An open-label, single-arm pilot study in patients with severe plaque-type psoriasis treated with an oral anti-inflammatory agent, apremilast
An open-label, single-arm pilot study in patients with severe plaque-type psoriasis treated with an oral anti-inflammatory agent, apremilast
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DOI：
10.1185/030079908x301866
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发表时间：
2008-05-01
影响因子：
2.3
通讯作者：
Kipnis, C.
中科院分区：
文献类型：
--
作者：
Gottlieb, A. B.;Strober, B.;Kipnis, C.
目的：评价阿普斯特对严重斑块型银屑病患者的临床和生物学活性。研究设计和方法：阿普斯特是一种磷酸二酯酶4抑制剂，在体外可抑制多种与银屑病发病有关的炎症因子的活性。患者口服 20 mg 阿普斯特，持续 29 天。对病变皮肤活检进行免疫组织学分析，以检测银屑病相关的炎症标志物。评估血液中脂多糖刺激的肿瘤坏死因子-α水平。银屑病面积和严重程度指数 (PASI)、静态医师整体评估和体表面积用于监测疾病严重程度。结果：共有 19 名患者参加了本研究，其中 17 名完成了研究。到第 29 天，表皮厚度比基线平均减少了 20.5%。在反应者中，真皮和表皮中的 T 细胞分别减少了 28.8% 和 42.6%。同样，真皮和表皮中的 CD11 c 细胞分别减少了 18.5% 和 40.2%。 19 名患者中有 14 名 (73.7%) 的 PASI 评分有所改善。 局限性：这是一项小型、单臂、开放标签的试点研究；因此既没有安慰剂也没有对照组。结论：阿普司特在严重斑块型银屑病患者中表现出生物活性并改善了银屑病临床疗效评分。大多数不良事件性质轻微。研究者判断两种不良事件（疲劳和头晕）为中度且与阿普斯特相关。此外，接受阿普斯特治疗29天的受试者没有出现临床相关的异常实验室检测结果。
Objective:To evaluate the clinical and biological activity of apremilast in patients with severe plaque-type psoriasis.Research design and methods: Apremilast, a phosphodiesterase-4 inhibitor, inhibits in vitro activity of multiple inflammatory factors implicated in the pathogenesis of psoriasis. Patients received 20 mg apremilast orally for 29 days. Immunohistological analysis was conducted on lesional-skin biopsies for psoriasis-associated inflammatory markers. Lipopolysaccharide-stimulated tumor necrosis factor-alpha levels were evaluated in blood. Psoriasis Area and Severity Index (PASI), static Physician's Global Assessment, and Body Surface Area were used to monitor disease severity.Results: There were 19 patients enrolled in this study, of whom 17 completed the study. Epidermal thickness was reduced by a mean of 20.5% from baseline to day 29. Among the responders, T cells were reduced by 28.8% and 42.6% in the dermis and epidermis, respectively. Similarly, CD11 c cells were reduced by 18.5% and 40.2% in the dermis and epidermis, respectively. Fourteen of the 19 (73.7%) patients demonstrated an improvement in their PASI scores.Limitations: This was a small, single-arm, open-label pilot study; therefore there was neither a placebo nor a comparison group.Conclusion: Apremilast demonstrated biological activity and improved psoriasis clinical efficacy scores in patients with severe plaque-type psoriasis. The majority of adverse events were mild in nature. Two adverse events (fatigue and dizziness) were judged by the investigator to be moderate and related to apremilast. In addition, there were no clinically-relevant abnormal laboratory test results in subjects treated with apremilast for 29 days.