罗氟司特 0.3% 乳膏：用于治疗慢性斑块状银屑病的磷酸二酯酶 4 抑制剂。

Massachusetts College of Pharmacy and Health Sciences, School of Pharmacy, Worcester, MA.

Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania; and.

Am J Ther. 2023;30(6):e535-e542. doi: 10.1097/MJT.0000000000001678.

BACKGROUND

Plaque psoriasis is a chronic dermatologic autoimmune disease that affects adults and children. Roflumilast 0.3% cream is currently the only topical phosphodiesterase 4 inhibitor indicated for the treatment of plaque psoriasis in patients 12 years or older.

PHARMACODYNAMICS AND PHARMACOKINETICS

Roflumilast inhibits phosphodiesterase 4 inhibitor enzyme leading to the accumulation of cyclic adenosine monophosphate, which suppresses the inflammatory mediators interferon-γ and tumor necrosis factor-α. Roflumilast, applied once daily, reaches steady state by day 15 and has a half life of approximately 4 days in adults. Roflumilast undergoes extensive hepatic metabolism by cytochrome P450 enzymes and conjugation. Roflumilast is 99% bound to plasma proteins.

CLINICAL TRIALS

Roflumilast efficacy and safety were evaluated in the DERMIS-1 and DERMIS-2 clinical trials. These identically designed, double-blind, vehicle-controlled phase 3 trials randomized 881 patients to roflumilast 0.3% cream or vehicle, applied once daily for 8 weeks. In DERMIS-1, the Investigator Global Assessment success rate was 42.4% with roflumilast 0.3% cream compared with 6.1% with the vehicle (32.3%-46.9%; P <0.001). Similarly, in DERMIS-2, the Investigator Global Assessment success rate was 37.5% with roflumilast 0.3% cream compared with 6.9% with the vehicle (20.8%-36.9%; P <0.001). Of 881 participants, 1% discontinued treatment with roflumilast cream due to adverse reactions compared with 1.3% treated with vehicle. Urticaria at the application site (0.3%) was the most common adverse reaction that led to discontinuation of roflumilast.

THERAPEUTIC ADVANCE

To date, topical corticosteroids are the most commonly used agents to treat mild plaque psoriasis. Sensitive areas are often challenging to treat with existing topical therapy, including corticosteroids. Topical roflumilast has shown to be effective in treating sensitive areas, including skin folds, and may be an alternative to systemic therapy for some patients. The Food and Drug Administration approved topical roflumilast for the treatment of plaque psoriasis, including intertriginous areas, for patients 12 years or older.

背景

斑块状银屑病是一种影响成人和儿童的慢性皮肤病。罗氟司特 0.3%乳膏是目前唯一被批准用于治疗 12 岁及以上斑块状银屑病患者的局部磷酸二酯酶 4 抑制剂。

药效学和药代动力学

罗氟司特抑制磷酸二酯酶 4 抑制剂酶，导致环腺苷单磷酸积累，从而抑制炎症介质干扰素-γ和肿瘤坏死因子-α。罗氟司特每天应用一次，在第 15 天达到稳态，成人的半衰期约为 4 天。罗氟司特主要通过细胞色素 P450 酶和结合进行广泛的肝代谢。罗氟司特与血浆蛋白的结合率为 99%。

临床试验

在 DERMIS-1 和 DERMIS-2 临床试验中评估了罗氟司特的疗效和安全性。这两项设计相同、双盲、安慰剂对照的 3 期临床试验将 881 例患者随机分为罗氟司特 0.3%乳膏或安慰剂组，每天一次应用 8 周。在 DERMIS-1 中，罗氟司特 0.3%乳膏的研究者全球评估成功率为 42.4%，而安慰剂组为 6.1%（32.3%-46.9%；P<0.001）。同样，在 DERMIS-2 中，罗氟司特 0.3%乳膏的研究者全球评估成功率为 37.5%，而安慰剂组为 6.9%（20.8%-36.9%；P<0.001）。在 881 名参与者中，因不良反应而停用罗氟司特乳膏的比例为 1%，而安慰剂组为 1.3%。应用部位荨麻疹（0.3%）是最常见的导致罗氟司特停药的不良反应。

治疗进展

迄今为止，局部皮质类固醇是治疗轻度斑块状银屑病最常用的药物。对于现有的局部治疗，包括皮质类固醇，敏感区域往往难以治疗。局部罗氟司特已被证明在治疗敏感区域（包括皮肤褶皱）方面有效，对于一些患者可能是全身治疗的替代方案。美国食品和药物管理局批准局部罗氟司特用于治疗 12 岁及以上斑块状银屑病，包括间擦部位。