title: Elevation of KL-6 serum levels in clinical trials of tumor necrosis factor inhibitors in patients with rheumatoid arthritis: a report from the Japan College of Rheumatology Ad Hoc Committee for Safety of Biological DMARDs.
abstract: OBJECTIVE
  The associations between elevated levels of serum Krebs von den Lungen-6 (KL-6) and treatment of rheumatoid arthritis (RA) with tumor necrosis factor (TNF) inhibitors were investigated in five Japanese clinical trials.
  
  
  METHODS
  Percentages and incidence rates were calculated for elevated serum KL-6 levels. Adverse events associated with elevated levels of serum KL-6 were investigated.
  
  
  RESULTS
  In RISING, a clinical trial for infliximab, 15.6 % of the enrolled patients met criterion B (KL-6 ≥500 U/ml and >1.5-fold increase over the baseline value) by week 54. In HIKARI, 7.8 % of the certolizumab pegol (CZP) group and 0 % of the placebo group met criterion B during the double-blind (DB) period (p = 0.003). In J-RAPID, 8.4 % of the methotrexate (MTX) + CZP and 3.9 % of the MTX + placebo groups met criterion B during the DB period. In GO-MONO, 1.8 % of the golimumab (GLM) and 1.3 % of the placebo groups met criterion B during the DB period. In GO-FORTH, 7.1 % of the MTX + GLM and 0 % of the MTX + placebo groups met criteron B during the DB period (p = 0.017). No adverse events accompanied the elevation of serum KL-6 levels in 95.7 % of these patients.
  
  
  CONCLUSIONS
  Serum KL-6 levels may increase during anti-TNF therapy without significant clinical events. In these patients, continuing treatment with TNF inhibitors under careful observation is a reasonable option.
authors.affiliation: The Ad Hoc Committee for the Safety of Biological DMARDs, Japan College of Rheumatology, 1-1-24 Toranomon, Minato-ku, Tokyo 105-0001, Japan. mharigai.mpha@tmd.ac.jp
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Harigai
authors.forename: Akito
authors.initials: A
authors.lastname: Takamura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
authors.forename: Makoto
authors.initials: M
authors.lastname: Dohi
authors.forename: Shintaro
authors.initials: S
authors.lastname: Hirata
authors.forename: Hideto
authors.initials: H
authors.lastname: Kameda
authors.forename: Hayato
authors.initials: H
authors.lastname: Nagasawa
authors.forename: Yohei
authors.initials: Y
authors.lastname: Seto
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy; D000068582:Certolizumab Pegol; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007140:Immunoglobulin Fab Fragments; C060192:MUC1 protein, human; D018396:Mucin-1; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D000068582:Certolizumab Pegol; D008727:Methotrexate