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

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. Japan College of Rheumatology 2012.