University Institute of Pharmaceutical Sciences-UGC Center of Advanced Studies, Panjab University, Chandigarh, India.
Department of Dermatology, and Venereology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
JAMA Dermatol. 2016 Jul 1;152(7):807-15. doi: 10.1001/jamadermatol.2016.0859.
Attempts to use topical cyclosporine in treatment of psoriasis have failed because of unfavorable physicochemical properties and inappropriate formulation design of the conventional dosage forms.
To evaluate the efficacy of topical cyclosporine using liposomal nanocarriers (lipogel) in limited chronic plaque psoriasis.
DESIGN, SETTING, AND, PARTICIPANTS: A single-center randomized clinical trial was conducted using a 3-arm parallel group, double-blind, vehicle and active comparator design and included 38 patients with chronic plaque psoriasis measuring less than or equal to 100 cm2 performed in a tertiary care hospital.
In the first arm, a total of 24 patients were randomized to receive either cyclosporine lipogel, 2.0% weight by weight (w/w), or placebo lipogel. In the second arm, 7 patients were randomized to receive cyclosporine lipogel, 2.0%, or conventional cyclosporine cream, 2.0% w/w. The third arm comprised 7 patients randomized with cyclosporine lipogel, 2.0% or standard clobetasol propionate cream, 0.05% w/w. Patients were examined twice weekly for 14 weeks, or until total lesional clearance was observed, whichever was earlier.
The primary outcome measure was the dermatological sum score (DSS) assessing erythema, scaling, and plaque elevation on a 4-point scale (0, absent; 1, minimal; 2, moderate; 3, severe).
In 38 patients (23 men and 15 women with a mean [SD] age range from 35 [8] to 40 [13] years), a 19% decrease in DSS score from a mean (SD) of 8.45 (0.67) to 6.82 (0.77) compared with baseline was observed after 2 weeks of treatment with cyclosporine lipogel, 2.0% w/w (P < .001; 95% CI, 13.77-24.51) in 59% of psoriasis lesional sites. At the end of the eighth week, a significant reduction (approximately 83%) in DSS was seen in all sites treated with cyclosporine lipogel, (P < .001; 95% CI, 77.48-88.22). At the end of the study period, complete clearance (ie, DSS = 0) was observed in 16 (41%) psoriasis lesional sites treated with cyclosporine lipogel, 85.7% of sites treated with clobetasol propionate cream, and none of the sites treated with conventional cyclosporine cream or placebo gel.
Topical liposomal formulation of cyclosporine, 2.0% w/w, is effective in treatment of limited chronic plaque psoriasis with a satisfactory safety profile. Future clinical trials should assess liposomal cyclosporine in larger study populations.
Clinical Trials Registry-India Identifier: CTRI/2011/12/002307.
由于常规剂型的环孢素物理化学性质不佳和制剂设计不当，尝试将局部环孢素用于治疗银屑病均以失败告终。
评估使用脂质体纳米载体（脂质体凝胶）治疗局限性慢性斑块状银屑病的疗效。
设计、地点和参与者：这是一项单中心随机临床试验，采用 3 臂平行分组、双盲、载体和阳性对照设计，纳入了 38 名患有慢性斑块状银屑病的患者，银屑病面积和严重程度指数（PASI）评分≤100cm2，在一家三级护理医院进行。
在第一组中，共有 24 名患者随机分为接受环孢素脂质体凝胶 2.0%（重量/重量）或安慰剂脂质体凝胶治疗。在第二组中，7 名患者随机分为接受环孢素脂质体凝胶 2.0%或常规环孢素乳膏 2.0% w/w 治疗。第三组由 7 名患者随机分组，接受环孢素脂质体凝胶 2.0%或标准丙酸氯倍他索乳膏 0.05% w/w 治疗。患者每周检查 2 次，持续 14 周，或直到观察到总皮损清除，以先达到者为准。
主要结局指标是评估红斑、鳞屑和斑块隆起的皮肤科总和评分（DSS），采用 4 分制（0，无；1，轻度；2，中度；3，重度）。
在 38 名患者（23 名男性和 15 名女性，平均[标准差]年龄范围为 35[8]至 40[13]岁）中，与基线相比，在接受环孢素脂质体凝胶 2.0% w/w 治疗 2 周后，DSS 评分从平均（标准差）8.45（0.67）下降到 6.82（0.77），下降了 19%（P < .001；95%置信区间，13.77-24.51），在 59%的银屑病皮损部位。在第 8 周末，所有接受环孢素脂质体凝胶治疗的部位 DSS 均显著降低（约 83%）（P < .001；95%置信区间，77.48-88.22）。在研究结束时，接受环孢素脂质体凝胶治疗的 16 个（41%）银屑病皮损部位达到完全清除（即 DSS=0），接受丙酸氯倍他索乳膏治疗的 85.7%的部位达到完全清除，而接受常规环孢素乳膏或安慰剂凝胶治疗的部位均未达到完全清除。
2.0% w/w 的局部脂质体环孢素制剂在治疗局限性慢性斑块状银屑病方面是有效的，且具有良好的安全性。未来的临床试验应在更大的研究人群中评估脂质体环孢素。
印度临床试验注册中心标识符：CTRI/2011/12/002307。
