title: Serum interleukin 6 before and after therapy with tocilizumab is a principal biomarker in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Biologic treatments including the humanized anti-interleukin 6 (anti-IL-6) receptor antibody tocilizumab (TCZ) provide therapeutic options for patients with rheumatoid arthritis (RA). We investigated useful biomarkers to predict the responsiveness to TCZ by measurement of serum proinflammatory cytokine concentrations.
  
  
  METHODS
  Serum samples were collected from 61 patients with RA before biologic treatment and at 4 weeks after initial administration of either TCZ (n = 32) or infliximab (IFX; n = 29) and from 13 healthy serum donor controls. Disease Activity Score of 28 joints (DAS28) was determined at baseline and after treatment.
  
  
  RESULTS
  Although IL-1β, IL-2, IL-6, IL-17A, IL-17F, interferon-α, and tumor necrosis factor-α (TNF-α) were all increased in sera from patients with RA compared with controls, only the IL-6 level was significantly correlated with DAS28 before treatment. The IL-6 level before treatment was positively correlated with DAS28 after TCZ treatment, and was significantly lower in TCZ-responsive patients (as judged by a post-treatment DAS28 < 3.2) than in TCZ-resistant patients (post-treatment DAS28 ≥ 3.2). DAS28 after TCZ was significantly lower than after administration of IFX in patients with low pretreatment IL-6 (< 51.5 pg/ml, the mean baseline value of IL-6 in all RA patients), but not in those with high pretreatment IL-6. These results indicate that low serum IL-6 is associated with a favorable response to TCZ.
  
  
  CONCLUSIONS
  Although both TNF-α and IL-6 are major targets of therapeutic intervention in RA, baseline serum IL-6 but not baseline TNF-α level is a potential biomarker reflecting disease activity. Measurement of serum IL-6 in RA before treatment may be useful to estimate residual disease activity after TCZ treatment and to predict responsiveness to TCZ treatment.
authors: First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
authors: Keiko
authors: K
authors: Shimamoto
authors: Tomoki
authors: T
authors: Ito
authors: Yoshio
authors: Y
authors: Ozaki
authors: Hideki
authors: H
authors: Amuro
authors: Akihiro
authors: A
authors: Tanaka
authors: Tohru
authors: T
authors: Nishizawa
authors: Yonsu
authors: Y
authors: Son
authors: Muneo
authors: M
authors: Inaba
authors: Shosaku
authors: S
authors: Nomura
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; C502936:tocilizumab
keywords: DISEASE ACTIVITY SCORE 28; INFLAMMATORY CYTOKINES; INFLIXIMAB; INTERLEUKIN 6; RHEUMATOID ARTHRITIS; TOCILIZUMAB; TUMOR NECROSIS FACTOR-α