PO:24:064 | IPF vs CTD-ILD: Survival and Lung Function from an Italian Real-World Cohort

Marco Fornaro¹, Donato Lacedonia², Lorenzo Cavagna³, Paolo Airò⁴, Marco Sebastiani⁵, Gianluca Sambataro⁶, Fabio Cacciapaglia⁷, Angelica Napoletano¹, Cosimo De Pace², Pasquale Tondo², Giulia Scioscia², Eleonora Pedretti⁴, Maria Grazia Lazzaroni⁴, Carlo Vancheri⁸, Andreina Manfredi⁹, Lorenzo Binchessi³, Rocco Capece³, Michele De Ceglie¹⁰, Massimo Giotta¹¹, Florenzo Iannone¹ | ¹Unit of Rheumatology, Department of Precision and Regenerative Medicine - Area Jonica DiMePRe-J, University of Bari, Bari, Italy; ²Department of Medical and Surgical Sciences, University of Foggia Foggia, Italy; ³Department of Internal Medicine and Therapeutics, University of Pavia, Division of Rheumatology, Fondazione IRCCS, Pavia, Italy; ⁴Rheumatology and Clinical Immunology Unit, Department of Clinical and Experimental Sciences, ASST Spedali Civili Brescia, Italy; ⁵Rheumatology Unit, AUSL Piacenza, Department of Medicine and Surgery, University of Parma, Parma, Italy; ⁶Department of Medicine and Surgery, University of Enna Kore, Enna, Italy; ⁷Rheumatology Service, F. Miulli Hospital and Department of Medicine and Surgery, LUM University, Casamassima, Italy; ⁸Department of Clinical and Experimental Medicine, Regional Referral Center for Rare Lung Diseases, Catania, Italy; ⁹Rheumatology Unit, IRCCS Santa Maria Nuova Reggio Emilia, University of Modena, Modena, Italy; ¹⁰DIM, Interdisciplinary Department of Medicine, Section of Diagnostic Imaging, University of Bari, Bari, Italy; ¹¹Health Prevention Department, Local Health Authority of Brindisi, Brindisi, Italy

Aim. To compare survival outcomes and pulmonary function trajectories in patients with idiopathic pulmonary fibrosis (IPF) versus connective tissue disease-associated interstitial lung disease (CTD-ILD), including detailed analysis of CTD subtypes.

Methods. This retrospective study included 410 ILD patients (154 IPF, 256 CTD-ILD) from six Italian tertiary centers. CTD-ILD subtypes analyzed were antisynthetase syndrome (ASyS, n=58), dermatomyositis (DM, n=55), systemic sclerosis (SSc, n=106), and Sjögren’s syndrome (SS, n=37). Pulmonary function was assessed at baseline and during follow-up (median 12 months), including FVC and DLCO. ILD patterns were categorized via HRCT. Five-year survival was evaluated with Kaplan–Meier analysis and multivariate Cox regression. Functional changes were analyzed using MANOVA for repeated measures.

Results. IPF patients were older (median age 70) and predominantly male (77%), while CTD-ILD patients were younger and mostly female. The UIP pattern was universal in IPF but present in <20% of CTD-ILD cases (Figure 1A). Five-year survival was significantly lower in IPF (SR: 13.14%, 95% CI: 4.77–21.5) compared to CTD-ILD (SR: 77.03%, 95% CI: 68.9–85.16; log-rank p<0.001) (Figure 1B). Among CTD subtypes, survival was similar: ASyS (SR:81.9%), DM (SR:69.2%), SSc (SR:78.9%), SS (SR:77.5%) (Figure 1C). Progressive ILD, as defined by INBUILD criteria, was less common in CTD-ILD groups, with the highest rates in DM (16.3%), followed by ASyS (13.2%), SSc (8.6%), and SS (2.7%). In multivariate analysis, CTD-ILD was associated with a markedly better prognosis (aHR 0.210; 95% CI 0.13–0.35). Male sex (aHR 1.980) and age (aHR 1.060 per year) were independent risk factors for death. Within CTD-ILD, pulmonary arterial hypertension was strongly associated with mortality (aHR 8.08). Pulmonary function analysis revealed contrasting trends. In IPF, FVC declined from 78% to 72% (-7.7% relative). In contrast, ASyS and DM patients showed FVC improvements: ASyS from 71% to 81% (+14.1%), DM from 69% to 78% (+13.0%). DLCO also improved in ASyS (+7.8%). No significant FVC or DLCO changes were observed in SSc and SS (Figure 1D). The ILD radiologic pattern, including UIP, did not significantly impact functional outcomes in CTD-ILD; the underlying diagnosis was the key determinant (p<0.001).

Conclusions. CTD-ILD patients have better survival and often stable or improving lung function, particularly in ASyS and DM, compared to the progressive decline seen in IPF. The prognosis is primarily shaped by the underlying rheumatic diagnosis rather than fibrotic pattern, supporting a diagnosis-centered management strategy.