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

Mod Rheumatol. 2013 Mar;23(2):284-96. doi: 10.1007/s10165-012-0657-2. Epub 2012 May 17.

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.

Conclusion: 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.

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy
  • Certolizumab Pegol
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunoglobulin Fab Fragments / adverse effects*
  • Immunoglobulin Fab Fragments / therapeutic use
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Mucin-1 / blood*
  • Polyethylene Glycols / adverse effects*
  • Polyethylene Glycols / therapeutic use
  • Severity of Illness Index
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Immunoglobulin Fab Fragments
  • MUC1 protein, human
  • Mucin-1
  • Tumor Necrosis Factor-alpha
  • Polyethylene Glycols
  • Certolizumab Pegol
  • Methotrexate