Seyger M, Abramovits W, Liljedahl M, Hoejen M N, Teng J
Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands.
Dermatology Treatment & Research Centre, Dallas, TX, USA.
J Eur Acad Dermatol Venereol. 2020 Sep;34(9):2026-2034. doi: 10.1111/jdv.16233. Epub 2020 Feb 19.
Fixed-dose combination of calcipotriol (50 μg/g; Cal) and betamethasone dipropionate (0.5 mg/g; BD) foam is approved for plaque psoriasis treatment in adults, with a paucity of data supporting use in adolescents.
To evaluate safety of 4 weeks' treatment with Cal/BD foam in adolescent patients with psoriasis, and additional safety outcomes in patients with more severe disease (HPA-axis cohort). Primary objectives included treatment-emergent adverse events (TEAEs) and systemic calcium levels in the overall population, and HPA-axis function, change in calcium excretion and the calcium:creatinine ratio in the HPA-axis cohort. Secondary objectives included exploratory efficacy endpoints [treatment success: change in Psoriasis Area and Severity Index (PASI)]. Systemic exposure to Cal/BD was also assessed.
A phase II, open-label, study (NCT02387853) in patients (12 to <17 years) with at least mild psoriasis, to evaluate Cal/BD foam applied once daily for ≤4 weeks.
In patients assigned to treatment (n = 106), 32 TEAEs occurred in 22 patients (20.8%). All but two TEAEs were mild; none led to study withdrawal or death. Changes (0-4 weeks) in albumin-corrected serum calcium (overall population) and urinary calcium excretion (HPA-axis cohort) were small, transient and not considered clinically relevant. In the HPA-axis cohort, no change in urinary calcium:creatinine ratio was observed and responses to adrenocorticotropic-hormone (ACTH) challenge did not suggest disruption of the HPA-axis. Prespecified treatment success on the body and scalp was achieved by 71.8% and 75.7% of the overall population, respectively. Mean PASI decreased by 82.0% vs. baseline at Week 4. Systemic exposure to Cal/BD was minimal.
Cal/BD foam was well tolerated in adolescent patients with body/scalp psoriasis. There was no evidence for dysregulation of the HPA-axis nor calcium homoeostasis in patients with more severe disease. Exploratory efficacy data in the overall population were encouraging.
卡泊三醇（50μg/g；Cal）和二丙酸倍他米松（0.5mg/g；BD）泡沫固定剂量复方已获批用于治疗成人斑块状银屑病，而支持其在青少年中使用的数据较少。
评估Cal/BD泡沫治疗青少年银屑病患者4周的安全性，以及病情更严重患者（下丘脑-垂体-肾上腺轴队列）的其他安全性指标。主要目标包括总体人群中的治疗突发不良事件（TEAE）和血清钙水平，以及下丘脑-垂体-肾上腺轴队列中的下丘脑-垂体-肾上腺轴功能、钙排泄变化和钙与肌酐比值。次要目标包括探索性疗效终点[治疗成功：银屑病面积和严重程度指数（PASI）变化]。还评估了Cal/BD的全身暴露情况。
一项针对至少患有轻度银屑病的12至<17岁患者的II期开放标签研究（NCT02387853），以评估每日一次外用Cal/BD泡沫，持续≤4周。
在分配接受治疗的患者（n = 106）中，22名患者（20.8%）发生了32起TEAE。除两起外，所有TEAE均为轻度；无一导致研究停药或死亡。白蛋白校正血清钙（总体人群）和尿钙排泄（下丘脑-垂体-肾上腺轴队列）在0至4周的变化较小、短暂且不被认为具有临床相关性。在下丘脑-垂体-肾上腺轴队列中，未观察到尿钙与肌酐比值的变化，对促肾上腺皮质激素（ACTH）刺激的反应也未提示下丘脑-垂体-肾上腺轴功能紊乱。总体人群中分别有71.8%和75.7%的患者在身体和头皮上达到了预定的治疗成功标准。第4周时，平均PASI较基线下降了82.0%。Cal/BD的全身暴露量极小。
Cal/BD泡沫在患有身体/头皮银屑病的青少年患者中耐受性良好。没有证据表明病情更严重的患者下丘脑-垂体-肾上腺轴失调或钙稳态失衡。总体人群中的探索性疗效数据令人鼓舞。
