Therapeutic drug monitoring of patients with psoriasis during tumour necrosis factor (TNF)-α antagonist treatment using a novel interleukin-8 reporter cell line

银屑病 肿瘤坏死因子α 医学 银屑病面积及严重程度指数 药理学 敌手 细胞因子 内科学 白细胞介素 受体拮抗剂 白细胞介素6 免疫学 受体
作者
Yutaka Kimura,Ryoko Shimada‐Omori,Toshiya Takahashi,Kenichiro Tsuchiyama,Yoshiyuki Kusakari,Kenshi Yamasaki,Rika Nishikawa,Chikako Nishigori,Setsuya Aiba
出处
期刊:British Journal of Dermatology [Wiley]
卷期号:175 (5): 979-987 被引量:4
标识
DOI:10.1111/bjd.14717
摘要

Tumour necrosis factor (TNF)‐α antagonist therapy is currently used for moderate and severe psoriasis. However, this treatment has several drawbacks, including interindividual variability in clinical response and secondary loss of effectiveness. To evaluate quantitatively the TNF‐α‐neutralizing activity of the plasma of patients with psoriasis during TNF‐α antagonist therapy and to determine poor responders objectively. We used a human interleukin‐8 reporter monocyte cell line, THP‐G8, that harbours a stable luciferase orange (SLO) gene under the control of the interleukin‐8 promoter. After confirming its dose‐dependent response to exogenous TNF‐α, we examined the suppressive activity of TNF‐α antagonists and of the patients’ plasma during TNF‐α antagonist therapy on TNF‐α‐induced SLO luciferase activity (TNF‐SLO‐LA). Pretreatment of TNF‐α with TNF‐α antagonists or with the plasma of patients with psoriasis who achieved 75% improvement in Psoriasis Area and Severity Index (PASI 75) dose dependently suppressed TNF‐SLO‐LA. There was a significant correlation between change in PASI and percentage suppression (inhibitory rate of a 1 : 2 dilution of patient plasma on TNF‐SLO‐LA). A percentage suppression of 50·3% has a positive predictive value of 87% of achieving PASI 75, with a sensitivity of 93% and a specificity of 80%. Therapeutic monitoring of patients with psoriasis during TNF‐α antagonist therapy using THP‐G8 can provide a useful tool to determine objectively the efficacy of the administered TNF‐α antagonists.
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