title: Therapeutic drug monitoring of patients with psoriasis during tumour necrosis factor (TNF)-α antagonist treatment using a novel interleukin-8 reporter cell line.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Shimada-Omori
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tsuchiyama
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kusakari
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamasaki
authors.affiliation: Division of Dermatology, Department of Internal Related Medicine, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Nishikawa
authors.affiliation: Division of Dermatology, Department of Internal Related Medicine, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Nishigori
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. saiba@med.tohoku.ac.jp.
authors.forename: S
authors.initials: S
authors.lastname: Aiba
mesh_terms: D000068879:Adalimumab / Q000276:immunology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000378:metabolism; D002460:Cell Line; D003879:Dermatologic Agents / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D000069285:Infliximab / Q000276:immunology / Q000627:therapeutic use; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D055815:Young Adult
chemical_list: D000906:Antibodies; D003879:Dermatologic Agents; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab