Longitudinal changes in KL6 levels predict acute exacerbation in fibrotic interstitial lung disease

Krebs von den Lungen-6 (KL-6) levels are potentially indicative markers of prospective acute exacerbation (AE) in interstitial lung disease (ILD); however, their longitudinal trends have not been sufficiently investigated. We investigated the predictive ability of patient-specific changes in serum KL-6 levels for predicting AE in patients with fibrotic ILD. We included patients with fibrotic ILDs from the RWD database in Japan who received antifibrotic therapy and had at least two serum KL-6 values during the follow-up. The outcome was AE defined based on primary diagnoses, emergency admission, and pulse/high-dose steroids on the day of or after admission. We used the joint regression model integrating longitudinal and survival analyses to assess the predictive ability of each patient's serial serum KL-6 measurements for AE. Among 939 patients with fibrotic ILDs, 194 (21%) patients experienced AE during follow-up (event rate, 0.13/person-year; 1-year incidence, 35%). The AE hazard ratio comparing patients with differing cumulative serum KL-6 levels was 1.54 (95% confidence interval: 1.20-1.98, p < 0.001). In conclusion, AE in fibrotic ILD patients on antifibrotic therapy may be predicted by high baseline KL-6 levels and their increasing trend. Serial KL-6 monitoring can serve as a valuable tool in a multifaceted approach.