Interstitial lung disease (ILD) is one of the major determinants of prognosis in idiopathic inflammatory myopathy (IIM), underscoring the importance of timely detection and longitudinal surveillance. The optimal surveillance interval and the utility of biomarkers for monitoring disease progression remain to be established. The objectives of this study were to characterize real-world diagnostic timelines in IIM-ILD, define distinct longitudinal KL-6 trajectories, and explore the value of long-term KL-6 monitoring in the detection of progressive pulmonary fibrosis (PPF).

IIM-ILD patients were retrospectively enrolled with demographic and clinical data collected. Diagnostic timelines from symptom onset to IIM and ILD diagnosis were characterized. Longitudinal KL-6 trajectories were identified using growth mixture model (GMM). PPF was assessed during follow-up.

Of 344 IIM-ILD patients, the most common initial manifestations were cutaneous (28.5%), respiratory (20.1%), muscular manifestations (12.8%), and arthritis (12.5%), whereas 29.1% never developed respiratory symptoms. Time to IIM or ILD diagnosis differed according to initial presentation. ILD and IIM were diagnosed concurrently in 23.0% of patients, while ILD preceded IIM in 49.7%; overall, 95.3% received an ILD diagnosis either before or within 1 year after IIM diagnosis, with diagnostic intervals varying across autoantibody subgroups. Longitudinal analysis of 146 IIM-ILD patients (861 measurements; median follow-up 31.5 months) identified three KL-6 trajectory classes: high-decreasing (50.7%), low-stable (31.5%), and fluctuating-decreasing (17.8%). Although baseline characteristics differed across trajectories, PPF incidence did not differ (P>0.05). Cross-sectionally, KL-6 levels were inversely correlated with FVC%pred and DLCO%pred (P<0.001), whereas longitudinal KL-6 changes were not associated with pulmonary function decline(P>0.05). Among 55 PPF cases, KL-6 levels increased at progression (P=0.026); 85.7% exceeded 500 U/mL and 70.9% increased relative to the last pre-PPF measurement.

Serial HRCT surveillance and close respiratory monitoring during at least the first year after IIM diagnosis may facilitate timely ILD detection. Long-term KL-6 trajectory patterns did not discriminate PPF risk. Increases at progression support KL-6 as a complementary role rather than standalone marker in routine disease monitoring.