New treatment paradigms for connective tissue disease-associated interstitial lung disease

Interstitial lung disease (ILD) is frequently observed in connective tissue disease (CTD) and is a major cause of mortality. In CTD-ILD, a marked variability in morphological patterns, time course and severity exists. In many patients, CTD-ILD is limited and inherently stable, although a significant proportion of patients have progressive disease. We review the utility of integration of the recently proposed disease behavior classification into the management of CTD-ILD, and recent advances in treatment approaches.

Recent studies on scleroderma-ILD (SSc-ILD) staging and short-term lung function trends provide important information, although accurate prognostic markers, particularly in limited/early CTD-ILD, are still needed. Most patients with progressive CTD-ILD stabilize on immunosuppression, as observed in recent SSc-ILD trials and CTD-ILD retrospective series. A minority of patients present with life-threatening acute/subacute ILD, requiring intense immunosuppression, with limited available guidance. A significant minority of CTD-ILD patients have progressive disease despite immunosuppression. Ongoing trials with antifibrotic agents and with biologic agents may reveal a potential role for their use/addition.

Ultimately, further research into the mechanisms linking autoimmunity to fibrosis and randomized controlled clinical trials are needed, with the aim of preventing irreversible damage of lung tissue, while minimizing burden of treatment.