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

Abstract

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.

Evaluation of ICAM‐1 expression and vascular changes in the skin of patients with plaque, pustular, and erythrodermic psoriasis

“…Its development depends on predisposing genetic factors, triggering external stimuli, and also changes in the immune system, with activation of T lymphocytes . These cells stimulate the release of proinflammatory cytokines, especially tumor necrosis factor alpha (TNF‐alpha) . Psoriasis can manifest in various forms (plaque, guttate, inverted, pustular, arthropathic, and erythrodermic psoriasis) and can be severe.…”

“…Psoriasis can manifest in various forms (plaque, guttate, inverted, pustular, arthropathic, and erythrodermic psoriasis) and can be severe. Severe psoriasis occurs in 20–30% of patients and, among these, 10–15% have associated psoriatic arthritis …”

Reporting the response to anti-tumour necrosis factor treatment

“…Although commercial enzyme‐linked immunosorbent assay systems detecting ADA and measuring drug levels exist, they are not standardized and are limited in use, especially because each individual biopharmaceutical requires specific tests for drug and ADA levels. In this issue of the BJD , Kimura and colleagues demonstrate the features of a cell line, THP‐G8, containing a luciferase gene under the control of the IL‐8 promoter, for therapeutic drug monitoring in psoriasis . The expression of IL‐8, a chemokine identified in psoriatic scales 30 years ago, is regulated by TNF and other innate factors.…”

“…The authors report a cell‐based in vitro testing system that allows measuring of the TNF‐dependent IL‐8 promoter activity and its relative suppression by monoclonal anti‐TNF antibodies or by plasma of patients treated with infliximab or adalimumab. The authors demonstrate in an elegant way a significant correlation between the degree of clinical improvement and the degree of suppression of the TNF–mediated IL‐8 promoter activity using plasma of patients treated with TNF antagonists . In a first small‐sized proof of concept study they monitored Psoriasis Area and Severity Index (PASI) changes, drug‐specific trough levels and ADA levels, and compared the data with the suppression of the luciferase activity in THP‐G8 cells incubated with patients’ plasma .…”

“…The authors demonstrate in an elegant way a significant correlation between the degree of clinical improvement and the degree of suppression of the TNF–mediated IL‐8 promoter activity using plasma of patients treated with TNF antagonists . In a first small‐sized proof of concept study they monitored Psoriasis Area and Severity Index (PASI) changes, drug‐specific trough levels and ADA levels, and compared the data with the suppression of the luciferase activity in THP‐G8 cells incubated with patients’ plasma . Presumably, this test can be used as an indicator for the therapeutic response to infliximab, adalimumab and similarly also to other TNF antagonists and biosimilars.…”