : 1 : 1 : 1) orismilast 20 mg, 30 mg or 40 mg, or placebo, twice daily. The primary endpoint was percentage change in Eczema Area and Severity Index (EASI); the secondary endpoints (all at week 16) included achievement of a score of clear (0) or almost clear (1) with ≥ 2-point improvement on the Investigator Global Assessment (IGA 0/1); achievement of a Peak Pruritus Numerical Rating Scale (PP-NRS) reduction of ≥ 4 points; and achievement of a reduction in EASI of 75%, 90% and 100% from baseline.
Overall, 233 patients were randomly assigned to orismilast 20 mg (n = 58), 30 mg (n = 61), 40 mg (n = 59) or placebo (n = 55). At week 16, reductions in EASI (percentage points) from baseline to week 16 were seen across orismilast groups and placebo (P > 0.05 for orismilast vs. placebo). Significantly more patients achieved IGA 0/1 with a ≥ 2-point improvement with orismilast 20 mg and 40 mg compared with placebo (P < 0.05). Significantly greater proportions of patients achieving a ≥ 4-point reduction in PP-NRS were demonstrated with orismilast at week 2. The safety profile was consistent with that of the PDE4 class, with no major safety concerns reported.
These data support the clinical relevance of selective PDE4B/D inhibition with orismilast, potentially offering a convenient, novel oral therapy for the treatment of AD.
特应性皮炎（AD）是一种慢性炎症性皮肤病，其特征为湿疹样皮肤病变和瘙痒。目前迫切需要有效且安全性良好的一线全身治疗方法，尤其是口服药物。奥瑞司他是一种新型的口服磷酸二酯酶4（PDE4）B/D抑制剂，正处于治疗中度至重度AD的研究阶段。
评估每日两次服用奥瑞司他治疗中度至重度AD患者的最佳剂量、疗效和安全性。
这项为期16周的多中心随机安慰剂对照IIb期剂量范围研究（NCT05469464）纳入了来自欧洲和美国48个中心的患者。中度至重度AD的成人患者被给予（1:1:1:1）奥瑞司他20mg、30mg或40mg，或安慰剂，每日两次。主要终点是湿疹面积和严重程度指数（EASI）的百分比变化；次要终点（均在第16周）包括在研究者整体评估（IGA 0/1）中达到清除（0）或几乎清除（1）且改善≥2分；达到瘙痒峰值数字评定量表（PP-NRS）降低≥4分；以及达到EASI较基线降低75%、90%和100%。
总体而言，233例患者被随机分配至奥瑞司他20mg组（n =
