Trajectory of Pulmonary Function Tests in Patients With Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD): Data from the German Network for Systemic Sclerosis

Abstract Background: Interstitial lung disease (ILD) is one of the leading causes of death in systemic sclerosis (SSc). The decline in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) in patients with SSc-ILD seems to be highly variable, but systematic investigation is needed.The aim of this analysis was to determine the decline of FVC and DLco over time in patients with SSc-ILD from the registry of the German Network for Systemic Sclerosis (DNSS). Patients and methods: Clinical data of 6,234 patients with SSc were collected in the German Network for Systemic Sclerosis registry. Patients who developed ILD during and had at least two measurements of FVC and DLco during follow up were included in the analysis. Disease progression was defined as ≥ 10% relative decline in FVC% pred. or ≥ 5 to < 10% decline in relative FVC pred. and 15% relative decline in DLCO% pred. from baseline.Change in FVC and DLco was analysed using a mixed model for repeated measures (MMRM) with random imputation of missing data and adjustment for a number of covariates. Results: 1313 patients with SSc-ILD and at least one measurement of FVC and DLco over time were included in the analysis. Mean follow-up time was 3.99 ± 1.79 years and 246 (19%) patients had disease progression. The observed all caused mortality in 417 patients with complete follow up was 6 (1.4%). Mean time to disease progression was 2.84 ± 1.72 years. The estimated average rate of decline in FVC % pred. was 7.33% per year in patients with ILD progression with a difference of 16.91% to non-progressors (p= <0.001).The estimated average rate of decline in DLco % pred. was 9.16% per year in patients with a difference of 12.09% to non-progressors (p= <0.001).Patients with progression were significantly older at time of ILD diagnosis compared to those who remained stable (50 ± 15 vs 47 ± 14, p=0.011). No differences between progressors and stable patients were observed in terms of BMI, smoking habits, antibody status, extension of skin involvement, prevalence of pulmonary hypertension, inflammatory markers, and treatment with steroids or immunosuppressants. Conclusion: Disease progression in SSc-ILD patients seems to occur within the first 5 years after ILD diagnosis, with a similar trend in FVC and DLco decline. Clinical factors associated with ILD progression remain unclear.