Serum KL-6 Elevation and Possible Pulmonary Involvement in Patients with Rheumatoid Arthritis Treated with Biological Agents

Backgrounds: Interstitial lung disease (ILD) is associated with rheumatoid arthritis (RA) itself and is also induced by biological and non-biological disease-modifying antirheumatic drugs. The glycoprotein Krebs von den Lungen-6 (KL-6) is reported to be a marker for the activity of ILD. Objectives: To elucidate the relationship between serum KL-6 levels in patients with RA treated with biological agents and pulmonary involvement on computed tomography of the chest. Methods: The subjects were 307 patients with RA treated with infliximab, etanercept, adalimumab, or tocilizumab. Medical records were reviewed to investigate serum KL-6 levels, disease activity, and pulmonary imaging findings. Results: Levels of KL-6 were abnormally elevated in 25 patients (8.1%): 15 patients (11.2%) treated with infliximab, 6 patients (4.4%) treated with etanercept, and 4 patients (22.2%) treated with adalimumab, but in no patients treated with tocilizumab. However, no clinical pulmonary events developed. Computed tomography of the chest showed the start or progression of interstitial fibrotic change in 5 of 25 (20%) patients with abnormal KL-6 values. The changes in disease activity did not differ significantly between patients who showed elevated KL-6 values and those who did not. Conclusions: Serum KL-6 levels were elevated in 8.1% of patients with RA treated with biological agents. Careful observation is necessary for these patients regarding lung fibrosis.