Progression-survival dissociation in connective tissue disease (CTD)-associated interstitial lung disease (ILD): CTD-ILD versus non-CTD ILD in real-world practice

Background Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a clinically relevant subtype of fibrotic ILD. We compared baseline characteristics, treatment patterns, transplant-free survival (TFS) and progression-free survival (PFS) between CTD-ILD and non-CTD ILD. Methods In the prospective German INSIGHTS-ILD registry, patients with known CTD status at baseline were classified as CTD-ILD or non-CTD ILD. TFS and PFS were analysed using Kaplan–Meier and log-rank tests. PFS was defined by a prespecified composite end-point including lung function decline, oxygen escalation, 6-min walk distance decline, respiratory hospitalisation, death or clinical worsening prompting any medical therapy escalation or switch. Cox models included the unadjusted Model A; Model B adjusted for age, sex, smoking, comorbidity count and baseline antifibrotic therapy; Model C additionally adjusted for baseline forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide; and Model D additionally adjusted for time since diagnosis. Results 332 patients (35.7%) had CTD-ILD and 598 (64.3%) had non-CTD ILD. Patients with CTD-ILD were younger, more often female and more frequently received immunomodulatory therapy, whereas antifibrotic use was similar between groups. TFS was similar at 1 year (90.8% versus 90.9%; p=0.57) and at 2 years (83.7% versus 81.9%). In contrast, PFS was higher in CTD-ILD at 1 year (71.8% versus 62.7%; p=0.0032) and 2 years (52.6% versus 41.7%), with less FVC decline over follow-up. CTD-ILD was associated with a lower risk of progression in the unadjusted model (HR 0.73, 95% CI 0.59–0.90; p=0.003) and across all adjusted models. Conclusion In routine care, CTD-ILD showed similar TFS but better PFS and less FVC decline than non-CTD ILD.